Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Proposed mechanism of SCN4B in the regulation of EMT in lung adenocarcinoma. All activating signaling pathways are indicated by blue solid arrows, while all inhibitory pathways are represented by red T-shaped termination lines. SCN4B , sodium channel β4 subunit; EMT, epithelial-mesenchymal transition; CDH2, N-cadherin; HDAC, histone deacetylase.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Protein-Protein interactions, Histone Deacetylase Assay

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Differential expression analysis of SCN4B in LUAD. (A) Differential expression analysis of SCN4B in LUAD and adjacent non-tumorous tissue. A paired Student's t-test was used. (B) Gene Expression Omnibus cohort ( GSE31210 ; Affymetrix GPL570 ): Comparison of SCN4B microarray intensity between tumor and normal lung tissues. Welch's t-test was used. (C) Diagnostic receiver operating characteristic curve analysis of SCN4B . ***P < 0.001, ****P<0.0001. AUC, area under the curve; SCN4B , sodium channel β4 subunit; LUAD, lung adenocarcinoma; TPM, transcripts per million; TPR, true positive rate; FPR, false positive rate.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Quantitative Proteomics, Gene Expression, Comparison, Microarray, Diagnostic Assay

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Differentially expressed genes associated with SCN4B in lung adenocarcinoma. (A) Volcano plot illustrating SCN4B-associated differentially expressed genes in the dataset. Red dots represent upregulated genes, blue dots indicate downregulated genes and gray dots denote non-significant genes. (B) Spearman's rank correlation analysis between SCN4B and selected genes. P.adj, adjusted P-value; SCN4B , sodium channel β4 subunit; TPM, transcripts per million.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques:

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Functional enrichment analysis of SCN4B-associated differentially expressed genes. (A) Gene Ontology functional enrichment analysis based on differences. (B) KEGG functional enrichment analysis. KEGG, Kyoto Encyclopedia of Genes and Genomes; BP, biological process; CC, cellular component; MF, molecular function; P adj, adjusted P-value.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Functional Assay

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Analysis of immune infiltration related to SCN4B . (A) Bubble plot of immune infiltration analysis. (B) Correlation analysis of SCN4B expression with tumor purity, M2 macrophage infiltration (quanTIseq) and NK cell infiltration (quanTIseq). Spearman correlation analysis was performed; Ρ-values and P-values are shown. SCN4B , sodium channel β4 subunit; NK, natural killer; quanTIseq, quantification of the tumor immune contexture from RNA sequencing; TPM, transcripts per million.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Expressing, RNA Sequencing

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: SCN4B expression in lung cancer tissues and normal tissues. Immunohistochemical staining images of SCN4B expression in normal lung tissue and lung adenocarcinoma tumor tissue were obtained from the online Human Protein Atlas database ( https://www.proteinatlas.org/ ). The magnification of the first row of images is ×100; scale bar, 200 µm; the magnification of the second row of images is ×400; scale bar, 50 µm. SCN4B , sodium channel β4 subunit.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Expressing, Immunohistochemical staining, Staining

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Prognostic analysis and clinical association analysis of SCN4B . (A) Kaplan-Meier survival curve for overall survival stratified by SCN4B expression. (B) Kaplan-Meier survival curve for disease-specific survival based on SCN4B expression levels. (C) Kaplan-Meier survival curve for the progression-free interval in patients with high vs. low SCN4B expression. (D) Comparison of SCN4B expression across T stages (T1-T4). (E) SCN4B expression in patients with or without lymph node metastasis. (F) SCN4B expression in patients with or without distant metastasis. (G) SCN4B expression across different tumor stages. (D and E) Kruskal-Wallis test. (F and G) Wilcoxon rank-sum test. ***P < 0.001. HR, hazard ratio; ns, not significant (P > 0.05); SCN4B , sodium channel β4 subunit; TPM, transcripts per million.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Expressing, Comparison

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Prognostic association of SCN4B in the GSE31210 cohort. Kaplan-Meier curves were generated by stratifying patients into high and low SCN4B expression groups using the median expression value as the cutoff. The ‘number at risk’ table below the plot indicates the counts remaining at risk at each time point. Groups were compared using the two-sided log-rank test (P=0.0042). SCN4B , sodium channel β4 subunit.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Generated, Expressing

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Basal expression of SCN4B across lung cell lines. (A) Representative western blot images: Lane 1, normal lung cells; lanes 2–6, lung cancer cell lines. GAPDH served as the loading control. For densitometric quantification, SCN4B was normalized to GAPDH and further normalized to the normal cells (=1). (B) Reverse transcription-quantitative PCR validation in the same panel of distinct cell lines as in (A) (normalized to GAPDH; 2 −ΔΔCq ). One-way ANOVA with Dunnett's post hoc test was used for statistical analysis. N=3 independent experiments. *P < 0.05, **P < 0.01, ****P < 0.0001. ns, not significant (P > 0.05); SCN4B , sodium channel β4 subunit.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Expressing, Western Blot, Control, Reverse Transcription, Real-time Polymerase Chain Reaction, Biomarker Discovery

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: Construction of SCN4B overexpression models in A549 and H1299 lung adenocarcinoma cell lines. After transfection with overexpression plasmids for 48 h in A549 and H1299 cells, the relative mRNA expression level changes of SCN4B in the cells were detected by reverse transcription-quantitative PCR. Data were analyzed using a two-tailed unpaired Student's t-test. N=3 independent experiments. **P < 0.01. SCN4B , sodium channel β4 subunit; oe, overexpression.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Over Expression, Transfection, Expressing, Reverse Transcription, Real-time Polymerase Chain Reaction, Two Tailed Test

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: SCN4B induces apoptosis and inhibits cell viability. (A) Changes in the viability of A549 and H1299 cells at different time points after transfection (0, 24, 48 and 72 h) were detected using a Cell Counting Kit-8 assay. Data were analyzed using two-way ANOVA with Bonferroni's post hoc test. Changes in the proportion of apoptotic cells after 48 h of transfection in (B) A549 and (C) H1299 cells labeled with PI/annexin V-FITC double staining were detected by flow cytometry. Data were analyzes using a two-tailed unpaired Student's t-test. N=3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. ns, not significant (P > 0.05); SCN4B , sodium channel β4 subunit; oe, overexpression; OD, optical density.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Transfection, Cell Counting, Labeling, Double Staining, Flow Cytometry, Two Tailed Test, Over Expression

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: SCN4B can inhibit the invasion and migration of lung cancer cells. (A) Changes in the invasion of A549 and H1299 LUAD cells 48 h after transfection with SCN4B overexpression plasmid were detected using a Transwell assay (magnification, ×100; scale bar, 100 µm). (B) Changes in the migration of A549 and H1299 LUAD cells 48 h after transfection with SCN4B overexpression plasmid were detected using a cell scratch assay (magnification, ×100; scale bar, 200 µm). Data were analyzed using a two-tailed unpaired Student's t-test. N=3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001. SCN4B , sodium channel β4 subunit; oe, overexpression; LUAD, lung adenocarcinoma.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Migration, Transfection, Over Expression, Plasmid Preparation, Transwell Assay, Wound Healing Assay, Two Tailed Test

Journal: Oncology Reports

Article Title: Suppressive role of SCN4B in the epithelial-mesenchymal transition of lung adenocarcinoma

doi: 10.3892/or.2026.9073

Figure Lengend Snippet: SCN4B can inhibit the epithelial-mesenchymal transition process of LUAD cells. The relative protein expression levels of SCN4B, E-cadherin, N-cadherin, Vimentin and Snail in A549 and H1299 LUAD cells 48 h after transfection with SCN4B overexpression plasmid were detected by western blotting. Data were analyzed using a two-tailed unpaired Student's t-test for each protein. N=3 independent experiments. ****P < 0.0001. SCN4B, sodium channel β4 subunit; oe, overexpression; LUAD, lung adenocarcinoma.

Article Snippet: The immunohistochemical expression patterns of SCN4B in adjacent non-tumor and LUAD tissues were obtained from the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ).

Techniques: Expressing, Transfection, Over Expression, Plasmid Preparation, Western Blot, Two Tailed Test

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Volcano plots of significantly differentially expressed genes (DEGs) in a CAG-length-dependent manner in the direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons of an HD mouse model allelic series (Q50, Q111, Q170, zQ175), as reported by translating ribosome affinity purification (TRAP) profiling. (B) Representative RNAScope in situ hybridization images showing striatal caudate nucleus SCN4B RNA (yellow) reduction across human HD grades 1-3 compared to pathologically normal (PN) caudate tissues. Scale bar, 5 µm. (C) Quantification of normalized (to PN) SCN4B puncta per cell. Data are shown as mean ± SD ( n =3 biological replicates per condition; 10 images (63x) per donor). One-sided t-test: ** p = 0.0031 (PN vs. HD1) and 0.0081 (PN vs. HD2); *** p = 0.0007 (PN vs. HD3).

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Affinity Purification, RNAscope, In Situ Hybridization

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the Scn4b knockdown (KD) approach in adult wild-type mice and the experimental timeline for behavioral testing. (B) Representative RNAScope in situ hybridization images of striatal tissue from mice injected with 5E12 vg/mouse of AAV PHP.eB hSyn::CRISPR/CasRx containing guides targeting Scn4b showing the reduction of Scn4b signal (yellow). FLuc denotes data from tissue with the guides targeting Firefly Luciferase, which is not present in the mouse genome. Scale bar, 25 µm (top) and 5 µm (bottom). (C) Relative quantification of Scn4b puncta count. Data are shown as mean ± SD ( n =4 mice per condition; 25 images (63x) per mouse). One-sided t-test: p = 0.0038. (D) Horizontal distance and (E) vertical time traveled as measured by open field test over a 30 min testing period. (F) Latency to fall in the rotarod test. (G) Stride length measured from paw prints from gait analysis. (H) Percentage of food pellets burrowed (by total mass) in the burrowing test. (I) Righting reflex time. Data are shown as mean ± SEM for all longitudinal time course data and mean ± SD for single-time-point comparisons ( n =8-10 mice per group). One-sided t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. (J) Schematic showing the Scn4b knockout (KO) approach in conditional Scn4b floxed mice and the experimental timeline for behavioral testing. (K) Representative RNAScope in situ hybridization FISH images of striatal tissue from mice injected with 5E12 vg/mouse of AAV PHP.eB hSyn::GFP/iCre virus showing the reduction of Scn4b signal (yellow). Scale bar, 1 mm (left), 75 µm (middle) and 15 µm (right). (L) Relative quantification of Scn4b signal intensity. Data are shown as mean ± SD ( n = 4 mice per condition; 10 images (40x) per mouse). (M) Horizontal distance and (N) vertical time traveled as measured by open field test over a 60 min testing period. (O) Number of falls during rotarod training and (P) latency to fall in the rotarod test. (Q) Measured stride length of the paw prints from gait analysis. (R) Righting reflex time. Data are shown as mean ± SEM for all line graphs and as mean ± SD for all bar graphs ( n =13 mice per group). One-sided t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. Figures in panels A and J were created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Knockdown, RNAscope, In Situ Hybridization, Injection, CRISPR, Luciferase, Quantitative Proteomics, Knock-Out, Virus

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the snRNA-seq experimental workflow. (B) UMAP representing all cell types captured from striatal tissue of the Scn4b KD and control ( FLuc ) mice. (C) Back-to-back bar chart showing the number of genes that are dysregulated in the striatum of Scn4b KD versus FLuc mice, per cell type (log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05). (D) Volcano plot showing significant DEGs (versus FLuc , log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05) in striatal matrix dSPNs and (E) iSPNs. (F) GO BP pathway enrichment analysis of Scn4b KD downregulated DEGs (versus FLuc ) in matrix dSPNs and iSPNs. (G) Venn diagram showing the overlap between downregulated DEGs of Scn4b KD mice and human HD in matrix dSPNs and (H) iSPNs. Fisher’s exact test p = 1.32 × 10 -7 and p = 1.61 × 10 -14 , respectively. (I) GO BP pathway enrichment analysis of the shared downregulated DEGs in matrix dSPNs and iSPNs from Scn4b KD mice and human HD. (J) Overlap of the Scn4b KD DEGs and top hub genes from Langfelder et al., 2016. Fisher’s exact test: p = 0.0097 (M2 dSPN.Matrix), 0.0771 (M2 iSPN.Matrix), 0.0337 (M25 dSPN.Matrix). Figure in panel A created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Control

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the Scn4b OX approach in the zQ175 HD model mice and the timeline used for behavioral testing. (B) Representative RNAScope in situ hybridization images of striatal tissue from mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b OX showing the reduction of Scn4b (yellow) in zQ175 vs. WT-GFP OX and the overexpression of Scn4b in only zQ175- Scn4b vs GFP OX. Scale bar, 10 µm. (C) Relative quantification of Scn4b expression across the experimental groups. Data are shown as mean ± SD ( n =3 mice per condition; 25 images (63x) per mouse). (D) Vertical time and (E) jump time parameters as measured by open field test over a 60 min testing period. (F) Latency to fall in the rotarod test. (G) Latency to cross in the beam walk test. (H) Grip strength measurement. For all tests, data are shown as mean ± SD ( n =7 mice per group). One-sided t-test for all parameters: * p ≤ 0.05, ** p ≤ 0.01. (I) Representative IF images (targeting EM48) of striatal sections from zQ175 mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b , showing the reduction of EM48+ mHTT aggregate signal (red) in Scn4b OX zQ175 mice. Scale bar, 20 µm. (J) Quantification of EM48+ mHTT aggregate count. Data are shown as mean ± SD ( n =4 mice per condition; 15 images (40x) per mouse). (K) Representative IF images (using the P90 antibody) of striatal sections from zQ175 mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b , showing the reduction of P90+ mHTT aggregate signal (red) in Scn4b OX zQ175 mice. Scale bar, 20 µm. (L) Quantification of P90+ mHTT aggregate count. Data are shown as mean ± SD ( n =3 mice per condition; 25 images (63x) per mouse). (M) Schematic representation of whole-cell clamp recording from the dorsal striatum. (N) The mean ± SEM of action potential thresholds for dorsal striatum SPNs from mice of the indicated genotypes. Figure in panel A created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: RNAscope, In Situ Hybridization, Injection, Over Expression, Quantitative Proteomics, Expressing

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the snRNA-seq experimental workflow. (B) UMAP representing all cell types captured from striatal tissue of all mice included in this OX study. (C) Back-to-back bar chart showing the number genes that are differentially expressed (DEGs) in the striatum of Scn4b OX mice (zQ175- Scn4b OX vs zQ175-GFP OX; log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05), per cell type. (D) Volcano plot showing these genes in matrix dSPNs and (E) iSPNs of Scn4b OX mice. X-axis limit is set to ±0.4 for visualization purposes; genes exceeding this range include Ttr (log 2 fold change = −0.778) and Cmss1 (log 2 fold change = −0.777) in dSPNs and Cmss1 (log 2 fold change = −0.818) in iSPNs. GO BP pathway enrichment analysis showing the upregulated and downregulated pathways of matrix (F) dSPNs and (G) iSPNs in the zQ175 and Scn4b OX comparisons. (H) Volcano plots showing genes that are changed in opposite directions in the zQ175 and Scn4b OX comparisons in matrix dSPNs and (I) iSPNs. GO BP pathway enrichment analysis of (J) genes that are downregulated in the Scn4b OX comparison and upregulated in the zQ175 comparison and (K) genes that are upregulated in the Scn4b OX comparison and downregulated in the zQ175 comparison. (L) Heatmap showing log 2 fold change of selected MMR genes in the zQ175 and Scn4b OX comparisons. *indicates significance using the log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05 cutoff. Figure in panel A created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Comparison

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Volcano plots of significantly differentially expressed genes (DEGs) in a CAG-length-dependent manner in the direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons of an HD mouse model allelic series (Q50, Q111, Q170, zQ175), as reported by translating ribosome affinity purification (TRAP) profiling. (B) Representative RNAScope in situ hybridization images showing striatal caudate nucleus SCN4B RNA (yellow) reduction across human HD grades 1-3 compared to pathologically normal (PN) caudate tissues. Scale bar, 5 µm. (C) Quantification of normalized (to PN) SCN4B puncta per cell. Data are shown as mean ± SD ( n =3 biological replicates per condition; 10 images (63x) per donor). One-sided t-test: ** p = 0.0031 (PN vs. HD1) and 0.0081 (PN vs. HD2); *** p = 0.0007 (PN vs. HD3).

Article Snippet: Male Scn4b floxed mice B6.129(SJL)- Scn4btm1.1Geh /RahJ (Jackson Laboratories stock #027530) were used at 8 weeks of age for the Scn4b conditional KO study.

Techniques: Affinity Purification, RNAscope, In Situ Hybridization

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the Scn4b knockdown (KD) approach in adult wild-type mice and the experimental timeline for behavioral testing. (B) Representative RNAScope in situ hybridization images of striatal tissue from mice injected with 5E12 vg/mouse of AAV PHP.eB hSyn::CRISPR/CasRx containing guides targeting Scn4b showing the reduction of Scn4b signal (yellow). FLuc denotes data from tissue with the guides targeting Firefly Luciferase, which is not present in the mouse genome. Scale bar, 25 µm (top) and 5 µm (bottom). (C) Relative quantification of Scn4b puncta count. Data are shown as mean ± SD ( n =4 mice per condition; 25 images (63x) per mouse). One-sided t-test: p = 0.0038. (D) Horizontal distance and (E) vertical time traveled as measured by open field test over a 30 min testing period. (F) Latency to fall in the rotarod test. (G) Stride length measured from paw prints from gait analysis. (H) Percentage of food pellets burrowed (by total mass) in the burrowing test. (I) Righting reflex time. Data are shown as mean ± SEM for all longitudinal time course data and mean ± SD for single-time-point comparisons ( n =8-10 mice per group). One-sided t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. (J) Schematic showing the Scn4b knockout (KO) approach in conditional Scn4b floxed mice and the experimental timeline for behavioral testing. (K) Representative RNAScope in situ hybridization FISH images of striatal tissue from mice injected with 5E12 vg/mouse of AAV PHP.eB hSyn::GFP/iCre virus showing the reduction of Scn4b signal (yellow). Scale bar, 1 mm (left), 75 µm (middle) and 15 µm (right). (L) Relative quantification of Scn4b signal intensity. Data are shown as mean ± SD ( n = 4 mice per condition; 10 images (40x) per mouse). (M) Horizontal distance and (N) vertical time traveled as measured by open field test over a 60 min testing period. (O) Number of falls during rotarod training and (P) latency to fall in the rotarod test. (Q) Measured stride length of the paw prints from gait analysis. (R) Righting reflex time. Data are shown as mean ± SEM for all line graphs and as mean ± SD for all bar graphs ( n =13 mice per group). One-sided t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. Figures in panels A and J were created with BioRender.

Article Snippet: Male Scn4b floxed mice B6.129(SJL)- Scn4btm1.1Geh /RahJ (Jackson Laboratories stock #027530) were used at 8 weeks of age for the Scn4b conditional KO study.

Techniques: Knockdown, RNAscope, In Situ Hybridization, Injection, CRISPR, Luciferase, Quantitative Proteomics, Knock-Out, Virus

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the snRNA-seq experimental workflow. (B) UMAP representing all cell types captured from striatal tissue of the Scn4b KD and control ( FLuc ) mice. (C) Back-to-back bar chart showing the number of genes that are dysregulated in the striatum of Scn4b KD versus FLuc mice, per cell type (log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05). (D) Volcano plot showing significant DEGs (versus FLuc , log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05) in striatal matrix dSPNs and (E) iSPNs. (F) GO BP pathway enrichment analysis of Scn4b KD downregulated DEGs (versus FLuc ) in matrix dSPNs and iSPNs. (G) Venn diagram showing the overlap between downregulated DEGs of Scn4b KD mice and human HD in matrix dSPNs and (H) iSPNs. Fisher’s exact test p = 1.32 × 10 -7 and p = 1.61 × 10 -14 , respectively. (I) GO BP pathway enrichment analysis of the shared downregulated DEGs in matrix dSPNs and iSPNs from Scn4b KD mice and human HD. (J) Overlap of the Scn4b KD DEGs and top hub genes from Langfelder et al., 2016. Fisher’s exact test: p = 0.0097 (M2 dSPN.Matrix), 0.0771 (M2 iSPN.Matrix), 0.0337 (M25 dSPN.Matrix). Figure in panel A created with BioRender.

Article Snippet: Male Scn4b floxed mice B6.129(SJL)- Scn4btm1.1Geh /RahJ (Jackson Laboratories stock #027530) were used at 8 weeks of age for the Scn4b conditional KO study.

Techniques: Control

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the Scn4b OX approach in the zQ175 HD model mice and the timeline used for behavioral testing. (B) Representative RNAScope in situ hybridization images of striatal tissue from mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b OX showing the reduction of Scn4b (yellow) in zQ175 vs. WT-GFP OX and the overexpression of Scn4b in only zQ175- Scn4b vs GFP OX. Scale bar, 10 µm. (C) Relative quantification of Scn4b expression across the experimental groups. Data are shown as mean ± SD ( n =3 mice per condition; 25 images (63x) per mouse). (D) Vertical time and (E) jump time parameters as measured by open field test over a 60 min testing period. (F) Latency to fall in the rotarod test. (G) Latency to cross in the beam walk test. (H) Grip strength measurement. For all tests, data are shown as mean ± SD ( n =7 mice per group). One-sided t-test for all parameters: * p ≤ 0.05, ** p ≤ 0.01. (I) Representative IF images (targeting EM48) of striatal sections from zQ175 mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b , showing the reduction of EM48+ mHTT aggregate signal (red) in Scn4b OX zQ175 mice. Scale bar, 20 µm. (J) Quantification of EM48+ mHTT aggregate count. Data are shown as mean ± SD ( n =4 mice per condition; 15 images (40x) per mouse). (K) Representative IF images (using the P90 antibody) of striatal sections from zQ175 mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b , showing the reduction of P90+ mHTT aggregate signal (red) in Scn4b OX zQ175 mice. Scale bar, 20 µm. (L) Quantification of P90+ mHTT aggregate count. Data are shown as mean ± SD ( n =3 mice per condition; 25 images (63x) per mouse). (M) Schematic representation of whole-cell clamp recording from the dorsal striatum. (N) The mean ± SEM of action potential thresholds for dorsal striatum SPNs from mice of the indicated genotypes. Figure in panel A created with BioRender.

Article Snippet: Male Scn4b floxed mice B6.129(SJL)- Scn4btm1.1Geh /RahJ (Jackson Laboratories stock #027530) were used at 8 weeks of age for the Scn4b conditional KO study.

Techniques: RNAscope, In Situ Hybridization, Injection, Over Expression, Quantitative Proteomics, Expressing

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the snRNA-seq experimental workflow. (B) UMAP representing all cell types captured from striatal tissue of all mice included in this OX study. (C) Back-to-back bar chart showing the number genes that are differentially expressed (DEGs) in the striatum of Scn4b OX mice (zQ175- Scn4b OX vs zQ175-GFP OX; log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05), per cell type. (D) Volcano plot showing these genes in matrix dSPNs and (E) iSPNs of Scn4b OX mice. X-axis limit is set to ±0.4 for visualization purposes; genes exceeding this range include Ttr (log 2 fold change = −0.778) and Cmss1 (log 2 fold change = −0.777) in dSPNs and Cmss1 (log 2 fold change = −0.818) in iSPNs. GO BP pathway enrichment analysis showing the upregulated and downregulated pathways of matrix (F) dSPNs and (G) iSPNs in the zQ175 and Scn4b OX comparisons. (H) Volcano plots showing genes that are changed in opposite directions in the zQ175 and Scn4b OX comparisons in matrix dSPNs and (I) iSPNs. GO BP pathway enrichment analysis of (J) genes that are downregulated in the Scn4b OX comparison and upregulated in the zQ175 comparison and (K) genes that are upregulated in the Scn4b OX comparison and downregulated in the zQ175 comparison. (L) Heatmap showing log 2 fold change of selected MMR genes in the zQ175 and Scn4b OX comparisons. *indicates significance using the log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05 cutoff. Figure in panel A created with BioRender.

Article Snippet: Male Scn4b floxed mice B6.129(SJL)- Scn4btm1.1Geh /RahJ (Jackson Laboratories stock #027530) were used at 8 weeks of age for the Scn4b conditional KO study.

Techniques: Comparison

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Volcano plots of significantly differentially expressed genes (DEGs) in a CAG-length-dependent manner in the direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons of an HD mouse model allelic series (Q50, Q111, Q170, zQ175), as reported by translating ribosome affinity purification (TRAP) profiling. (B) Representative RNAScope in situ hybridization images showing striatal caudate nucleus SCN4B RNA (yellow) reduction across human HD grades 1-3 compared to pathologically normal (PN) caudate tissues. Scale bar, 5 µm. (C) Quantification of normalized (to PN) SCN4B puncta per cell. Data are shown as mean ± SD ( n =3 biological replicates per condition; 10 images (63x) per donor). One-sided t-test: ** p = 0.0031 (PN vs. HD1) and 0.0081 (PN vs. HD2); *** p = 0.0007 (PN vs. HD3).

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Affinity Purification, RNAscope, In Situ Hybridization

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the Scn4b knockdown (KD) approach in adult wild-type mice and the experimental timeline for behavioral testing. (B) Representative RNAScope in situ hybridization images of striatal tissue from mice injected with 5E12 vg/mouse of AAV PHP.eB hSyn::CRISPR/CasRx containing guides targeting Scn4b showing the reduction of Scn4b signal (yellow). FLuc denotes data from tissue with the guides targeting Firefly Luciferase, which is not present in the mouse genome. Scale bar, 25 µm (top) and 5 µm (bottom). (C) Relative quantification of Scn4b puncta count. Data are shown as mean ± SD ( n =4 mice per condition; 25 images (63x) per mouse). One-sided t-test: p = 0.0038. (D) Horizontal distance and (E) vertical time traveled as measured by open field test over a 30 min testing period. (F) Latency to fall in the rotarod test. (G) Stride length measured from paw prints from gait analysis. (H) Percentage of food pellets burrowed (by total mass) in the burrowing test. (I) Righting reflex time. Data are shown as mean ± SEM for all longitudinal time course data and mean ± SD for single-time-point comparisons ( n =8-10 mice per group). One-sided t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. (J) Schematic showing the Scn4b knockout (KO) approach in conditional Scn4b floxed mice and the experimental timeline for behavioral testing. (K) Representative RNAScope in situ hybridization FISH images of striatal tissue from mice injected with 5E12 vg/mouse of AAV PHP.eB hSyn::GFP/iCre virus showing the reduction of Scn4b signal (yellow). Scale bar, 1 mm (left), 75 µm (middle) and 15 µm (right). (L) Relative quantification of Scn4b signal intensity. Data are shown as mean ± SD ( n = 4 mice per condition; 10 images (40x) per mouse). (M) Horizontal distance and (N) vertical time traveled as measured by open field test over a 60 min testing period. (O) Number of falls during rotarod training and (P) latency to fall in the rotarod test. (Q) Measured stride length of the paw prints from gait analysis. (R) Righting reflex time. Data are shown as mean ± SEM for all line graphs and as mean ± SD for all bar graphs ( n =13 mice per group). One-sided t-test: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001. Figures in panels A and J were created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Knockdown, RNAscope, In Situ Hybridization, Injection, CRISPR, Luciferase, Quantitative Proteomics, Knock-Out, Virus

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the snRNA-seq experimental workflow. (B) UMAP representing all cell types captured from striatal tissue of the Scn4b KD and control ( FLuc ) mice. (C) Back-to-back bar chart showing the number of genes that are dysregulated in the striatum of Scn4b KD versus FLuc mice, per cell type (log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05). (D) Volcano plot showing significant DEGs (versus FLuc , log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05) in striatal matrix dSPNs and (E) iSPNs. (F) GO BP pathway enrichment analysis of Scn4b KD downregulated DEGs (versus FLuc ) in matrix dSPNs and iSPNs. (G) Venn diagram showing the overlap between downregulated DEGs of Scn4b KD mice and human HD in matrix dSPNs and (H) iSPNs. Fisher’s exact test p = 1.32 × 10 -7 and p = 1.61 × 10 -14 , respectively. (I) GO BP pathway enrichment analysis of the shared downregulated DEGs in matrix dSPNs and iSPNs from Scn4b KD mice and human HD. (J) Overlap of the Scn4b KD DEGs and top hub genes from Langfelder et al., 2016. Fisher’s exact test: p = 0.0097 (M2 dSPN.Matrix), 0.0771 (M2 iSPN.Matrix), 0.0337 (M25 dSPN.Matrix). Figure in panel A created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Control

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the Scn4b OX approach in the zQ175 HD model mice and the timeline used for behavioral testing. (B) Representative RNAScope in situ hybridization images of striatal tissue from mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b OX showing the reduction of Scn4b (yellow) in zQ175 vs. WT-GFP OX and the overexpression of Scn4b in only zQ175- Scn4b vs GFP OX. Scale bar, 10 µm. (C) Relative quantification of Scn4b expression across the experimental groups. Data are shown as mean ± SD ( n =3 mice per condition; 25 images (63x) per mouse). (D) Vertical time and (E) jump time parameters as measured by open field test over a 60 min testing period. (F) Latency to fall in the rotarod test. (G) Latency to cross in the beam walk test. (H) Grip strength measurement. For all tests, data are shown as mean ± SD ( n =7 mice per group). One-sided t-test for all parameters: * p ≤ 0.05, ** p ≤ 0.01. (I) Representative IF images (targeting EM48) of striatal sections from zQ175 mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b , showing the reduction of EM48+ mHTT aggregate signal (red) in Scn4b OX zQ175 mice. Scale bar, 20 µm. (J) Quantification of EM48+ mHTT aggregate count. Data are shown as mean ± SD ( n =4 mice per condition; 15 images (40x) per mouse). (K) Representative IF images (using the P90 antibody) of striatal sections from zQ175 mice injected with 1E12 vg/mouse of AAV PHP.eB GPR88 ::GFP or GPR88 :: Scn4b , showing the reduction of P90+ mHTT aggregate signal (red) in Scn4b OX zQ175 mice. Scale bar, 20 µm. (L) Quantification of P90+ mHTT aggregate count. Data are shown as mean ± SD ( n =3 mice per condition; 25 images (63x) per mouse). (M) Schematic representation of whole-cell clamp recording from the dorsal striatum. (N) The mean ± SEM of action potential thresholds for dorsal striatum SPNs from mice of the indicated genotypes. Figure in panel A created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: RNAscope, In Situ Hybridization, Injection, Over Expression, Quantitative Proteomics, Expressing

Journal: bioRxiv

Article Title: Scn4b Modulates Huntington’s Disease Phenotype Severity in vivo

doi: 10.64898/2026.03.08.708251

Figure Lengend Snippet: (A) Schematic showing the snRNA-seq experimental workflow. (B) UMAP representing all cell types captured from striatal tissue of all mice included in this OX study. (C) Back-to-back bar chart showing the number genes that are differentially expressed (DEGs) in the striatum of Scn4b OX mice (zQ175- Scn4b OX vs zQ175-GFP OX; log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05), per cell type. (D) Volcano plot showing these genes in matrix dSPNs and (E) iSPNs of Scn4b OX mice. X-axis limit is set to ±0.4 for visualization purposes; genes exceeding this range include Ttr (log 2 fold change = −0.778) and Cmss1 (log 2 fold change = −0.777) in dSPNs and Cmss1 (log 2 fold change = −0.818) in iSPNs. GO BP pathway enrichment analysis showing the upregulated and downregulated pathways of matrix (F) dSPNs and (G) iSPNs in the zQ175 and Scn4b OX comparisons. (H) Volcano plots showing genes that are changed in opposite directions in the zQ175 and Scn4b OX comparisons in matrix dSPNs and (I) iSPNs. GO BP pathway enrichment analysis of (J) genes that are downregulated in the Scn4b OX comparison and upregulated in the zQ175 comparison and (K) genes that are upregulated in the Scn4b OX comparison and downregulated in the zQ175 comparison. (L) Heatmap showing log 2 fold change of selected MMR genes in the zQ175 and Scn4b OX comparisons. *indicates significance using the log 2 fold change abs( z ) >= 1 and p adj. FDR < 0.05 cutoff. Figure in panel A created with BioRender.

Article Snippet: The GFP sequence was replaced with Scn4b sequence, amplified from the mouse Scn4b cDNA ORF plasmid (Scn4b #MR226154; Origene, Rockville, MD) for the pAAV GPR88 :: Scn4b OX construct.

Techniques: Comparison

Journal: Biomarker Research

Article Title: Voltage-gated sodium channels in cancers

doi: 10.1186/s40364-024-00620-x

Figure Lengend Snippet: Summary evidence for VGSCs in cancers

Article Snippet: The Human Protein Atlas (HPA) database provides protein-staining data for SCN2A, SCN3A, SCN9A, SCN11A, and SCN4B.

Techniques: In Vivo, In Vitro, Expressing, Migration

Journal: Current opinion in genetics & development

Article Title: Genetics of Congenital Arrhythmia Syndromes: The Challenge of Variant Interpretation

doi: 10.1016/j.gde.2022.102004

Figure Lengend Snippet: ClinGen reappraisal of genes associated with inherited arrhythmia syndromes

Article Snippet: Table 1: ClinGen Class Long QT syndrome Brugada syndrome Catecholaminergic polymorphic VT Short QT syndrome Other Definitive KCNQ1, KCNH2, SCN5A, CALM1/2/3 SCN5A RYR2, CASQ2 (AR) , TRDN, TECRL KCNH2 CACNA1C (Timothy), KCNJ2 (Anderson-Tawil) Strong TRDN (AR) — — KCNQ1, SLC4A3 * KCNE1 (aLQTS), KCNE2 (aLQTS) Moderate CACNA1C — CASQ2(AD), CALM1/2/3 SLC4A3 * , KCNJ2 — Limited CAV3, KCNE1, KCNJ2 — — — — Disputed/ No evidence SNTA1, AKAP9, ANK2, KCNE2, KCNJ5, SCN4B 20 genes ANK2, KCNJ2, PKP2, SCN5A CACNA1C, CACNA2D1, CACNB2, SCN5A, SLC22A5 ** — Open in a separate window Adapted from ClinGen reappraisals of LQTS [ 4 ], BrS [ 5 ], and CPVT/SQTS [ 6 ].

Techniques: