Influenza Infection During Pregnancy and Risk of Seizures in Offspring.

Importance: Seizure is a common neurological problem among infants and children up to age 6 years. Prenatal exposure to maternal influenza infection has been reported to be associated with childhood seizures. Objective: To evaluate the association between maternal influenza infection and risk of childhood seizures. Designs, Setting, and Participants: This cohort study identified mother-offspring pairs from January 1, 2004, to December 31, 2013, using records in Taiwan's Maternal and Child Health Database. Mothers who had influenza infection during pregnancy and their first offspring were identified and assigned to the influenza group. Mothers in the control group were those without influenza during pregnancy and were matched 1:4 with mothers in the influenza group by maternal age, offspring sex, and date of delivery. Offspring were followed up until December 31, 2020. Data were analyzed between March 2023 and July 2024. Exposure: Diagnosis of influenza infection during pregnancy defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes 487.0, 487.1, and 487.8, or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes J09, J10, and J11. Main Outcomes and Measures: The primary outcome was the association between maternal influenza infection during pregnancy and risk of any type of seizures during childhood, including both epilepsy and febrile seizures. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression models. Pregnancy-related complications were collected as covariates. Results: A total of 1 316 107 mother-offspring pairs were enrolled, of whom 75 835 mothers (predominant maternal age, 25-29 years; 39 324 male offspring [51.9%]) were assigned to the influenza group and 1 240 272 were matched and assigned to the control group (n = 303 340; predominant maternal age, 30-34 years; 157 296 male offspring [51.9%]). In the influenza group, there was a slightly higher prevalence of placenta previa or abruption compared with the control group (1.6% [1241] vs 1.4% [4350]; P < .001). The cumulative risk of seizures was higher among offspring whose mothers had influenza infection. After controlling for potential confounders, the AHRs were 1.09 (95% CI, 1.05-1.14) for seizures, 1.11 (95% CI, 1.06-1.17) for febrile convulsions, and 1.04 (95% CI, 0.97-1.13) for epilepsy. In the subgroup analysis, no statistically significant differences were observed between the trimesters regarding the timing of influenza infection. Conclusions and Relevance: Results of this cohort study suggest that maternal influenza infection during pregnancy was associated with an increased risk of childhood seizures, especially febrile seizures, but not epilepsy. Further studies are needed to elucidate the mechanisms underlying childhood neurological development.

B4GALT1-dependent galectin-8 binding with TGF-ß receptor suppresses colorectal cancer progression and metastasis.

Transforming growth factor (TGF)-ß signaling is critical for epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis. Disruption of Smad-depednent TGF-ß signaling has been shown in CRC cells. However, TGF-ß receptor remains expressed on CRC cells. Here, we investigated whether the cooperation between tumor-associated N-glycosylation and a glycan-binding protein modulated the TGF-ß-driven signaling and metastasis of CRC. We showed that galectin-8, a galactose-binding lectin, hampered TGF-ß-induced EMT by interacting with the type II TGF-ß receptor and competing with TGF-ß binding. Depletion of galectin-8 promoted the migration of CRC cells by increasing TGF-ß-receptor-mediated RAS and Src signaling, which was attenuated after recombinant galectin-8 treatment. Treatment with recombinant galectin-8 also induces JNK-dependent apoptosis in CRC cells. The anti-migratory effect of galectin-8 depended on ß4-galactosyltransferase-I (B4GALT1), an enzyme involved in N-glycan synthesis. Increased B4GALT1 expression was observed in clinical CRC samples. Depletion of B4GALT1 reduced the metastatic potential of CRC cells. Furthermore, inducible expression of galectin-8 attenuated tumor development and metastasis of CRC cells in an intra-splenic injection model. Our results thus demonstrate that galectin-8 alters non-canonical TGF-ß response in CRC cells and suppresses CRC progression.

Simultaneously Boosting Direct and Indirect Urea Oxidation of Nickel Hydroxide via Strategic Yttrium Doping.

Urea electrolysis can address pressing environmental concerns caused by urea-containing wastewater while realizing energy-saving hydrogen production. Highly efficient and affordable electrocatalysts are indispensable for realizing the great potential of this emerging technology. Among the numerous candidates, α-Ni(OH)2 has the merits of good electrocatalytic activity, adjustable heteroelement doping, and low cost; consequently, it has received tremendous attention in the electrolytic fields. Herein, a Y3+-doping strategy is developed to effectively enhance the catalytic performance of nickel hydroxide in the urea oxidation reaction (UOR). Our results show that Y3+ incorporation successfully modulates the electronic structure of α-Ni(OH)2 by inducing Ni3+ formation in the crystal lattice to initiate direct UOR, facilitates the Ni3+/Ni2+ redox transition with higher current responses to promote indirect UOR, and maintains the structural stability of YNi-10 (Ni2+/Y3+ molar ratio = 1:0.1) during long-term UOR operation. Owing to these features, the obtained YNi-10 sample exhibits a higher current density (127 vs 79 mA cm-2 at 1.5 V), a lower Tafel slope (48 vs 75 mV dec-1), a larger potential difference between the UOR and oxygen evolution reaction (OER, 0.26 vs 0.22 V at 80 mA cm-2), a higher reaction rate constant (1.1 × 105 vs 3.1 × 103 cm3 mol-1 s-1), and a reduced activation energy of UOR (2.9 vs 14.8 kJ mol-1) compared with the Y-free counterpart (YNi-0). This study presents a promising strategy to simultaneously boost direct and indirect UORs, providing new insights for further developing high-performance electrocatalysts.

PIAS1 S510G variant acts as a genetic modifier of spinocerebellar ataxia type 3 by selectively impairing mutant ataxin-3 proteostasis.

Dysregulated protein homeostasis, characterized by abnormal protein accumulation and aggregation, is a key contributor to the progression of neurodegenerative disorders such as Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Previous studies have identified PIAS1 gene variants in patients with late-onset SCA3 and Huntington's disease. This study aims to elucidate the role of PIAS1 and its S510G variant in modulating the pathogenic mechanisms of SCA3. Through in vitro biochemical analyses and in vivo assays, we demonstrate that PIAS1 stabilizes both wild-type and mutant ataxin-3 (ATXN3). The PIAS1 S510G variant, however, selectively reduces the stability and SUMOylation of mutant ATXN3, thereby decreasing its aggregation and toxicity while maintaining the stability of wild-type ATXN3. This effect is mediated by a weakened interaction with the SUMO-conjugating enzyme UBC9 in the presence of mutant ATXN3. In Drosophila models, downregulation of dPIAS1 resulted in reduced levels of mutant ATXN3 and alleviated associated phenotypes, including retinal degeneration and motor dysfunction. Our findings suggest that the PIAS1 S510G variant acts as a genetic modifier of SCA3, highlighting the potential of targeting SUMOylation as a therapeutic strategy for this disease.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study.

BACKGROUND: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF. METHODS: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed. RESULTS: A total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200-250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar. CONCLUSIONS: It was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200-250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed.

A nonadjuvanted HLA-restricted peptide vaccine induced both T and B cell immunity against SARS-CoV-2 spike protein.

During COVID-19 pandemic, cases of postvaccination infections and restored SARS-CoV-2 virus have increased after full vaccination, which might be contributed to by immune surveillance escape or virus rebound. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides were designed based on the well-conserved S2 region of the SARS-CoV-2 spike protein regardless of rapid mutation and glycosylation hindrance. The UC peptides were characterized for its effect on immune molecules and cells by HLA-tetramer refolding assay for HLA-binding ability, by HLA-tetramer specific T cell assay for engaged cytotoxic T lymphocytes (CTLs) involvement, by HLA-dextramer T cell assay for B cell activation, by intracellular cytokine release assay for polarization of immune response, Th1 or Th2. The specific lysis activity assay of T cells was performed for direct activation of cytotoxic T lymphocytes by UC peptides. Mice were immunized for immunogenicity of UC peptides in vivo and immunized sera was assay for complement cytotoxicity assay. Results appeared that through the engagement of UC peptides and immune molecules, HLA-I and II, that CTLs elicited cytotoxic activity by recognizing SARS-CoV-2 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides also showed immunogenicity and generated a specific antibody in mice by both intramuscular injection and oral delivery without adjuvant formulation. In conclusion, a T-cell vaccine could provide long-lasting protection against SARS-CoV-2 either during reinfection or during SARS-CoV-2 rebound. Due to its ability to eradicate SARS-CoV-2 virus-infected cells, a COVID-19 T-cell vaccine might provide a solution to lower COVID-19 severity and long COVID-19.

Sushi Domain Containing 2 Dysfunction Contributes to Cancer Progression in Patients with Bladder Cancer.

Bladder cancer is the most prevalent type of cancer in Taiwan, and therefore, enhancing the diagnostic sensitivity of biomarkers for early-stage tumors and identifying therapeutic targets to improve patient survival rates are essential. Although Sushi Domain Containing 2 (SUSD2) dysfunction has been identified in several types of human cancer, its biological role in bladder cancer remains unclear. Analysis of The Cancer Genome Atlas revealed significantly higher expression of SUSD2 mRNA in bladder cancer tissues than in adjacent normal tissues. This elevated expression of SUSD2 significantly correlated with pathological stage (p = 0.029), pN stage (p < 0.001), and pM stage (p = 0.047). Univariate analysis revealed that high SUSD2 expression was associated with decreased overall survival (crude hazard ratio = 1.70, 95% confidence interval = 1.13-2.56, p = 0.01). Multivariate analysis revealed a significant correlation between high SUSD2 expression and poor survival outcomes (adjusted hazard ratio = 1.53, 95% confidence interval = 1.01-2.31, p = 0.043). IHC analysis revealed a significant correlation between elevated SUSD2 protein levels and unfavorable pathological stages (p < 0.001). SUSD2 suppression significantly reduced the proliferation, colony formation, and invasion of bladder cancer cells. In addition, cell cycle analysis revealed that SUSD2 knockdown induced G2/M phase arrestin bladder cancer cells. Tumor Immune Estimation Resource analysis indicated that expression of SUSD2 was significantly associated with macrophage infiltration and M2 macrophage polarization in bladder cancer. In addition, miR-383-5p directly targeted the 3'UTR of SUSD2, with its ectopic expression inhibiting the growth and motility of bladder cancer cells. Our study revealed that miR-383-5p/SUSD2 axis dysfunction may contribute to a poor prognosis for bladder cancer by affecting cell growth, metastasis, and the tumor microenvironment.

Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies.

The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis. In 47 HPRC-phased assemblies, SKIRT identifies a recurrent novel KIR2DS4/3DL1 fusion gene in the paternal haplotype of HG02630 and maternal haplotype of NA19240. Additionally, SKIRT accurately identifies eight structural variants and 15 novel nonsynonymous alleles, all of which are independently validated using short-read data or quantitative polymerase chain reaction. Our study has discovered a total of 570 novel alleles, among which eight haplotypes harbor at least one KIR gene duplication, six haplotypes have lost at least one framework gene, and 75 out of 94 haplotypes (79.8%) carry at least five novel alleles, thus confirming KIR genetic diversity. These findings are pivotal in providing insights into KIR gene diversity and serve as a solid foundation for understanding the functional consequences of KIR structural variations. High-resolution genome assemblies offer unprecedented opportunities to explore polymorphic regions that are challenging to investigate using short-read sequencing methods. The SKIRT pipeline emerges as a highly efficient tool, enabling the comprehensive detection of the complete spectrum of KIR alleles within human genome assemblies.

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth.

The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved. Here we unveil a low-complexity insert domain within TET2 that facilitates its biomolecular condensation with epigenetic modulators, such as UTX and MLL4. This co-condensation fosters a permissive chromatin environment for precise DNA demethylation. Disrupting low-complexity insert-mediated condensation alters the genomic binding of TET2 to cause promiscuous DNA demethylation and genome reorganization. These changes influence the expression of key genes implicated in leukaemogenesis to curtail leukaemia cell proliferation. Collectively, this study establishes the pivotal role of TET2 condensation in orchestrating precise DNA demethylation and gene transcription to support tumour cell growth.

Quality and resilience of health care from a medical center perspective.

National Taiwan University Hospital (NTUH) has demonstrated exceptional resilience and adaptability in its response to the COVID-19 pandemic. Since the outbreak in early 2020, NTUH has been at the forefront of Taiwan's healthcare system, taking proactive measures to prepare for and manage the pandemic. The hospital swiftly established dedicated outpatient clinics and wards, which were crucial in isolating and treating COVID-19 patients. NTUH also played a pivotal role in assisting the government with the development of diagnostic reagents and vaccines and contributing to the global effort to combat the disease. To address the long-term effects of COVID-19, NTUH established a special clinic for integrated care in September 2021, offering physical, occupational, and speech therapy to help patients recover and return to normal life. NTUH also shared its pandemic prevention experience internationally, participating in video conferences to discuss its preventive measures and best practices. In caring for frontline healthcare workers, NTUH established interdisciplinary care teams to provide psychological support, assistance with basic daily needs, and effective social, psychological, and mental health support programs. In conclusion, NTUH demonstrated efficient response capabilities and care for healthcare workers during the COVID-19 pandemic, providing valuable insights for future challenges in dealing with emerging infectious diseases.

Blended Phenotype of NOTCH3 and RNF213 Variants With Accelerated Large and Small Artery Crosstalk: A Case Report and Literature Review.

Objectives: Recent advancements in genome research have revealed not only the importance of variants associated with cerebrovascular diseases but also a notably high frequency of carriers harboring multiple variants, presenting with an elusive blended phenotype. In this study, we report the case of a 66-year-old man who experienced 3 stroke episodes over a 4-year period, starting at the age of 62 years. The patient presented with isolated infarcts in the left temporal pole with progressive stenosis in the ipsilateral middle cerebral artery based on large and small artery crosstalk. Methods: Exons 2-24 of the NOTCH3 gene were analyzed by direct genomic DNA sequencing. The presence of the p.Arg4810Lys variant of the ring finger protein 213 (RNF213) gene was evaluated using real-time PCR. Results: Diagnoses of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and RNF213-related vasculopathy were made based on the early-onset recurrent stroke episode, progressive intracranial artery stenosis, and presence of the heterozygous NOTCH3 p.Cys1250Arg and RNF213 p.Arg4810Lys variants. Discussion: Temporal pole infarcts could represent a blended phenotype of both variants. This case highlights the importance of large and small artery crosstalk and the pivotal role of genetic analysis in determining the pathogenesis of stroke and dementia.

Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway.

CDK4/6 inhibitors combined with endocrine therapy prolonged survival in hormone receptor (HR)-positive and HER2-negative advanced breast cancer. We investigated whether CDK4/6 inhibitors enhance radiosensitivity and their underlying mechanisms of this subtype of breast cancer. In vitro and in vivo experiments were conducted using two HR-positive and HER2-negative breast cancer cell lines (MCF-7 and T-47D), CDK4/6 inhibitors (ribociclib and palbociclib) and radiotherapy (RT) to assess the biological functions and mechanisms. The radiation-enhancing effect was assessed using clonogenic assays; γH2AX and 53BP1 levels were assessed by immunofluorescence to evaluate DNA damage. The levels of phospho (p)-ERK, c-Myc, and DNA-double strand break (DSB)-related molecules, p-DNA-PKcs, Rad51, and p-ATM, were assessed by western blotting. We used an NF-κB p65 transcription factor assay kit to evaluate NF-κB activity. We evaluated the antitumor effect of the combination of RT and ribociclib through the MCF-7 orthotopic xenograft model. The synergistic effects of combining RT with ribociclib and palbociclib pretreatment were demonstrated by clonogenic assay. CDK4/6 inhibitors synergistically increased the numbers of RT-induced γH2AX and 53BP1, downregulated the expression of p-DNA-PKcs, Rad51 and p-ATM activated by RT, and reduced RT-triggering p-ERK expression, NF-κB activation, and its down-streaming gene, c-Myc. Combined ribociclib and RT reduced the growth of MCF-7 cell xenograft tumors, and downregulated the immunohistochemical expression of p-ERK, p-NF-κB p65, and c-Myc compared to that in the control group. Combining CDK4/6 inhibitors enhanced radiosensitivity of HR-positive and HER2-negative breast cancer cells at least by reducing DNA-DSB repair and weakening the activation of ERK and NF-κB signaling by RT.

Ultrahigh humidity-resistance ppb-level formaldehyde sensing at room temperature induced by fluorinated dipole based "umbrella" and "bridge".

Formaldehyde (HCHO) is a major indoor pollutant that is extremely harmful to human health even at ppb-level. Meanwhile, ppb-level HCHO is also a potential disease marker in the exhalation of patients with respiratory diseases. Higher humidity resistance and lower practical limit of detection (pLOD) both have to be pursued for practical HCHO sensors. In this work, by assembling indium oxide (In2O3) and fluorinated dipole modified reduced graphene oxide (rGO), we prepared a high-performance room temperature HCHO sensor (In2O3 @ATQ-rGO). Excellent sensing properties toward HCHO under visible illumination have been achieved, including ultra-low pLOD of 3 ppb and high humidity-resistance. By control experiments and density functional theory calculation, it is indicated that the introduced fluorinated dipoles act as not only an "umbrella" to improve the humidity resistance of the composite, but also a "bridge" to accelerate the electron transport, improving the sensitivity of the material. The significant practicality and reliability of the obtained sensors were verified by in-situ simulation experiments using a 3 m3 test chamber with a humidity control system and by detection of the simulated lung disease patient's exhalation. This work provides an effective strategy of simultaneously achieving high humidity-resistance and low pLOD of room temperature formaldehyde sensing materials.

Stigmatization and Preferences in Monkeypox Vaccine Regimens.

A significant monkeypox (mpox) outbreak occurred in 2022, particularly involving sexual and gender minority (SGM) groups. Stigma and misperceptions have led to fear of being labeled a member of the SGM group when obtaining immunization for mpox. We hypothesized that the most recommended injection site, intradermal injection in the forearm, stresses stigmatization. We conducted an online survey in a medical center in Taiwan between May 2023 and June 2023 among adults who were going to receive the second preexposure vaccination. The questionnaire comprised questions about physical and psychological impacts of the first mpox vaccination and the preference for the second vaccination location and factors influencing the preference. A total of 2,827 individuals (98.4% male) completed the questionnaires. Intradermal injection in the forearm was related to greater physical and psychological impacts of local adverse events, especially discoloration. "Beauty," "scar," and "others' view" were the most significant factors influencing preference for vaccination regimens. Compared to intradermal injection in the forearm, subjects who cared about "others' views" were likely to prefer vaccination in the deltoid. The odds ratio for preferring intradermally injection in the deltoid over in the forearm was 1.88 (95% CI 1.38-2.56). The odds ratio for preferring subcutaneous injection in the deltoid over intradermally injection in the forearm was 1.69 (95% CI 1.23-2.32). The odds ratio for preferring intradermally injection in the deltoid regardless of the route over intradermally injection in the forearm was 2.11 (95% CI 1.53-2.92). This study demonstrated the adverse events of different mpox vaccination regimens and their association with stigma. Recognizing the factors affecting the preference for mpox vaccine regimens is crucial for easing the mental stress of vaccinee.

Minimum Fascia-Tumour Distance for Differentiating Deep Lobe From Superficial Lobe Benign Parotid Tumours: A Retrospective Study and Meta-Analysis.

BACKGROUND: This study was designed to evaluate the diagnostic efficacy of the minimum fascia-tumour distance (MFTD) in distinguishing deep-lobe benign parotid tumours from superficial-lobe tumours through both an original study and a meta-analysis. METHODS: In this study, we performed a retrospective analysis of data from 91 patients who had been diagnosed with benign parotid tumours. The MFTD values were sourced from preoperative ultrasound examinations. The locations of these tumours were confirmed through surgical findings. We assessed the diagnostic accuracy of MFTD by utilising receiver operating characteristic (ROC) curves. Additionally, we conducted a systematic review of the pertinent literature and performed a diagnostic meta-analysis to ascertain the overall diagnostic efficacy of MFTD in identifying benign parotid tumours. RESULTS: Patients with tumours in the deep lobe had a significantly greater MFTD than patients with tumours in the superficial lobe. Using a cutoff value of 3.50 mm for MFTD, we found an AUC of 0.93, a sensitivity of 81.8%, and a specificity of 98.8%. Our meta-analysis included seven studies covering a total of 1689 tumours. The pooled values for sensitivity, specificity, and diagnostic odds ratio (OR) of MFTD were 81.0%, 89.0%, and 32.2, respectively. The AUC of the summarised ROC curve of MFTD was 0.90. CONCLUSION: The MFTD demonstrated reliable diagnostic accuracy in identifying deep-lobe benign parotid tumours and may be incorporated into standard evaluations before parotidectomy.

Cyclin dependent kinase 9 inhibition reduced programmed death-ligand 1 expression and improved treatment efficacy in hepatocellular carcinoma.

The anti-programmed death-ligand 1 (PD-L1) antibody is a standard therapy for advanced hepatocellular carcinoma (HCC). Tumor expression of PD-L1 can be induced upon stimulus. Because cyclin-dependent kinase 9 (CDK9) inhibition reduces the expression of inducible proteins, we explored the influence of CDK9 inhibition on PD-L1 expression in HCC cells. We found that PD-L1 expression was low in HCC cells; however, IFN-γ treatment increased this expression. CDK9 inhibitors AZD4573 and atuveciclib reduced the IFN-γ induced PD-L1 expression in a dose-dependent manner. CDK9 knockdown yielded similar results, but CDK9 overexpression reversed the influence of the CDK9 inhibitors. In the orthotopic mouse model, mice treated with a CDK9 inhibitor and an anti-PD-L1 antibody had significantly smaller tumors and exhibited longer survival than mice treated with either agent. In conclusion, CDK9 inhibition could reduce the expression of PD-L1 in HCC cells. Using both CDK9 inhibitors and anti-PD-L1 antibodies is more effective than using either agent alone.