Enhanced Cr(VI) elimination from water by goethite-impregnated activated carbon coupled with weak electric field.

A weak electric field (WEF, 2 mA cm-2) was employed to promote Fe(III)/Fe(II) cycle on goethite-impregnated activated carbon (FeOOH@AC) filled in a continuous-flow column for enhanced Cr(VI) elimination from water. Surficial analysis and Cr species distribution showed that α-FeOOH of 0.2-1 µm was successfully synthesized and evenly loaded onto AC. Electron transfer from WEF to α-FeOOH was facilitated with AC as electron shuttles, thereby boosting Fe(III) reduction in the α-FeOOH. The generated Fe(II) reduced Cr(VI) and the resultant Cr(III) subsequently precipitated with OH- and Fe(III) to form Cr(OH)3 and (CrχFe1-χ)(OH)3. Therefore, the WEF-FeOOH@AC column exhibited a much lower Cr(VI) migration rate of 0.0018 cm PV-1 in comparison with 0.0037 cm PV-1 of the FeOOH@AC column, equal to 104 % higher Cr(VI) elimination capacity and 90 % longer column service life-span. Additionally, under different Cr(VI) loadings by varying either seepage velocities or influent Cr(VI) concentrations, the WEF-FeOOH@AC column maintained 1.0-1.5 folds higher Cr(VI) elimination and 0.9-1.4 folds longer longevity than those of the FeOOH@AC column owing to the interaction between FeOOH@AC and WEF. Our research demonstrated that WEF-FeOOH@AC was a potential method to promote Cr(VI) elimination from water and offer an effective strategy to facilitate Fe(III)/Fe(II) cycle in iron oxides.

Successful secukinumab treatment of generalized pustular psoriasis.

Generalized pustular psoriasis is a rare variant of psoriasis. Evidence recommending generalized pustular psoriasis treatment with secukinumab is limited. This report aims to evaluate the use of secukinumab in two patients with generalized pustular psoriasis. The standard treatment regimen for secukinumab was as follows: 300mg subcutaneously once weekly in weeks 0-4, followed by 300mg every four weeks. The efficacy was evaluated by analyzing the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). One patient had generalized pustular psoriasis, which had developed from palmoplantar pustulosis over 12 years. The second patient was an adolescent with recurrent generalized pustular psoriasis. The first patient achieved PASI-75 response by week 3 and both PASI-90 and a DLQI score of 0 were observed by week 8. The second patient achieved PASI-75 response by week 4 and complete clinical resolution, except for nail changes, and a DLQI of 0 by week 8, without any adverse events.

TRPM2 facilitates tumor progression of clear cell renal cell carcinoma by relieving Endoplasmic Reticulum Stress.

Clear cell renal cell carcinoma (ccRCC) has the highest incidence rate among all pathological types of kidney cancers. Although the role of transient receptor potential (TRP) ion channel TRPM2 has been studied in many cancers, its function in ccRCC is still unexplored. In this study, using the KIRC module of TCGA, we found that TRPM2 was upregulated in ccRCC tissues and was related to poor prognosis. Gene set enrichment analysis (GSEA) showed that TRPM2 was related to epithelial-to-mesenchymal transition (EMT), TCA cycle, fatty acid metabolism, and immune system-related functions. Functional experimental results indicated that TRPM2 could promote ccRCC progression. Furthermore, mechanism analysis showed that knocking out TRPM2 can reverse these phenotypes by increasing endoplasmic reticulum stress and decreasing EMT. We also investigated the potential role of TRPM2 in immune cell infiltration in the tumor microenvironment. Our study indicated that TRPM2 promotes ccRCC progression and may be a novel target for ccRCC therapy.

KDELR2-KIF20A axis facilitates bladder cancer growth and metastasis by enhancing Golgi-mediated secretion.

BACKGROUND: Bladder cancer (BCa) is a fatal form of cancer worldwide associated with a poor prognosis. Identifying novel drivers of growth and metastasis hold therapeutic potential for the disease. Transport homeostasis between the endoplasmic reticulum and Golgi and the secretion of matrix metalloproteinases (MMPs) mediated by Golgi have been reported to be closely associated with tumor progression. However, to date, mechanistic studies remain limited. RESULTS: Here, we identified KDELR2 as a potential risk factor with prognostic value in patients with BCa, especially those harbouring the KDELR2 amplification. In addition, we found that KDELR2 is a regulator of BCa cell proliferation and tumorigenicity based on bioinformatic analysis with functional studies. Mechanistically, we revealed that KDELR2 could regulate the expression of KIF20A, thus stimulating the expression of MMP2, MMP9 and MKI67. Functionally, the overexpression of KDELR2 and KIF20A markedly promoted proliferation, migration, and invasion in vitro and enhanced tumor growth in vivo, while knockdown of KDELR2 and KIF20A exerted the opposite effects. And the overexpression of KDELR2 also enhanced lymph node metastasis in vivo. CONCLUSIONS: Collectively, our findings clarified a hitherto unexplored mechanism of KDELR2-KIF20A axis in increasing Golgi-mediated secretion of MMPs to drive tumor progression in BCa.

M2-polarization-related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies, characterized by high mortality rate in urology. Unfortunately, reliable biomarkers for ccRCC diagnosis and prognosis remain lacking. Contactin-associated protein 1 (CNTNAP1) has yet to be thoroughly investigated in cancer, especially its relationship with immune infiltration or clinical outcomes of ccRCC. Here, we explored The Cancer Genome Atlas Kidney Clear Cell Carcinoma database (TCGA-KIRC) for prognostic significance, differential expression, and probable mechanism of CNTNAP1. The aberrant CNTNAP1 expression was also validated by the International Cancer Genome Consortium (ICGC) and ccRCC clinic samples. We used Database for Annotation, Visualization, and Integrated Discovery to perform the GO and KEGG enrichment. TIMER database was further utilized to assess its correlation with immune infiltration in ccRCC. The CellMiner database was used to analyze the relationship between CNTNAP1 expression and drug sensitivity. Results showed CNTNAP1 was upregulated in TCGA-KIRC, ICGC, and clinic samples. And CNTNAP1 expression was positively related to infiltration levels of cancer-associated fibroblast, regulatory T cells, and myeloid-derived suppressor cells, while negatively related to eosinophils. Furthermore, we observed CNTNAP1 was appreciably positively associated with alternatively activated macrophage (M2) in ccRCC. Finally, high CNTNAP1 expression was negatively correlated with nilotinib, crizotinib, eribulin mesylate, and vinorelbine. Collectively, these results strongly suggest that CNTNAP1 might act as an immunotherapeutic target and a promising novel biomarker for ccRCC.

Enhanced cadmium immobilization by sulfate-mediated microbial zero-valent iron corrosion.

A biotic iron (Fe0) treatment system combined with mixed microorganisms was applied to remediate cadmium (Cd)-contaminated groundwater under the intervention of sulfate. Due to hydrogenotrophic desulfuration effect, severe iron corrosion was observed in this microbe-collaborative Fe0 system according to surface morphology analysis as lots of secondary minerals (e.g. magnetite, green rust and lepidocrocite) were generated, which was essential for Cd(II) adsorption and immobilization. The sulfate-mediated biotic Fe0 system thereafter achieved a significantly enhanced Cd(II) removal efficiency of 86.1%, over 3.3 times than that in the abiotic Fe0 system. Increasing initial sulfate concentration could improve the removal of cadmium, which further proved that hydrogenotrophic desulfuration played a key role for enhanced Cd removal. According to the experimental results and current reports, the mechanism of Cd(II) removal was revealed into three pathways including adsorption to secondary iron minerals, co-precipitation with iron (hydr)oxides and formation of cadmium sulfide precipitation. Increasing Fe0 dosages showed positive correlation to Cd(II) removal and neutral pH was preferred to sulfate-mediated biotic Fe0 corrosion. These results indicated that sulfate-mediated biotic Fe0 corrosion could greatly relieve the limitation of Fe0 in Cd(II) immobilization, which could be a promising method to eliminate Cd(II) pollution from groundwater.

Solute carrier family 16 member 5 downregulation and its methylation might serve as a prognostic indicator of prostate cancer.

Prostate cancer (PCa), characterized by high invasion, metastasis, and recurrence, is the most prevalent malignant tumor in men worldwide. A clear understanding of the underlying molecular mechanisms and their role during PCa tumorigenesis can help develop prognostic and targeted therapies. We analyzed datasets from public databases, including the Cancer Genome Atlas (TCGA) and Oncomine and Gene Expression Profiling Interactive Analysis for differential expression of solute carrier family 16 member 5 (SLC16A5). We further investigated its relationship with clinical stage, pathological grade, and prognosis of PCa. The promoter methylation level of SLC16A5 in PCa was also investigated by UALCAN. We also utilized datasets from UCSC Xena to explore the prognostic role of SLC16A5 methylation levels and CpG site. Correlations between SLC16A5 and immune infiltration were discovered through TIMER. We observed significantly lower levels of SLC16A5 mRNA in PCa relative to normal tissues across six datasets from Oncomine database (p < .001) and 498 cases from TCGA database (p < .0001). SLC16A5 is strongly negatively regulated by its DNA methylation, with a Spearman of -0.81 and Pearson of -0.80 (p < .001). The aberrant SLC16A5 expression resulted in a significant relationship with clinical stage, pathological grade, and lower SLC16A5 mRNA expression, and its hypermethylation was related to a poorer PCa prognosis. SLC16A5 acted as an important factor for PCa diagnosis, with an AUC of 0.9038 (95% CI: 0.8597-0.9479; p < .0001). Besides, the aberrant SLC16A5 expression revealed close correlations with multiple immune cells. Overall, these results indicate that decreased SLC16A5 expression might be a potential biomarker for determining prognosis and immune infiltration in PCa. The positive SLC16A5 modulation might be a promising therapeutic target for PCa.

Efficacy and safety of sofosbuvir/velpatasvir in a real-world chronic hepatitis C genotype 3 cohort.

BACKGROUND AND AIM: Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. METHODS: We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. RESULTS: A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. CONCLUSION: The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.

Validation of the Expanded Baveno-VI Criteria for Screening Gastroscopy in Asian Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria. AIM: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection. METHODS: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV). RESULTS: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively. CONCLUSION: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.

Uptake, Accumulation, and Biomarkers of PM2.5-Associated Organophosphate Flame Retardants in C57BL/6 Mice after Chronic Exposure at Real Environmental Concentrations.

Although the bioaccumulation of organophosphate flame retardants (OPFRs) in aquatic organisms has been investigated, little information is available about their bioaccumulation in mammals following chronic inhalation exposure. To address this knowledge gap, C57BL/6 mice were exposed to 7 PM2.5-associated OPFRs via the trachea to study their bioaccumulation, tissue distribution, and urinary metabolites. Low (corresponding to the real PM2.5 concentrations occurring during winter in Guangzhou), medium, and high dosages were examined. After 72 days' exposure, ∑OPFR concentrations in tissues from mice in the medium dosage group decreased in the order of intestine > heart > stomach > testis > kidney > spleen > brain > liver > lung > muscle. Of the OPFRs detected in all three exposure groups, chlorinated alkyl OPFRs were most heavily accumulated in mice. We found a significant positive correlation between the bioaccumulation ratio and octanol-air partition coefficient (KOA) in mice tissues for low log KOW OPFR congeners (log KOW ≤ 4, p < 0.05). Three urinary metabolites (di-p-cresyl phosphate: DCrP, diphenyl phosphate: DPhP, dibutyl phosphate: DnBP) were detected from the high dosage group. These results provide important insights into the bioaccumulation potential of OPFRs in mammals and emphasize the health risk of chlorinated alkyl OPFRs.

Chemical identity and cardiovascular toxicity of hydrophobic organic components in PM2.5.

Numerous experimental and epidemiological studies have demonstrated that exposure to PM2.5 may result in pathogenesis of several major cardiovascular diseases (CVDs), which can be attributed to the combined adverse effects induced by the complicated components of PM2.5. Organic materials, which are major components of PM2.5, contain thousands of chemicals, and most of them are environmental hazards. However, the contamination profile and contribution to overall toxicity of PM2.5-bound organic components (OCs) have not been thoroughly evaluated yet. Herein, we aim to provide an overview of the literature on PM2.5-bound hydrophobic OCs, with an emphasis on the chemical identity and reported impairments on the cardiovascular system, including the potential exposure routes and mechanisms. We first provide an update on the worldwide mass concentration and composition data of PM2.5, and then, review the contamination profile of PM2.5-bound hydrophobic OCs, including constitution, concentration, distribution, formation, source, and identification. In particular, the link between exposure to PM2.5-bound hydrophobic OCs and CVDs and its possible underlying mechanisms are discussed to evaluate the possible risks of PM2.5-bound hydrophobic OCs on the cardiovascular system and to provide suggestions for future studies.

FOXP3 orchestrates H4K16 acetylation and H3K4 trimethylation for activation of multiple genes by recruiting MOF and causing displacement of PLU-1.

Both H4K16 acetylation and H3K4 trimethylation are required for gene activation. However, it is still largely unclear how these modifications are orchestrated by transcriptional factors. Here, we analyzed the mechanism of the transcriptional activation by FOXP3, an X-linked suppressor of autoimmune diseases and cancers. FOXP3 binds near transcriptional start sites of its target genes. By recruiting MOF and displacing histone H3K4 demethylase PLU-1, FOXP3 increases both H4K16 acetylation and H3K4 trimethylation at the FOXP3-associated chromatins of multiple FOXP3-activated genes. RNAi-mediated silencing of MOF reduced both gene activation and tumor suppression by FOXP3, while both somatic mutations in clinical cancer samples and targeted mutation of FOXP3 in mouse prostate epithelial cells disrupted nuclear localization of MOF. Our data demonstrate a pull-push model in which a single transcription factor orchestrates two epigenetic alterations necessary for gene activation and provide a mechanism for somatic inactivation of the FOXP3 protein function in cancer cells.

Activation of GATA binding protein 6 (GATA6) sustains oncogenic lineage-survival in esophageal adenocarcinoma.

Gene amplification is a tumor-specific event during malignant transformation. Recent studies have proposed a lineage-dependency (addiction) model of human cancer whereby amplification of certain lineage transcription factors predisposes a survival mechanism in tumor cells. These tumor cells are derived from tissues where the lineage factors play essential developmental and maintenance roles. Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a single gene, the embryonic endoderm transcription factor GATA6, as the selected target of the amplification. Overexpression of GATA6 is found in EACs that contain gene amplification. We find that EAC patients whose tumors carry GATA6 amplification have a poorer survival. We show that ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent growth in immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of GATA6 significantly reduces both cell proliferation and anchorage-independent growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal squamous cells. We show that activation of p38α signaling and up-regulation of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon GATA6 deprivation. We conclude that selective gene amplification of GATA6 during EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma.

c-Jun N-terminal kinase 1 (JNK1) is required for coordination of netrin signaling in axon guidance.

The JNK family of MAPKs is involved in a large variety of physiological and pathological processes in brain development, such as neural survival, migration, and polarity as well as axon regeneration. However, whether JNK activation is involved in axon guidance remains unknown. Here, we provide evidence indicating the JNK pathway is required for Netrin signaling in the developing nervous system. Netrin-1 increased JNK1, not JNK2 or JNK3, activity in the presence of deleted in colorectal cancer (DCC) or Down syndrome cell adhesion molecule (DSCAM), and expression of both of them further enhanced Netrin-1-induced JNK1 activity in vitro. Inhibition of JNK signaling either by a JNK inhibitor, SP600125, or expression of a dominant negative form of MKK4, a JNK upstream activator, blocked Netrin-1-induced JNK1 activation in HEK293 cells. Netrin-1 increased endogenous JNK activity in primary neurons. Netrin-1-induced JNK activation was inhibited either by the JNK inhibitor or an anti-DCC function-blocking antibody. Combination of the anti-DCC function-blocking antibody with expression of DSCAM shRNA in primary neurons totally abolished Netrin-1-induced JNK activation, whereas knockdown of DSCAM partially inhibited the Netrin-1 effect. In the developing spinal cord, phospho-JNK was strongly expressed in commissural axons before and as they crossed the floor plate, and Netrin-1 stimulation dramatically increased the level of endogenous phospho-JNK in commissural axon growth cones. Inhibition of JNK signaling either by JNK1 RNA interference (RNAi) or the JNK inhibitor suppressed Netrin-1-induced neurite outgrowth and axon attraction. Knockdown of JNK1 in ovo caused defects in spinal cord commissural axon projection and pathfinding. Our study reveals that JNK1 is important in the coordination of DCC and DSCAM in Netrin-mediated attractive signaling.

ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression.

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.

Hsa_circ_0086414/transducer of ERBB2 (TOB2) axis-driven lipid elimination and tumor suppression in clear cell renal cell cancer via perilipin 3.

BACKGROUND: Renal cell cancer (RCC) is characterized by abnormal lipid accumulation. However, the specific mechanism by which such lipid deposition is eliminated remains unclear. Circular RNAs (circRNAs) widely regulate various biological processes, but the effect of circRNAs on lipid metabolism in cancers, especially clear cell renal cell carcinoma (ccRCC), remains poorly understood. METHODS: The downregulated circRNA, hsa_circ_0086414, was identified from high-throughput RNA-sequencing data of human ccRCC and pair-matched normal tissues. The target relationship between circRNA_0086414 and miR-661, and the transducer of ERBB2 (TOB2) was predicted using publicly available software programs and verified by luciferase reporter assays. The clinical prognostic value of TOB2 was evaluated by bioinformatic analysis. The expression levels of circRNA_0086414, miR-661, TOB2, and perilipin 3 (PLIN3) were measured by quantitative reverse-transcription polymerase chain reaction or western blot analysis. Cell Counting Kit-8, transwell assays, and xenograft models were employed to assess the biological behaviors of the hsa_circ_0086414/TOB2 axis. Oil Red staining and triglyceride assay was conducted to assess lipid deposition. RESULTS: Herein, we identified a downregulated circRNA, hsa_circ_0086414. Functionally, the restored hsa_circ_0086414 inhibited ccRCC proliferation, metastasis, and lipid accumulation in vitro and in vivo. Furthermore, the downregulated TOB2 predicted adverse prognosis and promoted cancer progression and lipid deposition in ccRCC. Mechanically, the binding of hsa_circ_0086414 to miR-661, as a miRNA sponge, upregulates the expression of TOB2, wielding an anti-oncogene effect. Importantly, the restored hsa_circ_0086414/TOB2 axis significantly contributed to the elimination of lipid deposition by inhibiting the lipid metabolism regulator PLIN3 in ccRCC cells. CONCLUSIONS: Our data highlight the importance of the hsa_circ_0086414/TOB2/PLIN3 axis as a tumor suppressor and lipid eliminator in ccRCC. The positive modulation of the hsa_circ_0086414/TOB2 axis might lead to the development of novel treatment strategies for ccRCC.

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients: A 12-week randomized placebo-controlled phase III trial with long-term extension.

BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs . 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs . 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05108766.