Zhigang Ren

The low toxicity and cost‐effectiveness of light main‐group metal photochemical systems render them highly suitable for drug development, while the redox inertness of light main‐group metals significantly hinders this goal. Herein, through the in situ assembly of readily available lithium nitrate, methoxyacetic acid, and aniline substrates, an unprecedented, mild lithium‐based photochemical system capable of producing valuable nitro radicals is established. This system enables selective C(sp ² )–H (di‐)nitration of anilines for synthesizing nitro‐aromatic compounds as potential antitumor candidates. Further, replacing lithium nitrate with magnesium nitrate makes the reaction conditions milder, allowing lower‐energy green‐light irradiation for the (di‐)nitration. The two main‐group metal photochemical systems also enable direct late‐stage functionalization of complex drug molecules, eliminating the risk of transition metal residue and drastically simplifying the workup procedures of pharmaceutical manufacturing processes.

Gut microbiota dysbiosis has been closely associated with COVID‐19 progression, and probiotic supplementation has been regarded as a potential adjuvant therapy for COVID‐19. However, large‐scale clinical evidence regarding the efficacy of probiotics against the currently predominant Omicron variant remains scarce. This multicenter retrospective cohort study employed a 1:2 propensity score‐matched analysis of hospitalized Omicron‐infected patients from 10 hospitals in Henan Province (probiotics group: 4205 cases vs. control group: 8410 cases). The primary outcome was all‐cause mortality, and the secondary outcome was the incidence of composite disease progression. The results demonstrated that probiotic supplementation significantly reduced all‐cause mortality by 27% (hazard ratio [HR] = 0.73, 95% confidence interval: 0.654‒0.811), with more pronounced benefits observed in patients not receiving antiviral therapy (HR = 0.67) and those with severe disease (HR = 0.69). However, no significant difference was found in the composite disease progression outcome (HR = 1.05, p = .312). Safety assessment indicated that probiotic supplementation was generally well‐tolerated, although transient fluctuations in serum creatinine levels warranted attention. In conclusion, based on the real‐world evidence from a multicenter Omicron‐infected patients’ cohort, the probiotic supplementation could reduce the all‐cause mortality rate of hospitalized patients infected with Omicron, especially in severe cases and without antiviral treatments cases. This study provides the first large‐scale real‐world data and new microbiome‐modulating strategies against future respiratory viral infections.

Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide and early detection strategies and precise postoperative interventions must

Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor prognoses and the current first-line standard treatments remain unsatisfactory. Our study aimed to evaluate gemcitabine-based chemotherapy plus PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) for untreated unresectable iCCA. The propensity score matching (PSM) method was utilized to reduce potential confounders. Overall, 392 patients were included from 12 hospitals, with data from January 2016 to December 2024. In the full cohort analysis, the combination of GEMCIS/GEMOX with PD‑1/PD‑L1 inhibitors and TKIs significantly prolonged median OS compared to GEMCIS/GEMOX alone (26.7 vs. 15.3 months; hazard ratio [HR] 0.47, 95% CI: 0.35-0.63, P < 0.001). In the primary analysis, the combination strategy was associated with a median OS of 24.8 months (95% CI: 20.8-28.8), with corresponding HRs of 0.56 (95% CI: 0.38-0.83, P = 0.004) after PSM. Furthermore, in the combination cohort, the incidence of grade 3-4 hematological adverse events was 30%, compared with 27% in the chemotherapy cohort (P = 0.604). Importantly, our treatment strategy increased the rate of conversion surgery to 42% for locally advanced disease, ultimately resulting in improved overall outcomes (HR for OS: 0.17 [95% CI: 0.05-0.61]). Thus, combining gemcitabine-based chemotherapy with PD-1/PD-L1 inhibitors and TKIs may provide a promising treatment option for patients with unresectable iCCA.

Understanding of the metabolic determinants influencing immunotherapy responsiveness remains limited. Here we performed a multiomics analysis of tumor biopsies from patients with hepatocellular carcinoma (HCC) treated with immune checkpoint blockade (ICB) and revealed that heightened expression of OXCT1, a rate-limiting enzyme in ketone body metabolism, was negatively correlated with ICB efficacy, whereas its metabolic substrate, β-hydroxybutyrate (BHB), displayed an opposite effect. Mechanistically, glucose deprivation in HCC cells promotes AMPK-mediated OXCT1 S113 phosphorylation, which exposes the nuclear localization sequence of OXCT1 to trigger its nuclear translocation. Nucleus-translocated OXCT1 associates with IRF1 to locally consume BHB and suppress histone H3K9 BHB at the major histocompatibility complex class I (MHC-I) and chemokine gene loci, leading to repressed transcription of these immune genes. Targeting the AMPK-OXCT1-IRF1 axis sensitizes tumor cells to ICB upon ketogenic diet. These findings reveal a mechanism by which a non-canonical function of nuclear OXCT1 coordinates the interplay between ketone body metabolic reprogramming and immunotherapy responsiveness.

A selective, one-step aerobic chlorohydroxylation of electron-deficient alkenes has been achieved via electrophilic chlorine radical addition under Ce-LMCT photocatalytic conditions, thus overriding the polarity matching rule.

Growing evidence suggests a role for the gut microbiome in progression of cholangiocarcinoma (CCA), however, its diagnostic and therapeutic potential remains incompletely characterized. Here, metagenomic sequencing was performed on fecal samples ( n = 785) from individuals across East, Central, and Northwestern China. Gut microbial dysbiosis in CCA was characterized by depletion of short‐chain fatty acids‐producing species and enrichment of potential pathobionts ( Klebsiella aerogenes , Clostridium symbiosum ). Diagnostic models built using species‐level markers demonstrated superior performance, compared to pathway‐based models, achieving area under the curve (AUC) values of 98.63% and 99.42% in the discovery cohort, with robust cross‐regional validation (AUC = 80.89% and 80.43%). The model effectively distinguished CCA from hepatocellular carcinoma (AUC = 97.86%) and liver fibrosis (AUC = 98.73%) and nonalcoholic fatty liver disease (mean AUC = 96.86%). Analysis of public datasets encompassing 6847 samples across 31 studies and 11 disease states revealed moderate disease specificity influenced by biomarker overlap across conditions. Mechanistically, depleted Bifidobacterium pseudocatenulatum suppressed CCA progression, associated with inhibition of the PI3K‐AKT‐mTOR pathway. Collectively, this study supports the potential of fecal metagenomic signatures as a complementary noninvasive aid for CCA detection, and provides functional evidence for a candidate protective microbe.

Cancer patients are at an elevated risk for SARS-CoV-2 infection and require vigilant monitoring. The efficacy and safety of Azvudine in treating COVID-19