Small molecule inhibits KCNQ channels with a non-blocking mechanism.

Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.

Metastatic sites of baseline as predictors in recurrent or metastatic nasopharyngeal carinoma treated with PD-L1 inhibitor: a secondary analysis of multicenter, single-arm, phase II study (KL-A167).

Background: Immune checkpoint inhibitors (ICIs) show optimal treatment effects on recurrent or metastatic nasopharyngeal carcinoma(R/M NPC). Nonetheless, whether metastatic sites impact ICIs efficacy remains unclear.

Methods: We performed a secondary analysis of R/M NPC patients treated with KL-A167, a programmed cell death-ligand 1(PD-L1) inhibitor, based on a multicenter, single-arm, phase II study from China between 2019 and 2021 years, which represents the first and most comprehensive analysis of the effectiveness of a PD-L1 inhibitor in patients who have been previously treated.

Comprehensive analysis of the value of angiogenesis and stemness-related genes in the prognosis and immunotherapy of ovarian cancer.

Tumor angiogenesis and the presence of cancer stem cells (CSCs) are critical characteristics of tumors. Previous research has demonstrated that cancer stem cells promote tumor angiogenesis, while increased vascularity, in turn, fosters the growth of cancer stem cells. This creates a detrimental cycle that contributes to tumor progression.

Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: a single-arm phase 2 trial.

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with a poor prognosis. Therapeutic options for patients with advanced ACC who have failed standard treatments are limited. Single-agent immunotherapy as a second-line treatment has shown unsatisfactory clinical outcomes.

Harnessing the Systemic Immunoinflammatory Index as a Potential Predictive Tool for Recurrent or Metastatic Nasopharyngeal Carcinoma Undergoing PD-L1 Inhibitor.

Purpose: Immunotherapy has become the primary option for recurrent and metastatic nasopharyngeal cancer (R/M NPC) after failure of chemotherapy, but without good prognostic indicators. Our study aimed to assess the potential of the systemic immune-inflammation index (SII) in predicting the effectiveness of PD-L1 inhibitor therapy for R/M NPC.

Patients And Methods: The study cohort comprises of a prospective Phase 2 clinical trial population undergoing PD-L1 inhibitor for R/M NPC at 42 hospitals in China between 2019 and 2021.

The Effects of Gene Function of Endophytic Fungus OW 7.8 on Its Swainsonine Biosynthesis.

The gene in the endophytic fungus OW 7.8 isolated from was identified, and the gene knockout mutant Δ was first constructed in this study. Compared with OW 7.

Causal effect of gut microbiota on occurrence of herpes zoster and postherpetic neuralgia, and role of Tyzzerella 3.

Background: Previous research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN).

Methods: A total of 205 taxa of gut microbiota were regarded as exposures.

Lung immune prognostic index is associated with clinical outcomes in recurrent or metastatic (R/M) nasopharyngeal carcinoma receiving immunotherapy: Results from the multicenter, single-arm, phase 2 study.

Background: Immune-related biomarkers are linked to the outcomes of cancer immunotherapy. This study evaluates the baseline and longitudinal association between the lung immune prognostic index (LIPI) and immune checkpoint inhibitor outcomes in previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients.

Methods: Data from 153 R/M NPC patients (median age = 49.

Functional roles of the interaction of Moa1 with CENP-C and Rec8 in meiosis of .

The localization of the meiotic specific regulatory molecule Moa1 to the centromere is regulated by the kinetochore protein CENP-C, and participates in the cohesion of sister chromatids in the centromere region mediated by the cohesin Rec8. To examine the interaction of these proteins, we analyzed the interactions between Moa1 and Rec8, CENP-C by yeast two-hybrid assays and identified several amino acid residues in Moa1 required for the interaction with CENP-C and Rec8. The results revealed that the interaction between Moa1 and CENP-C is crucial for the Moa1 to participate in the regulation of monopolar attachment of sister kinetochores.

Combining [Lu]Lu-DOTA-TOC PRRT with PARP inhibitors to enhance treatment efficacy in small cell lung cancer.

Purpose: Small cell lung cancer (SCLC) is a highly aggressive tumor with neuroendocrine origin. Although SCLC frequently express somatostatin receptor type 2 (SSTR2), a significant clinical benefit of SSTR2-targeted radionuclide therapies of SCLC was not observed so far. We hypothesize that combination treatment with a PARP inhibitor (PARPi) could lead to radiosensitization and increase the effectiveness of SSTR2-targeted therapy in SCLC.

The effect of centromere protein Fta2 phosphorylation during meiosis.

During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear.

Joint association of physical activity and dietary quality with survival among US cancer survivors: a population-based cohort study.

Background: Limited studies have explored the joint effect of physical activity (PA) and dietary quality (DQ) on the mortality outcomes of the cancer population. The authors aim to investigate the separate and joint prognostic effect of PA and DQ on the survival of US cancer survivors.

Methods: Data of cancer survivors ( n =3007, representing 22 million cancer survivors) were from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018.

Associations and attributable burdens in late-life exposure to PM and its major components and depressive symptoms in middle-aged and older adults: A nationwide cohort study.

Background: Depression in late life has been associated with reduced quality of life and increased mortality. Whether the chronic fine particular matter (PM) and its components exposure are contributed to the older depression symptoms remains unclear.

Method: Middle-aged and older adults (>45 years) were selected from the China Health and Retirement Longitudinal Study during the four waves of interviews.

Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease.

Backgrounds: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD.

Methods: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included.

Association between triglyceride-glucose related indices with the all-cause and cause-specific mortality among the population with metabolic syndrome.

Background: Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown.

Method: Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years.

Association between systemic inflammatory indicators with the survival of chronic kidney disease: a prospective study based on NHANES.

Background: systemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the systemic inflammatory indicators could be optimal predictors for the survival of CKD remains less studied.

Methods: In this study, participants were selected from the datasets of the National Health and Nutrition Examination Survey (NHANES) between 1999 to 2018 years.

Phosphorylation of Rec8 cohesin complexes regulates mono-orientation of kinetochores in meiosis I.

In meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase I. The conserved meiosis-specific kinetochore protein meikin (Moa1 in fission yeast) associates with polo-like kinase: Plo1 and regulates both mono-orientation and cohesion protection. Although the phosphorylation of Rec8-S450 by Plo1 associated with Moa1 plays a key role in cohesion protection, how Moa1-Plo1 regulates mono-orientation remains elusive.

D-A-D organic fluorescent probes for NIR-II fluorescence imaging and efficient photothermal therapy of breast cancer.

Near-infrared second region (NIR-II) fluorescent probes are used in the diagnosis of early cancer due to their high tissue penetration. However, there are still few reports on organic small molecule fluorescent probes with NIR-II fluorescence imaging (NIR-II FI) combined with efficient photothermal therapy (PTT). In this study, planar cyclopentadithiophene (CPDT) was incorporated into the twisted structural skeleton (D-A-D), and the strong acceptor TTQ molecule (A) and the donor triphenylamine (D) were introduced to synthesize an organic small molecule (TCT) with enhanced NIR-II fluorescence emission performance.

Association between time from diagnosis to treatment and survival of patients with nasopharyngeal carcinoma: A population-based cohort study.

Background: Treatment delays have frequently been observed in cancer patients. Whether the treatment delays would impair the survival of patients with nasopharyngeal carcinoma (NPC) is still unclear.

Methods: The data were derived from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015.

circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer.

Objectives: To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients.

Methods: circRNA RNA-seq technology was used to screen differentially expressed circRNAs in CRC. Sanger sequencing was used to identify circRNA back-splice junction sites.