Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic sp. Strain.

A combined strategy of 2D-NMR-metabolomics-driven substructure tracking with genome mining led to the targeted discovery of 10 nocobactin-type lipopeptides (-) from the Arctic-derived phychrophillic sp. L-016, among which - are new compounds, named nocardimicins S-W. The phenoxazole moiety in -, featuring unique NMR values and correlations, was used as a probe for tracking nocardimicin analogues.

Incentive affects physicians' willingness to continue participating in urban-rural medical consortia: a comparative study of county and provincial hospitals in Central China.

Objectives: The World Health Organization asserts that incentives significantly impact physicians' participation in healthcare initiatives. China introduced incentive programs to boost involvement in urban-rural medical consortia. However, research is limited on: (a) the effectiveness of these incentives on physicians' willingness to continue participating, (b) disparities in incentive levels between county and provincial hospitals, and (c) the varying impact of incentives on physicians' continued participation in county versus provincial hospitals.

PD-1 blockade treatment in melanoma: Mechanism of response and tumor-intrinsic resistance.

Malignant melanoma is characterized by high immunogenicity, genetic heterogeneity, and diverse pathological manifestations, affecting both skin and mucosa over the body. Pembrolizumab and nivolumab, both anti-PD-1 monoclonal antibodies, were approved by the US FDA for unresectable or metastatic melanoma in 2011 and 2014, respectively, with enduring and transformative outcomes. Despite marked clinical achievements, only a subset of patients manifested a complete response.

Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts.

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components.

Split G-Quadruplex Programmed Recyclable AIE-Biosensor for Label-Free Detection of miRNA in Acute Kidney Injury.

We herein rationally designed a target-recyclable AIE-biosensor based on a split G-quadruplex for label-free detection of miRNA in acute kidney injury. Initially, the PG was in an "OFF" state, and the two split segments (G4-a and G4-b) of G4 were tethered at the two terminals of P1 and far away from each other due to the rigid duplex structure formed by the partially complementary intermediate sequences of P2 and P1, bringing MG with quenched fluorescence. In the presence of target, the 5'-PO P2 was displaced from PG probe and competitively hybridized with target, which led to G4-a and G4-b tending to form an intact intermolecular G-quadruplex, providing sites for MG intercalation, thus generating an activated "ON" fluorescence signal due to the restriction of intermolecular motion.

Mechanisms of ferroptosis and targeted therapeutic approaches in urological malignancies.

The prevalence of urological malignancies remains a significant global health concern, particularly given the challenging prognosis for patients in advanced disease stages. Consequently, there is a pressing need to explore the molecular mechanisms that regulate the development of urological malignancies to discover novel breakthroughs in diagnosis and treatment. Ferroptosis, characterized by iron-ion-dependent lipid peroxidation, is a form of programmed cell death (PCD) distinct from apoptosis, autophagy, and necrosis.

Dietary and lifestyle insulinemic potentials, plasma metabolome, and risk of diverticulitis: a prospective cohort study.

Background: Diet and lifestyle factors have been linked to developing diverticulitis. However, it remains largely unknown whether the associations are mediated by metabolic disturbance, such as hyperinsulinemia and corresponding metabolomic perturbations.

Objectives: We investigated associations of the insulinemic potential of diet, lifestyle (diet, physical activity, body weight), and metabolomic patterns with the risk of incident diverticulitis.

The Role of CDCA2 in tumor genesis, prognosis and future treatments.

The Cell Division Cycle Associated 2 (CDCA2) gene is responsible for encoding a targeting subunit of cell-cycle associated protein. CDCA2 plays a crucial role in various cellular processes, including chromosome segregation and decondensation, nuclear envelope reassembly, microtubule assembly, and DNA damage response. Additionally, CDCA2 is involved in multiple signaling pathways such as the PI3K/Akt pathway and p53 pathway.

Effects of calcium ions and cell wall deposition on the pollen viability of Paeonia lactiflora after cryopreservation.

Four cultivars of Paeonia lactiflora pollen have a different viability after cryopreservation, and that the difference of pollen viability is related to calcium ions and cell wall deposition. Cryopreservation is a vital technique for preserving germplasm resources, offering extensive application prospects. Understanding the factors influencing pollen viability after cryopreservation is crucial for the permanent preservation and exchange of pollen resources.

T7 RNA polymerase-mediated rolling circle transcription and the CRISPR-Cas13a cascade reaction for sensitive and specific detection of piRNA.

The aberrant expression of piRNAs in germ cells is a potential cause of male infertility. Establishing diagnostic methods with highly specific biomarkers for male infertility is important for accurate diagnosis and treatment of male infertility. In this study, we proposed a novel method combining rolling circle transcription (RCT) and Cas13a techniques, which utilized the high amplification efficiency of RCT and the two different RNase activities possessed by Cas13a, establishing a highly sensitive and specific assay for male infertility-associated piRNA.

Inflammation-free electrochemical in vivo sensing of dopamine with atomic-level engineered antioxidative single-atom catalyst.

Electrochemical methods with tissue-implantable microelectrodes provide an excellent platform for real-time monitoring the neurochemical dynamics in vivo due to their superior spatiotemporal resolution and high selectivity and sensitivity. Nevertheless, electrode implantation inevitably damages the brain tissue, upregulates reactive oxygen species level, and triggers neuroinflammatory response, resulting in unreliable quantification of neurochemical events. Herein, we report a multifunctional sensing platform for inflammation-free in vivo analysis with atomic-level engineered Fe single-atom catalyst that functions as both single-atom nanozyme with antioxidative activity and electrode material for dopamine oxidation.

Atom-pair engineering of single-atom nanozyme for boosting peroxidase-like activity.

Constructing atom-pair engineering and improving the activity of metal single-atom nanozyme (SAzyme) is significant but challenging. Herein, we design the atom-pair engineering of Zn-SA/CNCl SAzyme by simultaneously constructing Zn-N sites as catalytic sites and Zn-NCl sites as catalytic regulator. The Zn-NCl catalytic regulators effectively boost the peroxidase-like activities of Zn-N catalytic sites, resulting in a 346-fold, 1496-fold, and 133-fold increase in the maximal reaction velocity, the catalytic constant and the catalytic efficiency, compared to Zn-SA/CN SAzyme without the Zn-NCl catalytic regulator.

An Empirical Dietary Pattern Associated With the Gut Microbial Features in Relation to Colorectal Cancer Risk.

Background & Aims: Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited.

Methods: Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pksEscherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019).

Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass.

Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses.

Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk.

Importance: Aspirin reduces the risk of colorectal cancer (CRC). Identifying individuals more likely to benefit from regular aspirin use for CRC prevention is a high priority.

Objective: To assess whether aspirin use is associated with the risk of CRC across different lifestyle risk factors.