The gene is responsible for intrinsic resistance to various drugs and virulence in by regulating cell division.

exhibits intrinsic resistance to most antibiotics, hence leading to infections that are difficult to treat. To address this issue, the identification of new molecular targets is essential for the development or repositioning of therapeutic agents. This study demonstrated that the -knockout strain, Mab, became significantly susceptible to a range of antibiotics, not only but also exhibited susceptibility to rifabutin, bedaquiline, and linezolid .

Clinical Insights and Management Strategies for Acute Obstructive Suppurative Pancreatic Ductitis: A Retrospective Study of 82 Rare Cases.

Background And Aims: Acute obstructive suppurative pancreatic ductitis (AOSPD) is a rare condition with limited diagnostic and treatment information. This study aims to expand understanding by analyzing the clinical characteristics and management of AOSPD.

Methods: We analyzed 81 AOSPD cases (1993-2024) from the literature and 1 case from the First Affiliated Hospital of Anhui Medical University.

Sleeping and Eating Behavior Recognition of Horses Based on an Improved SlowFast Network.

The sleeping and eating behaviors of horses are important indicators of their health. With the development of the modern equine industry, timely monitoring and analysis of these behaviors can provide valuable data for assessing the physiological state of horses. To recognize horse behaviors in stalls, this study builds on the SlowFast algorithm, introducing a novel loss function to address data imbalance and integrating an SE attention module in the SlowFast algorithm's slow pathway to enhance behavior recognition accuracy.

A novel adjunctive diagnostic method for bone cancer: Osteosarcoma cell segmentation based on Twin Swin Transformer with multi-scale feature fusion.

Background: Osteosarcoma, the most common primary bone tumor originating from osteoblasts, poses a significant challenge in medical practice, particularly among adolescents. Conventional diagnostic methods heavily rely on manual analysis of magnetic resonance imaging (MRI) scans, which often fall short in providing accurate and timely diagnosis. This underscores the critical need for advancements in medical imaging technologies to improve the detection and characterization of osteosarcoma.

Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19.

The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CL), and papain-like protease (PL) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CL inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CL from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms.

Single-cell analysis reveals T cell dysfunction driven by macrophages and differential expression of transposable elements in severe COVID-19 patients.

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined.

Design and synthesis of Thieno[3, 2-b]pyridinone derivatives exhibiting potent activities against Mycobacterium tuberculosis in vivo by targeting Enoyl-ACP reductase.

In this study, a series of novel thieno [3, 2-b]pyridinone derivatives were designed and synthesized using a scaffold hopping strategy. Six compounds showed potent anti-mycobacterial activity (minimum inhibitory concentration (MIC) ≤ 1 μg/mL) against Mycobacterium tuberculosis (Mtb) UAlRa. Compound 6c displayed good activity against Mtb UAlRv (MIC = 0.

The neurotransmitter calcitonin gene-related peptide shapes an immunosuppressive microenvironment in medullary thyroid cancer.

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

Background: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting.

Measures of insulin resistance and beta cell function before and after treatment of HCV infection.

The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI <25 were enrolled in the study.

Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein.

Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process.

The impact of preoperative calcitonin screening on the prognosis of patients with medullary thyroid cancer: a retrospective multicenter cohort study.

Purpose: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery.

Methods: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023.

Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.

Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5' end sequences derived from cap-snatching in influenza virus mRNA.

Interlaminar Shear Strength Change and Storage Life Prediction of Carbon Fiber/Epoxy Composites with Hygrothermal Accelerated Aging.

In order to investigate the durability of fiber-reinforced polymer composites in hygrothermal environments, hygrothermal accelerate aging tests, for 360 days at 70 °C, RH70%; 70 °C, RH85%; 85 °C, RH70%; and 85 °C, RH85% and natural storage for 2 years in Guangzhou, China, were carried out for composite laminates. Then, the moisture absorption and interlaminar shear strength were measured. The hygrothermal damage mechanism of the composite was studied by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FSEM).

Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial.

Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants.

Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h.

Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

Background: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed.

Preclinical evaluation of the SARS-CoV-2 M inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir.

Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (M), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.

Recent advances in CRISPR-Cas9-based genome insertion technologies.

Programmable genome insertion (or knock-in) is vital for both fundamental and translational research. The continuously expanding number of CRISPR-based genome insertion strategies demonstrates the ongoing development in this field. Common methods for site-specific genome insertion rely on cellular double-strand breaks repair pathways, such as homology-directed repair, non-homologous end-joining, and microhomology-mediated end joining.

Clinical prediction models for cervical lymph node metastasis of papillary thyroid carcinoma.

Purpose: Accurate preoperative diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains an unsolved problem. This study aimed to construct a nomogram and scoring system for predicting LNM based on the clinical characteristics of patients with PTC.

Methods: 1400 patients with PTC who underwent thyroidectomy and lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled and randomly divided into training and internal testing sets.

[An evaluation of carrier detection for Spinal muscular atrophy using digital PCR assay].

Objective: To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.

Methods: Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay.