The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.

Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region.

A Novel Concept for Cleavable Linkers Applicable to Conjugation Chemistry - Design, Synthesis and Characterization.

Linkers with disulfide bonds are the only cleavable linkers that utilize physiological thiol gradients as a trigger to initiate the intracellular drug release cascade. Herein, we present a novel concept exploiting the thiol gradient phenomena to design a new class of cleavable linker with no disulfide bond. To support the concept, an electron-deficient sulfonamide-based cleavable linker amenable to conjugation of drug molecules with targeting agents, was developed.

Prognostic value of soluble programmed death-1 and soluble programmed death ligand-1 in severe traumatic brain injury patients.

Patients with traumatic brain injury (TBI) frequently exhibit concomitant immunosuppression. In this study, we evaluated the predictive values of soluble programmed death-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in patients with severe TBI. Peripheral blood sPD-1 and sPD-L1 levels were measured within 48 h of patient admission.

The association of preoperative radiotherapy and surgery for AJCC stage I-III rectal adenocarcinoma: a population-based study.

Background: With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma.

The Prevalence and Molecular Characterization of Bovine Leukemia Virus among Dairy Cattle in Henan Province, China.

Enzootic bovine leukosis, a neoplastic disease caused by the bovine leukemia virus (BLV), was the primary cancer affecting cattle in China before 1985. Although its prevalence decreased significantly between 1986 and 2000, enzootic bovine leukosis has been re-emerging since 2000. This re-emergence has been largely overlooked, possibly due to the latent nature of BLV infection or the perceived lack of sufficient evidence.

Risk and mediation analyses of hemoglobin glycation index and survival prognosis in patients with sepsis.

An increasing number of studies have reported the close relation of the hemoglobin glycation index (HGI) with metabolism, inflammation, and disease prognosis. However, the prognostic relationship between the HGI and patients with sepsis remains unclear. Thus, this study aimed to analyze the association between the HGI and all-cause mortality in patients with sepsis using data from the MIMIC-IV database.

Development of multiplex real-time PCR for simultaneous detection of SARS-CoV-2, CCoV, and FIPV.

Introduction: Coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), canine coronavirus (CCoV), and feline infectious peritonitis virus (FIPV), have the potential for interspecies transmission. These viruses can be present in complex environments where humans, dogs, and cats coexist, posing a significant threat to both human and animal safety.

Methods And Results: In this study, we developed a novel multiplex TaqMan-probe-based real-time PCR assay for the simultaneous detection and differentiation of SARS-CoV-2, CCoV, and FIPV.

Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro.

Background: Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses.

High-Performance Detection of in Milk Using Recombinase-Aided Amplification-Clustered Regularly Interspaced Short Palindromic Repeat-Cas13a-Lateral Flow Detection.

(), the microorganism responsible for bovine tuberculosis (bTB), is transferred to people by the ingestion of unpasteurized milk and unprocessed fermented milk products obtained from animals with the infection. The identification of in milk samples is of the utmost importance to successfully prevent zoonotic diseases and maintain food safety. This study presents a comprehensive description of a highly efficient molecular test utilizing recombinase-aided amplification (RPA)-clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) 13a-lateral flow detection (LFD) for detection.

Robust Offloading for Edge Computing-Assisted Sensing and Communication Systems: A Deep Reinforcement Learning Approach.

In this paper, we consider an integrated sensing, communication, and computation (ISCC) system to alleviate the spectrum congestion and computation burden problem. Specifically, while serving communication users, a base station (BS) actively engages in sensing targets and collaborates seamlessly with the edge server to concurrently process the acquired sensing data for efficient target recognition. A significant challenge in edge computing systems arises from the inherent uncertainty in computations, mainly stemming from the unpredictable complexity of tasks.

The association between type 2 diabetes and pulmonary cavitation revealed among IGRA-positive tuberculosis patients.

The co-occurrence of tuberculosis (TB) and diabetes mellitus (DM) presents a significant obstacle to TB eradication. Pulmonary cavitation can occur in severe cases of TB, particularly in patients with DM. From 1 May 2014 through 30 June 2019, we conducted a cross-sectional study of 1,658 smear- or culture-confirmed pulmonary TB (PTB) patients at the Second Department of Pulmonary Medicine and Tuberculosis, Shenzhen, China.

The Assessment of Natural Cross Pollination Properties of a Novel Male-Sterile-Female-Fertile Mutation in Soybean.

The value of a novel soybean male-sterile mutation in breeding practice was determined by its outcrossing properties. Then, the effects of different planting arrangements on the pod set characteristics of male-sterile plants were assessed by using orthogonal experiments at two sites. At the same time, the effects of male sterility on other traits were assessed in two CF populations.

Slik maintains tissue homeostasis by preventing JNK-mediated apoptosis.

Background: The c-Jun N-terminal kinase (JNK) pathway is an evolutionarily conserved regulator of cell death, which is essential for coordinating tissue homeostasis. In this study, we have characterized the Drosophila Ste20-like kinase Slik as a novel modulator of JNK pathway-mediated apoptotic cell death.

Results: First, ectopic JNK signaling-triggered cell death is enhanced by slik depletion whereas suppressed by Slik overexpression.

A participatory approach to understand the attitudes and perceptions towards priority endemic cattle diseases among dairy farmers and animal health experts in Henan province, China.

The dairy industry is threatened by a variety of endemic diseases and emerging diseases, and various control programs have been initiated in China. The increased application of evidence to policymaking can help improve the efficiency of disease control programs; however, the relevant research literature is currently lacking. The objective of this study was to gain an in-depth understanding of the attitudes and perceptions towards priority endemic diseases among dairy farmers and animal health experts by taking Henan province of China as the example and using semi-structured interviews and focus group discussions, respectively.

Expression and Functional Analysis of Gene Responding to High Ammonia Stress in Razor Clam ().

Ammonium transporter 1 (AMT1), a member of ammonia (NH/NH) transport proteins, has been found to have ammonia transport activity in plants and microorganisms. However, the functional characteristics and molecular mechanisms of AMT1 in mollusks remain unclear. The razor clam () is a suitable model species to explore the molecular mechanism of ammonia excretion because of the high concentration of ambient ammonia it is exposed to in the clam-fish-shrimp polyculture system.

Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer.

Background: The incidence of gastric cancer has long been at a high level in China, seriously affecting the health of Chinese people.

Aims: This case‒control study was performed to identify gene methylation biomarkers of gastric cancer susceptibility.

Methods: A total of 393 gastric cancer cases and 397 controls were included in this study.

Pharmacokinetic study of egg polysaccharide in rats and beagles using a H-labeling method.

egg polysaccharide (SEP) extracted from sea urchins has potential anticancer activity. However, little is known about its pharmacokinetic properties. To investigate the pharmacokinetics of SEP, it was radiolabeled with tritium.

Prevalence, distribution, and risk factors of bovine tuberculosis in dairy cattle in central China.

Bovine tuberculosis (bTB) is one of the priority epidemic diseases in dairy cattle in China. Continuous surveillance and evaluation of the control programs will help on improving the efficiency of bTB control policy. We designed this study to investigate both animal and herd level prevalence of bTB, as well as to determine the associated factors in dairy farms in Henan and Hubei provinces.

Prevalence and antimicrobial resistance of Salmonella and ESBL E. coli isolated from dairy cattle in Henan Province, China.

Salmonella and ESBL-producing E. coli pose a threat to public health through the food chain. A cross-sectional study was conducted to determine the prevalence and antimicrobial resistance of Salmonella and ESBL E.

Association between methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer.

Purpose: Altered DNA methylation, genetic alterations, and environmental factors are involved in tumorigenesis. As a tumor suppressor gene, abnormal methylation was found in gastric cancer (GC) tissues and was linked to the initiation, progression and prognosis of GC. In this study, the methylation level in peripheral blood leukocytes (PBLs) was detected to explore its relationship with GC risk and prognosis.

Evaluation of an ELISA for the diagnosis of bovine tuberculosis using milk samples from dairy cows in China.

Bovine tuberculosis (bTB) is an important zoonotic disease in developing countries including China. Lack of rapid and simple detection methods for surveillance affects efficient control and eradication of this disease. The objective of this study was to determine the feasibility of using an individual and bulk milk sample ELISA based on the fusion protein of four specific antigens (CFP10/ESAT-6/MPB70/MPB83) of Mycobacterium bovis for the rapid detection and surveillance of bTB in dairy cattle herds and to identify individual animal factors that affect its results.

The plant circadian clock regulates autophagy rhythm through transcription factor LUX ARRHYTHMO.

Autophagy is an evolutionarily conserved degradation pathway in eukaryotes; it plays a critical role in nutritional stress tolerance. The circadian clock is an endogenous timekeeping system that generates biological rhythms to adapt to daily changes in the environment. Accumulating evidence indicates that the circadian clock and autophagy are intimately interwoven in animals.