Revealing study and breeding implications for production traits and tail characteristics in Simmental cattle by GWAS.

Simmental cattle are renowned for their dual purpose as meat and dairy breeds. The study recorded phenotype data from 183 Simmental cattle and performed a Genome-Wide Association Study (GWAS) analysis to elucidate the genetic mechanisms underlying milk production, body size traits, and tail characteristics. Statistical analysis of phenotype data showed that season, parity, and age at first calving (AFC) factors had a significant effect on milk production ( < 0.

TtrAgo-mediated nucleic acid detection system and portable device for rapid detection of sexually transmitted diseases.

The development of rapid and multiplexed point-of-care (POC) diagnostic tools is vital for the prevention and control of sexually transmitted diseases (STIs). Here, we developed a POC-comprehensive Thermococcus thioreducensArgonaute (TtrAgo)-mediated nucleic acid detection system (POC-CANDY) and palm-sized portable detection device "Owl-1" for the simultaneous detection of Ureaplasma urealyticum, Chlamydia trachomatis, Neisseria gonorrhoeae, human papillomavirus types 16/18 and antibiotic resistance molecular markers [tetM, and gyrA mutation (S91F)]. Using recombinase polymerase amplification (RPA), the optimized POC-CANDY could finish the whole detection procedure within 55 min and achieve a limit of detection of 10 copies/μL.

Large Language Model Enhanced Logic Tensor Network for Stance Detection.

Social media platforms, rich in user-generated content, offer a unique perspective on public opinion, making stance detection an essential task in opinion mining. However, traditional deep neural networks for stance detection often suffer from limitations, including the requirement for large amounts of labeled data, uninterpretability of prediction results, and difficulty in incorporating human intentions and domain knowledge. This paper introduces the First-Order Logic Aggregated Reasoning framework (FOLAR), an innovative approach that integrates first-order logic (FOL) with large language models (LLMs) to enhance the interpretability and efficacy of stance detection.

Genome-wide pan-GPCR cell libraries accelerate drug discovery.

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors.

Hypericum sampsonii ameliorates radiodermatitis by inhibiting NLRP3 inflammasome activation.

Background: Radiodermatitis (RD) is an inflammatory lesion of skin mucosa caused by radiation, which causes itching and pain in patients' skin. Hypericum sampsonii has an anti-inflammatory effect. This study aims to explore the potential effect and mechanism of H.

RT-RPA-Ago detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSV) and B (HRSV) of HRSV.

Fine-tuning pH sensor H98 by remote essential residues in the hydrogen-bond network of mTASK-3.

TASK-3 generates a background K conductance which when inhibited by acidification depolarizes membrane potential and increases cell excitability. These channels sense pH by protonation of histidine residue H98, but recent evidence revealed that several other amino acid residues also contribute to TASK-3 pH sensitivity, suggesting that the pH sensitivity is determined by an intermolecular network. Here we use electrophysiology and molecular modeling to characterize the nature and requisite role(s) of multiple amino acids in pH sensing by TASK-3.

Complexin-1 enhances ultrasound neurotransmission in the mammalian auditory pathway.

Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV) neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex.

Recombinase polymerase amplification combined with Pyrococcus furiosus Argonaute for fast Salmonella spp. testing in food safety.

Foodborne illness caused by Salmonella spp. is one of the most prevalent public health problems globally, which have brought immeasurable economic burden and social impact to countries around the world. Neither current nucleic acid amplification detection method nor standard culture method (2-3 days) are suitable for field detection in areas with a heavy burden of Salmonella spp.

Implementation of micelle-enabled C(sp)-C(sp) cross-electrophile coupling in pharmaceutical synthesis.

A sustainable C(sp)-C(sp) cross-electrophile coupling was developed between readily available 5-bromophthalide and 1-benzyl-4-iodopiperidine under micellar conditions, leading to a key intermediate of one of our development compounds. Copper was found to play a crucial role as a co-catalyst in this dual catalysis system. The chemistry and process were successfully demonstrated in a kilo scale to deliver sufficient drug substance to the clinical campaigns.

Regulation of nuclear transcription by mitochondrial RNA in endothelial cells.

Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome. The caRNAs reported to date are transcribed from the nuclear genome. Here, leveraging a recently developed assay for detection of caRNAs and their genomic association, we report that mitochondrial RNAs (mtRNAs) are attached to the nuclear genome and constitute a subset of caRNA, thus termed mt-caRNA.

Cross-species comparison illuminates the importance of iron homeostasis for splenic anti-immunosenescence.

Although immunosenescence may result in increased morbidity and mortality, many mammals have evolved effective immune coping strategies to extend their lifespans. Thus, the immune systems of long-lived mammals present unique models to study healthy longevity. To identify the molecular clues of anti-immunosenescence, we first built high-quality reference genome for a long-lived myotis bat, and then compared three long-lived mammals (i.

Human Post-Translational SUMOylation Modification of SARS-CoV-2 Nucleocapsid Protein Enhances Its Interaction Affinity with Itself and Plays a Critical Role in Its Nuclear Translocation.

Viruses, such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infect hosts and take advantage of host cellular machinery for genome replication and new virion production. Identifying and elucidating host pathways for viral infection is critical for understanding the development of the viral life cycle and novel therapeutics. The SARS-CoV-2 N protein is critical for viral RNA (vRNA) genome packaging in new virion formation.

Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated.

The Dawn of a New Era: Targeting the "Undruggables" with Antibody-Based Therapeutics.

The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, and basic research. A plethora of chemical and genetic approaches have been devised to make antibodies accessible to more "undruggable" targets and equipped with new functions of illustrating or regulating biological processes more precisely. In this Review, in addition to introducing how naked antibodies and various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide conjugates, antibody-enzyme conjugates, etc.

Learning from real world data about combinatorial treatment selection for COVID-19.

COVID-19 is an unprecedented global pandemic with a serious negative impact on virtually every part of the world. Although much progress has been made in preventing and treating the disease, much remains to be learned about how best to treat the disease while considering patient and disease characteristics. This paper reports a case study of combinatorial treatment selection for COVID-19 based on real-world data from a large hospital in Southern China.

A Rapid Antimicrobial Resistance Diagnostic Platform for Staphylococcus aureus Using Recombinase Polymerase Amplification.

Antimicrobial resistance (AMR) has posed a global threat to public health. The Staphylococcus aureus strains have especially developed AMR to practically all antimicrobial medications. There is an unmet need for rapid and accurate detection of the S.

Diastereo- and enantioselective synthesis of biaryl aldehydes bearing both axial and central chirality.

We describe herein an intriguing method for the synthesis of biaryl aldehydes bearing both axial and central chirality through a desymmetric [3 + 2] cycloaddition reaction of activated isocyanides with prochiral biaryl dialdehydes under silver catalysis. This protocol features excellent enantioselectivity, 100% atom economy, good functional group compatibility, and operational simplicity.

pH-triggered cancer-targeting polymers: From extracellular accumulation to intracellular release.

Stimuli-responsive polymers are promising to achieve targeted delivery, improved stability during circulation, and controlled release of therapeutic and diagnostic agents. Among them, pH-responsive polymeric nanocarriers have attracted significant attention as pH varies in different body fluids (e.g.

Sensitive Imaging of Cellular RNA via Cascaded Proximity-Induced Fluorogenic Reactions.

Owing to its important biological functions, RNA has become a promising molecular biomarker of various diseases. With a dynamic change in its expression level and a relatively low amount within the complicated biological matrix, signal amplification detection based on DNA probes has been put forward, which is helpful for early diagnosis and prognostic prediction. However, conventional methods are confined to cell lysates or dead cells and are not only time-consuming in sample preparation but also inaccessible to the spatial-temporal information of target RNAs.

Duck CD8 T Cell Response to H5N1 Highly Pathogenic Avian Influenza Virus Infection In Vivo and In Vitro.

Domestic ducks are the important host for H5N1 highly pathogenic avian influenza virus (HPAIV) infection and epidemiology, but little is known about the duck T cell response to H5N1 AIV infection. In infection experiments of mallard ducks, we detected significantly increased CD8 cells and augmented expression of cytotoxicity-associated genes, including granzyme A and IFN-γ, in PBMCs from 5 to 9 d postinfection when the virus shedding was clearly decreased, which suggested the importance of the duck cytotoxic T cell response in eliminating H5N1 infection in vivo. Intriguingly, we found that a CD8 population of PBMCs was clearly upregulated in infected ducks from 7 to 9 d postinfection compared with uninfected ducks.

Simultaneous Construction of C-N Axial and Central Chirality via Silver-Catalyzed Desymmetrizative [3 + 2] Cycloaddition of Prochiral N-Aryl Maleimides with Activated Isocyanides.

Herein, we report an unprecedented strategy for the simultaneous construction of a remote C-N stereogenic axis and three contiguous stereogenic carbon centers via silver-catalyzed desymmetrizative [3 + 2] cycloaddition of prochiral -aryl maleimides with activated isocyanides. This method features operational simplicity, wide substrate scope, high efficiency, and good to excellent stereoselectivity. Notably, it represents the first example of catalytic enantioselective synthesis of C-N atropisomers with the use of activated isocyanides.

Cooperative catalysis-enabled C-N bond cleavage of biaryl lactams with activated isocyanides.

The catalytic reaction of biaryl lactams with activated isocyanides is reported for the first time. By employing a cooperative catalytic system, oxazole-containing axially chiral biaryl anilines were obtained in high yields with excellent enantioselectivities. The key to the success lies in the atroposelective amide C-N bond cleavage with activated isocyanides.