STAB2: an updated spatio-temporal cell atlas of the human and mouse brain.

The brain is constituted of heterogeneous types of neuronal and non-neuronal cells, which are organized into distinct anatomical regions, and show precise regulation of gene expression during development, aging and function. In the current database release, STAB2 provides a systematic cellular map of the human and mouse brain by integrating recently published large-scale single-cell and single-nucleus RNA-sequencing datasets from diverse regions and across lifespan. We applied a hierarchical strategy of unsupervised clustering on the integrated single-cell transcriptomic datasets to precisely annotate the cell types and subtypes in the human and mouse brain. Currently, STAB2 includes 71 and 61 different cell subtypes defined in the human and mouse brain, respectively. It covers 63 subregions and 15 developmental stages of human brain, and 38 subregions and 30 developmental stages of mouse brain, generating a comprehensive atlas for exploring spatiotemporal transcriptomic dynamics in the mammalian brain. We also augmented web interfaces for querying and visualizing the gene expression in specific cell types. STAB2 is freely available at https://mai.fudan.edu.cn/stab2.

E-value: a superior alternative to P-value and its adjustments in DNA methylation studies.

DNA methylation plays a crucial role in transcriptional regulation. Reduced representation bisulfite sequencing (RRBS) is a technique of increasing use for analyzing genome-wide methylation profiles. Many computational tools such as Metilene, MethylKit, BiSeq and DMRfinder have been developed to use RRBS data for the detection of the differentially methylated regions (DMRs) potentially involved in epigenetic regulations of gene expression. For DMR detection tools, as for countless other medical applications, P-values and their adjustments are among the most standard reporting statistics used to assess the statistical significance of biological findings. However, P-values are coming under increasing criticism relating to their questionable accuracy and relatively high levels of false positive or negative indications. Here, we propose a method to calculate E-values, as likelihood ratios falling into the null hypothesis over the entire parameter space, for DMR detection in RRBS data. We also provide the R package 'metevalue' as a user-friendly interface to implement E-value calculations into various DMR detection tools. To evaluate the performance of E-values, we generated various RRBS benchmarking datasets using our simulator 'RRBSsim' with eight samples in each experimental group. Our comprehensive benchmarking analyses showed that using E-values not only significantly improved accuracy, area under ROC curve and power, over that of P-values or adjusted P-values, but also reduced false discovery rates and type I errors. In applications using real RRBS data of CRL rats and a clinical trial on low-salt diet, the use of E-values detected biologically more relevant DMRs and also improved the negative association between DNA methylation and gene expression.

Opportunities and challenges for ChatGPT and large language models in biomedicine and health.

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically, we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction and medical education and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

GeneGPT: augmenting large language models with domain tools for improved access to biomedical information.

MOTIVATION: While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this article, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. RESULTS: Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: First, API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; second, GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; finally, different types of errors are enriched in different tasks, providing valuable insights for future improvements. AVAILABILITY AND IMPLEMENTATION: The GeneGPT code and data are publicly available at https://github.com/ncbi/GeneGPT.

Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate renal fibrosis in diabetic nephropathy by targeting Hedgehog/SMO signaling.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. In vitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.

Increasingly amplified stimulation mediated by TaNAC69-B is crucial for the leaf senescence in wheat.

Leaf senescence involves massive multidimensional alterations, such as nutrient redistribution, and is closely related to crop yield and quality. No apical meristem, Arabidopsis transcription activation factor, and Cup-shaped cotyledon (NAC)-type transcription factors integrate various signals and modulate an enormous number of target genes to ensure the appropriate progression of leaf senescence. However, few leaf senescence-related NACs have been functionally characterized in wheat. Based on our previous RNA-sequencing (RNA-seq) data, we focused on a NAC family member, TaNAC69-B, which is increasingly expressed during leaf senescence in wheat. Overexpression of TaNAC69-B led to precocious leaf senescence in wheat and Arabidopsis, and affected several agricultural traits in transgenic wheat. Moreover, impaired expression of TaNAC69-B by virus-induced gene silencing retarded the leaf senescence in wheat. By RNA-seq and quantitative real-time polymerase chain reaction analysis, we confirmed that some abscisic acid (ABA) biosynthesis genes, including AAO3 and its ortholog in wheat, TraesCS2B02G270600 (TaAO3-B), were elevated by the overexpression of TaNAC69-B. Consistently, we observed more severe ABA-induced leaf senescence in TaNAC69-B-OE wheat and Arabidopsis plants. Furthermore, we determined that TaNAC69-B bound to the NAC binding site core (CGT) on the promoter regions of AAO3 and TaAO3-B. Moreover, we confirmed elevated ABA levels in TaNAC69-B-OE wheat lines. Although TaNAC69-B shares 39.83% identity (amino acid) with AtNAP, TaNAC69-B did not completely restore the delayed leaf senescence in the atnap mutant. Collectively, our results revealed a positive feedback loop, consisting of TaNAC69-B, ABA biosynthesis and leaf senescence, that is essential for the regulation of leaf senescence in wheat.

Decreased spermatogonial numbers in boys with severe haematological diseases.

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions.

Plasmonic Gold Nanostar-Based Probes with Distance-Dependent Plasmon-Enhanced Fluorescence for Ultrasensitive DNA Methyltransferase Assay.

The ultrasensitive DNA methyltransferase (Dam MTase) assay is of high significance for biomedical research and clinical diagnosis because of its profound effect on gene regulation. However, detection sensitivity is still limited by shortcomings, including photobleaching and weak signal intensities of conventional fluorophores at low concentrations. Plasmonic nanostructures with ultrastrong electromagnetic fields and fluorescence enhancement capability that can overcome these intrinsic defects hold great potential for ultrasensitive bioanalysis. Herein, a silica-coated gold nanostars (Au NSTs@SiO2)-based plasmon-enhanced fluorescence (PEF) probe with 20 "hot spots" was developed for ultrasensitive detection of Dam MTase. Here, the Dam Mtase assay was achieved by detecting the byproduct PPi of the rolling circle amplification reaction. It is worth noting that, benefiting from the excellent fluorescence enhancement capability of Au NSTs originating from their 20 "hot spots", the detection limit of Dam Mtase was reduced by nearly 105 times. Moreover, the proposed Au NST-based PEF probe enabled versatile evaluation of Dam MTase inhibitors as well as endogenous Dam MTase detection in GW5100 and JM110 Escherichia coli cell lysates, demonstrating its potential in biomedical analysis.

Electrodeposited Poly(5-Amino-2-Naphthalenesulfonic Acid-co-o-Aminophenol) as the Electrode Material for Flexible Supercapacitor.

Copolymers of 5-amino-2-naphthalenesulfonic acid (ANS) and o-aminophenol (oAP) are electropolymerized on carbon cloth substrate from aqueous solutions, and the electropolymerization process is investigated using electrochemical quartz-crystal microbalance. The surface of the copolymer (PANS-co-oAP) appears rough and is capable to store charge as the battery-type electrode in 1 m H2 SO4 (102.9 mAh g-1 at 1 A g-1 ) or in 1 m ZnSO4 (79.75 mAh g-1 at 1 A g-1 ) aqueous solutions. Compared with PANS and PoAP, the high specific capacity of the PANS-co-oAP is originated from the increased number of electrochemically active sites and increased diffusion rates of ions. Evidence of amino/imino and hydroxyl/carbonyl groups redox processes and cation insertion and extraction are given by ex situ X-ray photoelectron spectroscopy. When used as the electrode material in the flexible solid-state supercapacitors, the specific capacitance is at 37.9 F g-1 which does not significantly alter with the bending angle. The flexible solid-state supercapacitor shows a specific energy of 5.4 Wh kg-1 and a power density of 250.3 W kg-1 at 0.5 A g-1 , and a high capacitance retention (88.2%) after 3000 cycles at 5 A g-1 is achieved.

γδ T cells and the PD-1/PD-L1 axis: a love-hate relationship in the tumor microenvironment.

Gamma delta (γδ) T cells demonstrate strong cytotoxicity against diverse cancer cell types in an MHC-independent manner, rendering them promising contenders for cancer therapy. Although amplification and adoptive transfer of γδ T cells are being evaluated in the clinic, their therapeutic efficacy remains unsatisfactory, primarily due to the influence of the immunosuppressive tumor microenvironment (TME). Currently, the utilization of targeted therapeutic antibodies against inhibitory immune checkpoint (ICP) molecules is a viable approach to counteract the immunosuppressive consequences of the TME. Notably, PD-1/PD-L1 checkpoint inhibitors are considered primary treatment options for diverse malignancies, with the objective of preserving the response of αß T cells. However, γδ T cells also infiltrate various human cancers and are important participants in cancer immunity, thereby influencing patient prognosis. Hence, it is imperative to comprehend the reciprocal impact of the PD-1/PD-L1 axis on γδ T cells. This understanding can serve as a therapeutic foundation for improving γδ T cells adoptive transfer therapy and may offer a novel avenue for future combined immunotherapeutic approaches.

Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status.

BACKGROUND: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered. PATIENTS AND METHODS: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses. RESULTS: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT. CONCLUSIONS: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

Development of a Dual Fluorescence Signal-Enhancement Immunosensor Based on Substrate Modification for Simultaneous Detection of Interleukin-6 and Procalcitonin.

High-sensitivity detection of biomarkers is of great significance to improve the accuracy of disease diagnosis and the rate of occult disease diagnosis. Using a substrate modification and two-color quantum dot (QD) nanobeads (QBs), we have developed a dual fluorescence signal-enhancement immunosensor for sensitive, simultaneous detection of interleukin 6 (IL-6) and procalcitonin (PCT) at low volumes (∼20 µL). First, the QBs compatible with QDs with different surface ligands were prepared by optimizing surfactants based on the microemulsion method. Through the use of a fluorescence-linked immunosorbent assay (FLISA), the feasibility of a dual signal-enhancement immunosensor was verified, and a 5-fold enhancement of fluorescence intensity was achieved after the directional coating of the antibodies on sulfhydryl functionalization (-SH) substrates and the preparation of QBs by using a polymer and silica double-protection method. Next, a simple polydimethylsiloxane (HS-PDMS) immunosensor with a low volume consumption was prepared. Under optimal conditions, we achieved the simultaneous detection of IL-6 and PCT with a linear range of 0.05-50 ng/mL, and the limit of detection (LOD) was 24 and 32 pg/mL, respectively. The result is comparable to two-color QBs-FLISA with a sulfhydryl microplate, even though only 20% of its volume was used. Thus, the dual fluorescence signal-enhancement HS-PDMS immunosensor offers the capability of early microvolume diagnosis of diseases, while the detection of inflammatory factors is clinically important for assisting disease diagnosis and determining disease progression.

A survey of recent methods for addressing AI fairness and bias in biomedicine.

OBJECTIVES: Artificial intelligence (AI) systems have the potential to revolutionize clinical practices, including improving diagnostic accuracy and surgical decision-making, while also reducing costs and manpower. However, it is important to recognize that these systems may perpetuate social inequities or demonstrate biases, such as those based on race or gender. Such biases can occur before, during, or after the development of AI models, making it critical to understand and address potential biases to enable the accurate and reliable application of AI models in clinical settings. To mitigate bias concerns during model development, we surveyed recent publications on different debiasing methods in the fields of biomedical natural language processing (NLP) or computer vision (CV). Then we discussed the methods, such as data perturbation and adversarial learning, that have been applied in the biomedical domain to address bias. METHODS: We performed our literature search on PubMed, ACM digital library, and IEEE Xplore of relevant articles published between January 2018 and December 2023 using multiple combinations of keywords. We then filtered the result of 10,041 articles automatically with loose constraints, and manually inspected the abstracts of the remaining 890 articles to identify the 55 articles included in this review. Additional articles in the references are also included in this review. We discuss each method and compare its strengths and weaknesses. Finally, we review other potential methods from the general domain that could be applied to biomedicine to address bias and improve fairness. RESULTS: The bias of AIs in biomedicine can originate from multiple sources such as insufficient data, sampling bias and the use of health-irrelevant features or race-adjusted algorithms. Existing debiasing methods that focus on algorithms can be categorized into distributional or algorithmic. Distributional methods include data augmentation, data perturbation, data reweighting methods, and federated learning. Algorithmic approaches include unsupervised representation learning, adversarial learning, disentangled representation learning, loss-based methods and causality-based methods.

Prognostic Value of a Combined Nomogram Model Integrating 3-Dimensional Deep Learning and Radiomics for Head and Neck Cancer.

OBJECTIVE: The preoperative prediction of the overall survival (OS) status of patients with head and neck cancer (HNC) is significant value for their individualized treatment and prognosis. This study aims to evaluate the impact of adding 3D deep learning features to radiomics models for predicting 5-year OS status. METHODS: Two hundred twenty cases from The Cancer Imaging Archive public dataset were included in this study; 2212 radiomics features and 304 deep features were extracted from each case. The features were selected by univariate analysis and the least absolute shrinkage and selection operator, and then grouped into a radiomics model containing Positron Emission Tomography /Computed Tomography (PET/CT) radiomics features score, a deep model containing deep features score, and a combined model containing PET/CT radiomics features score +3D deep features score. TumorStage model was also constructed using initial patient tumor node metastasis stage to compare the performance of the combined model. A nomogram was constructed to analyze the influence of deep features on the performance of the model. The 10-fold cross-validation of the average area under the receiver operating characteristic curve and calibration curve were used to evaluate performance, and Shapley Additive exPlanations (SHAP) was developed for interpretation. RESULTS: The TumorStage model, radiomics model, deep model, and the combined model achieved areas under the receiver operating characteristic curve of 0.604, 0.851, 0.840, and 0.895 on the train set and 0.571, 0.849, 0.832, and 0.900 on the test set. The combined model showed better performance of predicting the 5-year OS status of HNC patients than the radiomics model and deep model. The combined model was shown to provide a favorable fit in calibration curves and be clinically useful in decision curve analysis. SHAP summary plot and SHAP The SHAP summary plot and SHAP force plot visually interpreted the influence of deep features and radiomics features on the model results. CONCLUSIONS: In predicting 5-year OS status in patients with HNC, 3D deep features could provide richer features for combined model, which showed outperformance compared with the radiomics model and deep model.

Efficacy of transauricular vagus nerve stimulation for the treatment of chemotherapy-induced painful peripheral neuropathy: a randomized controlled exploratory study.

BACKGROUND: Chemotherapy-induced painful peripheral neuropathy (CIPN) is a common adverse event in cancer patients, and there is still a lack of effective treatment. Transauricular vagal nerve stimulation (taVNS) is a minimally invasive treatment, but there are few reports regarding its efficacy for CIPN. OBJECTIVE: To investigate the efficacy and possible mechanism of taVNS in patients with CIPN. METHODS: Twenty-seven patients with CIPN were randomly divided into a taVNS group (n = 14) and a sham stimulation (SS) group (n = 13). A numerical rating scale (NRS) for pain, NCICTCAE 4.0 (neurotoxicity classification), quantitative sensory test (QST), Short-Form-Health Survey-12 (SF-12), and Athens Insomnia Scale (AIS) were administered before the intervention (D-10) and on the day after the intervention (D0), and the inflammatory cytokines in plasma were also measured. The NRS, NCI-CTCAE 4.0, SF-12, and AIS were administered again at D30 and D90. RESULTS: Compared with the SS group, the NRS and AIS in the taVNS group were significantly lower at D0. The impact lasted until D30. There were no statistically significant differences in the NRS and AIS between the 2 groups at D90. On D30, the mental component score of the SF-12 was significantly higher in the taVNS group than in the SS group. No adverse events were found. There was no significant difference in QST and plasma inflammatory cytokines between the 2 groups. CONCLUSION: taVNS can relieve chemotherapy-induced neuropathic pain in the short term, can improve sleep status and quality of life, and is expected to become a novel clinical treatment method for CIPN.

Utilizing rubidium chloride as an effective and stable interface modification layer for high-efficiency solar cells.

The presence of interface defects between the perovskite layer and the underlying substrate has a significant impact on the power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs). S n O 2 thin films are employed in PSCs as electron transport layers to achieve high PCE. However, the significant lattice mismatch between S n O 2 and the perovskite material leads to a large number of uncoordinated defects at the interface between perovskite and substrate, resulting in recombination losses at the interface. In this study, rubidium chloride (RbCl) was introduced as the interface modification layer between the perovskite layer and the S n O 2 electron transport layer to enhance the PCE of PSCs. The research showed that the RbCl interface modification layer effectively passivated the under-coordinated defects of Sn ions and optimized the energy level alignment between the perovskite layer and the S n O 2 film. Moreover, the fabricated PSCs exhibited an open-circuit voltage of 1.11 V and a power conversion efficiency of 21.64%. Furthermore, the device maintained 80% of initial efficiency after storage for 30 days in an inert gas environment and 60% of the value after storage for 30 days in ambient air.

Single-neuron firing cascades underlie global spontaneous brain events.

The resting brain consumes enormous energy and shows highly organized spontaneous activity. To investigate how this activity is manifest among single neurons, we analyzed spiking discharges of ∼10,000 isolated cells recorded from multiple cortical and subcortical regions of the mouse brain during immobile rest. We found that firing of a significant proportion (∼70%) of neurons conformed to a ubiquitous, temporally sequenced cascade of spiking that was synchronized with global events and elapsed over timescales of 5 to 10 s. Across the brain, two intermixed populations of neurons supported orthogonal cascades. The relative phases of these cascades determined, at each moment, the response magnitude evoked by an external visual stimulus. Furthermore, the spiking of individual neurons embedded in these cascades was time locked to physiological indicators of arousal, including local field potential power, pupil diameter, and hippocampal ripples. These findings demonstrate that the large-scale coordination of low-frequency spontaneous activity, which is commonly observed in brain imaging and linked to arousal, sensory processing, and memory, is underpinned by sequential, large-scale temporal cascades of neuronal spiking across the brain.

Temperature adaptation patterns in Chinese cattle revealed by TRPM2 gene mutation analysis.

Cattle are sensitive to temperature fluctuations but adapt well to inclement weather conditions. When environmental temperatures exceed specific thresholds, heat stress becomes a critical concern for cattle. The TRPM2 gene, which resides on cattle chromosome 1 encodes a TRP channel protein, holding a unique capacity to sense temperature changes and facilitate rapid response to avoid heat stress. Here, we utilized the Bovine Genome Variation Database (BGVD) (http://animal.omics.pro/code/index.php/BosVar), and identified a missense mutation site, c.805A > G: p. Met269Val (rs527146862), within the TRPM2 gene. To elucidate the functional assessment of this mutation in temperature adaptation attributes of Chinese cattle, we genotyped 407 samples from 20 distinct breeds representing diverse climatic zones across China. The association analysis incorporates three temperature parameters and revealed compelling insights in terms of allele frequency. Interestingly, the prevalence of the wild-type allele A was notably higher among northern cattle breeds and this trend diminished gradually as observed in southern cattle populations. Conversely, the mutant-type allele G demonstrated a contrasting trend. Moreover, southern cattle exhibited markedly higher frequencies of GG and GA genotypes (P < 0.01). The presence of heterozygous and homozygous mutations appears to confer an enhanced capacity for adaptation to elevated temperatures. These results provide unequivocal correlation evidence between TRPM2 genotypes (AA, GA, GG) and environmental temperature parameters and comprehend the genetic mechanisms governing temperature adaptation in cattle. This provides valuable insights for strategic breed selection across diverse climatic regions, thereby aiding livestock production amid evolving climate challenges.

The TRPM2 gene encodes TRP channel protein that helps animals in combating heat stress. Twenty Chinese local cattle breeds were genotyped, and association analysis was performed. This investigation encompasses the distribution pattern of the missense mutation locus rs527146862 of the TRPM2 gene in southern, northern, and central cattle populations. The results demonstrated a significant relationship between rs527146862 locus and temperature adaptation attributes in Chinese cattle.

Aneurysmal Subarachnoid Hemorrhage and Sex Differences: Analysis of Epidemiology, Outcomes, and Risk Factors.

BACKGROUND: The differences in outcomes after aneurysmal subarachnoid hemorrhage (aSAH) between the sexes have not been concretely determined. This study aimed to evaluate the differences in epidemiology, outcomes, and risk factors between male and female patients with aSAH. METHODS: We performed a multicenter, retrospective study of patients with aSAH from 2017 to 2020. We investigated the epidemiological differences between the two sexes. Propensity score matching (PSM) was used to compare short-term outcomes between the sexes. Binary logarithmic regression was performed to investigate the odds ratio (OR) for dependent survival in patients of different sexes. RESULTS: A total of 5,407 consecutive patients with aSAH were included in this study, and the female-to-male ratio was 1.8:1. The peak incidence of aSAH occurred in the 6th and 7th decades in males and females, respectively. There were more female patients with internal carotid artery or posterior communicating artery aneurysms (53.2%), and there were more male patients with anterior cerebral artery or anterior communicating artery aneurysms (43.2%). The incidence of multiple aneurysms was greater in female patients (21.5% vs. 14.2%, P < 0.001). There was no significant difference in outcomes before and after PSM at discharge. The dependent survival risk was related only to the clinical condition on admission in women. In addition, age > 50 years (OR 1.88, 95% confidence interval 1.17-3.02; P = 0.01) and hypertension (OR 1.81, 95% confidence interval 1.25-2.61; P = 0.002) were also risk factors for male patients. CONCLUSIONS: There were more female patients with aneurysms than male patients in this study. Most aneurysm locations were different between the two groups. There was no significant difference in discharge outcomes before and after PSM. The risk factors for dependent survival were different between female and male patients.

Tetraborated Intrinsically Axial Chiral Multi-resonance Thermally Activated Delayed Fluorescence Materials.

Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diodes (CP-OLEDs) and 3D displays. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of the frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase the efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission with a maximum at 458/459 nm with a full width at half maximum of 27 nm, photoluminescence quantum yields of 90 %/91 %, and dissymmetry factors (|gPL|) of 6.8×10-4/8.5×10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with an external quantum efficiency of 30.1 % and |gEL| factors of 1.2×10-3.