The impact of residential environment on stroke onset and its spatial heterogeneity: A multiscale exploration in Shanghai.

BACKGROUND: Stroke is a worldwide concern due to its high disability and mortality rates, especially in many countries entering ageing societies. This study aims to understand the spatial heterogeneity of stroke onset and residential environment influence scopes from multiscale. METHODS: The 2013 to 2022 spatiotemporal distribution pattern of stroke onset was obtained via out-patient data from a hospital in Shanghai. Then nine residential environmental factors were selected to estimate the association of stroke onset by multiscale geographically weighted regression (MGWR), in three scenarios. RESULTS: Accessibility to pubs/bars (PUB) and building density (BD) were the top two residential environmental factors both for the entire sample and by gender. Stress-related environmental factors have a greater impact on the onset of stroke in men but are limited in scope. The population of elderly people have relevance to environmental variables heterogeneity. The indicators relating to unhealthy food and alcohol suggest that habit-inducing environmental factors have a limited impact on stroke onset, but rather that pre-existing habits play a greater role. CONCLUSIONS: MGWR analyses individual components across multiple bandwidths, revealing geographical disparities in the impact of elements that would otherwise be undetected on a global scale. Environmental factors have a limited impact on the onset of stroke. When society is faced with both heavy ageing and fiscal constraints, some of the blue-green space budgets can be scaled back to invest in more secure facilities.

Shellfish CO2 excretion is modulated by seawater carbonate chemistry but largely independent of pCO2.

Four species of shellfish, blue mussel (Mytilus galloprovincialis), Pacific abalone (Haliotis discus hannai), zhikong scallops (Chlamys farreri), and Pacific oyster (Crassostrea gigas), were exposed to decoupled carbonate system variables to investigate the impacts of different seawater carbonate parameters on the CO2 excretion process of mariculture shellfish. Six experimental groups with two levels of seawater pH (pH 8.1 and pH 7.7) and three levels of total alkalinity (TA = 1000, 2300, and 3600 µmol/kg, respectively) were established, while pH 8.1 and TA = 2300 µmol/kg was taken as control. Results showed that the CO2 excretion rates of these tested shellfish were significantly affected by the change in carbonate chemistry (P < 0.05). At the same TA level, animals incubated in the acidified group (pH 7.7) had a lower CO2 excretion rate than those in the control group (pH 8.1). In comparison, at the same pH level, the CO2 excretion rate increased when seawater TA level was elevated. No significant correlation between the CO2 excretion rate and seawater pCO2 levels (P > 0.05) was found; however, a significant correlation (P < 0.05) between CO2 excretion rate and TA-DIC (the difference between total alkalinity and dissolved inorganic carbon) was observed. Blue mussel has a significantly higher CO2 excretion rate than the other three species in the CO2 excretions per unit mass of soft parts, with no significant difference observed among these three species. However, in terms of CO2 excretion rate per unit mass of gills, abalone has the highest CO2 excretion rate, while significant differences were found between each species. Our studies indicate that the CO2 buffering capacity impacts the CO2 excretion rate of four shellfish species largely independent of pCO2. Since CO2 excretion is related to acid-base balancing, the results imply that the effects of other carbonate parameters, particularly the CO2 buffering capacity, should be studied to fully understand the mechanism of how acidification affects shellfish. Besides, the species difference in gill to soft parts proportion may contribute to the species difference in responding to ocean acidification.

Causal relationship between gut microbiota and pathological scars: a two-sample Mendelian randomization study.

Background: Pathological scars, including keloids and hypertrophic scars, represent a significant dermatological challenge, and emerging evidence suggests a potential role for the gut microbiota in this process. Methods: Utilizing a two-sample Mendelian randomization (MR) methodology, this study meticulously analyzed data from genome-wide association studies (GWASs) relevant to the gut microbiota, keloids, and hypertrophic scars. The integrity and reliability of the results were rigorously evaluated through sensitivity, heterogeneity, pleiotropy, and directionality analyses. Results: By employing inverse variance weighted (IVW) method, our findings revealed a causal influence of five bacterial taxa on keloid formation: class Melainabacteria, class Negativicutes, order Selenomonadales, family XIII, and genus Coprococcus2. Seven gut microbiota have been identified as having causal relationships with hypertrophic scars: class Alphaproteobacteria, family Clostridiaceae1, family Desulfovibrionaceae, genus Eubacterium coprostanoligenes group, genus Eubacterium fissicatena group, genus Erysipelotrichaceae UCG003 and genus Subdoligranulum. Additional sensitivity analyses further validated the robustness of the associations above. Conclusion: Overall, our MR analysis supports the hypothesis that gut microbiota is causally linked to pathological scar formation, providing pivotal insights for future mechanistic and clinical research in this domain.

Ventral zona incerta parvalbumin neurons modulate sensory-induced and stress-induced self-grooming via input-dependent mechanisms in mice.

Self-grooming is an innate stereotyped behavior influenced by sense and emotion. It is considered an important characteristic in various disease models. However, the neural circuit mechanism underlying sensory-induced and emotion-driven self-grooming remains unclear. We found that the ventral zona incerta (Ziv) was activated during spontaneous self-grooming (SG), corn oil-induced sensory self-grooming (OG), and tail suspension-induced stress self-grooming (TG). Optogenetic excitation of Ziv parvalbumin (PV) neurons increased the duration of SG. Conversely, optogenetic inhibition of ZivPV neurons significantly reduced self-grooming in all three models. Furthermore, glutamatergic inputs from the primary sensory cortex activated the Ziv and contributed to OG. Activation of GABAergic inputs from the central amygdala to the Ziv increased SG, OG, and TG, potentially through local negative regulation of the Ziv. These findings suggest that the Ziv may play a crucial role in processing sensory and emotional information related to self-grooming, making it a potential target for regulating stereotyped behavior.

Transformer Discharge Carbon-Trace Detection Based on Improved MSRCR Image-Enhancement Algorithm and YOLOv8 Model.

It is difficult to visually detect internal defects in a large transformer with a metal closure. For convenient internal inspection, a micro-robot was adopted, and an inspection method based on an image-enhancement algorithm and an improved deep-learning network was proposed in this paper. Considering the dim environment inside the transformer and the problems of irregular imaging distance and fluctuating supplementary light conditions during image acquisition with the internal-inspection robot, an improved MSRCR algorithm for image enhancement was proposed. It could analyze the local contrast of the image and enhance the details on multiple scales. At the same time, a white-balance algorithm was introduced to enhance the contrast and brightness and solve the problems of overexposure and color distortion. To improve the target recognition performance of complex carbon-trace defects, the SimAM mechanism was incorporated into the Backbone network of the YOLOv8 model to enhance the extraction of carbon-trace features. Meanwhile, the DyHead dynamic detection Head framework was constructed at the output of the YOLOv8 model to improve the perception of local carbon traces with different sizes. To improve the defect target recognition speed of the transformer-inspection robot, a pruning operation was carried out on the YOLOv8 model to remove redundant parameters, realize model lightness, and improve detection efficiency. To verify the effectiveness of the improved algorithm, the detection model was trained and validated with the carbon-trace dataset. The results showed that the MSH-YOLOv8 algorithm achieved an accuracy of 91.80%, which was 3.4 percentage points higher compared to the original YOLOv8 algorithm, and had a significant advantage over other mainstream target-detection algorithms. Meanwhile, the FPS of the proposed algorithm was up to 99.2, indicating that the model computation and model complexity were successfully reduced, which meets the requirements for engineering applications of the transformer internal-inspection robot.

The Discovery of Highly Efficient and Promising ABA Receptor Antagonists for Agricultural Applications Based on APAn Modification.

Abscisic acid (ABA) is one of the many naturally occurring phytohormones widely found in plants. This study focused on refining APAn, a series of previously developed agonism/antagonism switching probes. Twelve novel APAn analogues were synthesized by introducing varied branched or oxygen-containing chains at the C-6' position, and these were screened. Through germination assays conducted on A. thaliana, colza, and rice seeds, as well as investigations into stomatal movement, several highly active ABA receptor antagonists were identified. Microscale thermophoresis (MST) assays, molecular docking, and molecular dynamics simulation showed that they had stronger receptor affinity than ABA, while PP2C phosphatase assays indicated that the C-6'-tail chain extending from the 3' channel effectively prevented the ligand-receptor binary complex from binding to PP2C phosphatase, demonstrating strong antagonistic activity. These antagonists showed effective potential in promoting seed germination and stomatal opening of plants exposed to abiotic stress, particularly cold and salt stress, offering advantages for cultivating crops under adverse conditions. Moreover, their combined application with fluridone and gibberellic acid could provide more practical agricultural solutions, presenting new insights and tools for overcoming agricultural challenges.

Development and evaluation of a triplex droplet digital PCR method for differentiation of M. tuberculosis, M. bovis and BCG.

Introduction: Tuberculosis, caused by Mycobacterium tuberculosis complex (MTBC), remains a global health concern in both human and animals. However, the absence of rapid, accurate, and highly sensitive detection methods to differentiate the major pathogens of MTBC, including M. tuberculosis, M. bovis, and BCG, poses a potential challenge. Methods: In this study, we have established a triplex droplet digital polymerase chain reaction (ddPCR) method employing three types of probe fluorophores, with targets M. tuberculosis (targeting CFP-10-ESAT-6 gene of RD1 and Rv0222 genes of RD4), M. bovis (targeting CFP-10-ESATs-6 gene of RD1), and BCG (targeting Rv3871 and Rv3879c genes of ΔRD1), respectively. Results: Based on optimization of annealing temperature, sensitivity and repeatability, this method demonstrates a lower limit of detection (LOD) as 3.08 copies/reaction for M. tuberculosis, 4.47 copies/reaction for M. bovis and 3.59 copies/reaction for BCG, without cross-reaction to Mannheimia haemolytica, Mycoplasma bovis, Haemophilus parasuis, Escherichia coli, Pasteurella multocida, Ochrobactrum anthropi, Salmonella choleraesuis, Brucella melitensis, and Staphylococcus aureus, and showed repeatability with coefficients of variation (CV) lower than 10%. The method exhibits strong milk sample tolerance, the LOD of detecting in spike milk was 5 × 103 CFU/mL, which sensitivity is ten times higher than the triplex qPCR. 60 clinical DNA samples, including 20 milk, 20 tissue and 20 swab samples, were kept in China Animal Health and Epidemiology Center were tested by the triplex ddPCR and triplex qPCR. The triplex ddPCR presented a higher sensitivity (11.67%, 7/60) than that of the triplex qPCR method (8.33%, 5/60). The positive rates of M. tuberculosis, M. bovis, and BCG were 1.67, 10, and 0% by triplex ddPCR, and 1.67, 6.67, and 0% by triplex qPCR, with coincidence rates of 100, 96.7, and 100%, respectively. Discussion: Our data demonstrate that the established triplex ddPCR method is a sensitive, specific and rapid method for differentiation and identification of M. tuberculosis, M. bovis, and BCG.

Molecular Bidents with Two Electrophilic Warheads as a New Pharmacological Modality.

A systematic strategy to develop dual-warhead inhibitors is introduced to circumvent the limitations of conventional covalent inhibitors such as vulnerability to mutations of the corresponding nucleophilic residue. Currently, all FDA-approved covalent small molecules feature one electrophile, leaving open a facile route to acquired resistance. We conducted a systematic analysis of human proteins in the protein data bank to reveal ∼400 unique targets amendable to dual covalent inhibitors, which we term "molecular bidents". We demonstrated this strategy by targeting two kinases: MKK7 and EGFR. The designed compounds, ZNL-8162 and ZNL-0056, are ATP-competitive inhibitors that form two covalent bonds with cysteines and retain potency against single cysteine mutants. Therefore, molecular bidents represent a new pharmacological modality with the potential for improved selectivity, potency, and drug resistance profile.

Rapid and Amplification-free Nucleic Acid Detection with DNA Substrate-Mediated Autocatalysis of CRISPR/Cas12a.

To enable rapid and accurate point-of-care DNA detection, we have developed a single-step, amplification-free nucleic acid detection platform, a DNA substrate-mediated autocatalysis of CRISPR/Cas12a (DSAC). DSAC makes use of the trans-cleavage activity of Cas12a and target template-activated DNA substrate for dual signal amplifications. DSAC employs two distinct DNA substrate types: one that enhances signal amplification and the other that negatively modulates fluorescent signals. The positive inducer utilizes nicked- or loop-based DNA substrates to activate CRISPR/Cas12a, initiating trans-cleavage activity in a positive feedback loop, ultimately amplifying the fluorescent signals. The negative modulator, which involves competitor-based DNA substrates, competes with the probes for trans-cleaving, resulting in a signal decline in the presence of target DNA. These DNA substrate-based DSAC systems were adapted to fluorescence-based and paper-based lateral flow strip detection platforms. Our DSAC system accurately detected African swine fever virus (ASFV) in swine's blood samples at femtomolar sensitivity within 20 min. In contrast to the existing amplification-free CRISPR/Dx platforms, DSAC offers a cost-effective and straightforward detection method, requiring only the addition of a rationally designed DNA oligonucleotide. Notably, a common ASFV sequence-encoded DNA substrate can be directly applied to detect human nucleic acids through a dual crRNA targeting system. Consequently, our single-step DSAC system presents an alternative point-of-care diagnostic tool for the sensitive, accurate, and timely diagnosis of viral infections with potential applicability to human disease detection.

Ligand-Receptor Interaction-Induced Intracellular Phase Separation: A Global Disruption Strategy for Resistance-Free Lethality of Pathogenic Bacteria.

Addressing the global challenge of bacterial resistance demands innovative approaches, among which multitargeting is a widely used strategy. Current strategies of multitargeting, typically achieved through drug combinations or single agents inherently aiming at multiple targets, face challenges such as stringent pharmacokinetic and pharmacodynamic requirements and cytotoxicity concerns. In this report, we propose a bacterial-specific global disruption approach as a vastly expanded multitargeting strategy that effectively disrupts bacterial subcellular organization. This effect is achieved through a pioneering chemical design of ligand-receptor interaction-induced aggregation of small molecules, i.e., DNA-induced aggregation of a diarginine peptidomimetic within bacterial cells. These intracellular aggregates display affinity toward various proteins and thus substantially interfere with essential bacterial functions and rupture bacterial cell membranes in an "inside-out" manner, leading to robust antibacterial activities and suppression of drug resistance. Additionally, biochemical analysis of macromolecule binding affinity, cytoplasmic localization patterns, and bacterial stress responses suggests that this bacterial-specific intracellular aggregation mechanism is fundamentally different from nonselective classic DNA or membrane binding mechanisms. These mechanistic distinctions, along with the peptidomimetic's selective permeation of bacterial membranes, contribute to its favorable biocompatibility and pharmacokinetic properties, enabling its in vivo antimicrobial efficacy in several animal models, including mice-based superficial wound models, subcutaneous abscess models, and septicemia infection models. These results highlight the great promise of ligand-receptor interaction-induced intracellular aggregation in achieving a globally disruptive multitargeting effect, thereby offering potential applications in the treatment of malignant cells, including pathogens, tumor cells, and infected tissues.

Challenges to heart failure medication prescribing post-hospitalization.

OBJECTIVES: To determine the prevalence of heart failure (HF) medication prescribing on discharge post-HF-related admission. METHODS: A retrospective audit was conducted for 216 HF admissions over a period of 6 months; medication data from electronic records were collected for analysis. KEY FINDINGS: The prevalence of HF medication prescribing on discharge was: 32.9% (95% confidence interval: 26.6-39.6) renin-angiotensin-aldosterone system inhibitors, 10.6% (6.9-15.6) angiotensin receptor-neprilysin inhibitors, 31.5% (25.4-38.1) HF-specific beta-blockers, 42.6% (35.9-49.5) aldosterone receptor antagonists, and 11.6% (7.6-16.6) sodium-glucose cotransporter-2 inhibitors. CONCLUSION: HF medication prescribing remains relatively low despite the known benefits and recommendations listed in the guidelines.

Predicting the potential distribution change of the endangered Francois' langur (Trachypithecus francoisi) across its entire range in China under climate change.

The Francois' langur (Trachypithecus francoisi) is a rare primate species indicated as endangered and distributed in karst areas in northern Vietnam and southwestern China. However, research limited to specific nature reserves or sites has hampered holistic conservation management. A comprehensive map of the potential distribution for the Francois' langur is essential to advance conservation efforts and ensure coordinated management across regions. Here, we used 82 occurrence records of Francois' langur surveyed in Guangxi, Guizhou, and Chongqing from 2017 to 2020, along with 12 environmental variables, to build the potential habitat model under current and future climate (2030, 2050, 2070, and 2090s) using maximum entropy models (MaxEnt). Our results indicated that (1) precipitation- and temperature-associated bioclimatic variables contributed the most to the distribution of Francois' langur. Vegetation, water sources, and anthropogenic variables also affected its distribution; (2) a total of 144,207.44 km2 of potential suitable habitat across the entire range in China was estimated by the current model. Moderate- and high-suitability habitats accounted for only 23.76% (34,265.96 km2) of the predicted suitable habitat and were mainly distributed in southwest Guangxi, east of Chongqing, and the border between Guizhou and Chongqing; (3) the suitable habitats of Francois' langur will contract considerably under future climate change, and the habitat centroid will move in the southeast direction with a shifting distance of approximately 2.84 km/year from current to 2100. The habitat prediction of Francois' langur and the main drivers proposed in this study could provide essential insights for the future conservation of this endangered species. The existing distribution areas should be monitored and protected, but conservation beyond existing habitats should also be a focus of effort, especially in future expansion areas. This would ensure effective and timely protection under climate change and anthropogenic pressures.

Triptolide induced spermatogenesis dysfunction via ferroptosis activation by promoting K63-linked GPX4 polyubiquitination in spermatocytes.

Triptolide (TP) is a major bioactive compound derived from Tripterygium wilfordii Hook. F. (TwHF) known for its medicinal properties, but it also exhibits potential toxic effects. It has been demonstrated to induce severe male reproductive toxicity, yet the precise mechanism behind this remains unclear, which limits its broad clinical application. This study aimed to investigate the mechanisms underlying testicular damage and spermatogenesis dysfunction induced by TP in mice, using both mouse models and the spermatocyte-derived cell line GC-2spd. In the present study, it was found that TP displayed significant testicular microstructure damaged and spermatogenesis defects including lower concentration and abnormal morphology by promoting ROS formation, MDA production and restraining GSH level, glutathione peroxidase 4 (GPX4) expression in vivo. Furthermore, Ferrostatin-1 (FER-1), a ferroptosis inhibitor, was found to significantly reduce the accumulation of lipid peroxidation, alleviate testicular microstructural damage, and enhance spermatogenic function in mice. Besides, notably decreased cell viability, collapsed mitochondrial membrane potential, and elevated DNA damage were observed in vitro. The above-mentioned phenomenon could be reversed by pre-treatment of FER-1, indicating that ferroptosis participated in the TP-mediated spermatogenesis dysfunction. Mechanistically, TP could enhance GPX4 ubiquitin degradation via triggering K63-linked polyubiquitination of GPX4, thereby stimulating ferroptosis in spermatocytes. Functionally, GPX4 deletion intensified ferroptosis and exacerbated DNA damage in GC-2 cells, while GPX4 overexpression mitigated ferroptosis induced by TP. Overall, these findings for the first time indicated a vital role of ferroptosis in TP induced-testicular injury and spermatogenic dysfunction through promoting GPX4 K63-linked polyubiquitination, which hopefully offers a potential therapeutic avenue for TP-related male reproductive damage. In addition, this study also provides a theoretical foundation for the improved clinical application of TP or TwHF in the future.

SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells.

BACKGROUND: Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. RESULTS: In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. CONCLUSIONS: In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.

Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality.

Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice yield and quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm-2 and 11.0 t hm-2) and grain quality reaching the level of CK group. The adequate nitrogen supply in PCU group during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon-nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon-nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon-nitrogen metabolism to enhance rice quality.

Optimizing tradeoff strategies of soil microbial community between metabolic efficiency and resource acquisition along a natural regeneration chronosequence.

The tradeoff between community-level soil microbial metabolic efficiency and resource acquisition strategies during natural regeneration remains unclear. Herein, we examined variations in soil extracellular enzyme activity, microbial metabolic quotient (qCO2), and microbial carbon use efficiency (CUE) along a chronosequence of natural regeneration by sampling secondary forests at 1, 10, 20, 30, 40, and 100 years after rubber plantation (RP) clearance. The results showed that the natural logarithms of carbon (C)-, nitrogen (N)-, and phosphorus (P)-acquiring enzyme activities were 1:1.68:1.37 and 1:1.54:1.38 in the RP and secondary forests, respectively, thus demonstrating that microbial metabolism was co-limited by N and P. Moreover, the soil microbial C limitation initially increased (1-40 years) and later decreased (100 years). Overall, the qCO2 increased, decreased, and then increased again in the initial (< 10 years), middle (10-40 years), and late (100 years) successional stages, respectively. Except for specific P-acquiring enzyme activities, the changes in other indicators with natural regeneration were consistent in the dry and wet seasons. Both qCO2 and CUE were mainly predicted by microbial community composition and physiological traits. These results indicate that soil microbial communities could employ tradeoff strategies between metabolic efficiency and resource acquisition to cope with variations in resources. Our findings provide new information on tradeoff strategies between metabolic efficiency and resource acquisition during natural regeneration.

Accurate ab initio based potential energy surface and kinetics of the Cl + NH3 → HCl + NH2 reaction.

The gas-phase reaction Cl + NH3 → HCl + NH2 is a prototypical hydrogen abstraction reaction, whose minimum energy path involves several intermediate complexes. In this work, a full-dimensional, spin-orbit corrected potential energy surface (SOC PES) is constructed for the ground electronic state of the Cl + NH3 reaction. About 52 000 energy points are sampled and calculated at the UCCSD(T)-F12a/aug-cc-pVTZ level, in which the data points located in the entrance channel are spin-orbit corrected. The spin-orbit corrections are predicted by a fitted three-dimensional energy surface from about 7520 energy points in the entrance channel at the level of CASSCF (15e, 11o)/aug-cc-pVTZ. The fundamental-invariant neural network method is utilized to fit the SOC PES, resulting in a total root mean square error of 0.12 kcal mol-1. The calculated thermal rate constants of the Cl + NH3 → HCl + NH2 reaction on the SOC PES with the soft-zero-point energy constraint agree reasonably well with the available experimental values.

Depressive and mania mood state detection through voice as a biomarker using machine learning.

Introduction: Depressive and manic states contribute significantly to the global social burden, but objective detection tools are still lacking. This study investigates the feasibility of utilizing voice as a biomarker to detect these mood states. Methods:From real-world emotional journal voice recordings, 22 features were retrieved in this study, 21 of which showed significant differences among mood states. Additionally, we applied leave-one-subject-out strategy to train and validate four classification models: Chinese-speech-pretrain-GRU, Gate Recurrent Unit (GRU), Bi-directional Long Short-Term Memory (BiLSTM), and Linear Discriminant Analysis (LDA). Results: Our results indicated that the Chinese-speech-pretrain-GRU model performed the best, achieving sensitivities of 77.5% and 54.8% and specificities of 86.1% and 90.3% for detecting depressive and manic states, respectively, with an overall accuracy of 80.2%. Discussion: These findings show that machine learning can reliably differentiate between depressive and manic mood states via voice analysis, allowing for a more objective and precise approach to mood disorder assessment.

Improving assay feasibility and biocompatibility of 3D cyclic olefin copolymer microwells by superhydrophilic modification via ultrasonic spray deposition of polyvinyl alcohol.

Sample partitioning is a crucial step towards digitization of biological assays on polymer microfluidic platforms. However, effective liquid filling into microwells and long-term hydrophilicity remain a challenge in polymeric microfluidic devices, impeding the applicability in diagnostic and cell culture studies. To overcome this, a method to produce permanent superhydrophilic 3-dimensional microwells using cyclic olefin copolymer (COC) microfluidic chips is presented. The COC substrate is oxidized using UV treatment followed by ultrasonic spray coating of polyvinyl alcohol solution, offering uniform and long-term coating of high-aspect ratio microfeatures. The coated COC surfaces are UV-cured before bonding with a hydrophobic pressure-sensitive adhesive to drive selective filling into the wells. The surface hydrophilicity achieved using this method remains unchanged (water contact angle of 9°) for up to 6 months and the modified surface is characterized for physical (contact angle & surface energy, morphology, integrity of microfeatures and roughness), chemical composition (FTIR, Raman spectroscopy) and coating stability (pH, temperature, time). To establish the feasibility of the modified surface in biological applications, PVA-coated COC microfluidic chips are tested for DNA sensing (digital LAMP detection of CMV), and biocompatibility through protein adsorption and cell culture studies (cell adhesion, viability, and metabolic activity). Kidney and breast cells remained viable for the duration of testing (7 days) on this modified surface, and the coating did not affect the protein content, morphology or quality of the cultured cells. The ultrasonic spray coated system, coating with 0.25 % PVA for 15 cycles with 0.12 A current after UV oxidation, increased the surface energy of the COC (naturally hydrophobic) from 22.04 to 112.89 mJ/m2 and improved the filling efficiency from 40 % (native untreated COC) to 94 % in the microwells without interfering with the biocompatibility of the surface, proving to be an efficient, high-throughput and scalable method of microfluidic surface treatment for diagnostic and cell growth applications.

Production and evaluation of anti-BP26 monoclonal antibodies for the serological detection of animal brucellosis.

Brucella BP26 proves to be a highly immunogenic antigen with excellent specificity in brucellosis detection. In China, the authorized use of the Bp26-deleted vaccine M5ΔBP26 for preventing small ruminant brucellosis highlights the importance of developing accurate detection methods targeting BP26, particularly for the diagnosis of differentiation between infected and vaccinated animals (DIVA). Using the traditional mouse hybridoma technique, we successfully obtained 12 monoclonal antibodies (mAbs) targeting BP26. The efficacy of these mAbs in detecting various animal brucellosis cases using the competitive ELISA method was evaluated. Among them, only the E10 mAb exhibited significant efficiency, being inhibited by 100, 97.62, and 100% of brucellosis-positive sera from cattle, small ruminants, and canines, respectively. The E10-based competitive enzyme-linked immunosorbent assay (cELISA) outperformed the BP26-based indirect enzyme-linked immunosorbent assay (iELISA) in accuracy, particularly for cattle and small ruminant brucellosis, with cELISA sensitivity reaching 97.62% compared to 64.29% for iELISA for small ruminants. Although cELISA showed slightly lower specificity than iELISA, it still maintained high accuracy in canine brucellosis detection. The epitope of mAb E10 was identified in the amino acid sequence QPIYVYPDDKNNLKEPTITGY, suggesting its potential as a diagnostic antigen for brucellosis. In conclusion, the E10-based cELISA presents an effective means of detecting animal brucellosis, particularly significant for DIVA diagnosis in China, where the BP26-mutant vaccine is widely used.