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Myocardial ischemia-reperfusion injury (MIRI) most frequently happens in acute myocardial infarction (AMI) when rapid reperfusion is utilized to save the ischemia myocardium. MIRI is the main contributing of poor healing in AMI and is related to high mortality and disability rates around the worldwide. Currently, there is no effective precautionary measure for MIRI. Ferroptosis is a novel regulated cell death characterized by iron overload and reactive oxygen species (ROS) accumulation, which lead to death membrane lipid peroxidation. An increasing amount of studies indicates that ferroptosis plays a vital role in the occurrence and progression of MIRI. Given the crucial role of ferroptosis in MIRI, it is critical to understand the cardiomyocyte iron metabolism and investigate the molecular mechanisms of ferroptosis. In this review, we systematically summarize the molecular and metabolic pathways of ferroptosis in context of MIRI, which could provide novel understandings for the pathophysiological machine and new ideas for treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Under the background of dual carbon policy as well as energy conservation, blanks with variable thicknesses (BVTs) which act as structural components have drawn extensive attention due to their excellent strength and formability and reasonable load-bearing distribution characteristics, particularly in the field of automotive manufacturing. With these advantages, the manufacturing technologies of these plates using more efficient rolling methods have thus emerged. This article summarizes four methods and their characteristics for manufacturing plates with variable thicknesses based on rolling technology. In addition, a review is conducted on the latest research progress of the metal flow and rolling theories of existing plates with different thicknesses in the longitudinal and transverse direction.

Laparoscopic liver surgery is a newly developed minimally invasive technique and represents an inevitable trend in the future development of surgical methods. By using augmented reality (AR) technology to overlay preoperative CT models with intraoperative laparoscopic videos, surgeons can accurately locate blood vessels and tumors, significantly enhancing the safety and precision of surgeries. Point cloud registration technology is key to achieving this effect. However, there are two major challenges in registering the CT model with the point cloud surface reconstructed from intraoperative laparoscopy. First, the surface features of the organ are not prominent. Second, due to the limited field of view of the laparoscope, the reconstructed surface typically represents only a very small portion of the entire organ. To address these issues, this paper proposes the keypoint correspondence registration network (KCR-Net). This network first uses the neighborhood feature fusion module (NFFM) to aggregate and interact features from different regions and structures within a pair of point clouds to obtain comprehensive feature representations. Then, through correspondence generation, it directly generates keypoints and their corresponding weights, with keypoints located in the common structures of the point clouds to be registered, and corresponding weights learned automatically by the network. This approach enables accurate point cloud registration even under conditions of extremely low overlap. Experiments conducted on the ModelNet40, 3Dircadb, DePoLL demonstrate that our method achieves excellent registration accuracy and is capable of meeting the requirements of real-world scenarios.

Systemic sclerosis is a typical fibrotic disease of unknown etiology that is characterized by abnormal fibroblast activation and excessive deposition of extracellular matrix. Unfortunately, effective therapeutic approaches are lacking. FGF21 plays a key role in mediating a variety of biological activities. However, its specific function in systemic sclerosis is unclear. In this study, we found that the expression of FGF21 was significantly downregulated in fibrotic skin tissue and in TGF-β-stimulated fibroblasts. Furthermore, our studies demonstrated that treatment with recombinant FGF21 in the skin significantly alleviated bleomycin-induced and TBRI-activated fibrosis and inhibited the activation of fibroblasts, whereas skin fibrosis was exacerbated by deletion of FGF21. Mechanistically, FGF21 inhibits the activity of CK2α and promotes the degradation of GLI2. In conclusion, these results indicate that FGF21 attenuates skin fibrosis through the CK2α/GLI2 signaling pathway and therefore may be a potential therapeutic target for systemic sclerosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Herein, the work demonstrates an electrochemically paired electrolysis approach facilitating the efficient achievement of the electrooxidative 1,3-oxo/carboamination of arylcyclopropanes under mild conditions. The formation of 1,3-arylamination of arylcyclopropanes involves commercially available amine redox mediators through a radical-radical process. In addition, the successful execution of β-amino ketones also occurs under atmospheric conditions. The control experiments supported the existence of key benzylic radical intermediates in the reaction pathway.

The target of rapamycin (TOR) kinase is a central signaling hub that plays a crucial role in precisely orchestrating plant growth, development, and stress responses. This suggests that TOR is intricately involved in maintaining the balance between plant growth and stress responses. Nevertheless, despite the observed effects, the specific mechanisms through which TOR operates in these processes remain obscure. In this study, we investigated how the tomato ( Solanum lycopersicum ) TOR ( Sl TOR) affects plant growth and cold responses. We demonstrated that Sl TOR inhibition transcriptionally primes cold stress responses, consequently enhancing tomato cold tolerance. A widely targeted metabolomics analysis revealed the disruption of amino acid metabolism homeostasis under cold stress upon Sl TOR inhibition, which led to the accumulation of two important cryoprotective metabolites: salicylic acid (SA) and putrescine (Put). Next, we discovered Sl PGH1 (2-PHOSPHO-D-GLYCERATE HYDRO-LYASE 1) as a direct substrate of Sl TOR. Inhibiting Sl TOR led to increased SlCBF1 ( C-REPEAT-BINDING FACTOR 1 ) expression via Sl PGH1, potentially triggering the activation of cold-responsive genes and subsequent metabolic alterations. Our study provides a mechanistic framework that elucidates how Sl TOR modulates amino acid-related metabolism to enhance tomato cold tolerance, which sheds light on the complex interplay between growth and stress responses orchestrated by TOR., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

BACKGROUND This study aimed to compare the hemodynamic changes and the occurrence of oropharyngeal complications among patients undergoing tracheal intubation with an ordinary laryngoscope, video laryngoscope, and rigid video laryngoscope under general anesthesia. MATERIAL AND METHODS Patients undergoing elective tracheal intubation under general anesthesia were prospectively enrolled as study subjects. Hemodynamic indicators such as diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR), as well as the incidences of oropharyngeal complications, including dental injury, oral mucosal injury, hoarseness, sore throat, and dysphagia, were observed in the patients of 3 groups (group A: ordinary laryngoscope, group B: video laryngoscope, group C: rigid video laryngoscope). Observations were made after anesthesia induction (T₀), immediately after tracheal intubation (T₁), and at 5 min after intubation (T₂). RESULTS The HR at T1 in group A was significantly higher than in groups B and C (P<0.05). However, the difference in the number of tracheal intubations was statistically significant among the 3 groups (P<0.05); group C exhibited the highest first-time success rate of tracheal intubation (95%), whereas group A had the highest failure rate (5%). Significant differences were also noted in the incidences of oral mucosal injury and sore throat among the groups (P<0.05), with the highest incidence in group A and the lowest in group C. CONCLUSIONS Compared with the ordinary laryngoscope, tracheal intubation using a video or rigid video laryngoscope results in milder hemodynamic impacts and fewer intubation-related complications. The rigid video laryngoscope may be safer and more effective.

Motivation: Protein embedding, which represents proteins as numerical vectors, is a crucial step in various learning-based protein annotation/classification problems, including gene ontology prediction, protein-protein interaction prediction, and protein structure prediction. However, existing protein embedding methods are often computationally expensive due to their large number of parameters, which can reach millions or even billions. The growing availability of large-scale protein datasets and the need for efficient analysis tools have created a pressing demand for efficient protein embedding methods., Results: We propose a novel protein embedding approach based on multi-teacher distillation learning, which leverages the knowledge of multiple pre-trained protein embedding models to learn a compact and informative representation of proteins. Our method achieves comparable performance to state-of-the-art methods while significantly reducing computational costs and resource requirements. Specifically, our approach reduces computational time by ∼70% and maintains ±1.5% accuracy as the original large models. This makes our method well-suited for large-scale protein analysis and enables the bioinformatics community to perform protein embedding tasks more efficiently., Availability and Implementation: The source code of MTDP is available via https://github.com/KennthShang/MTDP., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: This study proposes a region-wide blood glucose management system to solve the problem of blood glucose management in patients with diabetes., Methods: A professional team of doctors, nurses and dietitians jointly developed a region-wide blood glucose management system. The system operates through a collaborative approach where each team member utilises their specialised role, such as data monitoring, algorithm development or patient support, to contribute to a comprehensive blood glucose management network. This integration ensures accurate glucose tracking, personalised feedback and timely adjustments to treatment plans. The system allows the patient to have a good treatment plan, giving comprehensive medical guidance, and the physician team is responsible for the patient's health status., Results: The region-wide blood glucose management system increased the overall blood glucose monitoring rate of patients and reduced the hospitalisation time (from 11.27 days to 9.52 days) and hospitalisation costs (from 12,173.8 yuan to 9502.4 yuan). At the same time, the system effectively counted the incidence and occurrence time of hyperglycaemia and hypoglycaemia adverse events, which can provide a reference for clinical prevention of adverse events., Conclusion: A region-wide blood glucose management system can improve medical efficiency, save medical resources and provide a strong guarantee for the health of patients with diabetes. Compared with the traditional diabetes management mode, the region-wide blood glucose management system is more systematic and standardised, meaning it can better meet the needs of patients with diabetes., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 He et al.)

Background: Incompatible insect technique (IIT) coupled with sterile insect technique (SIT) via the release of sterile male Wolbachia-infected mosquitoes is a promising tool for Aedes-borne disease control. Yet, real-world evidence on the suppressive effectiveness of IIT-SIT on mosquito abundance remains mostly limited to small semi-rural village and suburban localities over short trial durations. However, a large proportion of Aedes-borne diseases occur in dense, urban, and high-rise locations, limiting the applicability of previous studies for these settings with high disease burden. The sustainability and use of this technology over multiple years is also unknown., Methods: In this synthetic control study, we conducted a large-scale, field trial of IIT-SIT targeting Aedes aegypti among high-rise public housing estates in Singapore, an equatorial city state. Routinely collected data from a large, nationwide surveillance system of 57 990 unique mosquito traps, combined with a high-dimensional set of anthropogenic and environmental confounders were collected to ascertain mosquito abundance and its key drivers. Four townships were selected as the intervention groups (approximate population size of 607 872 residents as of 2022), wherein interventions that combined ITT with SIT over the course of the study period were conducted. Townships were subject to releases of wAlbB-SG male A aegypti mosquitoes twice a week. Data were assessed over the course of epidemiological weeks (EWs), which provide the finest temporal resolution of recorded Wolbachia release schedule and mosquito abundance data. A novel synthetic control framework was then developed to account for the non-randomised and staggered adoption setting of the intervention across trial sectors to identify the direct suppressive effectiveness of IIT-SIT on female A aegypti populations, the spillover effects in non-release areas, and the effect of the intervention on other mosquito populations such as Aedes albopictus. Furthermore, we recalculated effectiveness in terms of calendar time, time since intervention, and over multiple sites to examine heterogeneities in IIT-SIT effectiveness., Findings: Between EW27 2018 and EW26 2022, Wolbachia releases were conducted across 117 sectors, of which 97 had sufficient trap data, which were collected between EW8 2019 and EW26 2022. We found that Wolbachia-based IIT-SIT reduced wild-type female A aegypti populations by a mean of 62·01% (95% CI 60·68 to 63·26) by 3 months, 78·40% (77·56 to 79·18) by 6 months, and 91·32% (90·95 to 91·66) by at least 18 months of releases. We also found a smaller but non-negligible spillover suppression effect that gradually increased over time (mean spillover intervention effectiveness 61·02% [95% CI 57·89 to 63·72] in adjacent, non-intervention sectors). Although no consistent change in A albopictus populations was seen across the four intervention townships after Wolbachia releases, the average intervention effectiveness on the A albopictus population across all release sectors was -25·80% (95% CI -30·93 to -21·05), which was driven by increases in two towns., Interpretation: Our results demonstrate the potential of IIT-SIT for strengthening long-term, large-scale vector control in tropical cities, where dengue burden is the greatest. The effect of these interventions in different geographical settings should be assessed in future work., Funding: Singapore's Ministry of Finance, Ministry of Sustainability and the Environment, National Environment Agency, and National Robotics Program., Competing Interests: Declaration of interests DDY is a paid employee of Orinno Technology. EGK and YY are paid employees of Verily Life Sciences. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze the function of the left heart in patients with different courses of gout, the independent influencing factors for left heart functional changes, and interactions between left atrial and left ventricular functions., Methods: Patients with gout (n = 171) were selected; 87 patients with a disease course <10 years were included in Group I, and 84 patients with a disease course ≥10 years were included in Group II. Ninety-four healthy volunteers comprised the control group., Results: The intergroup differences in cardiac strain parameters were statistically significant (p < .05). Moreover, the differences gradually declined with disease progression. Multivariate logistic regression analysis showed that uric acid was an independent predictor of decreased left ventricular global longitudinal strain (LVGLS). Moreover, LVGLS had a positive effect on the left atrial systolic rate (LASr) and the left atrial systolic contraction time (LASct) but no interaction with the left atrial systolic contraction duration (LAScd)., Conclusion: The course of the disease significantly affected the function of the left heart in gout patients, and uric acid was observed to be an independent predictor of decreased LVGLS in gout patients., (© 2024 Wiley Periodicals LLC.)

China is facing a serious threat PAHs contaminated soil. To better understand the current state of soil PAH pollution in China and contribute to the development of feasible prevention and control measures and policies in the future. This study examines the spatiotemporal distributions of soil Polycyclic Aromatic Hydrocarbons (PAHs) pollution in China since 2000, and investigates the key factors influencing changes in levels of soil PAHs. The results of the survey on soil PAHs concentration levels in 716 areas were analyzed by visualization of ArcGIS pro data, correlation analysis and linear regression analysis, it was found that the increase in soil PAH pollution in China is concerning. The analysis indicates significant regional disparities, with pollution levels in the north being higher than in the south. Over the 20-year period, the median level of PAHs in soil increased by 476.8 μg/kg. Construction land areas that heavily rely on fossil fuels and industrial activities exhibit significantly higher concentrations of polycyclic aromatic hydrocarbons (PAHs) compared to other land use types. The study identifies key socio-economic factors linked to rising PAH levels, including energy consumption (notably coal and oil), industrial and domestic waste production. Coal consumption is highlighted as the leading factor in PAH concentration changes in 18 provinces, followed by industrial waste in 6 provinces. Future projections up to 2030 suggest continued influence of these factors on soil PAH levels. The research emphasizes the urgent necessity for comprehensive soil management policies to address the growing PAH pollution, offering insights into its dynamics and contributing factors in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We aimed to develop novel artificial intelligence (AI) models based on early pregnancy features to forecast the likelihood of recurrent gestational diabetes mellitus (GDM) before 14 weeks of gestation in subsequent pregnancies., Methods: This study involved a cohort of 588 women who had two consecutive singleton deliveries and were diagnosed with GDM during the index pregnancy. The least absolute shrinkage and selection operator (LASSO) regression analysis were used for feature selection. 5 AI algorithms, namely support vector machine (SVM), extreme gradient boosting (XGB), light gradient boosting (LGB), decision tree classifier (DTC), and random forest (RF) classifier, and traditional multivariate logistic regression (LR) model, were employed to construct predictive models for recurrent GDM., Results: 326 (55.4%) experienced GDM recurrence in subsequent pregnancy. In the training set (67% of the study sample), 13 features were selected for AI models construction. In the testing set (33% of the study sample), the AI models (LGB, RF, and XGB) exhibited outstanding discrimination, with AUROC values of 0.942, 0.936, and 0.924, respectively. The traditional LR model showed moderate discrimination (AUROC = 0.696). LGB, RF, and XGB models also demonstrated excellent calibration, while other models indicated a lack of fit. All AI models showed superior overall net benefits, with LGB, RF, and XGB outperforming the others., Conclusions: The proposed LGB model demonstrated exceptional accuracy, excellent calibration, and superior overall net benefits. These advancements have the potential to assist healthcare professionals in advising women with a history of GDM and in developing preventive strategies to mitigate the adverse effects on maternal and fetal well-being., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Frailty, a multidimensional indicator of suboptimal aging, reflects cumulative declines across multiple physiological systems. Although age-related changes have been reported in gut microbiota, their role in healthy aging remains unclear. In this study, we calculated frailty index (FI) from 33 health-related items to reflect the overall health status of 1,821 older adults (62-96 years, 55% female) and conducted multi-omics analysis using gut metagenomic sequencing data and plasma metabolomic data. We identified 18 microbial species and 17 metabolites shifted along with frailty severity, with stronger links observed in females. The associations of nine species, including various Clostridium species and Faecalibacterium prausnitzii, with FI were reproducible in two external populations. Plasma glycerol levels, white blood cell count and kidney function partially mediated these associations. A composite microbial score derived from FI significantly predicted 2-year mortality (adjusted hazard ratio across extreme quartiles, 2.86; 95% confidence interval, 1.38-5.93), highlighting the potential of microbiota-based strategies for risk stratification in older adults., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of β-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Retinal neovascular disease is the leading reason of vision impairment in all ages. Here, we figured out the function and mechanism of omega-3 polyunsaturated fatty acids (ω-3PUFAs) in hypoxia-induced retinal neovascularization by focusing on microglial pyroptosis. Microglia BV-2 cells were given ω-3PUFAs treatment and co-cultured with mouse retinal microvascular endothelial cells (MRMECs) under hypoxia. Tube formation assay, transwell assay and wound healing assay were utilized to monitor the MRMEC angiogenesis. Cell counting kit-8, western blot, lactate dehydrogenase assay, and enzyme-linked immunosorbent assay were used to assess pyroptosis of BV-2 cells. RNA sequencing and methylated RNA immunoprecipitation-polymerase chain reaction were utilized to identify the target gene of methyltransferase-like 14 (METTL14) and its N6-methyladenosine (m6A) level in BV-2 cells. BV-2 cells prominently enhanced MRMEC angiogenesis under hypoxia, but this effect was abolished after ω-3PUFAs treatment. ω-3PUFAs inhibited pyroptosis in hypoxia-induced BV-2 cells, and BV-2 cell pyroptosis boosted angiogenesis of MRMECs. Additionally, ω-3PUFAs markedly augment the expression of MELLL14 in BV-2 cells, and METTL14 knockdown promoted BV-2 cell pyroptosis and BV-2 cell-mediated angiogenesis in MEMECs. Mechanistically, interferon beta 1 (IFNB1) was a target of METTL14, and METTL14 silencing increased the mRNA expression and decreased the m6A modification of IFNB1 in BV-2 cells. Our results uncovered that ω-3PUFAs diminished hypoxia-induced retinal neovascularization through controlling microglial pyroptosis via METTL14-mediated m6A modification. This study offers a novel potential target for the treatment of retinal neovascular diseases., Competing Interests: Declarations. Conflict of Interest: The authors have no conflicts of interest to declare. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent to Publish: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Scientists must have an integrative understanding of ecology and evolution across spatial and temporal scales to predict how species will respond to global change. Although comprehensively investigating these processes in nature is challenging, the infrastructure and data from long-term ecological research networks can support cross-disciplinary investigations. We propose using these networks to advance our understanding of fundamental evolutionary processes and responses to global change. For ecologists, we outline how long-term ecological experiments can be expanded for evolutionary inquiry, and for evolutionary biologists, we illustrate how observed long-term ecological patterns may motivate new evolutionary questions. We advocate for collaborative, multi-site investigations and discuss barriers to conducting evolutionary work at network sites. Ultimately, these networks offer valuable information and opportunities to improve predictions of species' responses to global change., (© 2024. Springer Nature Limited.)

Studies of molecular and cellular functions of small-molecule inhibitors in cancer treatment, eliciting effects by targeting genome and epigenome associated proteins, requires measurement of drug-target engagement in single-cell resolution. Here we present EpiChem for in situ single-cell joint mapping of small molecules and multimodal epigenomic landscape. We demonstrate single-cell co-assays of three small molecules together with histone modifications, chromatin accessibility or target proteins in human colorectal cancer (CRC) organoids. Integrated multimodal analysis reveals diverse drug interactions in the context of chromatin states within heterogeneous CRC organoids. We further reveal drug genomic binding dynamics and adaptive epigenome across cell types after small-molecule drug treatment in CRC organoids. This method provides a unique tool to exploit the mechanisms of cell type-specific drug actions., (© 2024. The Author(s).)

Ferroptosis is a form of iron-dependent cell death that has attracted significant attention for its potential role in numerous diseases. Targeted inhibition of ferroptosis could be of potential use in treating diseases: such as drug induced liver injury (DILI). Ferroptosis can be antagonized by the xCT/GSH/GPX4, FSP1/CoQ 10 , DHODH/CoQ 10 , GCH1/BH 4 , and NRF2 pathways. Identifying novel anti-ferroptosis pathways will further promote our understanding of the biological nature of ferroptosis and help discover new drugs targeting ferroptosis related human diseases. In this study, we identified the clinically used drug mifepristone (RU486) as a novel ferroptosis inhibitor. Mechanistically, RU486 inhibits ferroptosis by inducing GSH synthesis pathway, which supplies GSH for glutathione-S-transferase (GST) mediated 4-HNE detoxification. Furthermore, RU486 induced RLIP76 and MRP1 export 4-HNE conjugate contributes to its anti-ferroptosis activity. Interestingly, RU486 induced GSH/GSTs/RLIP76&MRP1 anti-ferroptosis pathway acts independent of classic anti-ferroptosis systems: including xCT/GSH/GPX4, FSP1, DHODH, GCH1, SCD1 and FTH1. Moreover, NRF2 was identified to be important for RU486's anti-ferroptosis activity by inducing downstream gene expression. Importantly, in mouse model, RU486 showed strong protection effect on acetaminophen (APAP)-induced acute liver injury, evidenced by decreased ALT, AST level and histological recovery after APAP treatment. Interestingly, RU486 also decreased oxidative markers, including 4-HNE and MDA, and induced NRF2 activation as well as GSTs, MRP1 expression. Together, these data suggest NRF2/GSH/GST/RLIP76&MRP1 mediated detoxification pathway as an important independent anti-ferroptosis pathway act both in vitro and in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ubiquitination modifications permit the degradation of labelled target proteins with the assistance of proteasomes and lysosomes, which is the main protein degradation pathway in eukaryotic cells. Polyubiquitination modifications of proteins can also affect their functions. De-ubiquitinating enzymes reverse the process of ubiquitination via cleavage of the ubiquitin molecule, which is known as a de-ubiquitination. It was demonstrated that ubiquitination and de-ubiquitination play key regulatory roles in fatty acid transport, de novo synthesis, and desaturation in dairy mammary epithelial cells. In addition, natural plant extracts, such as stigmasterol, promote milk fat synthesis in epithelial cells via the ubiquitination pathway. This paper reviews the current research on ubiquitination and de-ubiquitination in dairy milk fat production, with a view to providing a reference for subsequent research on milk fat and exploring new directions for the improvement of milk quality.

Background: Although national policies in China are comprehensive and instructive, a wide disparity exists between different cities. The current status of public mental health services by region in China remains unclear. This study aimed to investigate policies related to public mental health services, the contact coverage of public mental health services and outcomes of service users., Methods: A cross-sectional study was carried out in Southern China, between April 2021 and March 2022.  Considering the geographical location, socioeconomic development levels, and prevalence of severe mental illness, four cities including Wuhan, Changsha, Guangzhou, and Shenzhen were selected. Relevant service providers were asked to report data on mental health policies and facility-related information, including mental health resources, registration rates of patients, management rates of patients, and medication rates of patients. Eligible patients were invited to report service user-related data, including contact coverage of public mental health services and their outcomes. SPSS 26.0 was used for data analysis., Results: The four cities in Southern China have made different efforts to develop public mental health services, primarily focusing on socio-economically disadvantaged individuals. Community health centers in Guangzhou and Shenzhen reported having more professional human resources on mental health and higher mental health budgets for patients. The contact coverage rates of most public mental services were higher than 80%. Patients in Changsha (B = 0.3; 95%CI: 0.1-0.5), Guangzhou (B = 0.2; 95%CI: 0.1-0.3), and Shenzhen (B = 0.3; 95%CI: 0.1-0.4) who received social medical assistance services reported higher levels of medication adherence. Patients in Wuhan (B = -6.5; 95%CI: -12.9--0.1), Guangzhou (B = -2.8; 95%CI: -5.5--0.1), and Shenzhen who received community-based rehabilitation services reported lower levels of disability (B = -2.6; 95%CI: -4.6--0.5)., Conclusions: There have been advances in public mental health services in the four Southern cities. The contact coverage rates of most public mental health services were higher than 80%. Patients' utilization of public mental services was associated with better health outcomes. To improve the quality of public mental health services, the government should try to engage service users, their family members, and supporters in the design, delivery, operationalization, and evaluation of these public mental health services in the future., (© 2024. The Author(s).)

Purpose: To investigate the consecutive changes in effusion-synovitis after primary arthroscopic treatment for patients with femoroacetabular impingement syndrome (FAIS) and to determine the effect of postoperative effusion-synovitis on clinical outcomes., Methods: Data from March 2021 through January 2022 was reviewed. Patients diagnosed with FAIS and undergoing hip arthroscopic treatment were included. Exclusion criteria were incomplete magnetic resonance imaging (MRI) data, prior history of hip surgery, labral reconstruction, and concomitant hip conditions. MRI (noncontrast 3.0 T) was performed preoperatively and 3, 6, and 12 months postoperatively, and the measurement of the largest femoral neck fluid thickness (FTM) and cross-sectional area (CSA) of the effusion-synovitis were collected. Preoperative and a minimum of 2-year postoperative patient-reported outcome (PRO) scores including visual analog scale (VAS), modified Harris Hip Score (mHHS), and International Hip Outcome Tool, 12-component form (iHOT-12) were collected and compared. Postoperative Tegner Activity Scale was also collected. The PROs and achievements of minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were compared between patients with and without postoperative effusion-synovitis. Multivariate linear regression analysis was performed to determine the effect of the effusion-synovitis size on PROs., Results: A total of 61 patients (61 hips) were included in the study. The 3-month postoperative FTM, CSA, and grade of effusion-synovitis presented a significant increase compared with the preoperative values (all P < .05). No significant differences were observed in the 6-month postoperative measurements compared with the preoperative values (all P > .05). At the 12-month follow-up, although there was a significant decrease in all measurements compared with the preoperative values (all P < .001), 39 patients (63.9%) still presented effusion-synovitis. Compared with the other 22 patients (36.1%) without effusion-synovitis, these patients presented inferior mHHS, iHOT-12 (all P < .05), as well as lower achievement of PASS of mHHS (82.1% vs 100%, P = .035) and iHOT-12 (38.5% vs 81.8%, P = .001). The achievement of MCID of mHHS (79.5% vs 77.3%, P = .839) and iHOT-12 (89.7% vs 95.5%, P = .839) were comparable between patients with and without effusion-synovitis. The postoperative sagittal CSA (beta = -.302, P = .039) were negatively related to mHHS in the regression analysis., Conclusions: After arthroscopic treatment for FAIS, the level of effusion-synovitis presented an initial increase, then followed by a subsequent decrease. Effusion-synovitis was significantly alleviated at 12 months compared with the preoperative level. Patients with postoperative effusion-synovitis had inferior clinical outcomes and lower achievement of PASS compared to those without., Level of Evidence: Level IV, retrospective case series., Competing Interests: Disclosures The authors report the following potential conflicts of interest or sources of funding: The Capital Health Research and Development of Special (No. 2022-2Z-40915) and Beijing Natural Science Foundation (No. 7244429)., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes., (© 2024. The Author(s).)

An ultra-broadband, low-profile, flexible, and transparent frequency selective rasorber (FSR) is designed based on indium tin oxide (ITO) film. The -1 dB transmission band of the resistive sheet and the bandpass FSS are 0.10 - 8.61 GHz and 3.09 - 7.09 GHz, respectively. By integrating the resistive sheet and the bandpass FSS, a transmission band ranging 1.95 - 6.27 GHz with |S 21 | larger than -3 dB is achieved, alongside an absorption band ranging 7.34 - 10.83 GHz with absorptance larger than 0.8. Additionally, the FSR presented in this paper is designed by single-layer bandpass FSS and adopts coplanar coupling to realize an ultrabroad transmission band. Its ultra-broadband absorption and transmission performance are verified through experiments and the working principles are analyzed through an equivalent circuit model (ECM). The proposed FSR possesses unique advantages integrating ultrabroad band, optical transparency, flexibility, low profile, and light weight. The proposed FSR exhibits the potential to reduce the out-of-band radar cross-section (RCS), with its optical transparency showing promise for window applications.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner., (© 2024. The Author(s).)

Osteosarcoma, the most prevalent malignant bone tumor, is notorious for its aggressive growth and invasiveness. The highly mutable genome of osteosarcoma has made identifying a key oncogene challenging, hindering the development of targeted treatments. Our study validates the effectiveness of XD23, an anti-cancer agent we previously identified, in curbing osteosarcoma proliferation, metastasis, EMT differentiation, and bone destruction and promoting osteosarcoma apoptosis. It further elucidated that XD23 thwarts osteosarcoma by suppressing DKK1 expression, which in turn activates the WNT-β/Catenin pathway. This research presents the concrete evidence of DKK1's involvement in osteosarcoma development, offering a foundation for the development of DKK1 inhibitors as novel treatments for this disease., Competing Interests: The authors declare that they have no known competing financial interests of personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Untargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability., (© 2024. The Author(s).)

Polyploid rice and its reverted diploid show rich phenotypic variation and strong heterosis, showing great breeding value. However, the genomic differences among tetraploids, counterpart common diploids, tetraploid-revertant diploids, and hybrid descendants are unclear. In this work, we bred a new excellent two-line hybrid rice variety, Y Liang You Duo Hui 14 (HTRM12), using Haitian tetraploid self-reverted diploid (HTRM2). Furthermore, we comparatively analyzed the important agronomic traits and genome-wide variations of those closest relatives, Haitian diploid (HT2), Haitian tetraploid (HT4), HTRM2, and HTRM12 in detail, based on multiple phenotypic investigations, genome resequencing, and bioinformatics analysis. The results of agronomic traits analysis and genome-wide variation analysis of single nucleotide polymorphism (SNP), insertion-deletion (InDel), and copy number variation (CNV) show that HT4 and HTRM2 had abundant phenotypic and genomic variations compared to HT2. HTRM2 can inherit important traits and variations from HT4. This implies that tetraploid self-reverted diploid has high potential in creating excellent breeding materials and in breeding breakthrough hybrid rice varieties. Our study verifies the feasibility that polyploid rice could be used as a mutation carrier for creating variations and provides genomic information, new breeding materials, and a new way of application for tetraploid rice breeding.

The importance of avian influenza virus (AIV) detection in clinical diagnosis and prognosis has been deeply recognized. In this study, the ultrasensitive detection of AIV subtype H5N1 was achieved by ICP-MS combined with DNA dendrimer-carried silver nanoparticle (AgNP) labeling. First, a magnetic control system was constructed by anchoring double-strand DNAs (dsDNAs) which contained a complementary sequence of H5N1 and two locked triggers on the surface of magnetic beads (MBs). When H5N1 was present, the two triggers were released and initiated dendrimer hybridization chain reactions which led to the generation of DNA dendrimer-carried AgNPs on the surface of the MBs. Finally, the AgNPs were collected via magnetic separation, digested by nitric acid, and tested using ICP-MS. The signal intensities of 107 Ag were positively correlated with the concentrations of H5N1. Notably, the DNA dendrimer assembly contributed to significant signal amplification and good sensitivity with the limit of detection as low as 2.0 × 10 -11 mol L -1 . Moreover, the method displayed favorable selectivity against mismatched H5N1 and good recoveries in human serum samples. It is a promising analytical tool for the H5N1 virus and other subtypes of AIV, and has potential value in clinical diagnosis and prognosis of infectious diseases.

Background: To estimate the global trends and disease burden of Clostridioides difficile infection (CDI) and its correlation with worldwide antibiotic consumption., Methods: Clostridioides difficile infection and antibiotic consumption data were retrieved from the Global Burden of Disease 2019, ResistanceMap-AntibiocUse, Food and Drug Administration (FDA) Adverse Event Reporting System, and Global Antimicrobial Resistance and Use Surveillance System. Jointpoint regression and age-period-cohort model were developed to show the global trends and burden of CDI. Correlation tests were calculated to explore the relationship between CDI and antibiotics., Results: Globally, CDI is the most significant one with a high-rocketing burden increase rate among 13 pathogens causing diarrheal deaths and disability-adjusted life years (DALYs). The age-standardised death rate (ASDR) increased from 0.19 in 1990 to 0.43 in 2019, in which the elderly and females are at higher risk. A rapid increase in ASDR in high to middle sociodemographic index (SDI) regions such as North America (average annual percentage change (AAPC) = 7.71%), Andean (AAPC = 7.82%), and Southern Latin America (AAPC = 11.08%) was identified. Antibiotic consumption has a significant positive correlation with CDI with different risk stratifications., Conclusions: The global burden of CDI has continuously increased for the past 30 years, especially in high to middle-SDI regions. World antibiotic consumption showed a strong positive correlation with CDI with different risk stratification. More effective prevention and control measures should be implemented in these critical regions, with a specific emphasis on vulnerable populations, to mitigate the spread of epidemics., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

This paper investigates the tensile properties and microstructures of Cu/Al clad sheets with an SUS304 interlayer after cryorolling and subsequent annealing and compares them with hot-rolled samples. The experimental results show that the inhibition of dynamic recovery by cryorolling enables the Cu/Al clad sheets to achieve a tensile strength of 302 MPa. After annealing, the tensile strength sharply drops to 159 MPa, while the elongation recovers to 29.0%. Compared with hot-rolled samples, the tensile strength of cryorolled samples is increased by 13.1% due to the effect of fine-grain strengthening. During the annealing process, the cryorolled samples exhibit improved elongation under a comparable strength with the hot-rolled samples, profiting from the higher degree of recrystallization and a higher proportion of annealing twins. The tensile properties of Cu/Al clad sheet with an SUS304 interlayer are strengthened by cryorolling and subsequent annealing, providing a new method for the fabrication of high-performance Cu/Al clad sheets.

Artemisia capillaris Thunb. (A. capillaris) is a well-known traditional Chinese herbal medicine with a wide range of pharmacological effects, such as soothing the liver and gallbladder, heat clearance, and detoxifying. Hence, its extract is commonly added to various traditional Chinese medicine formulas. Traditional Chinese medicine injection (TCMI) is a mature pharmaceutical dosage form developed using TCM theory combined with modern science and technology. Notably, allergic reactions, especially pseudo‑allergic reactions (PARs), greatly limited the use of these injections. Therefore, screening pseudo‑allergic components in A. capillaris extract is clinically significant. In the present study, we proposed a two-dimensional screening and identification system based on mas-related G protein-coupled receptor X2-HALO-tag/cell membrane chromatography (MrgX2-HALO-tag/CMC) high performance liquid chromatography mass spectrometry (HPLC-MS); seven potential active components were screened from 75 % ethanol extract of A. capillaris: NCA, CA, CCA, 1,3-diCQA, ICA-B, ICA-A, and ICA-C. The receptor-ligand interactions between these seven compounds and MrgX2 protein were analyzed using frontal analysis and molecular docking technology. Furthermore, a mast cell degranulation-related assay was used to assess the pseudo‑allergic activity of these compounds. The screened compounds can serve as ligands of MrgX2, and this study provides a research basis for pseudo‑allergic reactions caused by TCMIs containing A. capillaris., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

North China type coalfield are gradually mining deep, and the mixing of groundwater is intensified. Hydrogen and oxygen isotopes are important elements for tracing groundwater movement. The fractionation response mechanism under mining conditions is not clear. In this paper, combined with numerical simulation, MixSIAR isotope mixing model and other methods, according to the δD, δ 18 O and hydrochemical information of various water bodies, the impact of coal mining on hydrogen and oxygen isotope fractionation is analyzed from multiple perspectives. The results show that summer soil water is the main source of recharge for limestone water, accounting for 30.7%-41.5%, and the Zhan River is the main source of recharge for limestone water. Before groundwater recharge, evaporation leads to the increase of δ 18 O in surface water by 0.31‰-5.58‰, water loss by 1.81%-28.00%, the increase of δ 18 O in soil water by 0.47‰-6.33‰, and water loss by 2.74%-35.80%. Compared with the coal mining layer, the degree of hydrogen and oxygen isotope drift and water-rock interaction in the coal mine stopping layer are significantly improved. The results of numerical simulation show that the pumping activity reduces the 18 O concentration in the mining layer. The ion ratio is used as a new variable to eliminate the influence of water-rock interaction when calculating the mixing ratio. The results show that the limestone water is in a state of receiving external recharge, and mixing effect increases the δ 18 O in limestone water by 0.86‰ on average, and the δD increases by 0.72‰ on average. The research results explain the controlled process of hydrogen and oxygen isotope fractionation under mining conditions, which is of great significance to coal mine safety production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. The purpose of this study was to investigate the role of K Ca 3.1 in the migration of macrophages from EAT to adjacent atrial tissue during rapid pacing., Methods: Part 1: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + clodronate liposome (CL) group. Part 2: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + TRAM-34 group. HL-1 cells and RAW264.7 cells were co-cultured to explore the specific migratory mechanism of macrophages., Results: Depleting EAT macrophages significantly reduced macrophage infiltration in the adjacent atrium and the induction of AF in canines with rapid atrial pacing. TRAM-34 significantly inhibited the migration of macrophages from EAT to the adjacent atrium and electrical remodelling in canines with rapid atrial pacing. Compared with those of the control HL-1 cells, the secretion of CCL2 and the number of migrating macrophages in pacing HL-1 cells was significantly increased, which could be reversed by TRAM-34. Further in vitro experiments showed that K Ca 3.1 regulated CCL2 secretion through the p65/STAT3 signalling pathway., Conclusions: Inhibiting myocardial K Ca 3.1 reduced the migration of EAT macrophages to adjacent atrial muscles caused by rapid atrial pacing, thereby decreasing vulnerability to AF. The mechanism by which K Ca 3.1 regulates CCL2 may be related to the p65/STAT3 signalling pathway., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Increasing air pollution could undermine human health, but the causal link between air pollution and eye and ear health has not been well-studied. Based on four-week-level records of eye and ear health over 1991-2015 provided by the China Health and Nutrition Survey, we estimate the causal effect of air pollution on eye and ear health. Using two-stage least squares estimation, we find that eye or ear disease possibility rises 1.48% for a 10 μg/m 3 increase in four-week average PM 2.5 concentration. The impacts can last about 28 weeks and will be insignificant afterward. Females, individuals aged 60 years and over, with high exposure environments, relatively poor economic foundations, and low knowledge levels are more vulnerable to such negative influences. Behavioral channels like more smoking activities and less sleeping activities could partly explain this detrimental effect. Our findings enlighten how to minimize the impact of air pollution and protect public health., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Sandalwood essential oil is extracted from the heartwood part of mature sandalwood and is known for its pleasant fragrance and exceptional medicinal activities, including antimicrobial, antitumor, and anti-inflammatory properties. The (Z)-α-santalol and (Z)-β-santalol are the most vital ingredients contributing to sandalwood oil's bioactivities and unique woody odor characteristics. Metabolic engineering strategies have shown promise in transforming microorganisms such as yeast and bacteria into effective cell factories for enhancing the production of vital sesquiterpenes (santalene and santalol) found in sandalwood oil. This review aims to summarize sources of sandalwood oil, its components/ingredients, and its applications. It also highlights the biosynthesis of santalene and santalol and the various metabolic engineering strategies employed to reconstruct and enhance santalene and santalol biosynthesis pathways in heterologous hosts.

The multiattribute method (MAM) has emerged as a powerful tool for simultaneously screening multiple product quality attributes of therapeutic antibodies. One such potential critical quality attribute (CQA) is glycation, a common modification that can impact the heterogeneity, functional activity, and immunogenicity of therapeutic antibodies. However, current methods for monitoring glycation levels in MAM are rare and not sufficiently rapid and accurate. In this study, an improved mass spectrometry (MS)-based MAM was developed to simultaneously monitor glycation and other quality attributes including afucosylation. The method was evaluated using two therapeutic antibodies with different glycosylation site numbers. Treatment with IdeS, Endo F2, and dithiothreitol generated three distinct subunits, and the glycation results obtained were similar to those treated with PNGase F, which is routinely used to release glycans; the sample processing time was greatly reduced while providing additional quality attribute information. The MS-based MAM was also employed to assess the glycation progression following forced glycation in various buffer solutions. A significant increase in oxidation was observed when forced glycation was conducted in an ammonium bicarbonate buffer solution, and a total of 23 potential glycation sites and 4 significantly oxidized sites were identified. Notably, we found that ammonium bicarbonate was found to specifically stimulate oxidation, while glycation had a synergistic effect on oxidation. These findings establish this study as a novel methodology for achieving a technologically advanced platform and concept that enhances the efficacy of product development and quality control, characterized by its broad-spectrum, rapid, and accurate nature.

Mesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications., (© 2024. The Author(s).)

PM 2.5 , as one of the most harmful pollutant in the atmospheric environment and population health, has received much attention. We monitored PM 2.5 levels at five sampling sites in the Lanzhou City and collected PM 2.5 particles from two representative sites for cytotoxicity experiment. The cytotoxicity of PM 2.5 samples on A549 cells and migration ability of the cells were respectively detected by Cell Counting kit-8 (CCK-8) assay and scratch assay. We detected the levels of cellular inflammatory factors and oxidative damage-related biochemical indexes. RT-qPCR was used to detect the mRNA levels of NF-κB and epithelial-mesenchymal transition (EMT)-related genes. We found that the Lanlian Hotel station had the highest PM 2.5 annual average concentration. The annual average concentration change curve of PM 2.5 showed a roughly "U"-shaped distribution during the whole sampling period. The cytotoxicity experiment showed the viability of A549 cells decreased and the scratch healing rate increased in the 200 and 400 μg/mL PM 2.5 -treated groups. We also found 400 μg/mL PM 2.5 induced changes in the mRNA levels of NF-κB and EMT-related genes, the mRNA levels of IKK-α, NIK, and NF-κB in the 400 μg/mL PM 2.5 group were higher than those in the control group. The mRNA levels of E-cadherin decreased and α-SMA increased in the 400 μg/mL PM 2.5 groups, and the mRNA levels of Fibronectin increased in the 400 μg/mL PM 2.5 groups. Moreover, we found hydroxyl radical scavenging ability and T-AOC levels were lower, and LPO levels were higher in the 200 and 400 μg/mL PM 2.5 groups, and the SOD activity of cells in the 400 µg/mL PM 2.5 group decreased. And compared with the control group, the levels of TNF-α were higher in the 200 and 400 μg/mL PM 2.5 groups and the levels of IL-1 were higher in the 400 μg/mL PM 2.5 group. The results indicated that the cytotoxicity of atmospheric PM 2.5 was related to oxidative damage, inflammatory response, NF-κB activity and EMT., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polyhydroxyalkanoates (PHAs) could be used to make sustainable, biodegradable plastics. However, the precise and accurate mechanistic modeling of PHA biosynthesis, especially medium-chain-length PHA (mcl-PHA), for yield improvement remains a challenge to biology. PHA biosynthesis is typically triggered by nitrogen limitation and tends to peak at an optimal carbon-to-nitrogen (C/N) ratio. Specifically, simulation of the underlying dynamic regulation mechanisms for PHA bioprocess is a bottleneck owing to surfeit model complexity and current modeling philosophies for uncertainty. To address this issue, we proposed a quantum-like decision-making model to encode gene expression and regulation events as hidden layers by the general transformation of a density matrix, which uses the interference of probability amplitudes to provide an empirical-level description for PHA biosynthesis. We implemented our framework modeling the biosynthesis of mcl-PHA in Pseudomonas putida with respect to external C/N ratios, showing its optimization production at maximum PHA production of 13.81% cell dry mass (CDM) at the C/N ratio of 40:1. The results also suggest the degree of P. putida's preference in channeling carbon towards PHA production as part of the bacterium's adaptative behavior to nutrient stress using quantum formalism. Generic parameters (k D , k N and theta θ) obtained based on such quantum formulation, representing P. putida's PHA biosynthesis with respect to external C/N ratios, was discussed. This work offers a new perspective on the use of quantum theory for PHA production, demonstrating its application potential for other bioprocesses., (© 2024. The Author(s).)

Root-knot nematode (RKN) is one of the most damaging plant pathogen in the world. They exhibit a wide host range and cause serious crop losses. The cell wall, encasing every plant cell, plays a crucial role in defending of RKN invasion. Expansins are a group of cell wall proteins inducing cell wall loosening and extensibility. They are widely involved in the regulation of plant growth and the response to biotic and abiotic stresses. In this study, we have characterized the biological function of tobacco (Nicotiana tabacum) NtEXPA7, the homologue of Solyc08g080060.2 (SlEXPA18), of which the transcription level was significantly reduced in susceptible tomato upon RKN infection. The expression of NtEXPA7 was up-regulated after inoculation of RKNs. The NtEXPA7 protein resided in the cell wall. Overexpression of NtEXPA7 promoted the seedling growth of transgenic tobacco. Meanwhile the increased expression of NtEXPA7 was beneficial to enhance the resistance against RKNs. This study expands the understanding of biological role of expansin in coordinate plant growth and disease resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mas-related G protein-coupled receptor X2 (MrgprX2) plays a crucial role in anaphylactoid reactions and allergic diseases. Some antagonists with reasonable potency and selectivity have been reported. Cell membrane chromatography (CMC) is effective for discovering ligands. Protein-tag-based CMC models (e.g., SNAP tags and HALO tags) have enhanced performance but also increased nonspecific adsorption of small molecules. The Avi tag, a short peptide sequence, binds biotin specifically via BirA catalysis. Our study showed that 2-iminobiotin (IB) can be a BirA substrate, enabling the development of a new cell membrane stationary phase (CMSP) based on the chemical properties (modifying carboxyl silica gel and specifically labeling the Avi tag) of IB. First, we constructed the MrgprX2-Avi-tag HEK293T cell line. Next, we synthesized IB-modified silica gel (SiO 2 -IB) stepwise. Finally, we immobilized Avi-tagged MrgprX2 cell membranes on SiO 2 -IB under BirA catalysis. We characterized the developed CMSP and used it to establish a MrgprX2-Avi-tag/CMC-HPLC/MS two-dimensional screening platform, successfully screening vitexicarpin from Viticis Fructus extract via a 2D/CMC platform. In vitro and in vivo experiments confirmed that vitexicarpin targets the MrgprX2 receptor, demonstrating antiallergic effects. Our IB-Avi tag-based CMC approach effectively decreased nonspecific adsorption of the screening materials. The Avi-tag-based 2D/CMC platform is suitable for screening potential drug candidates.

Background and Objectives: Lactose intolerance and coeliac disease are common clinical nutrient malabsorption disorders, with an unclear pathogenesis and limited therapeutic options. It is widely believed that the gut microbiota plays an important role in many digestive disorders, but its role in lactose intolerance and coeliac disease is not yet clear. This study aimed to investigate the correlation between gut microbiota and lactose intolerance and coeliac disease., Materials and Methods: This study utilized the genome-wide association study database to investigate the association between gut microbiota and lactose intolerance and coeliac disease using Mendelian randomization (MR). The robustness of our findings was confirmed through subsequent analyses including Cochrane's Q statistic, MR-Egger Intercept Regression, MR-PRESSO Global Test and Leave-one-out methods., Results: By employing the inverse variance weighted method, we identified that family Veillonellaceae , genus Oxalobacter and Senegalimassilia were protective against lactose intolerance, whereas genus Anaerotruncus , Eubacterium rectale group and Ruminococcus2 were found to be risk factors for lactose intolerance. Regarding coeliac disease, class Bacilli and Gammaproteobacteria , family FamilyXIII and Veillonellaceae , genus Eisenbergiella , Lachnoclostridium , RuminococcaceaeUCG014 and Ruminococcus2 were identified as protective factors, while class Betaproteobacteria , genus Eubacterium xylanophilum group and Blautia were risk factors. Furthermore, reverse the MR analysis did not reveal any evidence of a causal relationship between lactose intolerance or coeliac disease and the bacteria identified in our study., Conclusion: This study provides novel insights into exploring the role of gut microbiota in lactose intolerance and coeliac disease; however, further experiments investigations are required to elucidate the specific underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Ran, Li, Zhang, Yang, Liu, Dong, Jia, Yang, Li, Guo, Zhou, Bao, Yuan, Wang and Zhou.)

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted., (© 2024. The Author(s).)

Genetic diversity is an essential indicator that echoes the natural selection and environmental adaptation of a species. Isolated small populations are vulnerable to genetic drift, inbreeding, and limited gene flow; thus, assessing their genetic diversity is critical in conservation. In this study, we studied the genetic diversity of black-and-white snub-nosed monkeys ( Rhinopithecus bieti ) using neutral microsatellites and five adaptive major histocompatibility complex (MHC) genes. Two DQA1 alleles, two DQB1 alleles, two DRB1 alleles, two DRB5 alleles, and three DPB1 alleles were isolated from a population. The results indicate that neutral microsatellites demonstrate a high degree of heterozygosity and polymorphism, while adaptive MHC genes display a high degree of heterozygosity and moderate polymorphism. The results also show that balancing selection has prominently influenced the MHC diversity of the species during evolution: (1) significant positive selection is identified at several amino acid sites (primarily at and near antigen-binding sites) of the DRB1 , DRB5 , and DQB1 genes; (2) phylogenetic analyses display the patterns of trans-species evolution for all MHC loci. This study provides valuable genetic diversity insights into black-and-white snub-nosed monkeys, which dwell at the highest altitude and have experienced the harshest environmental selection of all primates globally since the Pleistocene. Such results provide valuable scientific evidence and a reference for making or amending conservation strategies for this endangered primate species.

Using five complementary short- and long-read sequencing technologies, we phased and assembled >95% of each diploid human genome in a four-generation, 28-member family (CEPH 1463) allowing us to systematically assess de novo mutations (DNMs) and recombination. From this family, we estimate an average of 192 DNMs per generation, including 75.5 de novo single-nucleotide variants (SNVs), 7.4 non-tandem repeat indels, 79.6 de novo indels or structural variants (SVs) originating from tandem repeats, 7.7 centromeric de novo SVs and SNVs, and 12.4 de novo Y chromosome events per generation. STRs and VNTRs are the most mutable with 32 loci exhibiting recurrent mutation through the generations. We accurately assemble 288 centromeres and six Y chromosomes across the generations, documenting de novo SVs, and demonstrate that the DNM rate varies by an order of magnitude depending on repeat content, length, and sequence identity. We show a strong paternal bias (75-81%) for all forms of germline DNM, yet we estimate that 17% of de novo SNVs are postzygotic in origin with no paternal bias. We place all this variation in the context of a high-resolution recombination map (~3.5 kbp breakpoint resolution). We observe a strong maternal recombination bias (1.36 maternal:paternal ratio) with a consistent reduction in the number of crossovers with increasing paternal (r=0.85) and maternal (r=0.65) age. However, we observe no correlation between meiotic crossover locations and de novo SVs, arguing against non-allelic homologous recombination as a predominant mechanism. The use of multiple orthogonal technologies, near-telomere-to-telomere phased genome assemblies, and a multi-generation family to assess transmission has created the most comprehensive, publicly available "truth set" of all classes of genomic variants. The resource can be used to test and benchmark new algorithms and technologies to understand the most fundamental processes underlying human genetic variation., Competing Interests: Conflicts of interest E.E.E. is a scientific advisory board (SAB) member of Variant Bio, Inc. C.Lee is an SAB member of Nabsys and Genome Insight. D.P. has previously disclosed a patent application (no. EP19169090) relevant to Strand-seq. Z.K., C.N., E.D., C.F., C.Lambert, T.M., W.J.R., and M.A.E. are employees and shareholders of PacBio. Z.K. is a private shareholder in Phase Genomics. The other authors declare no competing interests.

Two general protocols for the regioselective electrochemically enabled sulfonylation cyclization of N -alkenylacrylamides with sodium sulfinates or sulfonyl hydrazides were described. These methods were carried out under mild, chemical oxidant-free, and transition-metal-free conditions with a broad substrate scope and good functional group tolerance to provide sulfonyl-containing 4-pyrrolin-2-ones, which is readily scalable to the gram scale.

Segmented RNA viruses are a complex group of RNA viruses with multisegment genomes. Reconstructing complete segmented viruses is crucial for advancing our understanding of viral diversity, evolution, and public health impact. Using metatranscriptomic data to identify known and novel segmented viruses has sped up the survey of segmented viruses in various ecosystems. However, the high genetic diversity and the difficulty in binning complete segmented genomes present significant challenges in segmented virus reconstruction. Current virus detection tools are primarily used to identify nonsegmented viral genomes. This study presents SegVir, a novel tool designed to identify segmented RNA viruses and reconstruct their complete genomes from complex metatranscriptomes. SegVir leverages both close and remote homology searches to accurately detect conserved and divergent viral segments. Additionally, we introduce a new method that can evaluate the genome completeness and conservation based on gene content. Our evaluations on simulated datasets demonstrate SegVir's superior sensitivity and precision compared to existing tools. Moreover, in experiments using real data, we identified some virus segments missing in the NCBI database, underscoring SegVir's potential to enhance viral metagenome analysis. The source code and supporting data of SegVir are available via https://github.com/HubertTang/SegVir., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account., Methods: Depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). HAMD-17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)-logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis., Results: The rate of depressive symptom in patients with PBC (n = 162) was higher than in healthy controls (n = 180) (52.5% vs. 16.1%; p < .001). HAMD-17 score was negatively associated with C4 levels and positively associated with levels of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TB), Immunoglobulin (Ig) G, and IgM (r = -0.162, 0.197, 0.355, 0.203, 0.182, 0.314, p < .05). In Lasso-logistic regression analysis, HAMD-17 score, human leukocyte antigen (HLA)-DRB1*03:01 allele, age, ALP levels, and IgM levels (odds ratio [OR] = 1.087, 7.353, 1.075, 1.009, 1.005; p < 0.05) were independent risk factors for cirrhosis. Elevated HAMD-17 score was also a discriminating factor for high risk of cirrhosis in patients with PBC in decision tree model., Conclusions: Depressive symptoms were associated with disease severity. Elevated HAMD-17 score was a risk factor for cirrhosis in patients with PBC., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)