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Herqupenoid A ( 1 ), a sesquiterpene-quinone hybrid with an unparalleled 5/5/6/5-fused ring skeleton based on a multicyclic caged 2,7-dioxatetracyclo[5.4.0.0 4,11 .0 5,9 ]hendecane fragment, was isolated from fungus Penicillium herquei . Its structure was assigned by extensive spectroscopic analyses, DP4+ computational method, and single-crystal X-ray diffraction. Further pharmacology research has established that compound 1 exhibited significant anti-inflammatory activity via inhibiting NF-κB-NLRP3 axis with an IC 50 value of 2.63 μM, which was stronger than the positive control dexamethasone. A putative biosynthetic pathway involving the key hemiacetal and aldol condensation reactions for 1 was also discussed.

Background: The present study investigated the function of G protein-coupled receptor kinase 2 (GRK2) in acute liver injury (ALI) by cisplatin, and investigated the protective effect of pharmacological inhibition of GRK2., Methods: ALI models were generated in global adult hemizygous (ALI-Grk2 ± ) mice and wild-type (WT) mice. Liver biochemistry parameters and histopathology were used to evaluate the severity of ALI and the protective effect of pharmacological inhibition of GRK2. GRK2-siRNA was used to knock down the expression of GRK2 in AML12 cells in vitro., Results: ALI model mice exhibited increased blood levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver pathology accompanied by imbalanced L-glutathione (GSH) levels. Cisplatin administration upregulated GKR2, p-GRK2 and NADPH oxidase 4 (NOX4) expression in the liver tissues of ALI model mice. Compared to WT mice injected with cisplatin, Grk2 ± mice that received cisplatin showed significant improvements in liver function and pathological performance, decreased NOX4 levels, reduced endoplasmic reticulum (ER) stress, and diminished liver cell apoptosis. In vitro, the transfection of AML12 cells with siRNA significantly reduced NOX4 expression and inhibited cisplatin-induced reactive oxygen species production, ER stress (increased levels of GRP94, GRP78, p-elF2α and CHOP) and apoptotic death. Moreover, pharmacological treatment with drugs that inhibit GRK2 (CP-25 or paroxetine) significantly ameliorated cisplatin-induced ALI by improving liver pathological manifestations, inhibiting oxidative stress and ER stress, and reducing liver cell apoptosis. Similar results were observed in vitro., Conclusions: GRK2 mediates the development of cisplatin-induced ALI by modulating NOX4 and ER stress. Pharmacological inhibition of GRK2 with CP-25 or paroxetine effectively alleviated ALI. GRK2 can be used as a potential target for the prevention and treatment of liver injury., Competing Interests: Declarations Ethics approval and consent to participate The present study was approved by the Subcommittee of the Institute of Clinical Pharmacology, Ethical Committee on Animal Research of Anhui Medical University (No. PZ-2021–015; Date: May 8th, 2021) and conducted according to the U.K. Animals (Scientific Procedures) Act, 1986 and our institutional guidelines for the care and use of animals. Consent for publication No applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Circular RNAs (circRNAs) function as essential regulatory elements with pivotal roles in various biological processes. However, their expression profiles and functional regulation during the differentiation of goat myoblasts have not been thoroughly explored. This study conducts an analysis of circRNA expression profiles during the proliferation phase (cultured in growth medium, GM) and differentiation phase (cultured in differentiation medium, DM1/DM5) of skeletal muscle satellite cells (MuSCs) in goats., Results: A total of 2,094 circRNAs were identified, among which 84 were differentially expressed as determined by pairwise comparisons across three distinct groups. Validation of the expression levels of six randomly selected circRNAs was performed using reverse transcription PCR (RT-PCR) and quantitative RT-PCR (qRT-PCR), with confirmation of their back-splicing junction sites. Enrichment analysis of the host genes associated with differentially expressed circRNAs (DEcircRNAs) indicated significant involvement in biological processes such as muscle contraction, muscle hypertrophy, and muscle tissue development. Additionally, these host genes were implicated in key signaling pathways, including Hippo, TGF-beta, and MAPK pathways. Subsequently, employing Cytoscape, we developed a circRNA-miRNA interaction network to elucidate the complex regulatory mechanisms underlying goat muscle development, encompassing 21 circRNAs and 47 miRNAs. Functional assays demonstrated that circTGFβ2 enhances myogenic differentiation in goats, potentially through a miRNA sponge mechanism., Conclusion: In conclusion, we identified the genome-wide expression profiles of circRNAs in goat MuSCs during both proliferation and differentiation phases, and established that circTGFβ2 plays a role in the regulation of myogenesis. This study offers a significant resource for the advanced exploration of the biological functions and mechanisms of circRNAs in the myogenesis of goats., Competing Interests: Declarations Ethics approval and consent to participate The Animal Care and Use Committee of the College of Animal Science and Technology, Sichuan Agricultural University, Sichuan, China, approved all of the animal care, slaughter, and experimental procedures in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals (Ministry of Science and Technology, China) [Approval No. SAU20231023]. Informed consent was obtained from the owner of Chengdu Xilingxue Agricultural Development Co., Ltd, before sampling Chengdu Ma goats for this study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Fine particulate matter (PM 2.5 ) induces ocular surface toxicity through pyroptosis, oxidative stress, autophagy, and inflammatory responses. However, the precise molecular pathways through which PM 2.5 causes corneal damage remain unclear. This study aims to investigate the underlying mechanisms by exposing human corneal epithelial cells (HCECs) to PM 2.5 ., Methods: After the morphology and chemical composition analysis of the PM samples, we conducted both in vivo and in vitro experiments to investigate PM 2.5 -induced corneal epithelial damage. We assessed corneal barrier function in HCECs using transepithelial electrical resistance (TEER) assays. To explore the molecular mechanisms of PM 2.5 -induced corneal epithelial damage, we performed whole-transcriptome resequencing, quantitative RT-PCR, and western blotting in vitro. In addition, we analyzed mouse corneas exposed to concentrated ambient PM 2.5 through immunofluorescence staining to observe the resulting changes in corneal epithelial protein expression in vivo., Results: Our results showed significant impairment of corneal epithelial barrier function in PM 2.5 -treated HCECs, as indicated by decreased TEER values. The expression of thrombospondin-1 (THBS1) and claudin-1, both key factors for maintaining corneal epithelial barrier integrity, was markedly reduced at the gene and protein levels in both in vitro and in vivo PM 2.5 exposure models. Moreover, the levels of tight junction-associated proteins, including occludin, zonula occludens-1 (ZO-1) and ZO-2, essential components of the corneal epithelial barrier, were significantly diminished in PM 2.5 -treated HCECs., Conclusion: PM 2.5 exposure leads to corneal epithelium damage by disrupting tight junction proteins and THBS1 expression. These findings provide insight into potential pathways for PM 2.5 -induced ocular toxicity and underscore the need for protective strategies against such environmental pollutants., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus-induced acute retinal necrosis and to explore the effect of viral genotypes on clinical manifestations., Methods: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase was estimated. Variations in viral genomes were detected by metagenomic sequencing., Results: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9 × 10 7 (1.1 × 10 7 -1.1 × 10 8 ) copies/mL. The average duration of retinitis was 5 ± 3 weeks. The average time required to reach the inflection point was 4.2 ± 1.6 days. Time required to reach the inflection point was correlated with the duration of retinitis ( P = 0.025). Patients with varicella-zoster virus carrying the p.S715* variation in ribonucleotide reductase ( RNR ) subunit 1 gene had lower initial viral loads (median 1.3 × 10 7 copies/mL) than those without (median 1.1 × 10 8 copies/mL; adjusted P = 0.030)., Conclusions: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in patients with acute retinal necrosis. Loss-of-function variation in RNR gene might be correlated with lower virulence of varicella-zoster virus., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

We have developed a novel fluorescence sensor based on upconversion nanoparticles (UCNPs) for the rapid and sensitive detection of trace aluminum ions (Al 3+ ). The sensor utilizes the inner filter effect (IFE) between the UCNPs and the xylenol orange-aluminum complex (XO-Al 3+ ), resulting in significant fluorescence quenching at 543 nm upon Al 3+ binding. This quenching correlates directly with the Al 3+ concentration, allowing for quantitative detection within a range of 0-30 μM and achieving an ultra-low detection limit of 0.19 μM. Selectivity of the sensor is enhanced by the incorporation of ascorbic acid, which masks interfering Fe 3+ ions, thus ensuring accurate determination of Al 3+ even in the presence of other metal ions. The UCNPs-XO sensor exhibits excellent stability and reproducibility, and minimal interference from commonly co-existing substances. This makes it suitable for the detection of Al 3+ in various matrices, including food products and environmental water samples. Our work offers a significant advancement in Al 3+ detection, with potential applications in food safety, environmental monitoring, and public health.

Breast cancer has become the malignant tumor with the first incidence and the second mortality among female cancers. Most female breast cancers belong to luminal-type breast cancer and HER2-positive breast cancer. These breast cancer cells all have different driving genes, which constantly promote the proliferation and metastasis of breast cancer cells. Signal transducer and activator of transcription 3 (STAT3) is an important breast cancer-related gene, which can promote the progress of breast cancer. It has been proved in clinical and basic research that over-expressed and constitutively activated STAT3 is involved in the progress, proliferation, metastasis and chemotherapy resistance of breast cancer. STAT3 is an important key target in luminal-type breast cancer and HER2-positive cancer, which has an important impact on the curative effect of related treatments. In breast cancer, the activation of STAT3 will change the spatial position of STAT3 protein and cause different phenotypic changes of breast cancer cells. In the current basic research and clinical research, small molecule inhibitors activated by targeting STAT3 can effectively treat breast cancer, and enhance the efficacy level of related treatment methods for luminal-type and HER2-positive breast cancers., (© 2024. The Author(s).)

Intracellular vesicles are typically transported by a small number of kinesin and dynein motors. However, the slow microtubule binding rate of kinesin-1 observed in in vitro biophysical studies suggests that long-range transport may require a high number of motors. To address the discrepancy in motor requirements between in vivo and in vitro studies, we reconstituted motility of 120-nm-diameter liposomes driven by multiple GFP-labeled kinesin-1 motors. Consistent with predictions based on previous binding rate measurements, we found that long-distance transport requires a high number of kinesin-1 motors. We hypothesized that this discrepancy from in vivo observations may arise from differences in motor organization and tested whether motor clustering can enhance transport efficiency using a DNA scaffold. Clustering just three motors improved liposome travel distances across a wide range of motor numbers. Our findings demonstrate that, independent of motor number, the arrangement of motors on a vesicle regulates transport distance, suggesting that differences in motor organization may explain the disparity between in vivo and in vitro motor requirements for long-range transport., Competing Interests: Competing Interests The authors declare no competing interests.

Introduction: In patients with frequent premature ventricular contractions (PVCs), palpitations may not always be directly caused by PVCs, and therefore, it is essential to establish symptom-rhythm correlations to determine the appropriate treatment. This study aims to analyze the palpitations and related factors in patients with frequent PVCs., Methods: The study enrolled patients with frequent PVCs who were not combined with other arrhythmias or structural heart disease. Through face-to-face consultation, patients were divided into symptomatic and asymptomatic groups. For symptomatic patients, the correlation between palpitations and PVC was further evaluated based on the temporal consistency of symptom onset and PVC occurrence. The demographic, clinical, and electrocardiogram features of the patients in each group were compared., Results: Of the 214 patients enrolled, 124(57.9%) experienced palpitations. Compared to the asymptomatic group, the symptomatic group had a higher proportion of females (63.7% vs. 47.8%; p = .020) and a higher proportion of subjects with anxiety (44.4% vs.14.4%; p = .000). Within the symptomatic patients, 72 (33.60%) who had palpitations that were clearly correlated with PVCs were classified as the PVC-relevant group. In this group, the PVC CI ratios were significantly lower (55% [52% -60%] vs. 62% [55% -67%]; p = .001) and the Post-PVC CI were longer (1170 [1027-1270] vs. 1083 [960-1180] ms; p = .018) than in the PVC-irrelevant group., Conclusion: A direct relationship between palpitations and PVCs could be established only in a minority of patients with frequent PVCs. PVCs with a relatively short PVC CI and a long post-PVC CI were more likely to cause palpitations, whereas palpitations lasting only a few seconds were more likely to be directly relevant to PVCs., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

A highly sensitive fluorescence sensor for monitoring low concentrations of hydrogen peroxide was designed. The sensor employs the commercially available palladium or platinum metal on activated charcoal as catalysts to decompose hydrogen peroxide into water and molecular oxygen. The produced oxygen concentration can be measured in real time using an oxygen-sensitive layer doped with photostable oxygen probes. The sensor exhibits high sensitivity that is able to measure hydrogen peroxide concentration down to 20 ppb and can measure hydrogen peroxide concentration in the range of 0.1-100 ppm and 0.02-100 ppm, respectively. The response is fully reversible and the typical response time is less than one minute, which makes it suitable to continuously measure hydrogen peroxide over a long duration. Due to the excellent batch-to-batch consistency of palladium or platinum metal on activated charcoal, the sensor can be massively produced with good reproducibility and affordable price, which holds great potential for constructing sensors for industrial and practical applications.

For a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level. To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran's Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy. In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the. results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors., (© 2024. The Author(s).)

Introduction: This cross-sectional study aimed to investigate dental practitioners' knowledge and practices regarding Caries risk assessment (CRA) in routine clinical practice in Guangzhou, China., Methods: An online questionnaire was disseminated to dental practitioners to gather socio-demographic information, factors associated with CRA, the implementation of preventive treatment, and the level of awareness regarding personalized preventive treatment in relation to CRA. Statistical analyses included descriptive statistics, Chi-square tests, ANOVA, MANCOVA, linear regression, and scatter plots., Results and Discussion: Out of the 695 dental practitioners who were contacted, 206 dentists participated in the online survey. However, out of the total number of dentists, 198 were successfully recruited, while the remaining 8 dentists had incomplete data in their questionnaires. 92.4% of dentists provided in-office fluoride treatments, and 73.2% held a strong belief in the correlation between current oral hygiene and tooth cavities. 23.7% of dentists evaluated caries risk on an individual basis, and a significant 41.9% never utilized a particular type of CRA. 53.5% of dentists recommended non-prescription fluoride rinses, whereas 51% advocated prescription fluoride treatments. Significant statistical relationships were found between the use of in-office fluoride and the effectiveness of restorative treatment ( P  < 0.05). Additionally, a significant association was discovered between the use of a specific form for CRA and the kind of dental school ( P  < 0.05). The study suggests that a significant number of dental practitioners in Guangzhou, China, do not utilize dedicated assessment forms for CRA in their routine professional activities. These findings highlight the im-portance of encouraging dentists to utilize CRA systems to effectively identify patients who are at risk of acquiring dental caries., 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. The handling editor KC declared a shared parent affiliation with the authors EN, RJ, XL and JY at the time of review., (© 2024 Nie, Jiang, Islam, Li and Yu.)

Objectives: Inferior vena cava (IVC) penetration is a prevalent complication following the placement of conical filters. However, there is a paucity of studies examining the penetration in smaller IVC. The objective of this study was to assess the time of penetration, the incidence of serious complications associated with penetration, and the process of IVC wall repair in the smaller IVC following the placement of a conical filter., Methods: Twenty pigs were randomly assigned to 2 groups and received either Celect or Denali filters. Weekly follow-up imaging using computed tomography venography (CTV) of the IVC was conducted to monitor the position of the IVC filter struts until at least 1 strut was observed to be penetrating the vessel wall. At necropsy, a comprehensive gross and histological examination was performed on the IVC and adjacent anatomical structures in all animals., Results: The puncture and cavography procedures were successfully conducted on all animals, and no significant differences were found in the mean diameter of the IVC between the Celect and Denali groups (15.89 ± 1.27 mm vs. 16.39 ± 1.39 mm, P > 0.05). All filters were implanted without complications. CTV detected IVC penetration within 9 weeks, which was confirmed during necropsy. The Celect group had a significantly earlier time of IVC penetration compared to the Denali group (2.43 ± 0.52 weeks vs. 6.81 ± 1.32 weeks, P ＜ 0.001). No evidence of filter tilt, fracture, migration, caval thromboses, retroperitoneal bleeding, wall hematoma, tearing of the IVC wall, or peripheral tissue and organ damage was observed during the CTV and subsequent necropsy. Additionally, histological analysis showed that the Celect group had a lower percentage area of collagen fiber compared to the Denali group (33.92% vs. 49.04%, P ＜ 0.001). The fiber proliferation was positively correlated linearly with the indwelling time of filter (r = 0.97, P ＜ 0.001)., Conclusions: Penetration can occur within a relatively brief period following the placement of the conical filter into the smaller IVC. Nevertheless, no short-term severe complications were observed in connection with the penetration. The proliferation of fibers in the IVC wall exhibited a positive linear correlation with the duration of filter indwelling., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Photoelectrochemical water splitting offers a promising approach for carbon neutrality, but its commercial prospects are still hampered by a lack of efficient and stable photoelectrodes with earth-abundant materials. Here, we report a strategy to construct an efficient photoanode with a coaxial nanobelt structure, comprising a buried-ZrS 3 /ZrOS n-p junction, for photoelectrochemical water splitting. The p-type ZrOS layer, formed on the surface of the n-type ZrS 3 nanobelt through a pulsed-ozone-treatment method, acts as a hole collection layer for hole extraction and a protective layer to shield the photoanode from photocorrosion. The resulting ZrS 3 /ZrOS photoanode exhibits light harvesting with good photo-to-current efficiencies across the whole visible region to over 650 nm. By further employing NiOOH/FeOOH as the oxygen evolution reaction cocatalyst, the ZrS 3 /ZrOS/NiOOH/FeOOH photoanode yields a photocurrent density of ~9.3 mA cm -2 at 1.23 V versus the reversible hydrogen electrode with an applied bias photon-to-current efficiency of ~3.2 % under simulated sunlight irradiation in an alkaline solution (pH=13.6). The conformal ZrOS layer enables ZrS 3 /ZrOS/NiOOH/FeOOH photoanode operation over 1000 hours in an alkaline solution without obvious performance degradation. This study, offering a promising approach to fabricate efficient and durable photoelectrodes with earth-abundant materials, advances the frontiers of photoelectrochemical water splitting., (© 2024 Wiley-VCH GmbH.)

Microplastics (MPs) in agricultural plastic film mulching system changes microbial functions and nutrient dynamics in soils. However, how biodegradable MPs impact the soil gross nitrogen (N) transformations and crop N uptake remain significantly unknown. In this study, we conducted a paired labeling 15 N tracer experiment and microbial N-cycling gene analysis to investigate the dynamics and mechanisms of soil gross N transformation processes in soils amended with conventional (polyethylene, PE) and biodegradable (polybutylene adipate co-terephthalate, PBAT) MPs at concentrations of 0 %, 0.5 %, and 2 % (w/w). The biodegradable MPs-amended soils showed higher gross N mineralization rates (0.5-16 times) and plant N uptake rates (16-32 %) than soils without MPs (CK) and with conventional MPs. The MPs (both PE and PBAT) with high concentration (2 %) increased gross N mineralization rates compared to low concentration (0.5 %). Compare to CK, MPs decreased the soil gross nitrification rates, except for PBAT with 2 % concentration; while PE with 0.5 % concentration and PBAT with 2 % concentration increased but PBAT with 0.5 % concentration decreased the gross N immobilization rates significantly. The results indicated that there were both a concentration effect and a material effect of MPs on soil gross N transformations. Biodegradable MPs increased N-cycling gene abundance by 60-103 %; while there was no difference in the abundance of total N-cycling genes between soils without MPs and with conventional MPs. In summary, biodegradable MPs increased N cycling gene abundance by providing enriched nutrient substrates and enhancing microbial biomass, thereby promoting gross N transformation processes and maize N uptake in short-term. These findings provide insights into the potential consequences associated with the exposure of biodegradable MPs, particularly their impact on soil N cycling processes., Competing Interests: Declaration of Competing Interest This manuscript has not been published before nor submitted to another journal for the consideration of publication. 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. Published by Elsevier B.V.)

Rationale and Objectives: This study aimed to investigate the relationship between minimum inferior vena cava (IVC) diameter magnification percentage and in-situ IVC thrombosis (iIVCT) after inferior vena cava filter (IVCF) placement in lower extremity deep vein thrombosis (LEDVT)., Methods: This was a single center retrospective study. Study sample consisted of patients with LEDVT who received computed tomography venography of IVC both before and after IVCF placement between January 2019 and October 2023. A propensity score matching (PSM) was also used in covariates including age, hypertension, and thrombus limbs. Multivariate Cox regression analyses were performed to mitigate the impact of selection bias and control for potential confounding variables. The incremental changes associated with minimum IVC diameter magnification percentage and iIVCT were evaluated with restricted cubic spines (RCS)., Results: 113 LEDVT patients (age 58.8 ± 17.8 years, 57.5% male) were included. Multivariate Cox regression analyses revealed a significant positive association between the minimum IVC diameter magnification percentage and the incidence of iIVCT after adjusting for the age, hypertension, and thrombus limbs (adjusted hazard risk [HR] = 1.02, 95% CI, 1.01 to 1.02, p < .001), suggesting minimum IVC diameter magnification percentage was an independent risk factor for iIVCT. Moreover, after using PSM, the association remained significant (HR=1.01, 95% CI, 1.01 to 1.02, p < .001). RCS analysis showed a non-linear dose-response association (s-shaped fitting curve) between minimum IVC diameter magnification percentage and iIVCT risk (nonlinear p = .041). The fitting curve indicated a threshold effect (overall p = .005), with a smaller magnification percentage being negatively associated with the incidence of iIVCT, presenting continuously decreasing HR at levels of magnification percentage < 37.3%., Conclusion: A decreasing minimum IVC diameter magnification percentage is consistently associated with a decreasing risk of iIVCT following IVCF placement when the percentage is < 37.3%, indicating that it is a protective factor against iIVCT incidence. WHAT THIS PAPER ADDS?: This single-center retrospective study, which designed to investigate the relationship between minimum inferior vena cava diameter magnification percentage and in-situ inferior vena cava thrombosis (iIVCT) following inferior vena cava filter (IVCF) placement in lower extremity deep vein thrombosis in 113 patients, demonstrated that decreasing minimum IVC diameter magnification percentage is consistently associated with a decreasing risk of iIVCT following IVCF placement when the percentage is < 37.3%, indicating that it is a protective factor against iIVCT incidence., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The content of the manuscript is original, and it has not been published or accepted for publication., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction., 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.)

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack of a detailed understanding of oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. The role of protein lactylation, a newly unraveled post-translational modification that orchestrates gene expression, remains largely elusive in the pathogenesis of iCCA., Methods: Proteomics analysis of clinical iCCA specimens and adjacent tissues was performed to screen for proteins aberrantly lactylated in iCCA. Mass spectrometry, macromolecule interaction and cell behavioral studies were employed to identify the specific lactylation sites on the candidate protein(s) and to decipher the downstream mechanisms responsible for iCCA development, which were subsequently validated using a xenograft tumor model and clinical samples., Results: Nucleolin (NCL), the most abundant RNA-binding protein in the nucleolus, was identified as a functional lactylation target that correlates with iCCA occurrence and progression. NCL was lactylated predominantly at lysine 477 by the acyltransferase P300 in response to a hyperactivity of glycolysis, and promoted the proliferation and invasion of iCCA cells. Mechanistically, lactylated NCL bound to the primary transcript of MAP kinase-activating death domain protein (MADD) and led to efficient translation of MADD by circumventing alternative splicing that generates a premature termination codon. NCL lactylation, MADD translation and subsequent ERK activation promoted xenograft tumor growth and were associated with overall survival in patients with iCCA., Conclusion: NCL is lactylated to upregulate MADD through an RNA splicing-dependent mechanism, which potentiates iCCA pathogenesis via the MAPK pathway. Our findings reveal a novel link between metabolic reprogramming and canonical tumor-initiating events, and uncover biomarkers that can potentially be used for prognostic evaluation or targeted treatment of iCCA., Impact and Implications: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive liver malignancy with largely uncharacterized pathogenetic mechanisms. Herein, we demonstrated that glycolysis promotes P300-catalyzed lactylation of nucleolin, which upregulates MAP kinase-activating death domain protein (MADD) through precise mRNA splicing and activates ERK signaling to drive iCCA development. These findings unravel a novel link between metabolic rewiring and canonical oncogenic pathways, and reveal new biomarkers for prognostic assessment and targeting of clinical iCCA., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

At present, gum-injected meat appeared in the market, which has seriously damaged the legitimate rights and interests of consumers. Therefore, a method for the determination of carrageenan and konjac gum in livestock meat and meat products by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. The samples were hydrolyzed by hydrogen nitrate. After centrifugation and dilution, the supernatants were detected by the UPLC-MS/MS and the concentration of target compounds in samples were calibrated by the matrix calibration curves. A good linear relationship was observed in the concentration range of 5-100 μg/mL with correlation coefficients of more than 0.995. The limits of detection (LODs) and limits of quantification (LOQs) were found to be 20 and 50 mg/kg, respectively. The recoveries at three spiked levels (50, 100 and 500 mg/kg) in blank matrix were in the range of 84.8-108.6% with the relative standard deviations between 1.5% and 6.4%. The method has the advantages of convenient, accurate and efficient, and can be used as an effective method for detecting carrageenan and konjac gum in the different kinds of livestock meat and meat products.

The study aims to investigate the potential of training efficient deep learning models by using 2.5D (2.5-Dimension) masks of sICH. Furthermore, it intends to evaluate and compare the predictive performance of a joint model incorporating four types of features with standalone 2.5D deep learning, radiomics, radiology, and clinical models for early expansion in sICH. A total of 254 sICH patients were enrolled retrospectively and divided into two groups according to whether the hematoma was enlarged or not. The 2.5D mask of sICH is constructed with the maximum axial, coronal and sagittal planes of the hematoma, which is used to train the deep learning model and extract deep learning features. Predictive models were built on clinic, radiology, radiomics and deep learning features separately and four type features jointly. The diagnostic performance of each model was measured using the receiver operating characteristic curve (AUC), Accuracy, Recall, F1 and decision curve analysis (DCA). The AUCs of the clinic model, radiology model, radiomics model, deep learning model, joint model, and nomogram model on the train set (training and Cross-validation) were 0.639, 0.682, 0.859, 0.807, 0.939, and 0.942, respectively, while the AUCs on the test set (external validation) were 0.680, 0.758, 0.802, 0.857, 0.929, and 0.926. Decision curve analysis showed that the joint model was superior to the other models and demonstrated good consistency between the predicted probability of early hematoma expansion and the actual occurrence probability. Our study demonstrates that the joint model is a more efficient and robust prediction model, as verified by multicenter data. This finding highlights the potential clinical utility of a multifactorial prediction model that integrates various data sources for prognostication in patients with intracerebral hemorrhage. The Critical Relevance Statement: Combining 2.5D deep learning features with clinic features, radiology markers, and radiomics signatures to establish a joint model enabling physicians to conduct better-individualized assessments the risk of early expansion of sICH., (© 2024. The Author(s).)

Accurate solute solubility measuring and modeling in supercritical carbon dioxide (ScCO 2 ) would address the best working conditions and thermodynamic boundaries for material processing with this type of fluid. Theory- and data-driven methods are two general modeling approaches. Using theory-driven methods, the solubility is estimated based on the principles of thermodynamics, while data-driven methods are developed by training the algorithms. Despite acceptance of each of these methods, more experimental solubility data are still needed to promote modeling performances. In this study, for the first time, solubility of morphine sulfate is determined and modeled by a set of 13 semi-empirical (theory-driven) and random forest (data-driven) models. Using a laboratory system with an ultraviolet-visible (UV-Vis) spectroscopy, the experimental solubilities including 48 data points were obtained at different temperatures (308-338 K) and pressures (12-27 MPa). The minimum (0.806 × 10 -5 ) and maximum (5.902 × 10 -5 ) equilibrium mole fractions were observed at working pressures of 12 and 27 MPa, respectively, both at the same temperature of 338 K. It was indicated that random forest model (with AARD% of 1.29%) had an excellent predictive performance against semi-empirical models (with AARD% from 9.33 to 19.76%). The results showed that solute molecular weight had the highest effect on random forest modeling. Using modeling results from Chrastil and Bartle models, total and vaporization enthalpies of dissolution of morphine sulfate in ScCO 2 were found to be 35.12 and 59.04 kJ/mole, respectively., (© 2024. The Author(s).)

The liver plays an important role in regulating lipid metabolism in animals. This study investigated the function and mechanism of lncLLM in liver lipid metabolism in hens at the peak of egg production. The effect of lncLLM on intracellular lipid content in LMH cells was evaluated by qPCR, Oil Red O staining, and detection of triglyceride (TG) and cholesterol (TC) content. The interaction between lncLLM and MYH9 was confirmed by RNA purification chromatin fractionation (CHIRP) and RNA immunoprecipitation (RIP) analysis. The results showed that lncLLM increased the intracellular content of TG and TC and promoted the expression of genes related to lipid synthesis. It was further found that lncLLM had a negative regulatory effect on the expression level of MYH9 protein in LMH cells. The intracellular TG and TC content of MYH9 knockdown cells increased, and the expression of genes related to lipid decomposition was significantly reduced. In addition, this study confirmed that the role of lncLLM is at least partly through mediating the ubiquitination of MYH9 protein to accelerate the degradation of MYH9 protein. This discovery provides a new molecular target for improving egg-laying performance in hens and treating fatty liver disease in humans.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, HeLa, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9 f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner., (© 2024 Wiley-VCH GmbH.)

Excellent germplasm resources are the foundation for cultivating high-quality, disease-resistant, and stress-tolerant varieties. In this study, simple sequence repeat (SSR) markers were used to identify 138 potato accessions collected from worldwide, and genetic cluster analysis was used to characterize the genetic diversity of the tested germplasm resources. The Potato virus Y (PVY) resistance of these potato accessions was identified by artificial friction inoculation combined with molecular marker detection, and potato accessions with different PVY resistance were screened based on disease index and incidence rate. Using SSR markers, 138 potato accessions were identified, and the results showed that the genetic distances between the tested potato germplasm resources ranged from 0.025 to 0.660, and the genetic similarity coefficients ranged from 0.489 to 0.975. The 138 accessions could be clustered into five subgroups using Unweighted Pair-Group Method with Arithmetic Mean (UPGMA). Among them, Z173, Biyin No. 4, Suyin No. 2, XN995, XN987, Biyin No 22, Bibiao104, Sarpo mira, XN996, XN979, Desiree, RUNSHI, Actrice, Jia 1219, Heyin No 12, and Moyin No.1 have relatively distant genetic relationship with another 122 accessions. Based on the disease index, the following different accessions were screened: five highly resistant, 11 resistant, 45 moderately resistant, 35 susceptible, and 42 highly susceptible. Fourteen resource materials with good resistance (disease index ≤ 33.74%, and a grading of high resistance (HR) or medium resistance (MR); incidence rate ≤ 67.58%) were identified. By combining genetic cluster analysis and PVY resistance identification, six accessions showed PVY resistance and had distant genetic relationships with other accessions selected which provided important materials for disease resistance breeding and quality improvement of potato. In this study, the genetic diversity and PVY resistance of global potato germplasm resources was explored, and potato germplasm materials with important utilization value were screened. The results obtained in this study could provide important references for the research and utilization of global potato germplasm resources., 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 Gao, Tian, Du, Zhao, Jiang, Zhang and Lv.)

Background: Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. "EMERALD" is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions., Methods: The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and  (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions., Discussion: This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector's contribution to addressing the growing burden of non-communicable diseases in China., Trial Registration: The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024)., (© 2024. The Author(s).)

Background: Implantable Collamer Lense (ICL) presents a viable alternative to conventional refractive surgeries, but their impact on corneal microstructure remains unclear. By employing in vivo confocal microscopy (IVCM), we examined changes in stromal and endothelial cells following the insertion of V4c ICLs, with the goal of enhancing post-surgical care and outcomes., Methods: In this longitudinal investigation, we conducted detailed preoperative assessments on 103 eyes from 53 participants. Follow-up evaluations were carried out after surgery at set intervals: one day, one week, one month, three months, six months, and twelve months. We used IVCM to analyze changes in stromal and endothelial cells. To assess differences between pre- and post-surgery variables and to investigate correlations with age, axial length (AL), and spherical equivalent refraction (SER), we applied a repeated measures mixed-effects model, with statistical significance set at P < 0.05., Results: No vision-threatening complications were reported post-surgery. Significant reductions in stromal cell density (SCD) were observed postoperatively, with anterior and mid- SCD reaching their lowest values at 3 months and posterior SCD at 1 month, remaining below baseline at 12 months. endothelial cell density (ECD) and percentage of hexagonal cells (PHC) decreased initially, recovering by 12 months. Conversely, endothelial cellular area (ECA) and coefficient of variation of cell size (CoV) increased postoperatively, with the most significant change at 1 week. Endothelial deposits were detected in 49 of 101 eyes on postoperative day 1, half of them were absorbed within 3 months post-surgery. Changes in posterior SCD were negatively related to AL, while AL, SER, lens thickness showed associated with endothelium changes., Conclusion: Our findings elucidate the corneal microstructural changes following V4c ICL implantation, particularly the significant early reductions in stromal and endothelial cell densities. We recommend careful management of viscoelastics during surgery to minimize endothelial deposits that may harm the endothelium. Enhanced early postoperative monitoring and these surgical adjustments can lead to improved surgical and post-surgical care, ultimately supporting better patient recovery., (© 2024. The Author(s).)

Background: Chronic periodontitis may induce erectile dysfunction (ED), however, the specific mechanism involved is unclear. The endothelial glycocalyx (eGlx) is a structure that can regulate endothelial nitric oxide synthase (eNOS) phosphorylation on the cavity surface of vessels., Aim: To investigate whether chronic periodontitis leads to ED by affecting the eGlx., Methods: Twenty-four 4-week-old male Sprague‒Dawley rats were randomly divided into four groups (n = 6): the control group, chronic periodontitis group, chronic periodontitis + heparin group (subcutaneous heparin 200 U/kg/day, 7 days), and control + heparin group. Four weeks after the induction of periodontitis in the rats, the maximum intra-cavernous pressure/mean arterial pressure (ICPmax/MAP), serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), heparin sulfate (HS), syndecan-1 (SDC-1), heparanase (HPSE), eNOS, and phosphor-eNOS (p-eNOS) concentration were measured, and the eGlx of the penile corpus cavernosum was observed by transmission electron microscopy (TEM)., Outcomes: Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in the penile corpus cavernosum, and resulting in the inhibition of the erectile function., Results: Serum CRP, TNF-α, and IL-6 levels and HPSE expression in penile cavernous tissue were significantly greater in the chronic periodontitis group than in the control group and the chronic periodontitis + heparin group (P < 0.05). The average thickness of the eGlx muscle in the penile corpus cavernosum in the chronic periodontitis group was significantly lower than those in the control group and chronic periodontitis + heparin group (P < 0.05). The HS concentration, SDC-1 expression, p-eNOS/eNOS, NO concentration, and ICPmax/MAP in the chronic periodontitis group were significantly lower than those in the control group and chronic periodontitis+ heparin group (P < 0.01)., Clinical Implications: The eGlx on penile cavernosum vessels may be a new therapeutic target for the treatment of ED., Strengths and Limitations: This study revealed that chronic periodontitis promotes the decomposition of vascular eGlx in the rat penile corpus cavernosum, however, it is not clear whether chronic periodontitis inhibits the synthesis of eGlx., Conclusion: Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in penile cavernous tissue, and resulting in the inhibition of the erectile function. Heparin inhibited eGlx decomposition and improved erectile function in rats with chronic periodontitis., (© 2024 American Society of Andrology and European Academy of Andrology.)

Cell-cell communication (CCC) through ligand-receptor (L-R) pairs forms the cornerstone for complex functionalities in multicellular organisms. Deciphering such intercellular signaling can contribute to unraveling disease mechanisms and enable targeted therapy. Nonetheless, notable biases and inconsistencies are evident among the inferential outcomes generated by current methods for inferring CCC network. To fill this gap, we developed collectNET (http://health.tsinghua.edu.cn/collectnet) as a comprehensive web platform for analyzing CCC network, with efficient calculation, hierarchical browsing, comprehensive statistics, advanced searching, and intuitive visualization. collectNET provides a reliable online inference service with prior knowledge of three public L-R databases and systematic integration of three mainstream inference methods. Additionally, collectNET has assembled a human CCC atlas, including 126 785 significant communication pairs based on 343 023 cells. We anticipate that collectNET will benefit researchers in gaining a more holistic understanding of cell development and differentiation mechanisms. Database URL: http://health.tsinghua.edu.cn/collectnet., (© The Author(s) 2024. Published by Oxford University Press.)

Liver ultrasound is widely used in clinical practice due to its advantages of non-invasiveness, non-radiation, and real-time imaging. Accurate segmentation of the liver region in ultrasound images is essential for accelerating the auxiliary diagnosis of liver-related diseases. This paper proposes BACANet, a deep learning algorithm designed for real-time liver ultrasound segmentation. Our approach utilizes a lightweight network backbone for liver feature extraction and incorporates a convolutional attention mechanism to enhance the network's ability to capture global contextual information. To improve early localization of liver boundaries, we developed a selective large kernel convolution module for boundary feature extraction and introduced explicit liver boundary supervision. Additionally, we designed an enhanced attention gate to efficiently convey liver body and boundary features to the decoder to enhance the feature representation capability. Experimental results across multiple datasets demonstrate that BACANet effectively completes the task of liver ultrasound segmentation, achieving a balance between inference speed and segmentation accuracy. On a public dataset, BACANet achieved a DSC of 0.921 and an IOU of 0.854. On a private test dataset, BACANet achieved a DSC of 0.950 and an IOU of 0.907, with an inference time of approximately 0.32 s per image on a CPU processor., (© 2024. The Author(s).)

Mitophagy influences the progression and prognosis of ischemic stroke (IS). However, whether DNA methylation in the brain is associated with altered mitophagy in hypoxia-injured neurons remains unclear. Here, miR-138-5p was found to be highly expressed in exosomes secreted by astrocytes stimulated with oxygen and glucose deprivation/re-oxygenation (OGD/R), which could influence the recovery of OGD/R-injured neurons through autophagy. Mechanistically, miR-138-5p promotes the stable expression of Ras homolog enriched in brain like 1(Rhebl1) through DNA-methyltransferase-3a (DNMT3A), thereby enhancing ubiquitin-dependent mitophagy to maintain mitochondrial homeostasis. Furthermore, we employed glycosylation engineering and bioorthogonal click reactions to load mirna onto the surface of microglia and deliver them to injured region utilising the inflammatory chemotactic properties of microglia to achieve drug-targeted delivery to the central nervous system (CNS). Our findings demonstrate miR-138-5p improves mitochondrial function in neurons through the miR-138-5p/DNMT3A/Rhebl1 axis. Additionally, our engineered cell vector-targeted delivery system could be promising for treating IS. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that miR-138-5p in exosomes secreted by astrocytes under hypoxia plays a critical role in the treatment of hypoxia-injured neurons. And we find a new target of miR-138-5p, DNMT3A, which affects neuronal mitophagy and thus exerts a protective effect by regulating the methylation of Rbebl1. Furthermore, we have developed a carrier delivery system by combining miR-138-5p with the cell membrane of microglia and utilized the inflammatory chemotactic properties of microglia to deliver this system to the brain via intravenous injection. This groundbreaking study not only provides a novel therapeutic approach for ischemia-reperfusion treatment but also establishes a solid theoretical foundation for further research on targeted drug delivery for central nervous system diseases with promising clinical applications., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In recent years, as societal awareness of the risks associated with primary osteoporosis (POP) has deepened, numerous studies have explored the relationship between POP and Traditional Chinese Medicine (TCM) constitution types. To further clarify the TCM constitution types closely associated with POP and provide evidence-based medical support for the prevention and treatment of osteoporosis from a TCM perspective, we have employed evidence-based methods to investigate the relationship between POP and TCM constitution types., Methods: We conducted a comprehensive search of observational studies on the relationship between POP and TCM constitutional types in databases, including PubMed, Embase, MEDLINE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journal Database (VIP), up to October 2023., Results: After literature selection, data extraction, and bias assessment, 29 studies were included in the meta-analysis, comprising 20 cross-sectional studies and 9 case-control studies. Using R software (version 4.2.3), we analyzed the distribution of TCM constitutional types in POP patients and compared the TCM constitutional types between POP patients and healthy individuals. The meta-analysis results revealed that in POP patients, Yang-deficiency constitution accounted for 22.7% (95% CI: 19.8-25.8%), Yin-deficiency constitution accounted for 15.8% (95% CI: 13.0-18.6%), and Qi-deficiency constitution accounted for 14.1% (95% CI: 12.2-16.0%). The proportions of the three mentioned TCM constitutions all exceed that of the Balanced constitution, with the balanced constitution accounting for 12.3% (95% CI: 7.4-18.1%). The proportions of Yang-deficiency, Yin-deficiency, and Qi-deficiency constitutions were higher in POP patients compared to healthy individuals, with odds ratios (OR) of 2.36 (95% CI: 1.43-3.89), 1.69 (95% CI: 1.36-2.04), and 1.80 (95% CI: 1.23-2.64), respectively, while the Balanced type was lower in POP patients with an OR of 0.16 (95% CI: 0.11-0.23) compared to healthy individuals., Conclusion: The evidence suggests that the Yang-deficiency constitution, Yin-deficiency constitution, and Qi-deficiency constitution are the predominant TCM constitutional types in POP patients. Furthermore, Yang-deficiency constitution, Yin-deficiency constitution, and Qi-deficiency constitution may serve as potential risk factors for POP, while the Balanced constitution may act as a protective factor., Competing Interests: The authors declare no conflict of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Public health emergencies influence urban carbon emissions, yet an in-depth understanding of deviations between regional emissions under such emergencies and normal levels is lacking. Inspired by the concept of resilience, we introduce the concept of regional carbon resilience and propose four resilience indicators covering periods during and after emergencies. A synthetic difference-in-differences model is employed to compute these indicators, providing a more suitable approach than traditional methods assuming unchanged levels before and after emergencies. Using the COVID-19 pandemic in China as a case study, focusing on the power and industry sectors, we find that over 40% regions exhibit strong resilience (> 0.9). Average in-resilience (0.764 and 0.783) is higher than post-resilience (0.534 and 0.598) in both sectors, indicating lower resilience during than after emergencies. Significant differences in resilience performance exist across regions, with Hebei (0.93) and Hangzhou (0.92) as top performers, and Qinghai (0.29) and Guiyang (0.36) as the least resilient. Furthermore, a preliminary correlation analysis identifies 22 factors affecting carbon resilience; higher energy consumption, stronger industrial production, and a healthier regional economy positively contribute to resilience with coefficients over + 0.3, while pandemic severity negatively impacts resilience, with coefficients up to -0.58. These findings provide valuable references for policymaking to achieve carbon neutrality goals., (© 2024. The Author(s).)

Endosymbionts provide essential nutrients for hosts, promoting growth, development, and reproduction. However, the molecular regulation of nutrient transport from endosymbiont to host is not well understood. Here, we used bioinformatic analysis, RNA-Sequencing, luciferase assays, RNA immunoprecipitation, and in situ hybridization to show that a bacteriocyte-distributed MRP4 gene (multidrug resistance-associated protein 4) is negatively regulated by a host (aphid)-specific microRNA (miR-3024). Targeted metabolomics, microbiome analysis, vitamin B6 (VB6) supplements, 3D modeling/molecular docking, in vitro binding assays (voltage clamp recording and microscale thermophoresis), and functional complementation of Escherichia coli were jointly used to show that the miR-3024/ MRP4 axis controls endosymbiont ( Serratia )-produced VB6 transport to the host. The supplementation of miR-3024 increased the mortality of aphids, but partial rescue was achieved by providing an external source of VB6. The use of miR-3024 as part of a sustainable aphid pest-control strategy was evaluated by safety assessments in nontarget organisms (pollinators, predators, and entomopathogenic fungi) using virus-induced gene silencing assays and the expression of miR-3024 in transgenic tobacco. The supplementation of miR-3024 suppresses MRP4 expression, restricting the number of membrane channels, inhibiting VB6 transport, and ultimately killing the host. Under aphids facing stress conditions, the endosymbiont titer is decreased, and the VB6 production is also down-regulated, while the aphid's autonomous inhibition of miR-3024 enhances the expression of MRP4 and then increases the VB6 transport which finally ensures the VB6 homeostasis. The results confirm that miR-3024 regulates nutrient transport in the endosymbiont-host system and is a suitable target for sustainable pest control., Competing Interests: Competing interests statement:The authors declare no competing interest.

Biodegradable film mulching has attracted considerable attention as an alternative to conventional plastic film mulching. However, biodegradable films generate transitory microplastics during the film degradation. How much of this transitory microplastics is being formed and their impact on soil health during long-term use of biodegradable plastic film are not known. Here, we quantified the amounts of microplastics (0.1-5 mm in size) in the topsoil (0-20 cm) of two cotton fields with different mulching cultivations: (1) continuous use of conventional (polyethylene, PE) film for 23 years (Plot 1), and (2) 15 years use of conventional film followed by 8 years of biodegradable (polybutylene adipate-co-terephthalate, PBAT) film (Plot 2). We further assessed the impacts of the microplastics on selected soil health parameters, with a focus on soil carbon contents and fluxes. The total amount of microplastics was larger in Plot 2 (8507 particles kg -1 ) than in Plot 1 (6767 particles kg -1 ). The microplastics (0.1-1 mm) were identified as derived from PBAT and PE in Plot 2; while in Plot 1, the microplastics were identified as PE. Microplastics > 1 mm were exclusively identified as PE in both plots. Soil organic carbon was higher (27 vs. 30 g C kg -1 soil) but dissolved organic carbon (120 vs. 74 mg C kg -1 soil) and microbial biomass carbon were lower (413 vs. 246 mg C kg -1 soil) in Plot 2 compared to the Plot 1. Based on 13 C natural abundance, we found that in Plot 2, carbon flow was dominated from micro- (<0.25 mm) to macroaggregates (0.25-2 and >2 mm), whereas in Plot 1, carbon flow occurred between large and small macroaggregates, and from micro-to macroaggregates. Thus, long-term application of biodegradable film changed the abundance of microplastics, and organic carbon accumulation compared to conventional polyethylene film mulching., 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: Causal association between chronic obstructive pulmonary disease (COPD) and heart failure (HF) has been controversial. This study used Mendelian Randomization (MR) analysis to clarify the potential causal connection between these two conditions., Objectives: The purpose of the study was to investigate the causal relationship between COPD and HF based on the hypothesis that the genetic predisposition to COPD could lead to an increased risk of developing HF METHODS: A two-sample MR analysis of genetic data was performed for COPD and HF. This study was based on genome-wide association study (GWAS) data, including 6,915 patients with confirmed COPD and 186,723 controls. The odds ratios (ORs) and their 95 % confidence intervals (95 %CIs) were estimated using a fixed effects inverse variance weighting (IVW) method. Several supplementary statistical methods, including MR-Egger, weighted median, maximum likelihood, penalized weighted median, and random effects IVW, were applied to enhance the robustness of findings. Moreover, MR-PRESSO was employed as an alternative method for statistical detection., Results: Pooled data for HF were obtained from different GWASs, including 4,7309 confirmed HF patients and 930,014 controls. The MR analysis, based on the IVW model, revealed that COPD was significantly associated with an increased risk of HF. Specifically, the obtained findings showed that COPD patients had a higher risk of developing HF (Model 1: OR = 1.068, 95 %CI: 1.006-1.134, p = 0.031; Model 2: OR = 1.038, 95 %CI: 1.006-1.071, p = 0.020), indicating a causal relationship between COPD and HF. No evidence was found to suggest a reverse causal effect of HF on COPD incidence., Conclusion: The MR analysis substantiates a causal link between COPD and HF, with no evidence supporting a reverse causation from HF to COPD. These findings underscore the importance of proactive COPD management as a potential strategy to prevent the development of HF, highlighting the need for targeted interventions in patients with COPD to mitigate their risk of HF., 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. Published by Elsevier Inc.)

The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para-lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH., (© 2024 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are crucial for properties of synaptic plasticity, such as long-term potentiation (LTP). LTP impairment can occur early in the onset of Alzheimer's disease (AD). The downregulation or decreased abundance of AMPAR expression in the postsynaptic membrane is closely associated with LTP impairment. Ceftriaxone (Cef) can improve LTP impairment in the early stages of AD in a mouse model. The purpose of this study was to explore the mechanism underlying this process from the aspects of AMPAR expression and ubiquitination degree. In this study, we found that β-amyloid (Aβ) treatment induced hippocampal LTP impairment and AMPAR downregulation and ubiquitination. Cef pretreatment ameliorated Aβ-induced hippocampal LTP impairment, reduced AMPAR ubiquitination, and increased AMPAR expression, especially in the plasma membrane, in Aβ-treated mice. Administration of USP46 siRNA and DHK (a specific blocker of glutamate transporter-1) significantly inhibited the above effects of Cef, suggesting a role for anti-AMPAR ubiquitination and upregulation of glutamate transporter-1 (GLT-1) in the Cef-induced improvements mentioned above. The above findings demonstrate that pretreatment with Cef effectively mitigated Aβ-induced impairment of hippocampal LTP by suppressing the ubiquitination process of AMPARs in a GLT-1-dependent manner. These results provide novel insights into the underlying mechanisms elucidating the anti-AD by Cef., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Obesity is associated with the incidence and poor prognosis of thyroid cancer, but the mechanism is not fully understood. The aim of this study was to investigate the effects of human adipose-derived stem cells (ADSCs) on the invasion and migration of thyroid cancer cells., Methods: ADSCs-conditioned medium (ADSC-CM) was collected to culture thyroid cancer cell lines TPC-1 cells and BCPAP cells. The effects of ADSCs on thyroid cancer cell proliferation were determined by CCK8 and EdU assays, and the effects on migration were determined by Transwell and wound closure assays. Leptin neutralizing antibodies (NAB) were added to ADSC-CM to block leptin. In animal experiments, TPC-1 cells and BCPAP cells were injected into the tail vein of nude mice, and the leptin receptor antagonist peptide allo-aca was injected subcutaneously to block the leptin pathway. The number and size of metastatic lung tumours were observed after 8 weeks., Results: ADSC-CM significantly promoted the invasion and migration of thyroid cancer cells and upregulated their matrix metalloproteinase 2 (MMP-2) levels, while NAB with the addition of leptin reduced the invasion and migration of thyroid cancer cells and downregulated MMP-2 levels. Allo-aca treatment reduced the number of metastatic lung nodules formed by thyroid cancer cells in nude mice and reduced the diameter of metastatic lesions., Conclusion: ADSCs upregulate MMP-2 levels of thyroid cancer cells through exocrine leptin, thereby promoting cancer cell migration, which may be one of the key mechanisms by which obesity increases the invasiveness of thyroid cancer.

To plant crops (especially dry crops such as water spinach) with concomitant electricity recovery, a hanging-submerged-plant-pot system (HSPP) is developed. The HSPP consists of a soil pot (anodic) partially submerged under the water surface of a cathode tank. The microbial communities changed with conditions were also investigated. It was found that with chemical fertilizers the closed-circuit voltage (CCV, with 1 kΩ) was stable (approximately 250 mV) within 28 d; however, without fertilizer, the water spinach could adjust to the environment to obtain a better power output (approximately 3 mW m -2 ) at day 28. The microbial-community analyses revealed that the Pseudomonas sp. was the only exoeletrogens found in the anode pots. Using a secondary design of HSPP, for a better water-level adjustment, the maximum power output of each plant was found to be approximately 27.1 mW m -2 . During operation, high temperature resulted in low oxygen solubility, and low CCV as well. At this time, it is yet to be concluded whether the submerged water level significantly affects electricity generation., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is characterized by progressive motor neuron degeneration, leading to widespread weakness and respiratory failure. While a variety of mechanisms have been proposed as causes of this disease, a full understanding remains elusive. Electrophysiological alterations, including increased motor axon excitability, likely play an important role in disease progression. There remains a critical need for non-animal disease models that can integrate electrophysiological tools to better understand underlying mechanisms, track disease progression, and evaluate potential therapeutic interventions. This review explores the integration of electrophysiological technologies with ALS disease models. It covers cellular and clinical electrophysiological tools and their applications in ALS research. Additionally, we examine conventional animal models and highlight advancements in humanized models and 3D organoid technologies. By bridging the gap between these models, we aim to enhance our understanding of ALS pathogenesis and facilitate the development of new therapeutic strategies., Competing Interests: SR has equity in and serves as a consultant and scientific advisor to Myolex, Inc and Haystack Diagnostics, companies that design impedance devices for clinical and research use; he is also a member of Myolex’s Board of Directors. The companies also have an option to license patented impedance technology of which SR is named as an inventor. The remaining 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 Ren, Wang, Jiang, Liu, Alsmaan, Jiang, Rutkove and Tian.)

Introduction: The association of air pollution with bone mineral density (BMD) has attracted increasing attention. However, establishing a causal relationship remains uncertain., Methods: We conducted a Mendelian randomization (MR) study employing PM 2.5 , PM 2.5-10 , PM 10 , nitrogen dioxide, and nitrogen oxides as exposures and BMD as the outcome to explore the causality between air pollution and the occurrence of decreased BMD., Results: By employing the IVW method, we identified a negative causality between air pollution (PM 2.5 , PM 10 , and nitrogen oxides) and BMD., Conclusions: Our findings demonstrate that PM 2.5 , PM 10 and nitrogen oxides exposure may contribute to decreased BMD., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

Mixed forests often increase their stability and species richness in comparison to pure stands. However, a comprehensive understanding of the effects of mixed forests on soil properties, bacterial community diversity, and soil nitrogen cycling remains elusive. This study investigated soil samples from pure Robinia pseudoacacia stands, pure Quercus variabilis stands, and mixed stands of both species in the southern foothills of the Taihang Mountains. Utilizing high-throughput sequencing and real-time fluorescence quantitative PCR, this study analyzed the bacterial community structure and the abundance of nitrogen-cycling functional genes within soils from different stands. The results demonstrated that Proteobacteria, Acidobacteria, and Actinobacteria were the dominant bacterial groups across all three forest soil types. The mixed-forest soil exhibited a higher relative abundance of Firmicutes and Bacteroidetes, while Nitrospirae and Crenarchaeota were most abundant in the pure R . pseudoacacia stand soils. Employing FAPROTAX for predictive bacterial function analysis in various soil layers, this study found that nitrogen-cycling processes such as nitrification and denitrification were most prominent in pure R . pseudoacacia soils. Whether in surface or deeper soil layers, the abundance of AOB amoA , nirS , and nirK genes was typically highest in pure R . pseudoacacia stand soils. In conclusion, the mixed forest of R . pseudoacacia and Q . variabilis can moderate the intensity of nitrification and denitrification processes, consequently reducing soil nitrogen loss.

Cardiac development requires precise gene expression programs at each developmental stage guided by multiple signaling pathways and transcription factors (TFs). MESP1 is transiently expressed in mesoderm, and is essential for subsequent cardiac development, while the precise mechanism regulating its own transcription and mesoderm cell fate is not fully understood. Therefore, we developed a high content screen assay to identify regulators of MESP1 expression in mesodermal cells differentiated from human pluripotent stem cells (hPSCs). The screen identified CYT387, a JAK1/JAK2 kinase inhibitor, as a potent activator of MESP1 expression, which was also found to promote cardiomyocyte differentiation in vitro. Mechanistic studies found that JAK inhibition promotes MESP1 expression by reducing cytoplasmic calcium concentration and subsequently activating canonical WNT signaling. Our study identified a role of JAK signaling in early mesodermal cells, and sheds light on the connection between the JAK-STAT pathway and transcriptional regulation of MESP1, which expands our understanding of mesoderm and cardiac development., 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 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: For medical diagnosis, clinicians typically begin with a patient's chief concerns, followed by questions about symptoms and medical history, physical examinations, and requests for necessary auxiliary examinations to gather comprehensive medical information. This complex medical investigation process has yet to be modeled by existing artificial intelligence (AI) methodologies., Objective: The aim of this study was to develop an AI-driven medical inquiry assistant for clinical diagnosis that provides inquiry recommendations by simulating clinicians' medical investigating logic via reinforcement learning., Methods: We compiled multicenter, deidentified outpatient electronic health records from 76 hospitals in Shenzhen, China, spanning the period from July to November 2021. These records consisted of both unstructured textual information and structured laboratory test results. We first performed feature extraction and standardization using natural language processing techniques and then used a reinforcement learning actor-critic framework to explore the rational and effective inquiry logic. To align the inquiry process with actual clinical practice, we segmented the inquiry into 4 stages: inquiring about symptoms and medical history, conducting physical examinations, requesting auxiliary examinations, and terminating the inquiry with a diagnosis. External validation was conducted to validate the inquiry logic of the AI model., Results: This study focused on 2 retrospective inquiry-and-diagnosis tasks in the emergency and pediatrics departments. The emergency departments provided records of 339,020 consultations including mainly children (median age 5.2, IQR 2.6-26.1 years) with various types of upper respiratory tract infections (250,638/339,020, 73.93%). The pediatrics department provided records of 561,659 consultations, mainly of children (median age 3.8, IQR 2.0-5.7 years) with various types of upper respiratory tract infections (498,408/561,659, 88.73%). When conducting its own inquiries in both scenarios, the AI model demonstrated high diagnostic performance, with areas under the receiver operating characteristic curve of 0.955 (95% CI 0.953-0.956) and 0.943 (95% CI 0.941-0.944), respectively. When the AI model was used in a simulated collaboration with physicians, it notably reduced the average number of physicians' inquiries to 46% (6.037/13.26; 95% CI 6.009-6.064) and 43% (6.245/14.364; 95% CI 6.225-6.269) while achieving areas under the receiver operating characteristic curve of 0.972 (95% CI 0.970-0.973) and 0.968 (95% CI 0.967-0.969) in the scenarios. External validation revealed a normalized Kendall τ distance of 0.323 (95% CI 0.301-0.346), indicating the inquiry consistency of the AI model with physicians., Conclusions: This retrospective analysis of predominantly respiratory pediatric presentations in emergency and pediatrics departments demonstrated that an AI-driven diagnostic assistant had high diagnostic performance both in stand-alone use and in simulated collaboration with clinicians. Its investigation process was found to be consistent with the clinicians' medical investigation logic. These findings highlight the diagnostic assistant's promise in assisting the decision-making processes of health care professionals., (©Xuan Zou, Weijie He, Yu Huang, Yi Ouyang, Zhen Zhang, Yu Wu, Yongsheng Wu, Lili Feng, Sheng Wu, Mengqi Yang, Xuyan Chen, Yefeng Zheng, Rui Jiang, Ting Chen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.08.2024.)

Amidst growing skepticism towards globalization and rising digital trade, this study investigates the impact of Restrictions on Cross-Border Data Flows (RCDF) on Domestic Value Chains (DVCs) stability. As global value chains participation declines, the stability of DVCs-integral to internal economic dynamics-becomes crucial. This study situates within a framework exploring the role of innovation and RCDF in the increasingly interconnected global trade. Using a panel data fixed effect model, our analysis provides insights into the varying effects of RCDF on DVCs stability across countries with diverse economic structures and technological advancement levels. This approach allows for a nuanced understanding of the interplay between digital trade policies, value chain stability, and innovation. RCDF tend to disrupt DVCs by negatively impacting innovation, which necessitates proactive policy measures to mitigate these effects. In contrast, low-income countries experience a less detrimental impact; RCDF may even aid in integrating their DVCs into Global Value Chains, enhancing economic stability. It underscores the need for dynamic, adaptable policies and global collaboration to harmonize digital trade standards, thus offering guidance for policy-making in the context of an interconnected global economy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Irritable bowel syndrome (IBS) significantly impacts individuals due to its prevalence and negative effect on quality of life. Current genome-wide association studies (GWAS) have only identified a small number of crucial single nucleotide polymorphisms (SNPs), not fully elucidating IBS's pathogenesis., Objective: To identify genomic loci at which common genetic variation influence IBS susceptibility., Methods: Combining independent cohorts that in total comprise 65,840 cases of IBS and 788,652 controls, we performed a meta-analysis of genome-wide association studies (GWAS) of IBS. We also carried out gene mapping and pathway enrichment to gain insights into the underlying genes and pathways through which the associated loci contribute to disease susceptibility. Furthermore, we performed transcriptome analysis to deepen our understanding. IBS risk models were developed by combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. We detect the phenotype association for IBS utilizing PRS-based phenome-wide association (PheWAS) analyses, linkage disequilibrium score regression, and Mendelian randomization., Results: The GWAS meta-analysis identified 10 IBS risk loci, seven of which were novel (rs12755507, rs34209273, rs34365748, rs67427799, rs2587363, rs13321176, rs1546559). Multiple methods identified nine promising IBS candidate gene (PRRC2A, COP1, CADM2, LRP1B, SUGT1, MED12L, P2RY14, PHF2, SHISA6) at 10 GWAS loci. Transcriptome validation also revealed differential expression of these genes. Phenome-wide associations between PRS-IBS and nine traits (neuroticism, diaphragmatic hernia, asthma, diverticulosis, cholelithiasis, depression, insomnia, COPD, and BMI) were identified. The six diseases (asthma, diaphragmatic hernia, diverticulosis, insomnia major depressive disorder and neuroticism) were found to show genetic association with IBS and only major depressive disorder and neuroticism were found to show causality with IBS., Conclusion: We identified seven novel risk loci for IBS and highlight the substantial influence on genetic risk harboured. Our findings offer novel insights into aetiology and phenotypic association of IBS and lay the foundation for therapeutic targets and interventional strategies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A universal coordinate system that can ensemble the huge number of cells and capture their heterogeneities is of vital importance for constructing large-scale cell atlases as references for molecular and cellular studies. Studies have shown that cells exhibit multifaceted heterogeneities in their transcriptomic features at multiple resolutions. This nature of complexity makes it hard to design a fixed coordinate system through a combination of known features. It is desirable to build a learnable universal coordinate model that can capture major heterogeneities and serve as a controlled generative model for data augmentation. We developed UniCoord, a specially-tuned joint-VAE model to represent single-cell transcriptomic data in a lower-dimensional latent space with high interpretability. Each latent dimension can represent either discrete or continuous feature, and either supervised by prior knowledge or unsupervised. The latent dimensions can be easily reconfigured to generate pseudo transcriptomic profiles with desired properties. UniCoord can also be used as a pre-trained model to analyze new data with unseen cell types and thus can serve as a feasible framework for cell annotation and comparison. UniCoord provides a prototype for a learnable universal coordinate framework to enable better analysis and generation of cells with highly orchestrated functions and heterogeneities., (© 2024. The Author(s).)

Background: The mechanism by which a state of low testosterone leads to erectile dysfunction (ED) has not been determined. Endocan is a novel marker of endothelial function. However, whether endocan is involved in the regulation of erectile function under low testosterone levels remains unclear., Aim: In this study we sought to determine whether a low-testosterone state inhibits erectile function by regulating endocan expression in the endothelial cells of the rat penile corpus cavernosum., Methods: Thirty-six male Sprague-Dawley rats aged 8 weeks were randomly assigned to 6 groups (n = 6 per group) as follows: (1) control, (2) castration, (3) castration + testosterone treatment (treated with 3 mg/kg testosterone propionate per 2 days), (4) control + transfection (4 weeks after castration, injected with lentiviral vector (1 × 108 transduction units/mL, 10 μL), (5) castration + transfection, or (6) castration + empty transfection. One week after the injection, we measured the maximal intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone and nitric oxide (NO) levels, and the expression of endocan, phospho-endothelial NO synthase (p-eNOS), eNOS, phospho-protein kinase B (p-AKT), and AKT in the rat penile corpus cavernosum., Outcomes: Under a low-androgen state, the expression of endocan in the rat penile corpus cavernosum was significantly increased, which inhibited the AKT/eNOS/NO signaling pathway and resulted in ED., Results: In the castration group, the expression of endocan in the rat penile corpus cavernosum was significantly higher than that in the control group (P < .05). Additionally, the levels of p-AKT/AKT, p-eNOS/eNOS, and NO in the rat penile corpus cavernosum and ICPmax/MAP were significantly lower in the castration group than in the control group (P < .05). In the castration + transfection group compared with the castration group there was a significant decrease in the expression of endocan (P < .05) and an increase in the ratios of p-AKT/AKT, p-eNOS/eNOS, and ICPmax/MAP (P < .05) in the rat penile corpus cavernosum., Clinical Implications: Downregulating the expression of endocan in the penile corpus cavernosum may be a feasible approach for treating ED caused by hypoandrogenism., Strengths and Limitations: The results of this study indicte that endocan may affect NO levels and erectile function through multiple signaling pathways, but further experiments are needed to clarify the relationship between endocan and androgens., Conclusion: A low-testosterone state inhibits the AKT/eNOS/NO signaling pathway by increasing the expression of endocan in the rat penile corpus cavernosum and impairing erectile function in rats. Decreasing the expression of endocan in the penile corpus cavernosum can improve erectile function in rats with low testosterone levels., (© Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diabetes mellitus commonly causes endothelial cell and smooth muscle cell death in penile cavernous tissue., Aim: The study sought to study the mode of cell death in the penile cavernous tissue in type 1 diabetic rats., Methods: A total of 36 Sprague Dawley rats 10 weeks of age were randomly divided into 2 groups: a normoglycemic group and type 1 diabetic group (intraperitoneal injection of Streptozotocin (STZ), 60 mg/kg). We randomly selected 6 rats from each group for tests at the end of 11, 14, and 18 weeks of age, respectively. All rats were able to eat and drink freely. The ratio of maximum intracavernous pressure to mean arterial pressure, concentration of serum testosterone, level of nitric oxide in the penile cavernosum, and expression of active caspase-1 (pyroptosis) and active caspase-3 (apoptosis) were determined., Outcomes: At the end of weeks 4 and 8 of type 1 diabetes, the proportions of endothelial cells and smooth muscle cells undergoing apoptosis and pyroptosis in penile cavernous tissue are different., Results: The ratio of maximum intracavernous pressure to mean arterial pressure and nitric oxide levels were significantly lower in the 4- and 8-week diabetic groups than in the normoglycemic group (P < .01). Penile endothelial cell pyroptosis (5.67 ± 0.81%), smooth muscle cell apoptosis (23.72 ± 0.48%), total cell pyroptosis (9.67 ± 0.73%), and total apoptosis (10.52 ± 1.45%) were significantly greater in the 4-week diabetic group than in the normoglycemic group (P < .01). The proportion of endothelial cell pyroptosis (24.4 ± 3.69%), endothelial cell apoptosis (22.13 ± 2.43%), total cell pyroptosis (14.75 ± 0.93%), and total apoptosis (14.82 ± 1.08%) in the penile tissues of the 8-week diabetic group were significantly greater than those in the normoglycemic group (P < .01).The 8-week survival proportions of diabetic endothelial cells (38.86 ± 8.85%) and smooth muscle cells (44.46 ± 2.94%) was significantly lower than the 4-week survival proportions of endothelial cells (93.17 ± 8.07%) and smooth muscle cells (75.12 ± 4.76%) (P < .05)., Clinical Translation: Inhibition of cell death by different methods at different stages may be the key to the treatment of type 1 diabetes-induced erectile dysfunction., Strengths and Limitations: The effect of type 1 diabetes on other types of cell death in penile cavernous tissue needs further study., Conclusion: The mode of death of endothelial cells in the cavernous tissue of the penis in the early stage in diabetic rats is dominated by pyroptosis, and the death of smooth muscle cells is dominated by apoptosis. Endothelial cell and smooth muscle cell death are not consistent at different stages of diabetes progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)