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Extracellular lysophosphatidate and sphingosine 1-phosphate (S1P) are important bioactive lipids, which signal through G-protein-coupled receptors to stimulate cell growth and survival. The lysophosphatidate and S1P signals are terminated partly by degradation through three broad-specificity lipid phosphate phosphatases (LPPs) on the cell surface. Significantly, the expression of LPP1 and LPP3 is decreased in many cancers, and this increases the impact of lysophosphatidate and S1P signaling. However, relatively little is known about the physiological or pharmacological regulation of the expression of the different LPPs. We now show that treating several malignant and nonmalignant cell lines with 1 μg/ml tetracycline, doxycycline, or minocycline significantly increased the extracellular degradation of lysophosphatidate. S1P degradation was also increased in cells that expressed high LPP3 activity. These results depended on an increase in the stabilities of the three LPPs and increased expression on the plasma membrane. We tested the physiological significance of these results and showed that treating rats with doxycycline accelerated the clearance of lysophosphatidate, but not S1P, from the circulation. However, administering 100 mg/kg/day doxycycline to mice decreased plasma concentrations of lysophosphatidate and S1P. This study demonstrates a completely new property of tetracyclines in increasing the plasma membrane expression of the LPPs.

Autotaxin (ATX) is a secreted enzyme, which produces extracellular lysophosphatidate (LPA) from lysophosphatidylcholine (LPC). LPA activates six G protein-coupled receptors and this is essential for vasculogenesis during embryonic development. ATX is also involved in wound healing and inflammation, and in tumor growth, metastasis, and chemo-resistance. It is, therefore, important to understand how ATX is regulated. It was proposed that ATX activity is inhibited by its product LPA, or a related lipid called sphingosine 1-phosphate (S1P). We now show that this apparent inhibition is ineffective at the high concentrations of LPC that occur in vivo. Instead, feedback regulation by LPA and S1P is mediated by inhibition of ATX expression resulting from phosphatidylinositol-3-kinase activation. Inhibiting ATX activity in mice with ONO-8430506 severely decreased plasma LPA concentrations and increased ATX mRNA in adipose tissue, which is a major site of ATX production. Consequently, the amount of inhibitor-bound ATX protein in the plasma increased. We, therefore, demonstrate the concept that accumulation of LPA in the circulation decreases ATX production. However, this feedback regulation can be overcome by the inflammatory cytokines, TNF-α or interleukin 1β. This enables high LPA and ATX levels to coexist in inflammatory conditions. The results are discussed in terms of ATX regulation in wound healing and cancer.

Lipid phosphate phosphatase-1 (LPP1) degrades lysophosphatidate (LPA) and attenuates receptor-mediated signaling. LPP1 expression is low in many cancer cells and tumors compared with normal tissues. It was hypothesized from studies with cultured cells that increasing LPP1 activity would decrease tumor growth and metastasis. This hypothesis has never been tested in vivo. To do this, we inducibly expressed LPP1 or a catalytically inactive mutant in cancer cells. Expressing active LPP1 increased extracellular LPA degradation by 5-fold. It also decreased the stimulation of Ca2+ transients by LPA, a nondephosphorylatable LPA1/2 receptor agonist and a protease-activated receptor-1 peptide. The latter results demonstrate that LPP1 has effects downstream of receptor activation. Decreased Ca2+ mobilization and Rho activation contributed to the effects of LPP1 in attenuating the LPA-induced migration of MDA-MB-231 breast cancer cells and their growth in 3D culture. Increasing LPP1 expression in breast and thyroid cancer cells decreased tumor growth and the metastasis by up to 80% compared with expression of inactive LPP1 or green fluorescent protein in syngeneic and xenograft mouse models. The present work demonstrates for the first time that increasing the LPP1 activity in three lines of aggressive cancer cells decreases their abilities to produce tumors and metastases in mice.

Metal-tolerant microbes with plant growth-promoting traits represent a promising biological amendment for enhancing the phytostabilization of contaminated soils. However, the relationship between phytostabilization efficiency and microbial consortium composition and diversity remains unclear. This study selected three cadmium (Cd) resistant plant growth promoting bacteria (PGPB) from Bacillus, Pseudomonas, and Rhodopseudomonas were selected as candidates for biochar-based microbial inoculants. In our pot experiment with single, dual, and triple inoculations, a more diverse microbial consortium significantly increased root Cd accumulation and aboveground biomass. Triple inoculation boosted root Cd accumulation by 56.4 %-121.5 % and belowground biomass by 4.8 %-46.2 %, compared to dual and single inoculations. However, this trend was not observed in the aboveground parts of the plants, resulting in a decrease in the translocation factor of Cd in ryegrass. Microbial inoculation altered the structure of the rhizosphere bacterial community, especially the triple microbial inoculation treatment, which showed significant differences compared to the other treatment groups. However, there were no significant changes in alpha diversity. Increased soil pH and its positive interaction with soil enzymes significantly contributed to the phytostabilization efficiency of biochar-based microbial inoculation, whereas the contribution of rhizosphere bacterial communities was much less significant. In summary, metal-tolerant PGPB inoculation can promote phytostabilization efficiency and enhance metal immobilization in soil, reducing their threat to organisms and the environment., 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.)

Cadmium has been identified as an environmental pollutant and a carcinogen. N 6 -methyladenosine (m 6 A) plays a crucial role in the development of lung tumors, but the mechanisms remain incompletely clarified. In present study, our data demonstrated that prolonged treatment of 1 μmol/L CdSO 4 for 40 passages in bronchial epithelial cells (Beas-2B cells) resulted in the development of a malignant phenotype, which manifested as boosted proliferation, migration and invasion capacity as well as apoptosis reduction. Proteomic assay revealed that in passage 40 cells, 350 proteins showed differentially expressed in comparison to control, and these proteins were primarily enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of "pathways in cancer" and "Chemical carcinoma-reactive oxygen species". Moreover, the mRNAs of Nuclear factor kappa B (NF-κB) p65 and NAD(P)H: quinone oxidoreductase 1 (NQO1), the key signaling molecules in these two signaling pathways, were predicted to contain m 6 A modification sites with high confidence. The subsequent experimental results indicated that levels of m 6 A and Fat mass and obesity associated protein (FTO) elevated, while Alkylated DNA repair protein alkB homolog 5 (ALKBH5) and YTH Domain Containing Protein 2 (YTHDC2) reduced with the increasing of cadmium treatment generations. Furthermore, the reduction of m 6 A levels by 3-deazide adenosine (DAA, m 6 A inhibitor) was found to significantly inhibit malignant characteristics of cadmium-induced cells, activate molecules involved in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, and inhibit the activity of NF-κB. It is also noteworthy that the results based on animals indicate that the relevant indicators and biological changes are partially similar to cell experiments. In detail, m 6 A modification levels in lung tissue were observed to increase while the expressions of FTO, ALKBH5 and YTHDC2 were found to drop. Additionally, immunofluorescence examination illustrated the co-localization of the m 6 A regulatory proteins FTO and YTHDC2 with NF-κB. The presented data collectively suggest that chronic cadmium treatment may impact the m 6 A level through influencing regulatory proteins, which could potentially trigger oxidative stress and apoptosis by regulating transcription factors such as NF-κB and NRF2. In conclusion, our study provides a scientific foundation for understanding cadmium toxicity and offers novel insights for treating cadmium-induced lung diseases., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: (a) All methods in the manuscript were performed in accordance with the relevant guidelines and regulations. (b) The animal tests were approved by Dali University’s Experimental Animal Ethics Committee (approval NO. 2023-P2-204). (c) The informed consent of all participants: Not applicable. Consent for publication: Consent for publication of the article has been obtained from all participants., (© 2025. The Author(s).)

Identification of the pollution source of surface water in a chemical park was difficult because many industrial enterprises with complex wastewater components and similar characteristics are located there. Therefore, a national-level chemical park in Jiaxing City was studied, and wastewater samples from ten batches of seven key enterprises in the park were collected and analyzed using 3D excitation emission matrix spectrometry （EEMS） and gas chromatography-mass spectrometry （GC-MS）. Parallel factor analysis was used to extract common components of EEMS spectra from different batches of drainage in the same enterprise to construct an EEMS characteristic data matrix. Furthermore, specific substances with high detection rates or that could effectively distinguish other enterprise drainage were screened out from the GC-MS data to construct a GC-MS characteristic data matrix. Pollution source identification was attempted with different models based on different data matrices. The results showed that regardless of whether being based on the EEMS original data matrix, the EEMS characteristic data matrix, or the GC-MS characteristic data matrix, the identification accuracy of the BP neural network model was not high, only 71.43%, 76.19%, and 71.43%, respectively, which was slightly higher than that of the support vector machine model （76.19%, 76.19%, and 57.14%）. However, when the EEMS and GC-MS characteristic data fusion matrix were used, the pollution source identification performance was significantly improved. The identification accuracy, macro precision, macro recall, and macro harmonic mean of the support vector machine model for the wastewater of the seven enterprises were 95.24%, 96.43%, 95.24%, and 95.10%, respectively, while the performance of the BP neural network model was better, with all four indicators close to 100%. The study provides an effective method for identifying surface water pollution sources in chemical parks.

Red soil occupies an important position in China's agriculturally cultivated land resources. However, its low pH value, high aluminum concentration, and inefficient phosphorus utilization limit the productivity of acidic red soil farmland. Plant roots exhibit remarkable plasticity, capable of absorbing water and nutrients and modulating root system architecture in response to biotic and abiotic stresses, either autonomously or through rhizosphere microorganisms. This study primarily investigates the regulatory effects of rhizosphere microorganisms, including plant growth-promoting rhizobacteria, such as arbuscular mycorrhizal fungi and rhizobia, and synthetic microbial consortia, on plant root system architecture. These regulatory mechanisms encompass the production of hormones, the release of volatile organic compounds, nitrogen fixation, phosphorus solubilization, and the improvement of rhizospheric soil structure. Such mechanisms can influence root biomass, branching, lateral roots, and root hair growth. Furthermore, we summarize new visualization methods for plant root system architecture and rhizosphere microorganisms, providing technical support for studying the regulation of root system architecture by rhizosphere microbes. Under acidic soil conditions, rhizosphere microorganisms serve as a crucial regulatory strategy. By adjusting plant root system architecture, they can enhance the productivity of acidic soils, representing a potential solution for ameliorating the constraints of acidic soils.

Aims: Obesity, as a worldwide healthcare problem, has become more prevalent. ZFP36 is a well-known RNA-binding protein and involved in the posttranscriptional regulation of many physiological processes. Whether the adipose ZFP36 plays a role in obesity and insulin resistance remains unclear., Methods: The expression levels of ZFP36 were analyzed in adipose tissues of obese patients, diet-induced obese mice, ob/ob mice and db/db mice. To determine whether adipose ZFP36 protects against the diet-induced obesity, we generated adipose-specific ZFP36 knockout (ZFP36 AKO ) mice, which were subjected to high-fat-diet (HFD) for 16 weeks. To explore the specific molecular mechanisms of ZFP36 regulating metabolic disorders, we used gene array assay of control and ZFP36-deficient adipose tissue, and assessed the pathways in vitro and vivo., Results: Western blotting and RT-PCR were performed to determine the downregulating level of ZFP36 in adipose tissues of obese patients, diet-induced obese mice, ob/ob mice and db/db mice. Relative to control mice, ZFP36 AKO mice were more susceptible to HFD-induced obesity, along with insulin resistance, glucose tolerance, and increased metabolic disorders. The obesity of ZFP36 AKO mice was attributed to hypertrophy of adipocytes in white adipose tissue via decreased expression of Perilipin1 (PLIN1), adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL). We discovered that ZFP36 oppositely regulated RNF128 expression by repressing the mRNA stability and translation of RNF128, a negative regulator of Sirt1 expression., Conclusions: This study suggests that ZFP36 in adipose tissue plays an important role in diet-induced obesity, and identifies a novel molecular signaling pathway of ZFP36/RNF128/Sirt1 involved in obesity., Competing Interests: Declaration of competing interest The authors declare to have no conflict of interest in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Green electricity-driven alkenol electrosynthesis via electrocatalytic alkynol semihydrogenation represents a sustainable route to conventional thermocatalysis. Both the electrocatalyst and electrolyte strongly impact the semihydrogenation performance. Despite significant progress in developing sophisticated electrocatalysts, a well-designed electrolyte in conjunction with industrial catalysts is an attractive strategy to advance the industrialization process of electrocatalytic alkynol semihydrogenation, but remains unexplored. Here, we develop a dimethyl sulfoxide (DMSO)-H 2 O cosolvent electrolyte for electrocatalytic alkynol semihydrogenation. At an alkynol conversion of about 100%, the DMSO-H 2 O electrolyte compared to the DMSO-free counterpart enables the alkenol selectivity on Cu catalysts to be promoted from 60-70% to over 90% at all measured current densities; meanwhile, the reaction rate is slightly decreased due to the inhibited water dissociation. Mechanistic studies reveal that the strong hydrogen-bond interactions between DMSO and H 2 O suppress the dissociation of interfacial H 2 O, leading to a decreased H* coverage at the electrode surface. The decreased H* coverage hinders the overhydrogenation of alkynols and favors the production of alkenols. Remarkably, the DMSO-induced enhancement of alkenol selectivity is applicable to a set of commercial catalysts and to the semihydrogenation of various alkynols. Eventually, a scaled-up 3 × 100 cm 2 electrolyzer stack is established to achieve an alkynol conversion of ∼96% and an alkenol selectivity of ∼95% in the cosolvent electrolyte. This work not only presents an electrolyte strategy for boosting alkenol electrosynthesis, but also highlights the possibility of sustainable alkenol electro-production.

Although N 6 -methyladenosine (m 6 A) and its regulatory proteins were involved in multiple cellular damage processes, the roles of m 6 A and its regulatory proteins in cadmium-induced pulmonary cell damage remain largely unknown. Our present data indicated that cadmium exposure caused serious damage in bronchial epithelial cells, as evidenced by reduction of cell viability and elevation of oxidative damage and apoptosis. These processes were accompanied by alterations of m 6 A modification and its regulatory proteins (FTO, ALKBH5, YTHDC2). It is noteworthy that pretreatment with the m 6 A agonist entacapone (ENT) markedly attenuated the detrimental effects of cadmium, including cell death, oxidative damage, and the activation of the nuclear factor erythroid 2-related factor 2 (NRF2）signalling pathway. Conversely, the detrimental effects of CdSO 4 were significantly exacerbated when m 6 A levels were inhibited by 3-deazidyladenosine (DAA). Further prediction result revealed that multiple m 6 A-modified sites occur on NRF2 mRNA with high confidence level, implicating that m 6 A modification on NRF2 mRNA may affect the protein expression of NRF2. In conclusion, our data together suggest that m 6 A modification play critical roles in cadmium-induced bronchial epithelial cell damage, during which NRF2 signaling pathway may act as an important bridge for m 6 A modification to regulate cellular damage. This study offer a promising avenue for further investigation into the mechanisms underlying cadmium-induced bronchial epithelial cell damage from the perspective of RNA epigenetics., 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.)

Coxsackievirus A6 (CVA6) is a primary pathogen associated with hand, foot, and mouth disease (HFMD) and is typified by fever, rashes or herpetic lesions at distinct locations. Although HFMD patients exhibit mild symptoms, a subset of patients may develop severe complications, such as viral encephalitis, myocarditis, pneumonia, and neurological disorders. However, in addition to rodent models, such as the CVA6-infected mouse model, no definitive nonhuman primate animal model or related research or analysis tool is available, which makes the development of suitable nonhuman primate animal models particularly crucial. In this study, 3- to 4-month-old rhesus monkeys were infected via the respiratory or digestive tract, and the pathogenic, pathological, and immunological alterations following CVA6 infection were investigated. The results revealed that the infected rhesus monkeys exhibited symptoms similar to those of patients, including signs of HFMD, blood cell changes, viremia, viral excretion, and inflammatory reactions during the acute phase (1-11 days). Pathological observations revealed inflammatory reactions in the intestinal and lymph node tissues. Notably, the acute symptoms gradually waned in the recovery phase (12-120 days), and a high level of neutralizing antibodies was sustained. Intriguingly, no significant disparity was observed between the infections initiated via the respiratory or digestive tract in terms of clinical symptoms, hemogram results or virus shedding. Overall, this study yielded a comprehensive dataset regarding the physiological, pathological, and immunological outcomes of CVA6 infection in a primate host, enhancing our comprehension of the mechanism of CVA6 infection and providing essential data for related vaccine and drug 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 Elsevier Inc. All rights reserved.)

Organic fouling and biofouling represents a critical challenge encountered by the membrane-based water treatment process. Herein, a piezoelectric PVDF membrane (PEM), capable of generating electrical responses to hydraulic pressure stimuli, was synthesized and employed for mitigating the fouling in surface water treatment. The surface-hydrophobilized PEM demonstrated sensitive and enhanced underwater output performance in response to increasing transmembrane pressure (TMP) during constant-flux filtration, with signals reaching up to ∼800 mV at a TMP of ∼80 kPa. This in-situ piezoelectric response significantly reduced TMP growth in both short-term (1 h) and long-term (15 days) filtration trials, demonstrating a strong capability to mitigate membrane fouling. Moreover, continuous piezoelectric stimulation effectively inhibited microbial activity and the accumulation of extracellular polymeric substances (EPS) on PEM surface, surpassing the dominant electrokinetic repulsion mechanisms observed in short-term trials. Microbial community analysis suggests that this evolution is primarily due to the targeted impact of piezoelectric stimulation on microbial metabolic behavior. The piezoelectric-induced electrical microenvironment inhibited the growth of microbes associated with high EPS production while promoting the proliferation of electrically active microbes involved in biopolymer digestion. In addition, the PEM demonstrated enhanced permeate quality throughout the filtration process, with DOC and UV 254 removal rates increasing from 11.7 % and 15.6 % initially to 28.6 % and 19.5 % by the 15th day, respectively. Given the performance and self-powered capability of PEM compared to current electrified antifouling methods that require an external power supply, these attributes are anticipated to hold practical significance in developing innovative and energy-efficient strategies for mitigating both organic fouling and biofouling., 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.)

Regenerated cellulose (RC) films are considered a sustainable packaging material that can replace non-degradable petroleum-based plastics. However, their susceptibility to water vapor and oxygen can limit their effectiveness in protecting products. This study introduces a novel approach for enhancing RC films to create durable, flexible, hydrophobic, high-barrier, and biodegradable packaging materials. By exploring the impact of ascorbic acid coagulation bath treatment and plasma-enhanced chemical vapor deposition (PECVD) on the properties of RC films, we found that the coagulation bath treatment facilitated the organized reconfiguration of cellulose chains, while PECVD applied a dense SiO x coating on the film surface. The results demonstrated a significant enhancement in water vapor and oxygen barrier properties of the composite film, almost reaching the level of commercial barrier films. Moreover, the composite film displayed exceptional biodegradability, fully degrading in soil within 35 days. Additionally, it showcased impressive mechanical strength, hydrophobic characteristics, and freshness preservation, positioning it as a valuable option for bio-based high-barrier packaging 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 Elsevier Inc. All rights reserved.)

Purpose: Medical school educators face challenges determining which new and emerging topics to incorporate into medical school curricula, and how to do so. A study was conducted to gain a better understanding of the integration of emerging topics related to microbiology and immunology in the undergraduate medical curriculum (UME)., Methods: An anonymous survey with 17 questions was emailed to medical school faculty who teach immunology and/or microbiology through the DR-Ed listserv, the American Society for Microbiology (ASM) Connect listserv, and attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop. Participants were asked about experiences, perceptions, and the decision-making process regarding integrating emerging topics into UME., Results: The top emerging topics that were added to the curriculum or considered for addition in the last 10 years included COVID-19, Zika virus, mRNA vaccines, and Mpox (formerly known as monkeypox). Most respondents reported lectures and active learning as the major methods for topic delivery, with most faculty indicating that formative assessment was the best way to assess emerging topics. Content experts and course directors were the most cited individuals making these decisions. Top reasons for incorporating emerging topics into curricula included preparing students for clinical treatment of cases, followed by demonstrating the importance of basic science, and opportunities to integrate basic science into other disciplines. Challenges for incorporating these topics included making room in an already crowded curriculum, followed by content overload for students., Conclusions: This study describes the rationale for integrating emerging topics related to microbiology and immunology into UME, and identifies the current new and emerging topics, as well as the main methods of integration and assessment. These results may be used by medical educators to inform curricular decisions at their institutions. Future studies will include developing innovative learning modules that overcome barriers to integration.

Background: The scholarship of teaching and learning (SoTL) is a field of academic research that focuses on improving learning through reflective and informed teaching. Currently, most SoTL-related work is faculty-driven; however, student involvement in SoTL has been shown to benefit both learners and educators. Our study aims to develop a framework for increasing medical students' interest, confidence, and engagement in SoTL., Methods: A student-led SoTL interest group was developed and a year-round program of SoTL was designed and delivered by student leaders of the group under the guidance of a faculty advisor. Individual post-session surveys were administered to evaluate participants' perceptions of each session. Pre- and post-program surveys were administered to evaluate the program impact., Results: The year-round SoTL program consistently attracted the participation of medical students and faculty. Survey responses indicated strong medical student interest in the program and positive impact of the program. Increased interest and confidence in medical education research were reported by the student participants. The program design provided opportunities for student participants to network and receive ongoing feedback about medical education research they were interested or involved in., Conclusion: Our study provides insights for developing a framework that other institutions can reference and build upon to educate and engage students in SoTL.

Triple-negative breast cancer (TNBC) seriously threatens women's health, and long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play fundamental roles in TNBC. This study aimed to identify lncRNAs that represent effective targets for the early diagnosis or treatment of TNBC. Here, we utilized the TCGA database to analyze differentially expressed genes, and survival analysis and ROC curve analysis were also performed. Notably, we identified a novel lncRNA, AC112721.1, that is significantly overexpressed in TNBC and is associated with poor overall survival in TNBC patients. Loss- and gain-of-function experiments revealed that AC112721.1 significantly promoted cell proliferation and migration, suppressed cell apoptosis in vitro and inhibited tumorigenesis in vivo. Further study of the mechanisms underlying these effects revealed that AC112721.1 regulates the Ras pathway by directly binding to THBS1 protein and functions as a ceRNA by sponging miR-491-5p to increase the expression of C2CD2L, thereby influencing the progression of TNBC. Our findings indicate that AC112721.1 may represent a new biomarker for evaluating TNBC prognosis and treating TNBC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Twenty breast cancer samples and 20 paracancerous tissues were collected from 30 patients who underwent surgery at the First People’s Hospital of Yunnan Province. The protocol was approved by the Ethical Committee of First People’s Hospital of Yunnan Province (No. KMUST-MEC-016). Informed consent was obtained from all the human subjects. The animal experiments were approved by the Animal Ethics Committee of Kunming University of Science and Technology (PZWH (dian) K2024-0001). Research on human subjects adheres to the Declaration of Helsinki principles., (© 2024. The Author(s).)

Background: Sleep apnea syndrome (SAS) is associated with hypertension and vascular remodeling. Hypoxia-inducible factor-1α (HIF-1α) and the Hippo-YAP pathway are implicated in these processes, but their specific roles remain unclear. This study investigated the HIF-1α/Hippo-YAP pathway in SAS-related hypertension., Methods: We established a rat model of SAS-induced hypertension via chronic intermittent hypoxia (CIH). Rats were treated with siRNA targeting HIF-1α. Blood pressure, inflammation, oxidative stress, vascular remodeling, and VSMC function were assessed. In vitro experiments with A7r5 cells and human aortic smooth muscle cells (HAoSMCs) explored the effects of HIF-1α silencing and YAP1 overexpression., Results: Compared with the control group, the CIH group presented significant increases in both HIF-1α and YAP1 expression, which correlated with increased blood pressure and vascular changes. HIF-1α silencing reduced hypertension, oxidative stress, inflammation, and the severity of vascular remodeling. Specifically, siRNA treatment for HIF-1α normalized blood pressure, decreased the levels of oxidative damage markers (increased SOD and decreased MDA), and reversed the changes in the levels of inflammatory markers (decreased high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and soluble E-selectin (sE-s)). Structural analyses revealed reduced vascular smooth muscle cell proliferation and collagen deposition, along with normalization of cellular markers, such as α-SMA and TGF-β1. Furthermore, the Hippo-YAP pathway appeared to mediate these effects, as evidenced by altered YAP1 expression and activity upon HIF-1α modulation., Conclusions: Our findings demonstrate the significance of the HIF-1α/Hippo-YAP pathway in CIH-induced hypertension and vascular remodeling. HIF-1α contributes to these pathophysiological processes by promoting oxidative stress, inflammation, and aberrant VSMC behavior. Targeting this pathway could offer new therapeutic strategies for CIH-related cardiovascular complications in SAS patients., Competing Interests: Declarations. Ethics approval and consent to participate: The animal study protocols received approval from the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, adhering to both national guidelines and the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: There are no declared conflicts of interest., (© 2024. The Author(s).)

Sheep are one of the globally significant livestock, providing meat, dairy products, and wool for human life, playing an indispensable role in human civilization. Despite significant advancements in microbiome research in recent years, most studies have focused solely on the rumen, lacking a comprehensive study covering the microbiome of different gastrointestinal tract (GIT) regions in sheep. In this study, we collected 338 samples from 10 different regions of the sheep GIT and systematically investigated their microbiome signatures, including community structure, enterotypes, interactions among taxa, and microbial community assembly. Our results showed that the bacterial diversity of sheep GIT exhibited a U-shaped pattern along the GIT, with the lowest diversity in the jejunum. The bacterial community composition and enterotype varied along the GIT, mainly divided into three distinct groups (four-chambered stomach, small intestine, and large intestine). The rumen had the highest total number of bacterial taxa, unique taxa, and unique functions, while the enterotypes were the same in the three regions of the large intestine. The bacterial co-occurrence networks differed greatly between different GIT regions, with more positive correlations than negative ones. Furthermore, we found that the assembly processes of bacterial communities in the four-chambered stomach and small intestine were mainly stochastic, while those in the large intestine were mainly shaped by deterministic processes, with a higher ecological niche width than other GIT regions. Our results reveal the spatial pattern of bacterial communities in the sheep GIT and the intrinsic mechanisms of bacterial community assembly, laying the foundation for microbial interventions to improve sheep productivity and sustainable farming., Importance: Sheep's gastrointestinal tract harbors a diverse microbial community crucial for immune system balance, nutrient digestion, and overall health. We explored the microbial community composition, community types (enterotypes), bacterial interactions, and ecological processes in 10 gastrointestinal regions of 36 six-month-old Hu sheep raised under same diets and environmental conditions. Our findings revealed a unique U-shaped pattern of bacterial diversity from the rumen to the rectum, with the lowest diversity in the jejunum. The composition and enterotypes of bacterial communities varied spatially along the gastrointestinal tract, primarily categorized into three distinct groups. The rumen exhibited the highest abundance of bacterial taxa, unique taxa, and unique functions, while the enterotypes in the three regions of the large intestine were consistent. We explored the assembly processes of bacterial communities, elucidating how they find their ecological niches based on their characteristics and environmental demands. The assembly processes in the four-chambered stomach and small intestine resembled random selection, where bacterial positioning depended on luck and chance, while in the large intestine, it appeared more deterministic, with specific bacteria likely selected based on their unique skills and environmental requirements. This study enhances our understanding of microbial coexistence and interactions in complex ecosystems, with implications for improving animal productivity, disease treatment, and the development of novel microbial formulations.

Background: Maternal smoking around birth (MSAB) and early-life breastfeeding (BAB) represent critical factors that may exert enduring effects on neuropsychiatric health. Although previous research has examined these exposures separately, the combined impact of both on disorders such as ADHD, ASD, BD, MDD, ANX, and SCZ remains unclear. This study aims to evaluate the causal relationships between MSAB and BAB and the risk of developing these neuropsychiatric disorders through Mendelian randomization (MR) analysis., Methods: A two-sample MR analysis was conducted to investigate the potential causal effects of MSAB and BAB on a range of neuropsychiatric disorders. Genetic variants associated with MSAB and BAB were obtained from genome-wide association studies (GWAS), while summary data for neuropsychiatric disorders were gathered from large GWAS consortia. The primary MR analysis was conducted using the inverse-variance weighted (IVW) method, with additional sensitivity analyses performed to confirm the robustness of the findings. A False Discovery Rate (FDR) correction was applied to control for the issue of multiple comparisons and reduce the risk of Type I errors., Results: The IVW analysis indicated that there were significant associations between MSAB and an increased risk of the following conditions: The IVW analysis indicated significant associations between MSAB and an increased risk of ADHD (odds ratio [OR] = 5.36, 95 % confidence interval [CI] = 2.58-7.63, p-value for false discovery rate [PFDR] = 0.004) and major depressive disorder (MDD) (OR = 1.92, 95 % CI = 1.29-2.88, PFDR = 0. Furthermore, significant associations were observed between MSAB and an increased risk of bipolar disorder (BD) (OR = 6.33, 95 % CI = 1.56-8.73, PFDR = 0.020), anxiety disorders (ANX) (OR = 1.03, 95 % CI = 1.00-1.05, PFDR = 0.039), and attention deficit hyperactivity disorder (ADHD) (OR = 5.36, 95 % CI = 2.58-7.63, PFDR = 0.004). No significant associations were identified between MSAB and Autism Spectrum Disorder (ASD) or Schizophrenia (SCZ). In contrast, the results indicated that BAB was associated with a protective effect against ADHD (OR = 0.17, 95 % CI = 0.04-0.63, PFDR = 0.025), MDD (OR = 0.26, 95 % CI = 0.12-0.58, PFDR = 0.006), and ANX (OR = 0.96, 95 % CI = 0.49-0.99, PFDR = 0.030). No significant effects of BAB were observed for ASD, BD, or SCZ., Conclusions: This study shows that maternal smoking around the time of birth increases the risk of attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), bipolar disorder (BD), and anxiety disorders (ANX). In contrast, breastfeeding during infancy offers protective benefits against ADHD, MDD, and ANX. These findings underscore the vital importance of maternal health behaviours during the perinatal and infant feeding periods. They also highlight the need for targeted public health interventions aimed at reducing the risk of neuropsychiatric disorders., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Detecting programmed death ligand 1 (PD-L1) expression based on immunohistochemical (IHC) staining is an important guide for the treatment of lung cancer with immune checkpoint inhibitors. However, this method has problems such as high staining costs, tumor heterogeneity, and subjective differences among pathologists. Therefore, the application of deep learning models to segment and quantitatively predict PD-L1 expression in digital sections of Hematoxylin and eosin (H&E) stained lung squamous cell carcinoma is of great significance., Methods: We constructed a dataset comprising H&E-stained digital sections of lung squamous cell carcinoma and used a Transformer Unet (TransUnet) deep learning network with an encoder-decoder design to segment PD-L1 negative and positive regions and quantitatively predict the tumor cell positive score (TPS)., Results: The results showed that the dice similarity coefficient (DSC) and intersection overunion (IoU) of deep learning for PD-L1 expression segmentation of H&E-stained digital slides of lung squamous cell carcinoma were 80 and 72%, respectively, which were better than the other seven cutting-edge segmentation models. The root mean square error (RMSE) of quantitative prediction TPS was 26.8, and the intra-group correlation coefficients with the gold standard was 0.92 (95% CI: 0.90-0.93), which was better than the consistency between the results of five pathologists and the gold standard., Conclusion: The deep learning model is capable of segmenting and quantitatively predicting PD-L1 expression in H&E-stained digital sections of lung squamous cell carcinoma, which has significant implications for the application and guidance of immune checkpoint inhibitor treatments. And the link to the code is https://github.com/Baron-Huang/PD-L1-prediction-via-HE-image., 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 Wang, Deng, Huang, Ma, Zhao, Feng, Wang, Zhao, Chen, Zhong, He, Ma, Feng and Xiao.)

Microbial methane oxidation plays a significant role in regulating methane emissions from lakes and reservoirs. However, the differences in methane oxidation activity and methanotrophic community between lakes and reservoirs remain inadequately characterized. In this study, sediment and water samples were collected from the large shallow lake (Dianchi) and deep reservoirs (Dongfeng and Hongjiadu) located in karst area, Southwest China. The results indicated that the rates of aerobic oxidation of methane (AeOM) in lake sediment ranged from 7.1 to 27.7 μg g -1 d -1 , which was higher than that in reservoirs sediment (1.92 to 11.56 μg g -1 d -1 ). Similarly, the average AeOM in the water column of lake (104.7 μg L -1 d -1 ) was much higher than that of reservoirs (46 μg L -1 d -1 ). The content of sediment organic carbon and dissolved inorganic carbon were important factors that influenced the rates of AeOM in sediment and water column, respectively. 16S rRNA genes sequencing revealed a higher relative abundance of methanotrophs in lake sediments compared to reservoir sediments. The dominant methanotrophic taxa in lake was Methylococcaceae (type Ib), while Methylomonadaceae (type Ia) was predominant in reservoirs. Meanwhile, anaerobic methane-oxidizing microorganisms Candidatus Methylomirabilis and Candidatus Methanoperedens were also abundant in sediments of reservoirs. However, metatranscriptomic analysis revealed that the type I methanotrophs, especially Methylobacter, was most active in the sediment of both lake and reservoir. Water depth and conductivity could be the key controlling factors of the structures of methanotrophic communities in sediment and water column, respectively. Metagenome-assembled genomes suggested that type I methanotrophs exhibited greater motility, as evidenced by a higher number of flagellar assembly genes, while type II methanotrophs demonstrated advantages in metabolic processes such as carbon, phosphorus, and methane metabolism., 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.)

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets from the same tissues revealed a strong correlation between the chromatin contacts and chromatin state at distal enhancers, as well as gene expression patterns at predicted target genes. We predicted target genes of 15,098 candidate enhancers and used them to annotate target genes of homologous candidate enhancers in the human genome that harbor risk variants of human diseases. We present evidence that schizophrenia and other adult disease risk variants are frequently found in fetal enhancers, providing support for the hypothesis of fetal origins of adult diseases., Competing Interests: Competing interests: B.R. is a cofounder and shareholder of Arima Genomics and Epigenome Technologies. A.A. is currently an employee of Meta. A.D.S. is an employee of Arima Genomics. The other authors declare no competing interests., (© 2024. The Author(s).)

The emerging of lysosomal targeting chimera (LYTAC) expands the field of targeted protein degradation (TPD) to include the extracellular proteins for precise depletion. However, most of the reported LYTACs either induce ubiquitous degradation of the protein of interest (POI) in a broad range of tissues or specifically target liver cells. More tissue-selective degraders are highly desirable. Herein, we describe the development of cyclic RGD (cRGD) peptide-antibody conjugates as a novel class of integrin targeting chimeras (ITACs) with potential cancer selectivity. Our results indicate that the ITACs are able to recruit integrin to induce the degradation of both soluble and membrane targets in the lysosome. We observed higher efficiency of ITACs on degrading membrane protein in cancer cells, providing a promising platform for cancer-selective TPD strategy., (© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.)

Comprehensive functional genome annotation is crucial to elucidate the molecular mechanisms of agronomic traits in livestock, yet systematic functional annotation of the sheep genome is lacking. Here, we generated 92 transcriptomic and epigenomic data sets from nine major tissues, along with whole-genome data from 2357 individuals across 29 breeds worldwide, and 4006 phenotypic data related to tail fat weight. We constructed the first multi-tissue epigenome atlas in terms of functional elements, chromatin states, and their functions and explored the utility of the functional elements in interpreting phenotypic variation during sheep domestication and improvement. Particularly, we identified a total of 753,723 nonredundant functional elements, with over 60% being novel. We found tissue-specific promoters and enhancers related to sensory abilities and immune response that were highly enriched in genomic regions influenced by domestication, while longissimus dorsi tissue-specific active enhancers and tail fat tissue-specific active promoters were highly enriched in genomic regions influenced by breeding and improvement. Notably, a variant, Chr13:51760995A>C, located in an enhancer region, was identified as a causal variant for tail fat deposition based on multi-layered data sets. Overall, this research provides foundational resources and a successful case for future investigations of complex traits in sheep through the integration of multi-omics data sets., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

The phosphorus (P) availability in soils is influenced by microbes, particularly those containing the gene responsible for phosphate solubilization. The present study investigated the community structure, diversity, and co-occurrence networks of phoD -harboring bacteria in karst and non-karst citrus orchard soils across a planting duration gradient, natural forests, and abandoned land, as well as the soil total P (TP) and available P (AP) contents and enzyme activities. The soil AP contents were lower in the karst regions than in the non-karst regions, while the soil organic carbon (C; SOC), exchangeable calcium, and microbial biomass nitrogen (N) contents; alkaline phosphatase (ALP) and β-Glucuronidase activities; and pH had the opposite trends. In addition, the soil AP and SOC contents and the ALP and acid phosphatase (ACP) activities in the karst regions decreased with an increase in the planting years, whereas the AP, TP, and microbial biomass P contents and ACP activities in the non-karst regions increased. The diversity indices and network complexity of phoD -harboring bacteria were higher in the karst regions than in the non-karst regions, with marked community differences between different planting years in the non-karst regions. The soil AP was significantly and positively correlated with the rare genera Pelagicola , Methylobacter , Streptomyces , and Micromonospora in the karst regions and Roseivivax , Collimonas , Methylobacterium , Ralstonia , and Phyllobacterium in the non-karst regions. Structural Equation Modeling showed that citrus cultivation altered the soil pH, SOC, and total N, and, in turn, the phoD -harboring bacterial community structure and diversity, which led to changes in the ALP activity and P availability. Thus, the rare genera of the phoD -harboring bacteria, influenced by the pH and SOC, highly regulated the availability of P in the karst and non-karst citrus orchard soils.

Chinese seedless breadfruit is rich in starch, lipids, and protein. To explore the interactions among these macromolecules during food processing, the seedless breadfruit starch-endogenous lipid-endogenous protein complex was investigated. Native seedless breadfruit starches are categorized as low-resistant-content starch [low-resistant starch (LRS)] or high-resistant starch (HRS). After complexation, dual self-assembly mechanisms occur after complexation. Initially, for the LRS group, long chains of amylopectin and amylose participate in complexation due to the migration from the short side chain of amylopectin, leading to an increase in RS content compared to the native starch. In contrast, amylose participated in complexation in the HRS group, which showed higher digestibility than that of raw starch. According to chemometric analysis, the HRS group complex possesses a more compact external and internal nanomicrostructure, leading to its weaker digestibility kinetics compared to the LRS group complex. This study provides a fundamental basis for the comprehensive application of novel multicomponent foods.

Meat quality is a complex trait that exhibits significant variation across pig breeds, and the regulatory mechanisms governing pork meat quality are not fully elucidated. We compared the transcriptomics and metabolomics of the longissimus dorsi (LD) muscle between the Songliao Black Pig (SBP) and Large White × Landrace Pig (LWLDP) to investigate breed-specific differences in meat quality and underlying regulatory pathways. The results showed that SBP meat had a higher marbling score and backfat thickness, a richer color, a lower shear force, and reduced drip loss. Fatty acid (FA) analysis identified 15 significant FAs in the LWLDP, with docosahexaenoic acid (DHA) in the SBP, while amino acid (AA) analysis revealed no breed-based differences. Transcriptome analysis identified 134 upregulated and 362 downregulated genes in the SBP. Protein-protein interaction (PPI) network analysis found 25 key genes, which are associated with muscle development, fat deposition, and overall meat quality, while genes in the insulin signaling pathway, such as PPP1R3B, PPARGC1A, SOCS1, EIF4E, PRKAR2A, PRKAG2, and FASN, play a crucial role in balancing fat metabolism and catabolism. Metabolomic analysis identified 89 upregulated and 10 downregulated metabolites in the SBP, primarily involved in fructose and mannose metabolism, amino acid biosynthesis, nucleotide sugar metabolism, and glucagon signaling pathways. Gene-metabolite association analysis found that the PPP1R3B gene had a strong association with Thr-Leu, Maltol, D-myo-Inositol-4-phosphate, and Fructose-6-phosphate, while MYOG correlated with Mannose-6-phosphate, Fructose-1-phosphate, Mannose-1-phosphate, and Glucose-6-phosphate. In contrast, NR4A3 and PPARGC1A showed a strong negative correlation with most upregulated metabolites. In conclusion, this study identified functional genes, elucidated the mechanisms associated with meat quality traits, and identified gene-metabolite associations involved in energy metabolism, muscle development, and fat deposition, providing valuable insights into the molecular mechanisms that regulate meat quality between pig breeds.

In this study, a polyvinyl alcohol/polyethylene glycol/hydroxypropyltrimethyl ammonium chloride chitosan (PVA/PEG/HACC) ternary composite hydrogel was synthesized using electron-beam radiation. The materials were thoroughly characterized via Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, Brunauer-Emmett-Teller analysis, gelation fraction tests, and swelling rate tests. Systematic adsorption experiments revealed that the rate of adsorption of calf thymus DNA (ctDNA) by the PVA/PEG/HACC hydrogel reached 89%. The adsorption process followed the Langmuir isotherm and pseudo-second-order kinetic model. This process was mainly characterized by monolayer chemical adsorption, with intraparticle diffusion playing a crucial role. In addition, the process was spontaneous, with higher temperatures enhancing adsorption. The possible adsorption mechanisms included electrostatic interactions, hydrogen bonding, and van der Waals forces. The maximum ctDNA desorption rate was 81.67%. The adsorption rate remained at 71.39% after five adsorption-desorption cycles. The bioactivity of the PVA/PEG/HACC hydrogel was validated by antibacterial, cytotoxicity, and apoptosis tests. The results of this study demonstrated the crucial application potential of adsorbent materials in DNA adsorption and biomedical applications.

We disclose a gold-mediated photocyclization method for the efficient synthesis of acrylamide-derived β-lactams and 3,4-dihydroquinolin-2-ones, two privileged bioactive scaffolds. The protocol proceeds with ease, providing good yields of product while exhibiting excellent functional group tolerance at low catalyst loadings in sustainable solvents. Additionally, reaction times are significantly reduced compared with prior-art methods. Notably, the present gold system exhibits superior performance in activating poorly conjugated substrates, which are typically unreactive with other photocatalysts, highlighting the exceptional position of this organogold system among modern photocatalysts.

As a chromatin remodelling factor, high mobility group A1 (HMGA1) plays various roles in both physiological and pathological conditions. However, its role in DNA damage response and DNA damage-based chemotherapy remains largely unexplored. In this study, we report the poly ADP-ribosylation (PARylation) of HMGA1 during DNA damage, leading to desensitization of esophageal squamous cell carcinoma (ESCC) cells to the poly(ADP-ribose) polymerase 1 (PARP1) inhibitor, olaparib. We found that HMGA1 accumulates at sites of DNA damage, where it interacts with PARP1 and undergoes PARylation at residues E47 and E50 in its conserved AT-hook domain. This modification enhances the accumulation of Ku70/Ku80 at the site of DNA damage and activates the DNA-dependent protein kinase catalytic subunit, facilitating nonhomologous end-joining repair. In both subcutaneous tumour models and genetically engineered mouse models of in situ esophageal cancer, HMGA1 interference increased tumour sensitivity to olaparib. Moreover, HMGA1 was highly expressed in ESCC tissues and positively correlated with PARP1 levels as well as poor prognosis in ESCC patients. Taken together, these findings reveal a mechanistic link between HMGA1 and PARP1 in regulating cell responses to DNA damage and suggest that targeting HMGA1 could be a promising strategy to increase cancer cell sensitivity to olaparib., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Biological hydroxyapatite (BHA) is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity. The clinical application of mateiral size is based on the principle of bone defect area adaptation, which contributes to diversity of BHA sizes. However, different sizes correspond to different hierarchical levels of bone biomimicry. As the size changes, the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation, leading to unstable bone graft outcomes. Therefore, this paper reviews the size effect of clinical BHA, analyzes the multilevel structure of natural bone, proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA, and further analyzes the size-media-ted osteo-coagulo-immunomodulation. Based on the hierarchical levels of bone and its osteo-coagulo-immunomodulation effect, we provide a new understanding of the biological principle of the size effect of biomaterials and a theoretical basis for the basic research and clinical application of different size BHA materials.

Understanding the unique role of supramolecular chirality in nano-protein/cell interactions, as opposed to molecular chirality, is crucial for elucidating the origin of life. However, this aspect has received inadequate attention. In this study, L/D-glutamic acid-based amphiphiles (L/D-GluC16), which possess molecular chirality, were synthesized. Additionally, through the manipulation of solvent effects, left/right-handed helical nanofibers (M/P-GluC16), endowed with supramolecular chirality, were assembled from L/D-GluC16. With the aid of molecular dynamics (MD) simulations, the interaction between M/P-GluC16, L/D-GluC16, and a model protein (bovine serum albumin, BSA) was investigated at the thermodynamic and spatial orientational levels. Combined with the experimental result of protein adsorption efficiency, a more favorable chirality-dependent binding of M/P-GluC16 to protein compared to L/D-GluC16 was confirmed. Furthermore, driven by the binding-induced conformational changes and subsequent functional disruptions of proteins, M/P-GluC16 exhibited a greater chirality-specific cancer cell inhibitory efficacy compared to L/D-GluC16, highlighting the more significant impact of supramolecular chirality on nano-protein/cell interactions than molecular chirality., 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.)

Objectives: Cerebral venous sinus thrombosis (CVST) is a rare but serious manifestation of venous thrombosis in patients with antiphospholipid syndrome (APS). This study investigated the risk factors, clinical characteristics and prognosis of CVST in APS patients., Methods: This retrospective cohort study included all thrombotic APS (tAPS) patients from Peking Union Medical College Hospital (PUMCH) from April 2005 to August 2023. Demographic characteristics, laboratory data and thrombotic risk factors were compared between tAPS-CVST group and tAPS-non-CVST group. Kaplan-Meier survival analysis was utilized to compare the recanalization rate and the recurrence rate., Results: A total of 453 APS patients were enrolled, and 40 (8.8%) APS patients were with CVST. The median age of the APS-CVST patients was 27 (21.25, 32.75) years, and 72.5% were females. In 50% of these patients, CVST was the initial symptom of APS, with headache being the most prevalent clinical symptom (95%). Involvement of more than two venous sinuses were observed in 79.5% of patients, with the transverse sinus (79.5%) and sigmoid sinus (74.4%) being the most commonly affected sites. Oral contraceptives, intracranial infections and malignancy were identified as risk factors of APS-CVST. There were no statistically significant differences in baseline characteristics or the distribution of antiphospholipid antibodies profiles between the two groups. After a median follow-up of 24 (12, 52) months, 21 patients (52.5%) experienced recanalization, and 13 patients (32.5%) had a thrombotic recurrence. Survival analysis indicated that adequate anticoagulant therapy significantly contributed to recanalization (HR 6.27, 95% CI 2.616-15.02, P = 0.003), while continuous anticoagulant therapy was highly effective in reducing the recurrence of thrombotic events (HR 0.14, 95% CI 0.0447-0.4328, P = 0.0007)., Conclusion: CVST should be considered in APS patients who experience sudden onset headaches, particularly those with thrombotic risk factors, such as the use of oral contraceptives, intracranial infections and malignancy. Continuous and adequate anticoagulant therapy is pivotal and beneficial for achieving recanalization and prevention of recurrence. Key Points • The prevalence of CVST in patients with APS may be underestimated. • APS-CVST is associated with special risk factors, including pregnancy, intracranial infection, oral contraceptives and tumors. • Long-term and adequate anticoagulation therapy can increase the vascular recanalization rate and reduce thrombosis recurrence., Competing Interests: Declarations. Conflicting interests: All authors declare that there are no conflicts of interest., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

The strategy of re-organogenesis provides an optimal framework for restoring complex organ structures and functions in adult damage. While the focus has often been on restoring organogenesis stem cells, there is limited investigations of reverting the environmental niche to support this approach. The guiding principle of "Nature selects the fittest to survive" drives the intricate dynamic changes in cellular events within the niche environment, especially through immune surveillance. The extracellular matrix (ECM) serves as the "self-associated molecular patterns" of the niche, containing extensive data on cell-niche reaction data and acting as the active tuner of immune surveillance. In this study, hyaluronic acid (HA) is identified as a unique component of the ECM in cranial osteo-organogenesis. Mechanistically, HA activates the Cluster of Differentiation 44 (CD44)-Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Regulated Kinase (ERK)-Ets Variant 1/5 (ETV1/5)- Mannose Receptor C-Type 1 (MRC1) axis in macrophages, establishing a distinct immune surveillance during osteo-organogenesis. Furthermore, HA is utilized as a novel engineered material for an "Osteo-organogenesis niche", restoring immune surveillance and synergistically regulating stem cells to achieve re-osteo-organogenesis in cranial defects of rats. Taken together, the study unveils a previously unknown strategy for leveraging re-organogenesis by utilizing "organogenesis niche" ECM engineered materials to manipulate immune surveillance, thereby comprehensively regulating stem cells and other tissue cells effectively for re-organogenesis., (© 2024 Wiley‐VCH GmbH.)

The classical traditional Chinese medicine formula Huangqi-Guizhi-Wuwutang (HGW) has been shown to enhance sperm production. However, the bioactive components and comprehensive mechanisms underlying the therapeutic effects remain unclear. The present study investigates the potential active ingredients and underlying mechanisms of HGW against spermatogenesis dysfunction. The chemical components of HGW were analyzed by mass spectrometry. And then the "components-targets-pathway-disease" network was constructed using network pharmacology research methods, which aimed to identify the key active components and potential targets of HGW in treating oligospermia. Experimental validation was finally conducted in animal model. The male-specific pathogen-free Kunming mice were divided into five groups: Sham group, Model group, and HGW groups (8, 16, and 32 g/kg of HGW by gavage for 35 days). Chemical profile and network pharmacology results revealed that potential bioactive compounds were dihydrocinnacasside, isomucronulatol, and 6-gingerol, and the mechanism of which was enriched in regulating spermatogenic stem cells (SSCs), endocrine function, and apoptosis. The administration of HGW significantly improved oligospermia in mice. HGW significantly upregulated the expression of marker proteins in SSCs and the potential targets within the testis simultaneously. Our data indicates that HGW enhances the proliferation of SSCs, and HGW can be a promising therapeutic candidate for oligospermia., (© 2024 John Wiley & Sons Ltd.)

The proliferation and differentiation of skeletal muscle satellite cells (SMSCs) are responsible for the development of skeletal muscle. In our previous study, circ_002156 was found to be highly expressed in caprine Longissimus Dorsi muscle, but the regulatory role of the circular RNAs (circRNA) in goat SMSCs remains unclear. In this study, the authenticity of circ_002156 was validated, and its structurally characteristic and cellular localization as well as tissue expression of circ_002156 and its parent genes were investigated. Moreover, the effects of circ_002156 on the viability, proliferation, and differentiation of SMSCs were also studied. The circ_002156 is located on caprine chromosome 19 with a length of 36,478. The circRNA structurally originates from myosin heavy chain 2 ( MYH2 ), MYH1 , and MYH4 as well as intergenic sequences among the parent genes. RT-PCR and Sanger sequencing confirmed the authenticity of circ_002156. Most circ_002156 (55.5%) was expressed in the nuclei of SMSCs, while 44.5% of circ_002156 was located in the cytoplasm. The circ_002156 and its three parent genes had higher expression levels in the triceps brachii , quadriceps femoris , and longissimus dorsi muscle tissues than in the other five tissues. The expression of circ_002156 and its parent genes MYH1 and MYH4 reached the maximum on day 8 of differentiation, while MYH2 in expression reached the peak on day 4 after differentiation. The Pearson correlation coefficients revealed that circ_002156 had moderate or high positive correlations with the three parent genes in the expression of both quadriceps femoris muscle and SMSCs during different differentiation stages. The small interfering RNA circ_002156 (named si-circ_002156) remarkably increased the viability of the SMSCs. The si-circ_002156 also increased the number and parentage of Edu-labeled positive SMSCs as well as the expression levels of four cell proliferation marker genes. These suggest that circ_002156 inhibited the proliferation of SMSCs. Meanwhile, si-circ_002156 decreased the area of MyHC-labeled positive myotubes, the myotube fusion index, and myotube size as well as the expression of its three parent genes and four cell differentiation marker genes, suggesting a positive effect of circ_002156 on the differentiation of SMSCs. This study contributes to a better understanding of the roles of circ_002156 in the proliferation and differentiation of SMSCs.

Background: Atrial fibrillation (AF) and obstructive sleep apnea (OSA) are often comorbid and associated with increased risk of cardiovascular events such as stroke. We evaluated the effectiveness, safety, healthcare resource utilization, and costs of rivaroxaban versus warfarin in patients with nonvalvular AF (NVAF) and comorbid OSA., Methods: We used the IQVIA PharMetrics ® Plus adjudicated claims database to evaluate patients with NVAF, OSA, and moderate-to-severe stroke risk who initiated rivaroxaban or warfarin between November 2011 and December 2022. We adjusted for potential confounders with propensity score overlap weighting. Primary endpoints were evaluated based on intent-to-treat (ITT) and on-treatment follow-up to compare stroke or systemic embolism risk, major bleeding risk, all-cause healthcare resource utilization (inpatient hospitalizations, emergency department visits, outpatient visits, and pharmacy fills), and costs (per patient per year [PPPY]) by treatment cohort., Results: In total, 14,765 patients were included (9133 received rivaroxaban; 5632 received warfarin). Rivaroxaban significantly reduced stroke or systemic embolism versus warfarin by 26% (ITT-hazard ratio, 0.74 [95% CI 0.60-0.91]; P = 0.004) and 30% (on-treatment-hazard ratio, 0.70 [95% CI 0.55-0.89]; P = 0.004). Major bleeding was not significantly different between rivaroxaban and warfarin in either analysis. All-cause healthcare resource utilization was significantly reduced with rivaroxaban versus warfarin, leading to significantly reduced PPPY costs., Conclusions: Among patients with NVAF and OSA, rivaroxaban was associated with a significant reduction in stroke or systemic embolism risk versus warfarin with no difference in major bleeding. Rivaroxaban significantly reduced healthcare resource utilization and costs compared with warfarin, providing support for the use of rivaroxaban in this population., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: AN has served as a consultant for Abbott, Biosense Webster, Biotronik, Boston Scientific, iRhythm, and Janssen Scientific Affairs, LLC. SM has nothing to disclose. CC, YZ, AKC, BB, and VA are employees of Janssen Scientific Affairs, LLC and hold stock in Johnson & Johnson., (© 2024. The Author(s).)

The tripartite motif (TRIM) protein family has been shown to play important roles in the occurrence and development of various tumors. However, the biological functions of TRIM47 and its regulatory mechanism in hepatocellular carcinoma (HCC) remain unexplored. Here, we showed that TRIM47 was upregulated in HCC tissues compared with adjacent normal tissues, especially at advanced stages, and associated with poor prognosis in HCC patients. Functional studies demonstrated that TRIM47 enhanced the migration and invasion ability of HCC cells in vitro and in vivo. Mechanistically, TRIM47 promotes HCC metastasis through interacting with SNAI1 and inhibiting its degradation by proteasome. Moreover, TRIM47 was di-methylated by CARM1 at its arginine 210 (R210) and arginine 582 (R582), which protected TRIM47 from the ubiquitination and degradation mediated by E3 ubiquitin ligase complex CRL4 CRBN . Collectively, our study reveals a pro-metastasis role of TRIM47 in HCC, unveils a unique mechanism controlling TRIM47 stability by CARM1 mediated arginine methylation, and highlights the role of the CARM1-CRL4 CRBN -TRIM47-SNAI1 axis in HCC metastasis. This work may provide potential therapeutic targets for metastatic HCC treatment., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: All animal interventions were approved by approved by the Animal Ethics Committee of Wuhan University of Science and Technology., (© 2024. The Author(s).)

Parkinson's disease (PD) is typically marked by motor dysfunction accompanied by loss of dopaminergic (DA) neurons and aggravated oxidative stress in the substantia nigra pars compacta (SNpc). Atractylenolide-I (ATR-I) is a potent antioxidant sesquiterpene with neuroprotective properties. However, whether ATR-I plays a neuroprotective role against oxidative stress in PD remains unclear. The objective of this study was to explore the mechanism of antioxidant action of ATR-I in PD models both in vivo and in vitro. Here, we show that ATR-I alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice. Moreover, ATR-I treatment effectively reduced DA neuron loss and increased tyrosine hydroxylase expression in the SNpc of MPTP-induced mice. Additionally, ATR-I inhibited oxidative stress (as manifested by elevated superoxide dismutase and glutathione peroxidase activities, and reduced malondialdehyde content) in MPTP-induced mice and attenuated reactive oxygen species levels in 1-methyl-4-phenylpyridinum (MPP + )-treated SH-SY5Y cells. Finally, ATR-I upregulated expressions of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), NF-E2-related factor-2 (Nrf2), and heme oxygenase-1 in MPTP-induced mice and MPP + -treated SH-SY5Y cells, but had little effect on these factors in the presence of the SIRT1 inhibitor EX527. Taken together, these findings indicated that the important antioxidant role of ATR-I in MPTP/MPP + -mediated oxidative stress and the pathogenesis of PD through the SIRT1/PGC-1α/Nrf2 axis, highlighting its potential as a therapeutic option for PD., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arsenic can cause extensive toxic damage after entering the body of humans and animals by altering a variety of events. As the most common form of methylation modification of RNA in eukaryotic cells, N 6 -methyladenosine (m 6 A) is widely involved in regulating RNA processing, translation and degradation, thus playing important role in various pathophysiological processes. Emerging studies have demonstrated that m 6 A modification is synergistically mediated by methyltransferases, demethylases and methyl-binding proteins. Recently, emerging studies have shown that m 6 A modification and its regulatory proteins play important roles in arsenic toxicity through mediating various key signaling pathways. We comprehensively analyzed the mechanisms by which m 6 A modification and its regulatory proteins contribute to arsenic toxicity. Our reviews offer a scientific foundation for the development of preventive and control strategies to mitigate arsenic-induced toxicity, with an emphasis on an epigenetic approach., Competing Interests: 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., (© 2024 The Authors.)

Industrial CO 2 emissions contribute to pollution and greenhouse effects, highlighting the importance of carbon capture. Potassium carbonate (K 2 CO 3 ) is an effective CO 2 absorbent, yet its liquid-phase absorption faces issues like diffusion resistance and corrosion risks. In this work, the solid adsorbents were developed with K 2 CO 3 immobilized on the selected porous supports. Al 2 O 3 had an optimum CO 2 adsorption capacity of 0.82 mmol g -1 . After further optimization of its pore structure, the self-prepared support Al 2 O 3 -2, which has an average pore diameter of 11.89 nm and a pore volume of 0.59 cm 3 g -1 , achieved a maximum CO 2 adsorption capacity of 1.12 mmol g -1 following K 2 CO 3 impregnation. Additionally, the relationship between support structure and CO 2 adsorption efficiency was also analyzed. The connectivity of the pores and the large pore diameter of the support may play a key role in enhancing CO 2 adsorption performance. During 10 cycles of testing, the K 2 CO 3 -based adsorbents demonstrated consistent high CO 2 adsorption capacity with negligible degradation.

Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects. We identified 32 rumen microbiota biomarkers including Bifidobacterium that were associated with FD-traits (P adj <0.05). Further, utilizing five MR methods, we identified eight causal associations between marker genera and FD-traits (P adj <0.05), including Butyrivibrio, Olsenella, p-2534-18B5 gut group, Prevotellaceae UCG-003, and Pseudobutyrivibrio causing forward causal effects on FD, and changes in Flexilinea and Suttonella induced by FD. To our knowledge, this is the inaugural attempt to employ MR in sheep to investigate the causal relationships between gastrointestinal microbiota and complex phenotypes, underscoring the potential for developing interventions related to adipose deposition in sheep from the perspective of the rumen microbiome., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval All animal experiments and procedures were conducted under the approval and guidance of the Animal Ethics Committee of Lanzhou University (Nos.: 2020-01 and 2021-02)., (© 2024. The Author(s).)