Abnormal amino acid synthesis and glutathione metabolism may affect PCOS blastocyst development: an examination of in vitro mouse blastocysts model utilizing RNA-sequencing.

BACKGROUND: Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5-10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage. METHODS: The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group. RESULTS: There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group. CONCLUSION: This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.

Progress and challenges in bacterial infection theranostics based on functional metal nanoparticles.

The rapid proliferation and infection of bacteria, especially multidrug-resistant bacteria, have become a great threat to global public health. Focusing on the emergence of "super drug-resistant bacteria" caused by the abuse of antibiotics and the insufficient and delayed early diagnosis of bacterial diseases, it is of great research significance to develop new technologies and methods for early targeted detection and treatment of bacterial infection. The exceptional effects of metal nanoparticles based on their unique physical and chemical properties make such systems ideal for the detection and treatment of bacterial infection both in vitro and in vivo. Metal nanoparticles also have admirable clinical application prospects due to their broad antibacterial spectrum, various antibacterial mechanisms and excellent biocompatibility. Herein, we summarized the research progress concerning the mechanism of metal nanoparticles in terms of antibacterial activity together with the detection of bacterial. Representative achievements are selected to illustrate the proof-of-concept in vitro and in vivo applications. Based on these observations, we also give a brief discussion on the current problems and perspective outlook of metal nanoparticles in the diagnosis and treatment of bacterial infection.

DDX19A promotes gastric cancer cell proliferation and migration by activating the PI3K/AKT pathway.

BACKGROUND: DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role in gastric cancer remains unclear. The present study aimed to explore the role and underlying mechanism of DDX19A in the development of gastric cancer. METHODS: The expression of DDX19A in gastric cancer and paracancerous tissues was evaluated through quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The biological functions of DDX19A in gastric cancer were determined using CCK8, plate colony-forming, and Transwell migration assays. The specific mechanism of DDX19A in gastric cancer cells was studied using western blotting, RNA-binding protein immunoprecipitation, mRNA half-life detection, and nuclear and cytoplasmic RNA isolation. RESULTS: DDX19A was highly expressed in gastric cancer and positively associated with malignant clinicopathological features and poor prognosis. Additionally, DDX19A promoted gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition phenotypes. Mechanistically, DDX19A activated the PI3K/AKT pathway by upregulating phosphatidylinositol-3-kinase (PIK3CA) expression. Furthermore, DDX19A interacted with PIK3CA mRNA, stabilized it, and facilitated its export from the nucleus. CONCLUSIONS: Our study reveals a novel mechanism whereby DDX19A promotes the proliferation and migration of gastric cancer cells by enhancing the stability and nuclear export of PIK3CA mRNA, thereby activating the PI3K/AKT pathway.

Mineralized aggregates based on native protein phase transition for non-destructive diagnosis of seborrheic skin by surface-enhanced Raman spectroscopy.

The non-homeostasis of sebum secretion by the sebaceous glands in a complicated microenvironment dramatically impacts the skin health of many people in the world. However, the complexity and hydrophobicity of sebum mean a lack of diagnostic tools, which makes it challenging to determine the reason behind cortical imbalances. Herein, a biomimetic mineralized aggregates (PTL@Au and PTB@Au) strategy has been proposed, which could obtain molecular information about sebum by surface-enhanced Raman spectroscopy (SERS). The breaking of disulfide bonds leads to changes in hydrogen bonding, which transform the natural protein into amyloid-like phase transition protein with ß-sheets. It provides sites for the nucleation and crystallization of gold nanocrystals to build mineralized aggregates. The mineralized aggregates show robust adhesion stability at the interfaces of different materials through hydrogen bonding and electrostatic interactions. The stabilization, hydrophobicity (contact angle: 134°), and optical transmission (75%) of the structure could result in superior SERS performance for sebum analysis. It should be noted that this enables the sebum detection of clinical samples while ensuring safety. Such generalized bionic mineralization construction and diagnosis methods also serve as an advanced paradigm for a range of biomedical applications.

Application of genome tagging technology in elucidating the function of sperm-specific protein 411 (Ssp411).

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.

Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.

Establishment of an Embryo Implantation Model In Vitro.

Embryo implantation is the first step in the establishment of a successful pregnancy. An in vitro model for embryo implantation is critical for basic biological research, drug development, and screening. This paper presents a simple, rapid, and highly efficient in vitro model for embryo implantation. In this protocol, we first introduce mouse blastocyst acquisition and human endometrial adenocarcinoma cells (Ishikawa) preparation for implantation, followed by the co-culture method for mouse embryos and Ishikawa cells. Finally, we conducted a study to assess the impact of varying concentrations of 17-ß-estradiol (E2) and progesterone (P4) on embryo adhesion rates based on this model. Our findings revealed that high concentrations of E2 significantly reduced embryo adhesion, whereas the addition of progesterone could restore the adhesion rate. This model offers a simple and fast platform for evaluating and screening molecules involved in the adhesion process, such as cytokines, drugs, and transcription factors controlling implantation and endometrial receptivity.

Cell Membrane Engineered Polypeptide Nanonets Mimicking Macrophage Aggregates for Enhanced Antibacterial Treatment.

Drug-resistant bacterial infections and their lipopolysaccharide-related inflammatory complications continue to pose significant challenges in traditional treatments. Inspired by the rapid initiation of resident macrophages to form aggregates for efficient antibacterial action, this study proposes a multifunctional and enhanced antibacterial strategy through the construction of novel biomimetic cell membrane polypeptide nanonets (R-DPB-TA-Ce). The design involves the fusion of end-terminal lipidated polypeptides containing side-chain cationic boronic acid groups (DNPLBA) with cell membrane intercalation engineering (R-DPB), followed by coordination with the tannic acid-cerium complex (TA-Ce) to assemble into a biomimetic nanonet through boronic acid-polyphenol-metal ion interactions. In addition to the ability of RAW 264.7 macrophages cell membrane components' (R) ability to neutralize lipopolysaccharide (LPS), R-DPB-TA-Ce demonstrated enhanced capture of bacteria and its LPS, leveraging nanoconfinement-enhanced multiple interactions based on the boronic acid-polyphenol nanonets skeleton combined with polysaccharide. Utilizing these advantages, indocyanine green (ICG) is further employed as a model drug for delivery, showcasing the exceptional treatment effect of R-DPB-TA-Ce as a new biomimetic assembled drug delivery system in antibacterial, anti-inflammatory, and wound healing promotion. Thus, this strategy of mimicking macrophage aggregates is anticipated to be further applicable to various types of cell membrane engineering for enhanced antibacterial treatment.

Data-Driven Subtypes of Multiple System Atrophy and Their Implications for Prognosis.

Background: While multiple system atrophy (MSA) presents with high heterogeneous motor and nonmotor symptoms, the associations between clinical phenotypes and prognosis are unclear. Objective: We aimed to evaluate clinical phenotypes of MSA using data-driven approach and measure the impact of phenotypes on survival and bedbound status. Methods: 193 MSA patients were recruited from Xuanwu Hospital Capital Medical University, whose history, motor and non-motor symptoms were examined using cluster analysis. Ninety-five participants were followed-up via telephone after a mean of 31.87 months. We employed Kaplan- Meier analysis to examine survival and performed Cox and logistic regression analyses to identify factors associated with survival and bedbound status. Results: We identified four clinical profiles of MSA: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse. The overall median survival was 7.75 years (95% CI 7.19-8.31). After adjusting for years from symptom onset to diagnosis, age and sex, patients in the malignant diffuse and rigid akinetic-dominant clusters had greater risk of death than sleep and mood disorder-dominant cluster. Furthermore, patients in the malignant diffuse and rigid akinetic-dominant clusters had higher risk of being bedbound than cerebellar symptom-dominant cluster. Conclusions: The malignant diffuse and sleep and mood disorder-dominant were identified besides the two classical subtypes, parkinsonism, and cerebellar symptom-variant. Patients with rigid-akinetic motor profiles have a worse prognosis than cerebellar symptom-dominant profiles in general. Diffuse symptoms, especially postural instability, and cognitive alterations at diagnosis, indicate rapid functional loss and disease progression. The different profiles and prognoses might indicate varied underlying pathological mechanisms.

Multiple system atrophy (MSA) is a complex disease that can affect both movement and non-movement functions of patients. However, we do not know much about how these different symptoms relate to how the patient's health might change over time. In this study, we looked at 193 MSA patients to learn more about if the patients can be distinguished into different subgroups at diagnosis and if the subgroups might be associated with their survival and ability to move in the future. We found four main subgroups of patients: group 1 characterized by the dysfunction of cerebellum (a part of the brain), group 2 characterized by sleep and mood problems, group 3 characterized by rigidity and slow movements, and group 4 with diffuse symptoms mentioned above. After tracking 95 patients for nearly 32 months, we found that those characterized by rigidity and slow movements, and those with diffuse symptoms had a higher chance of dying compared to those characterized by sleep and mood problems. Group 3 and 4 also had a higher chance of becoming unable to move out of bed. This suggests that patients with severe symptoms of rigidity and slowness at diagnosis tend to have a worse outlook than those without. And if multiple MSA symptoms are found when the patient is diagnosed, especially trouble with thinking, are also signs that the disease is getting worse quickly. By understanding these disease patterns, we can better tailor treatments and provide better support for people with MSA.

Improved Patient Adherence to Family-Based Helicobacter pylori Infection Control and Management Strategy in Central China and Its Influencing Factors.

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Couples' preconception urinary essential trace elements concentration and spontaneous abortion risk: A nested case-control study in a community population.

BACKGROUND: Previous studies have indicated a correlation between maternal imbalances in essential trace elements during pregnancy and the occurrence of spontaneous abortion (SA). Nonetheless, the impact of these elements from both partners and during the preconception period remains unexplored. OBJECTIVE: This study sought to evaluate the relationship between preconception essential trace elements and spontaneous abortion (SA) based on husband-wife dyads. METHODS: This study selected 390 couples with spontaneous abortion (SA) and 390 matched couples with live births from a preconception cohort of 33,687 couples. Urine samples collected prior to pregnancy were analyzed for ten essential trace elements (Se, Cr, Mo, Cu, Zn, Fe, Mn, V, Co, and Ni) using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Multivariate conditional logistic regression analysis identified that elevated concentrations of Zn (OR = 0.73) and Ni (OR = 0.69) in couples were associated with a reduced risk of SA, whereas elevated levels of Cr (OR = 1.30) and Mn (OR = 1.39) were linked to an increased risk. Restricted cubic spline models suggested a U-shaped association between couples' Cu and Co concentrations and SA. Bayesian Kernel Machine Regression further supported a U-shaped relationship between the mixture of ten elements and SA, showing significant protection at the 50th and 55th percentiles compared to the 10th percentile. Additionally, the effects of Cr, Zn, Mn, and Ni on SA varied when the concentrations of the other nine elements were held constant at their 25th, 50th, and 75th percentiles. Stratified analysis revealed that maternal Cu (OR = 0.43) and Fe (OR = 0.63) reduced the risk of SA when paternal Cu and Fe were in the lower quartile. Conversely, maternal Cu (OR = 2.03) and Fe (OR = 1.77) increased the risk of SA when paternal concentrations were in the higher quartile. Similar patterns were observed for Cr, Mn, Co, and Zn. CONCLUSION: Elevated urinary concentrations of Zn and Ni in couples were associated with a reduced risk of SA, while higher levels of Cr and Mn were linked to an increased risk. Cu, Co, and a mixture of ten essential trace elements exhibited a U-shaped relationship with SA. The impact of certain essential trace elements (Cu, Fe, Cr, Mn, Co, and Zn) on SA in one partner was influenced by their concentrations in the other partner.

Honeycomb-like triazine-based conjugated microporous polymers exhibiting simultaneous and ultrasensitive detection of fifteen polycyclic aromatic hydrocarbons using solid-phase microextraction technique.

BACKGROUND: Since the severe hazard to the ecosystem and widespread distribution through biological and man-made ways of polycyclic aromatic hydrocarbons (PAHs), it is very urgent to establish the ultrasensitive analytical method to quantitatively and directly monitor PAHs in real samples. However, because of the complicated environmental matrix and their trace concentration, the pre-concentration process is a necessary step to analyze of these compounds. In this study, solid phase microextraction (SPME) technique was proposed to separate and enrich fifteen trace PAHs from environmental samples. RESULTS: In this work, a honeycomb-like triazine-based conjugated microporous polymers (T-CMPs) were prepared by Yamamoto reaction and firstly used as SPME coating material for the ultrasensitive direct-immersion-SPME of PAHs prior to high performance liquid chromatography-fluorescence detector (HPLC-FLD). The synthesized T-CMPs was characterized using various spectroscopy and electron microscopy techniques. The unique porous network of T-CMPs might deliver abundant adsorption sites for PAHs. Orthogonal experimental design (OED) was used to investigate the influence of four experimental parameters on the enrichment ability. Under optimal situation, a wide linear range (which lasted from 0.003 to 1000 µg L-1) with the coefficients of determination (R2) varying 0.9981 to 0.9993 was obtained. The limits of detection (LODs) for the analytes varied from 0.001 to 1.650 µg L-1, and the limits of quantification (LOQs) were between 0.003 and 4.960 µg L-1. The proposed method was effectively employed to the simultaneous and ultrasensitive detection of fifteen PAHs in industrial wastewaters. The relative recoveries for PAHs analysis varied from 74.6 % to 105 % with the relative standard deviations (RSD) of 0.1 %-7.5 % in real water samples. SIGNIFICANCE: The prepared SPME coating material exhibited a simultaneous, high extraction and adsorption capacity for fifteen PAHs due to its honeycomb-like porous structure, ultra-large specific surface area, strong π-π stacking, and hydrophobic interactions. The present research developed a novel strategy for the construction of SPME fiber coating composites and demonstrated great application potential in the field of sample pretreatment and environmental analytical chemistry.

High-voltage and dendrite-free zinc-iodine flow battery.

Zn-I2 flow batteries, with a standard voltage of 1.29 V based on the redox potential gap between the Zn2+-negolyte (-0.76 vs. SHE) and I2-posolyte (0.53 vs. SHE), are gaining attention for their safety, sustainability, and environmental-friendliness. However, the significant growth of Zn dendrites and the formation of dead Zn generally prevent them from being cycled at high current density (>80 mA cm-2). In addition, the crossover of Zn2+ across cation-exchange-membrane also limits their cycle stability. Herein, we propose a chelated Zn(P2O7)26- (donated as Zn(PPi)26-) negolyte, which facilitates dendrite-free Zn plating and effectively prevents Zn2+ crossover. Remarkably, the utilization of chelated Zn(PPi)26- as a negolyte shifts the Zn2+/Zn plating/stripping potential to -1.08 V (vs. SHE), increasing cell voltage to 1.61 V. Such high voltage Zn-I2 flow battery shows a promising stability over 250 cycles at a high current density of 200 mA cm-2, and a high power density up to 606.5 mW cm-2.

Components, Formulations, Deliveries, and Combinations of Tumor Vaccines.

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

Joint diffusion: mutual consistency-driven diffusion model for PET-MRI co-reconstruction.

Objective. Positron Emission Tomography and Magnetic Resonance Imaging (PET-MRI) systems can obtain functional and anatomical scans. But PET suffers from a low signal-to-noise ratio, while MRI are time-consuming. To address time-consuming, an effective strategy involves reducing k-space data collection, albeit at the cost of lowering image quality. This study aims to leverage the inherent complementarity within PET-MRI data to enhance the image quality of PET-MRI.Approach. A novel PET-MRI joint reconstruction model, termed MC-Diffusion, is proposed in the Bayesian framework. The joint reconstruction problem is transformed into a joint regularization problem, where data fidelity terms of PET and MRI are expressed independently. The regular term, the derivative of the logarithm of the joint probability distribution of PET and MRI, employs a joint score-based diffusion model for learning. The diffusion model involves the forward diffusion process and the reverse diffusion process. The forward diffusion process adds noise to transform a complex joint data distribution into a known joint prior distribution for PET and MRI simultaneously, resembling a denoiser. The reverse diffusion process removes noise using a denoiser to revert the joint prior distribution to the original joint data distribution, effectively utilizing joint probability distribution to describe the correlations of PET and MRI for improved quality of joint reconstruction.Main results. Qualitative and quantitative improvements are observed with the MC-Diffusion model. Comparative analysis against LPLS and Joint ISAT-net on the ADNI dataset demonstrates superior performance by exploiting complementary information between PET and MRI. The MC-Diffusion model effectively enhances the quality of PET and MRI images.Significance. This study employs the MC-Diffusion model to enhance the quality of PET-MRI images by integrating the fundamental principles of PET and MRI modalities and leveraging their inherent complementarity. Furthermore, utilizing the diffusion model to learn the joint probability distribution of PET and MRI, thereby elucidating their latent correlation, facilitates a more profound comprehension of the priors obtained through deep learning, contrasting with black-box prior or artificially constructed structural similarities.

A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH.

Time-restricted feeding (TRF) is a potent dietary intervention for improving metabolic diseases, including metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH). However, the mechanism of this efficacy has remained elusive. Here, we show that TRF improves MASLD, which is associated with a significant enrichment of Ruminococcus torques (R. torques). Mechanistically, R. torques suppresses the intestinal HIF-2α-ceramide pathway via the production of 2-hydroxy-4-methylpentanoic acid (HMP). We identify rtMor as a 4-methyl-2-oxopentanoate reductase that synthesizes HMP in R. torques. Finally, we show that either the colonization of R. torques or oral HMP supplementation can ameliorate inflammation and fibrosis in a MASH mouse model. These findings identify R. torques and HMP as potential TRF mimetics for the treatment of metabolic disorders.

Impacts of land cover changes on summer surface ozone in China during 2000-2019.

China implemented continuous forestation and experienced significant greening tendency in the past several decades. While the ecological project brings benefits to regional carbon assimilation, it also affects surface ozone (O3) pollution level through perturbations in biogenic emissions and dry deposition. Here, we use a coupled chemistry-vegetation model to assess the impacts of land use and land cover change (LULCC) on summertime surface O3 in China during 2000-2019. The LULCC is found to enhance O3 by 1-2 ppbv in already-polluted areas. In contrast, moderate reductions of -0.4 to -0.8 ppbv are predicted in southern China where the largest forest cover changes locate. Such inconsistency is attributed to the background chemical regimes with positive O3 changes over VOC-limited regions but negative changes in NOx-limited regions. The net contribution of LULCC to O3 budget in China is 24.17 Kg/s, in which the positive contribution by more isoprene emissions almost triples the negative effects by the increased dry deposition. Although the LULCC-induced O3 perturbation is much lower than the effects of anthropogenic emissions, forest expansion has exacerbated regional O3 pollution in North China Plain and is expected to further enhance surface O3 with continuous forestation in the future.

Dynamic memristor for physical reservoir computing.

Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.

Neutrophil Extracellular Traps-Inspired Bismuth-Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections.

Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug-resistant bacteria, rendering ineffective immune responses and even life-threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid-catechol interaction, the multifunctional bismuth-based polypeptide nanonets (PLBA-Bi-Fe-TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid-functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement-enhanced high-contact network-driven multiple efficiency, PLBA-Bi-Fe-TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic-resistant bacterial biofilms, while Fe-TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro-inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial-associated infections at all stages through synergetic treatment.

Understanding the influencing factors of foreign language teachers' work engagement: A meta-analytic structural equation model.

The work engagement of foreign language teachers enhances both their performance and the quality of instruction. Recent studies have highlighted the pivotal roles of emotional intelligence, job burnout, and self-efficacy in fostering teachers' work engagement. Despite this, the complex interactions between these factors in the context of foreign language teaching remain underexplored. This study conducts a meta-analytic review to examine the connections among work engagement, emotional intelligence, burnout, and self-efficacy among foreign language educators. Utilizing a chain mediation model, it probes the mechanism through which emotional intelligence impacts work engagement, based on an analysis of 49 scholarly articles. Results from the meta-analysis robustly validate the hypothesized model. Specifically, emotional intelligence contributes to work engagement via four distinct routes: direct mediation through self-efficacy, direct mediation through job burnout, and chain mediation involving self-efficacy and job burnout. Of the evaluated factors, emotional intelligence had the most significant impact on enhancing work engagement. Implications of these findings may facilitate the training and ongoing professional development of foreign language teachers.