Biogeographic distribution, assembly processes and potential nutrient cycling functions of myxobacteria communities in typical agricultural soils in China.

Predatory myxobacteria are important soil micropredators with the potential to regulate soil microbial community structure and ecosystem function. However, the biogeographic distribution patterns, assembly processes, and potential nutrient cycling functions of myxobacteria communities in typical agricultural soils in China are still poorly understood. High-throughput sequencing, phylogenetic zero modeling, and the multi-nutrient cycling index were used to assess the biogeographic distribution, assembly processes, and soil ecosystem functions of predation myxobacteria communities in typical agricultural soils of six long-term fertilization ecological experimental stations. The results demonstrated a hump-shaped distribution of myxobacteria α-diversity along the latitudinal gradient and significant differences in myxobacteria ß-diversity in typical agricultural soils (P < 0.05). Bacterial richness, soil organic carbon, and pH were the most important predictors of myxobacteria α-diversity, whereas geographic factors and soil pH were the most significant ecological predictors of myxobacteria ß-diversity. Myxobacteria community assembly is dominated by deterministic processes, especially homogeneous selection, primarily driven by soil pH and bacterial richness. In addition, we revealed the ecological significance of myxobacteria communities in typical agricultural soil microbial networks and the potential link between myxobacteria communities and soil nutrient cycling. These findings enhance our understanding of the biogeographic distribution, community assembly, ecological predictors, and relationships with soil nutrient cycling of myxobacteria communities in typical agricultural soils, paving the way for a more predictive understanding of the effect of predatory myxobacteria communities on soil ecosystem function, which is essential for the development of sustainable agriculture.

Genotypic diversity of staphylococcal enterotoxin B gene (seb) and its association with molecular characterization and antimicrobial resistance of Staphylococcus aureus from retail food.

To investigate the expression pattern of staphylococcal enterotoxin B (SEB) in food and the genotypic diversity of SEB-encoding gene in association with molecular characteristics and antimicrobial resistance of S. aureus, 498 isolates from retail food were screened for seb gene and detected for SEB production in S. aureus. In addition, the seb nucleotide sequences, virulence genes, resistance genes, antimicrobial susceptibility and molecular characteristics of S. aureus were examined. A total of 45 (9.0 %) seb-positive S. aureus strains were identified, all of which expressed SEB. The detection rate of SEB-production strains was significantly higher from dairy-related sources than those from other sources (P < 0.05). In vitro simulations showed that S. aureus could grow and express SEB in both milk and pork, with SEB expression exceeding 20 ng/g after 1 day of storage at room temperature. There were 2 distinct SEB genotyping (SEB1 and SEB2) in the SEB amino acid sequences of the 45 isolates, including 4 amino acid differences (Ala-13Val, Ser14Ala, Asn192Ser, and Met222Leu). There was no significant difference (P > 0.05) in SEB production between SEB1 and SEB2 genotyping strains. Based on MLST clustering analysis, the same molecular type strains were found to have the same SEB genotyping, virulence gene profile, resistance gene profile and drug resistance profile. Among them, the dominant molecular types of SEB1 and SEB2 strains were CC1-ST188-t189 and CC59-ST59-t437, respectively. Compared to the CC1-ST188-t189 clonal strain, the CC59-ST59-t437 clonal strain carried a higher number of virulence and resistance genes and exhibited a broader resistance profile. Therefore, understanding the characteristics of the strains and their expression patterns in food can be effective in preventing food poisoning incidents.

A novel low sampling rate and cost-efficient active sampler for medium/long-term monitoring of gaseous pollutants.

Active sampling is a dependable approach for gaseous pollutants monitoring, offering high accuracy and precision that is unaffected by environmental factors such as wind and temperature in comparison to passive sampling. To measure long-term average concentrations while minimizing the use of materials, a reduced sampling rate is necessary. Thus, this study aims to develop a novel low sampling rate (down to 1 mL/min) and cost-efficient active sampler (LASP) for medium/long-term monitoring of gaseous pollutants. The LASP mainly consisted of a syringe pump, a Y-shaped fitting with two one-way valves, and a control unit for intermittent operation. Results showed that LASP can obtain a sampling rate of less than 1 mL/min and sampling rate exhibited a high level of stability. Daily average concentrations measurements for nitrogen dioxide and formaldehyde by LASP had normalized mean biases of 2.8% and 5.2%, respectively. These numbers were - 5.8% and 6.1% for weekly-average samplings. This study demonstrated applications of LASP in real outdoor (daily-average) and indoor (weekly-average) air quality measurements. It worked well with low noise levels, and without interfering with occupants' daily activities. LASP can assist in improving our ability to monitor air quality and pollutants emissions, thereby supporting health research and policy development. ENVIRONMENTAL IMPLICATION: Gaseous air pollution is an important hazardous factor threatening human health. Medium/long-term air quality monitoring is essential for outdoor and indoor air quality assessment and control. However, air sampler for medium/long-term sampling is lacking. This study developed a novel low sampling rate and cost-efficient active sampler and applied it to medium/long-term air sampling. The sampler can work at a sampling rate of less than 1 mL/min. This technology provides a feasible strategy for medium/long-term monitoring of gaseous air pollutants in both environments and emission hotspots.

Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection.

Although no longer a public health emergency of international concern, COVID-19 remains a persistent and critical health concern. The development of effective antiviral drugs could serve as the ultimate piece of the puzzle to curbing this global crisis. 3-chymotrypsin-like protease (3CLpro), with its substrate specificity mirroring that of the main picornavirus 3C protease and conserved across various coronaviruses, emerges as an ideal candidate for broad-spectrum antiviral drug development. Moreover, it holds the potential as a reliable contingency option to combat emerging SARS-CoV-2 variants. In this light, the approved drugs, promising candidates, and de-novo small molecule therapeutics targeting 3CLpro since the COVID-19 outbreak in 2020 are discussed. Emphasizing the significance of diverse structural characteristics in inhibitors, be they peptidomimetic or nonpeptidic, with a shared mission to minimize the risk of cross-resistance. Moreover, the authors propose an innovative optimization strategy for 3CLpro reversible covalent PROTACs, optimizing pharmacodynamics and pharmacokinetics to better prepare for potential future viral outbreaks.

Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

PM2.5 triggers autophagic degradation of Caveolin-1 via endoplasmic reticulum stress (ERS) to enhance the TGF-ß1/Smad3 axis promoting pulmonary fibrosis.

Air pollution is highly associated with respiratory diseases. However, the influence and mechanism of particulate matter with aerodynamic equal to or less than 2.5 µm (PM2.5) in lung homeostasis remain unclear. Herein, we demonstrated the induction of pulmonary fibrosis (PF) by PM2.5 exposure. The animal model showed that PM2.5 exposure could activate the oxidative stress and inflammation response, promoting epithelial-mesenchymal transition and accumulation of collagen, high expression of pro-fibrotic factors, and pathological characteristics of fibrosis. The proteomic analysis indicated that PM2.5 exposure decreased the expression of caveolin-1 (Cav-1), and many differential proteins were enriched in the TGF-ß1/Smad, endoplasmic reticulum stress (ERS) and autophagy pathways. Combining in vivo and in vitro experiments, it was found that PM2.5 exposure could reduce Cav-1 protein levels and activate TGF-ß1/Smad3 signaling pathways through ERS and autophagy pathways, thereby inducing cell apoptosis and promoting pulmonary fibrosis. However, inhibiting ERS could alleviate the occurrence of autophagy, and blocking the autophagy system could increase the level of Cav-1 protein and inhibit TGF- ß 1/Smad3 signaling pathway to improve pulmonary fibrosis. Therefore, we demonstrated that the exposure of PM2.5 could enhance the ERS induced-autophagy-mediated Cav-1 degradation, thus activating the TGF-ß1/Smad3 axis to promote pneumonocytes apoptosis and overproduction of extracellular matrix (ECM), finally aggravating PF. Moreover, our findings revealed that intermittent exposure to high doses of PM2.5 was more toxic than continuous exposure to low dose.

Prognostic value of circulating tumor DNA in operable non-small cell lung cancer: a systematic review and reconstructed individual patient-data based meta-analysis.

BACKGROUND: This reconstructed individual patient data (IPD)-based meta-analysis is aimed to summarize the current findings and comprehensively investigate the predictive value of circulating tumor DNA (ctDNA) in operable non-small cell lung cancer (NSCLC). METHODS: PubMed, Cochrane and Embase were searched to include potentially eligible studies. The primary outcomes included progression-free survival (DFS) by ctDNA status at baseline, postoperative, and longitudinal timepoints. The IPD-based survival data was retracted and used in reconstructed IPD-based meta-analysis. Subgroup analysis was implemented based on the baseline characteristics. RESULTS: Totally, 28 studies were involved, including 15 full-length articles (1686 patients) for IPD-based synthesis and 20 studies for conventional meta-analysis. The IPD-based meta-analysis discovered that patients with positive ctDNA status at the baseline (hazard ratio, HR = 3.73, 95% confidential interval, CI: 2.95-4.72), postoperative (3.96, 2.19-7.16), or longitudinal timepoints (12.33, 8.72-17.43) showed significantly higher risk of recurrence. Patients with persistent ctDNA-negative status had the lowest recurrence rate, and the negative conversion of ctDNA from baseline to postoperative timepoints was correlated with elevated DFS. Subgroup analyses suggested that stage II-III patients with ctDNA-positive status may achieve preferable therapeutic outcomes. CONCLUSIONS: Plasm ctDNA monitoring shows excellent clinical significance at the tested timepoints. Perioperative conversion of ctDNA status may indicate the therapeutic effect of radical surgery. Postoperative adjuvant therapy may be determined according to the ctDNA status. TRAIL REGISTRATION: CRD42022304445.

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity.

Leveraging the specificity of antibody to deliver cytotoxic agent into tumor, antibody-drug conjugates (ADCs) have become one of the hotspots in the development of anticancer therapies. Although significant progress has been achieved, there remain challenges to overcome, including limited penetration into solid tumors and potential immunogenicity. Fully human single-domain antibodies (UdAbs), with their small size and human nature, represent a promising approach for addressing these challenges. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycosylated cell surface protein that rarely expressed in normal adult tissues but overexpressed in diverse cancers, taking part in tumorigenesis, progression, and metastasis. In this study, we investigated the therapeutic potential of UdADC targeting CEACAM5. We performed biopanning in our library and obtained an antibody candidate B9, which bound potently and specifically to CEACAM5 protein (KD = 4.84 nM) and possessed excellent biophysical properties (low aggregation tendency, high homogeneity, and thermal stability). The conjugation of B9 with a potent cytotoxic agent, monomethyl auristatin E (MMAE), exhibited superior antitumor efficacy against CEACAM5-expressing human gastric cancer cell line MKN-45, human pancreatic carcinoma cell line BxPC-3 and human colorectal cancer cell line LS174T with IC50 values of 38.14, 25.60, and 101.4 nM, respectively. In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

Oryza sativa L. Indica Seed Coat Ameliorated Concanavalin A-Induced Acute Hepatitis in Mice via MDM2/p53 and PKCα/MAPK1 Signaling Pathways.

Acute hepatitis (AH) is a common liver disease with an increasing number of patients each year, requiring the development of new treatments. Hence, our work aimed to evaluate the therapeutic effect of Oryza sativa L. indica (purple rice) seed coat on concanavalin A (ConA)-induced AH and further reveal its potential mechanisms. Purple rice seed coat extract (PRE) was extracted with hydrochloric acid ethanol and analyzed through a widely targeted components method. We evaluated the effects of PRE on AH through histopathological examination, liver function, gut microbiota composition, and the intestinal barrier. The potential targets of PRE on AH were predicted by bioinformatics. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining, and corresponding kits were used to investigate PRE effects on predicting targets and associated signaling pathways in AH mice. In AH model mice, PRE treatment increased transformed mouse 3T3 cell double minute 2 (MDM2) expression to inhibit apoptosis; it also markedly downregulated protein kinase C alpha (PKCα), prostaglandin-endoperoxide synthase 1 (PTGS1), and mitogen-activated protein kinase 1 (MAPK1) activity to alleviate inflammation. Thus, PRE treatment also recovered the intestinal barrier, decreased the lipopolysaccharide (LPS) levels of plasma and the liver, enhanced liver function, and improved the composition of intestinal microbiota. In general, PRE targeting MDM2, PKCα, MAPK1, and PTGS1 ameliorated ConA-induced AH by attenuating inflammation and apoptosis, restoring the intestinal barrier, enhancing the liver function, and improving the gut microbiota, which revealed that the purple rice seed coat might hold possibilities as a therapeutic option for AH.

Red Rice Seed Coat Targeting SPHK2 Ameliorated Alcoholic Liver Disease via Restored Intestinal Barrier and Improved Gut Microbiota in Mice.

Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativa L.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid-ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.

Comprehensive single-cell analysis reveals novel anergic antigen-presenting cell subtypes in human sepsis.

Background: Sepsis is a life-threatening condition with high mortality. A few studies have emerged utilizing single-cell RNA sequencing (scRNA-seq) to analyze gene expression at the single-cell resolution in sepsis, but a comprehensive high-resolution analysis of blood antigen-presenting cells has not been conducted. Methods: All published human scRNA-seq data were downloaded from the single cell portal database. After manually curating the dataset, we extracted all antigen-presenting cells, including dendritic cells (DCs) and monocytes, for identification of cell subpopulations and their gene profiling and intercellular interactions between septic patients and healthy controls. Finally, we further validated the findings by performing deconvolution analysis on bulk RNA sequencing (RNA-seq) data and flow cytometry. Results: Within the traditional DC populations, we discovered novel anergic DC subtypes characterized by low major histocompatibility complex class II expression. Notably, these anergic DC subtypes showed a significant increase in septic patients. Additionally, we found that a previously reported immunosuppressive monocyte subtype, Mono1, exhibited a similar gene expression profile to these anergic DCs. The consistency of our findings was confirmed through validation using bulk RNA-seq and flow cytometry, ensuring accurate identification of cell subtypes and gene expression patterns. Conclusions: This study represents the first comprehensive single-cell analysis of antigen-presenting cells in human sepsis, revealing novel disease-associated anergic DC subtypes. These findings provide new insights into the cellular mechanisms of immune dysregulation in bacterial sepsis.

The pseudoenzyme ADPRHL1 affects cardiac function by regulating the ROCK pathway.

BACKGROUND: Pseudoenzymes, catalytically deficient variants of active enzymes, have a wide range of regulatory functions. ADP-ribosylhydrolase-like 1 (ADPRHL1), a pseudoenzyme belonging to a small group of ADP-ribosylhydrolase enzymes that lacks the amino acid residues necessary for catalytic activity, may have a significant role in heart development based on accumulating evidence. However, the specific function of ADPRHL1 in this process has not been elucidated. To investigate the role of ADPRHL1 in the heart, we generated the first in vitro human embryonic stem cell model with an ADPRHL1 knockout. METHOD: Using the CRISPR/Cas9 system, we generated ADPRHL1 knockout in the human embryonic stem cell (hESC) H9 line. The cells were differentiated into cardiomyocytes using a chemically defined and xeno-free method. We employed confocal laser microscopy to detect calcium transients and microelectrode array (MEA) to assess the electrophysiological activity of ADPRHL1 deficiency cardiomyocytes. Additionally, we investigated the cellular mechanism of ADPRHL1 by Bulk RNA sequencing and western blot. RESULTS: The results indicate that the absence of ADPRHL1 in cardiomyocytes led to adhered abnormally, as well as perturbations in calcium transients and electrophysiological activity. We also revealed that disruption of focal adhesion formation in these cardiomyocytes was due to an excessive upregulation of the ROCK-myosin II pathway. Notably, inhibition of ROCK and myosin II effectively restores focal adhesions in ADPRHL1-deficient cardiomyocytes and improved electrical conduction and calcium activity. CONCLUSIONS: Our findings demonstrate that ADPRHL1 plays a critical role in maintaining the proper function of cardiomyocytes by regulating the ROCK-myosin II pathway, suggesting that it may serve as a potential drug target for the treatment of ADPRHL1-related diseases.

RUNX1 promotes proliferation and migration in non-small cell lung cancer cell lines via the mTOR pathway.

RUNX1, a member of the RUNX family of metazoan transcription factors, participates in the regulation of differentiation, proliferation, and other processes involved in growth and development. It also functions in the occurrence and development of tumors. However, the role and mechanism of action of RUNX1 in non-small cell lung cancer (NSCLC) are not yet clear. We used a bioinformatics approach as well as in vitro and in vivo assays to evaluate the role of RUNX1 in NSCLC as the molecular mechanisms underlying its effects. Using the TCGA, GEO, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan-Meier databases, we screened the differentially expressed genes (DEGs) and found that RUNX1 was highly expressed in lung cancer and was associated with a poor prognosis. Immunohistochemical staining based on tissue chips from 110 samples showed that the expression of RUNX1 in lung cancer tissues was higher than that in adjacent normal tissues and was positively correlated with lymph node metastasis and TNM staging. In vitro experiments, we found that RUNX1 overexpression promoted cell proliferation and migration functions and affected downstream functional proteins by regulating the activity of the mTOR pathway, as confirmed by an analysis using the mTOR pathway inhibitor rapamycin. In addition, RUNX1 affected PD-L1 expression via the mTOR pathway. These results indicate that RUNX1 is a potential therapeutic target for NSCLC.

Risk factors for hypotension in patients with hemodialysis-associated superior vena cava syndrome.

OBJECTIVE: We analyzed the risk factors for hypotension in patients with hemodialysis-associated superior vena cava syndrome (SVCS) and effectiveness of endovascular intervention in hypotension related to SVCS. METHODS: This was a retrospective cohort study. A total of 194 maintenance hemodialysis patients diagnosed with SVCS who were admitted to the Department of Nephrology, West China Hospital of Sichuan University from January 2019 to December 2021 were selected and divided into a hypotension group and a nonhypotension group. Demographic and clinical data were compared. Hypotension simply refers to blood pressure levels of <90/60 mm Hg on a nondialysis day. All patients received endovascular intervention. RESULTS: Hypotension was found in 85 of the 194 patients. The following factors were significantly different between the hypotension and nonhypotension groups: body mass index, history of hypertension, tunneled-cuffed catheter as the means of dialysis access, azygos ectasis, SVC stenosis of >70% or occlusion, occlusion at the cavitary junction, serum calcium, diastolic left ventricular (LV) posterior wall thickness, LV end-diastolic volume, stroke output, and LV ejection fraction. Multivariate logistic regression analysis showed that hypertension history (OR, 0.314; P = .027), tunneled-cuffed catheter as vascular access (OR, 3.997; P < .001), SVC stenosis of >70% or occlusion (OR, 5.243; P < .001), LV posterior wall thickness (OR, 0.772; P = .044), and serum calcium (OR, 0.146; P = .005) were independent risk factors for hypotension. The mean values of systolic and diastolic blood pressure after intravascular treatment were significantly elevated from those before intervention (P < .001). The primary patency rates of SVC were 66.8%, 58.7%, and 50.0% at 3, 6, and 12 months after the procedure. CONCLUSIONS: The incidence of hypotension in patients with hemodialysis-associated SVCS is high. The identification of risk factors of hemodialysis-related hypotension provides insight into potential treatment strategies. Endovascular treatment is expected to improve hypotension related to SVCS in hemodialysis patients.

Cancer-associated fibroblasts in hematologic malignancies: elucidating roles and spotlighting therapeutic targets.

Hematologic malignancies comprise a diverse range of blood, bone marrow, and organ-related disorders that present significant challenges due to drug resistance, relapse, and treatment failure. Cancer-associated fibroblasts (CAFs) represent a critical component of the tumor microenvironment (TME) and have recently emerged as potential therapeutic targets. In this comprehensive review, we summarize the latest findings on the roles of CAFs in various hematologic malignancies, including acute leukemia, multiple myeloma, chronic lymphocytic leukemia, myeloproliferative neoplasms, and lymphoma. We also explore their involvement in tumor progression, drug resistance, and the various signaling pathways implicated in their activation and function. While the underlying mechanisms and the existence of multiple CAF subtypes pose challenges, targeting CAFs and their associated pathways offers a promising avenue for the development of innovative treatments to improve patient outcomes in hematologic malignancies.

Passive array micro-magnetic stimulation device based on multi-carrier wireless flexible control for magnetic neuromodulation.

Objective.The passive micro-magnetic stimulation (µMS) devices typically consist of an external transmitting coil and a single internal micro-coil, which enables a point-to-point energy supply from the external coil to the internal coil and the realization of magnetic neuromodulation via wireless energy transmission. The internal array of micro coils can achieve multi-target stimulation without movement, which improves the focus and effectiveness of magnetic stimulations. However, achieving a free selection of an appropriate external coil to deliver energy to a particular internal array of micro-coils for multiple stimulation targets has been challenging. To address this challenge, this study uses a multi-carrier modulation technique to transmit the energy of the external coil.Approach.In this study, a theoretical model of a multi-carrier resonant compensation network for the arrayµMS is established based on the principle of magnetically coupled resonance. The resonant frequency coupling parameter corresponding to each micro-coil of the arrayµMS is determined, and the magnetic field interference between the external coil and its non-resonant micro-coils is eliminated. Therefore, an effective magnetic stimulation threshold for a micro-coil corresponding to the target is determined, and wireless free control of the internal micro-coil array is achieved by using an external transmitting coil.Main results.The passiveµMS array model is designed using a multi-carrier wireless modulation method, and its synergistic modulation of the magnetic stimulation of synaptic plasticity long-term potentiation in multiple hippocampal regions is investigated using hippocampal isolated brain slices.Significance.The results presented in this study could provide theoretical and experimental bases for implantable micro-magnetic device-targeted therapy, introducing an efficient method for diagnosis and treatment of neurological diseases and providing innovative ideas for in-depth application of micro-magnetic stimulation in the neuroscience field.

miR-30a-3p Regulates Autophagy in the Involution of Mice Mammary Glands.

The mammary gland undergoes intensive remodeling during the lactation cycle, and the involution process of mammary gland contains extensive epithelial cells involved in the process of autophagy. Our studies of mice mammary glands suggest that miR-30a-3p expression was low during involution compared with its high expression in the mammary glands of lactating mice. Then, we revealed that miR-30a-3p negatively regulated autophagy by autophagy related 12 (Atg12) in mouse mammary gland epithelial cells (MMECs). Restoring ATG12, knocking down autophagy related 5 (Atg5), starvation, and Rapamycin were used to further confirm this conclusion. Overexpression of miR-30a-3p inhibited autophagy and altered mammary structure in the involution of the mammary glands of mice, which was indicative of alteration in mammary remodeling. Taken together, these results elucidated the molecular mechanisms of miR-30a-3p as a key induction mediator of autophagy by targeting Atg12 within the transition period between lactation and involution in mammary glands.

The therapeutic effects of fermented milk with lactic acid bacteria from traditional Daqu on hypertensive mice.

Lactic acid bacteria (LAB), a type of microorganisms widely utilized in functional foods, have gained significant research attention in recent years. Certain strains possess the proteolytic ability to release potentially antihypertensive peptides from dairy proteins, which prompted us to explore the LAB strains from an understudied and unique ingredient, Daqu. We screened for 67 strains of LAB strains from traditional Daqu using the calcium dissolution ring method. Sixteen strains exhibiting ACE inhibition (ACE-I) activity exceeding 50% were chosen for 16S rDNA sequencing and safety assessment. It is noteworthy that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 exhibited significant ACE-I activity, which was the result of strains fermentation in reconstituted skim milk. These 2 strains did not exhibit hemolytic activity or antibiotic resistance. They also did not produce biogenic amines and showed high survival rates in the gastrointestinal tract. Additionally, Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 fermented milk exhibited a notable reduction in blood pressure levels in spontaneously hypertensive rats (SHR) compared with negative controls in SHR. Importantly, no adverse effect was observed in normal Wistar-Kyoto rats (WKY rats). Through the analysis of physiological, serum, and urine-related indicators, it was observed that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 have the potential to promote weight gain in SHR, alleviate excessive heart rate, improve renal function indicators, and effectively regulate blood sugar and uric acid levels in SHR. These 2 strains showed optimal properties in lowering blood pressure and have the potential to be used in functional dairy products in the future.

Targeted and non-targeted screening of flame retardants in rural and urban honey.

Flame retardants (FRs) are often added to commercial products to achieve flammability resistance, but they are not chemically bonded to the materials, so, they can be easily released into the environment during the production and disposal processes. When honeybees travel to collect nectar during the pollination process, they are prone to be contaminated by chemicals in the air. Therefore, honey contamination has been proposed as an indicator of the pollution status in a particular region. To date, the occurrence of flame retardants in urban honey has yet to be explored. In this study, a direct injection method was used, coupled with LC-QTOF-MS, to analyze honey samples. This method was applied to urban (n = 100) and rural (n = 100) honey samples from the Quebec province (Canada), and the levels of flame retardants in urban and rural honey samples were not significantly different. In the targeted approach, two of the target FRs, tris(2-butoxyethyl) phosphate (TBOEP) and triphenyl phosphate (TPHP), were detected and confirmed at an average trace concentration (<1 ng mL-1). Additionally, a non-targeted screening workflow with an in-house-built library was developed and validated to screen for flame retardants in honey. Tris (2-chloropropyl) phosphate (TCIPP) was identified in honey using the non-targeted screening workflow and confirmed using a pure analytical standard, but there are other compounds detected in the non-targeted analysis that have yet to be validated. This study was the first to report FR compounds based on a direct injection method, coupled with a non-targeted screening workflow, at a trace level in a honey matrix. It also showed that a non-targeted workflow was effective to detect and identify unknown compounds present in the honey sample; hence, this provided a novel angle for the occurrence of FRs in air, with honey as a bio-indicator.

Hybrid Crosslinked Solid Polymer Electrolyte via In-Situ Solidification Enables High-Performance Solid-State Lithium Metal Batteries.

Solid-state lithium-metal batteries constructed by in-situ solidification of cyclic ether are considered to be a critical strategy for the next generation of solid-state batteries with high energy density and safety. However, the poor thermal/electrochemical stability of linear polyethers and severe interfacial reactions limit its further development. Herein, in-situ ring-opening hybrid crosslinked polymerization is proposed for organic/inorganic hybrid polymer electrolyte (HCPE) with superior ionic conductivity of 2.22 × 10-3 S cm-1 at 30 °C, ultrahigh Li+ transference number of 0.88, and wide electrochemical stability window of 5.2 V. These allow highly stable lithium stripping/plating cycling for over 1000 h at 1 mA cm-2 , which also reveal a well-defined interfacial stabilization mechanism. Thus, HCPE endows assembled solid-state lithium-metal batteries with excellent long-cycle performance over 600 cycles at 2 C (25 °C) and superior capacity retention of 92.1%. More importantly, the proposed noncombustible HCPE opens up a new frontier to promote the practical application of high safety and high energy density solid-state batteries via in-situ solidification.