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Abstract During bacterial cytokinesis, polymers of the bacterial tubulin FtsZ coalesce into the Z ring to orchestrate divisome assembly and septal cell wall synthesis. Previous studies have found that Z ring condensation and stability is critical for successful cell division. However, how FtsZ filaments condense into a Z ring remains enigmatic and whether septal cell wall synthesis can feedback to the Z ring has not been investigated. Here, we show that FtsZ-associated proteins (Zaps) play important roles in Z ring condensation and stability, and discover septal cell wall synthesis as a novel player for Z ring condensation and stabilization in Escherichia coli and Caulobacter crescentus. Moreover, we find that the interaction between the Z ring membrane anchor, FtsA, and components of the septal cell wall synthetic complex are critical for septal cell wall synthesis-mediated Z ring condensation. Altogether, these findings suggest that the divisome is a self-enhancing machine in these two gram-negative bacteria, where the Z ring and the septal cell wall synthetic complex communicate with and reinforce each other to ensure robustness of cell division.

Abstract Background The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE. Methods A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed. Results A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P

Calcification of cartilage by hydroxyapatite is a hallmark of osteoarthritis and its deposition strongly correlates with the severity of osteoarthritis. However, no effective strategies are available to date on the prevention of hydroxyapatite deposition within the osteoarthritic cartilage and its role in the pathogenesis of this degenerative condition is still controversial. Therefore, the present work aims at uncovering the pathogenic mechanism of intra-cartilaginous hydroxyapatite in osteoarthritis and developing feasible strategies to counter its detrimental effects. With the use of in vitro and in vivo models of osteoarthritis, hydroxyapatite crystallites deposited in the cartilage are found to be phagocytized by resident chondrocytes and processed by the lysosomes of those cells. This results in lysosomal membrane permeabilization (LMP) and release of cathepsin B (CTSB) into the cytosol. The cytosolic CTSB, in turn, activates NOD-like receptor protein-3 (NLRP3) inflammasomes and subsequently instigates chondrocyte pyroptosis. Inhibition of LMP and CTSB in vivo are effective in managing the progression of osteoarthritis. The present work provides a conceptual therapeutic solution for the prevention of osteoarthritis via alleviation of lysosomal destabilization.

Abstract Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single‐cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV‐releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

Abstract Recurrent spontaneous abortion (RSA) is a serious condition that adversely affects women's health. Differentially expressed proteins (DEPs) in plasma of patients experiencing RSA is helpful to find new therapeutic targets and identified with mass spectrometry. In 57 DEPs, 21 were upregulated and 36 were downregulated in RSA. Gene ontology analyses indicated that identified DEPs were associated with cell proliferation, including significantly downregulated insulin‐like growth factor binding protein 2 (IGFBP2). Immunohistochemical result using clinical decidual tissues also showed that IGFBP2 expression was significantly decreased in RSA trophoblasts. Cell proliferation assay indicated that IGFBP2 treatment increased the proliferation and mRNA expressions of PCNA and Ki67 in trophoblast cells. Transcriptome sequencing experiments and Kyoto Encyclopedia of Genes and Genomes analyses revealed that gene expression for components in PI3K‐Akt pathway in trophoblasts was significantly upregulated following IGFBP2 treatment. To confirm bioinformatics findings, we did cell‐based experiments and found that treatment of inhibitors for insulin‐like growth factor (IGF)‐1 receptor‐PI3K‐Akt pathway significantly reduced IGFBP2‐induced trophoblast cell proliferation and mRNA expressions of PCNA and Ki67. Our findings suggest that IGFBP2 may increase trophoblast proliferation through the PI3K‐Akt signaling pathway to affect pregnancy outcomes and that IGFBP2 may be a new target for future research and treatment of RSA.

Abstract At present, reports on the arc interruption and decomposition behavior of a C4F7N/air gas mixture especially the biosafety of its by‐products are limited. Herein, a 57% C4F7N/43% air gas mixture was employed as an arc‐quenching medium to conduct 200 breaking tests on a load switch (630 A/24 kV). The arc interruption and decomposition behavior of the gas mixture were evaluated, and the biosafety of the decomposition products was assessed based on an acute inhalation toxicity test. It was found that the average arcing time of the 200 breakings was about 10.1 ms and that breakings were basically completed at the zero‐crossing of the second or third current half‐cycle. The gas mixture after breaking decomposed dramatically (the C4F7N content decreased by 75.6%), generating a large number of gaseous by‐products (CO, CF4, C2F6, C3F8, CF3CN, C4F8, CO2, C4F10N2, C3F6, C2N2, etc.) as well as solid by‐products (carbon particles). The lethal concentration of 50% (LC50, 4 h) of C4F7N/air after 200 breakings was 31 ppm (male mice) and 34 ppm (female mice), respectively, and the toxicity was classified as Grade 1. In general, C4F7N has an arc interruption capability, albeit weaker than that of SF6 under the same conditions. After breaking, the C4F7N gas mixture has a relatively high acute inhalation toxicity, and relevant safety protection measures for research or operation personnel are strictly needed.

Summary Butenyl‐spinosyn, a promising biopesticide produced by Saccharopolyspora pogona, exhibits stronger insecticidal activity and a broader pesticidal spectrum. However, its titre in the wild‐type S. pogona strain is too low to meet the industrial production requirements. Deletion of non‐target natural product biosynthetic gene clusters resident in the genome of S. pogona could reduce the consumption of synthetic precursors, thereby promoting the biosynthesis of butenyl‐spinosyn. However, it has always been a challenge for scientists to genetically engineer S. pogona. In this study, the Latour gene knockout system (linear DNA fragment recombineering system) was established in S. pogona. Using the Latour system, a hybrid NRPS‐T1PKS cluster (˜20 kb) which was responsible for phthoxazolin biosynthesis was efficiently deleted in S. pogona. The resultant mutant S. pogona‐Δura4‐Δc14 exhibited an extended logarithmic phase, increased biomass and a lower glucose consumption rate. Importantly, the production of butenyl‐spinosyn in S. pogona‐Δura4‐Δc14 was increased by 4.72‐fold compared with that in the wild‐type strain. qRT‐PCR analysis revealed that phthoxazolin biosynthetic gene cluster deletion could promote the expression of the butenyl‐spinosyn biosynthetic gene cluster. Furthermore, a TetR family transcriptional regulatory gene that could regulate the butenyl‐spinosyn biosynthesis has been identified from the phthoxazolin biosynthetic gene cluster. Because dozens of natural product biosynthetic gene clusters exist in the genome of S. pogona, the strategy reported here will be used to further promote the production of butenyl‐spinosyn by deleting other secondary metabolite synthetic gene clusters.

Summary: Intestinal dysbiosis is prominent in systemic sclerosis (SSc), but it remains unknown how it contributes to microvascular injury and fibrosis that are hallmarks of this disease. Trimethylamine (TMA) is generated by the gut microbiome and in the host converted by flavin-containing monooxygenase (FMO3) into trimethylamine N-oxide (TMAO), which has been implicated in chronic cardiovascular and metabolic diseases. Using cell culture systems and patient biopsies, we now show that TMAO reprograms skin fibroblasts, vascular endothelial cells, and adipocytic progenitor cells into myofibroblasts via the putative TMAO receptor protein R-like endoplasmic reticulum kinase (PERK). Remarkably, FMO3 was detected in skin fibroblasts and its expression stimulated by TGF-β1. Moreover, FMO3 was elevated in SSc skin biopsies and in SSc fibroblasts. A meta-organismal pathway thus might in SSc link gut microbiome to vascular remodeling and fibrosis via stromal cell reprogramming, implicating the FMO3-TMAO-PERK axis in pathogenesis, and as a promising target for therapy.

Using the first-principles theory, the geometric and electronic properties of the Ru-doped PtTe2 (Ru-PtTe2) monolayer, and its sensing performance for three VOCs biomarkers, namely, 2-propenal (C3H4O), acetone (C3H6O) and isoprene (C5H8), were analyzed, to expound its potential for exhaled breath analysis and diagnosis of lung cancer. It was found that the Ru-substitution on the surface of the pristine PtTe2 surface with a Te atom is energy-favorable, with the formation energy of −1.22 eV. Upon adsorption of the three VOC gas species, chemisorption was identified with the adsorption energies of −1.72, −1.12 and −1.80 eV for C3H4O, C3H6O and C5H8, respectively. The Ru-doping results in a strong magnetic property for the PtTe2 monolayer, whereas the gas adsorption eliminates this magnetic behavior. The electronic properties reveal the sensing mechanism of the Ru-PtTe2 monolayer for gas detection, and the bandgap change indicates its admirable positive sensing response for the three gas species. Therefore, we conclude that the Ru-PtTe2 monolayer is a promising sensing material to realize the diagnosis of lung cancer through exhaled gas detection, with a remarkable decrease in its electrical conductivity. This work paves the way for further exploration of the PtTe2-based gas sensor for early diagnosis of lung cancer, and we hope that more sensing materials can be investigated using the PtTe2 monolayer.

Given the serious threat of lung cancer due to the strong concealment at early stage, primary diagnosis becomes quite essential to guarantee human health. The adsorption behaviors of introduced Ir-CNT upon two categories of typical gases of lung cancer (aniline and o-toluidine) have been investigated based on DFT method. At the same time, the sensing characteristics towards these two gases were conducted as well by our prepared sensors prepared by drying the Ir deposited CNT aqueous solution onto the interdigital electrode substrate. Results indicate that Ir-CNT based material can be desirable and promising for sensing upon exhaled gas of lung cancer patient, because of the excellent adsorptions upon two kinds of main typical gases. Such strong interactions of Ir-CNT towards typical gas adsorbed leads to the significant electronic redistributions of the modified surface, thereby causing apparent reduction in conductivity after adsorptions. This could be detected by a practical prepared resistivity-type sensor. Our theoretical calculations are in good accordance with the experimental results, which demonstrate the feasibility of Ir-CNT for potential application in the near future in the field of lung cancer diagnosis.

Titanium alloys have promising potential for applications in marine nuclear power systems owing to their exceptional mechanical and corrosion properties. Nevertheless, their radiation resistivity is a determining factor for their extensive use as structural materials in nuclear energy systems. In this study, the radiation resistivity of Ti–5Al–3V–3Zr–Cr (Ti-5331) alloys with three different microstructures was examined using a combination of characterization techniques including positron annihilation Doppler broadening spectroscopy (DBS), Elastic Recoil Detection Analysis (ERDA), Transmission Electron Microscope (TEM), Small-Angle X-ray scattering (SAXS) and nanoindentation. The results reveal that the equiaxed structure, bimodal structure, and Widmanstatten structure of Ti-5331 alloy obtained through different annealing processes exhibit differences in the number of interfaces and the content of the β phase. The α/β interfaces can significantly enhance the radiation resistance of titanium alloys by inhibiting the diffusion of helium atoms after helium ion irradiation. Notably, the alloy with a bimodal structure exhibited the best overall radiation resistivity, showing small defect size, low hardening effect, and low swelling rate of 0.003%. Moreover, the size of helium bubbles of the bimodal structure is half of that in the equiaxed structure and Widmanstatten structure. Thus, the bimodal structure of the Ti-5331 alloy possesses superior radiation resistivity.

Abstract Antioxidant-rich diets serve as protective factors in preventing obesity. The composite dietary antioxidant index (CDAI) represents a novel, comprehensive metric for assessing the antioxidant capacity of diets. Our objective is to investigate the relationship between the CDAI and obesity prevalence among adults in the United States. Dietary and anthropometric information about adults aged 20 years and older were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. The CDAI was derived from six dietary antioxidants. Obesity is defined as a body mass index (BMI, kg/m2) ≥ 30 kg/m2, and abdominal obesity as a waist circumference (WC, cm) ≥ 102 cm for men and ≥ 88 cm for women. The relationship between CDAI and obesity, including abdominal obesity, was analyzed using logistic regression and subgroup analyses. A total of 25,553 participants were analyzed. With higher tertiles of the CDAI, both obesity (41.28% vs. 38.62 vs. 35.09%, P

Abstract Background The purpose of this study is to explore the feasibility and accuracy of a robot-assisted technique in four-corner fusion compared with traditional freehand operation. Methods Twenty cadaver specimens were randomly assigned to the robot-assisted group and freehand groups. Three screws were placed percutaneously to fix the capitate-lunate joint, lunate-triquetrum joint, and triquetrum-hamate-capitate joint in each specimen by robot-assisted or freehand technique. The offset between the actual and planned screw positions was determined by merging the images of intraoperative and postoperative CT scans in the robot-assisted group. The centrality of the screw, time-consuming, drilling attempts, and radiation exposure were compared between the two groups. Results The mean offset between the actual and planned screw position was 1.09 (SD: 0.56) mm. The offset at the start point of the screw was significantly lower than that at the endpoint. There was no significant difference in the centrality of the screws, surgical time between the two groups. The number of drilling attempts and the radiation dose received by surgeons were significantly lower in the robot-assisted group. Conclusions Although there was no significant difference in screw centrality between the two groups, the slight offset between the actual and planned screw positions confirmed the feasibility of the robot-assisted technique in four-corner fusion. The robot-assisted technique has advantages in reducing the difficulty of surgery and protecting the surgeon from exposure to large doses of radiation.

Abstract Aims Night blindness (NB), an important manifestation of VA deficiency, may be associated with the odds of diabetes. The aim of this study was to explore the probable association between NB history and diabetes in Chinese community-dwelling adults. Methods This multi-center, cross-sectional study enrolled a total of 5664 participants aged 18–82 years from eight sites in China. Information on demographics and medical history was collected using a standardized questionnaire. Diabetes was diagnosed based on the oral glucose tolerance test or a self-reported history. NB history was ascertained by a face-to-face interview with reference to the recommendation by the World Health Organization. Logistic regression analysis was used to evaluate the association between NB history and the odds of diabetes. Results A total of 5049 participants were finally included, with 252 ascertained with NB history and 1076 with diabetes. The mean age of included participants was 52.9 years, and the percentage of participants with NB history was significantly higher in participants with diabetes than those without (7.0% vs. 4.5%). The multivariable adjusted odds ratio for diabetes was 1.41 (95% confidence interval 1.06, 1.89) in participants with NB history compared with those without. Furthermore, mediation analysis showed that obesity, as assessed by waist-height ratio, partially mediated the relationship between NB history and increased odds of diabetes. Conclusions The results suggest that NB history might be associated with increased odds of diabetes in Chinese community-dwelling adults.

Abstract Background Aflatoxin B1 (AFB1) is a prevalent contaminant in agricultural products, presenting significant risks to animal health. CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test. The efficacy of Bacillus CotA laccase in animals, however, remains to be confirmed. A 2 × 2 factorial design was used to investigate the effects of Bacillus CotA laccase level (0 or 1 U/kg), AFB1 challenge (challenged or unchallenged) and their interactions on ducks. The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviating AFB1 toxicosis of ducks. Results Bacillus CotA laccase alleviated AFB1-induced declines in growth performance of ducks accompanied by improved average daily gain (ADG) and lower feed/gain ratio (F/G). Bacillus CotA laccase ameliorated AFB1-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio (VH/CD) and the mRNA expression of tight junction protein 1 (TJP1) and zonula occluden-1 (ZO-1) as well as decreasing the expression of inflammation-related genes in the jejunum of ducks. Amino acid metabolome showed that Bacillus CotA laccase ameliorated AFB1-induced amino acid metabolism disorders evidenced by increasing the level of glutamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks. Bacillus CotA laccase ameliorated AFB1-induced liver injury testified by suppressing oxidative stress, inhibiting apoptosis, and downregulating the expression of hepatic metabolic enzyme related genes of ducks. Moreover, Bacillus CotA laccase degraded AFB1 in digestive tract of ducks, resulting in the reduced absorption level of AFB1 across intestinal epithelium testified by the decreased level of AFB1-DNA adduct in the liver, and the reduced content of AFB1 residues in liver and feces of ducks. Conclusions Bacillus CotA laccase effectively improved the growth performance, intestinal health, amino acid metabolism and hepatic aflatoxin metabolism of ducks fed AFB1 diets, highlighting its potential as an efficient and safe feed enzyme for AFB1 degradation in animal production. Graphical Abstract

Abstract Background Lipid metabolism dysregulation is a key characteristic of hepatocellular carcinoma (HCC) onset and progression. Elevated expression of immunoglobulin (Ig), especially the Igκ free light chain with a unique Vκ4-1/Jκ3 rearrangement in cancer cells, is linked to increased malignancy and has been implicated in colon cancer tumorigenesis. However, the role of Igκ in HCC carcinogenesis remains unclear. The aim of this study was to elucidate the pivotal roles of hepatocyte-derived Igκ in HCC development. Methods The rearrangement sequence and expression level of hepatocyte-derived Igκ in HCC cells were determined via RT-PCR, Sanger sequencing, immunohistochemistry, and western blot analysis. The function of Igκ in HCC tumorigenesis was assessed by silencing Igκ using siRNA or gRNA in various HCC cell lines. To assess the role of Igκ in HCC pathogenesis in vivo, a mouse model with hepatocyte-specific Igκ knockout and diethylnitrosamine (DEN) and carbon tetrachloride (CCL4)-induced HCC was utilized. The molecular mechanism by which Igκ affects HCC tumorigenesis was investigated through multiomics analyses, quantitative real-time PCR, immunoprecipitation, mass spectrometry, immunofluorescence, and metabolite detection. Results We confirmed that Igκ, especially Vκ4-1/Jκ3-Igκ, is highly expressed in human HCC cells. Igκ depletion inhibited HCC cell proliferation and migration in vitro, and hepatocyte-specific Igκ deficiency ameliorated HCC progression in mice with DEN and CCL4-induced HCC in vivo. Mechanistically, Vκ4-1/Jκ3-Igκ interacts with electron transfer flavoprotein subunit α (ETFA), delaying its protein degradation. Loss of Igκ led to a decrease in the expression of mitochondrial respiratory chain complexes III and IV, resulting in aberrant fatty acid β-oxidation (FAO) and lipid accumulation, which in turn inhibited HCC cell proliferation and migration. Conclusion Our findings indicate that the Igκ/ETFA axis deregulates fatty acid β-oxidation, contributing to HCC progression, which suggests that targeting fatty acid metabolism may be an effective HCC treatment strategy. The results of this study suggest that hepatocyte-derived Vκ4-1/Jκ3-Igκ may serve as a promising therapeutic target for HCC.

Background: Yi-Shen-Gu-Tai-Ke-Li (YSGTKL), a renowned traditional herbal formula, has demonstrated clinical efficacy in addressing recurrent spontaneous abortion (RSA). Despite its widespread utilization in China, the current body of evidence regarding the effectiveness of its herbal components remains insufficient, and the underlying mechanisms of action remain enigmatic. This study endeavors to unravel the mechanisms responsible for the therapeutic effectiveness of YSGTKL in treating RSA, particularly within the context of female fitness and athletic populations. Methods: YSGTKL comprises various herbal plants, selected based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Specific drug targets associated with RSA were meticulously identified and corroborated using multiple reputable sources, including DrugBank, GeneCards, and Online Mendelian Inheritance in Man. The GEO database was leveraged to pinpoint differentially expressed genes (DEGs) relevant to RSA within female fitness and athletic populations. Subsequently, a comprehensive drug-compound-gene-disease network was meticulously constructed and visualized using Cytoscape software. Functional insights were gleaned through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Within this network, a subset of hub genes was discerned through a protein-protein interaction (PPI) network analysis, specifically tailored to female fitness and athletic populations. To validate key active ingredients and core targets, molecular docking analyses were meticulously performed, taking into account the unique physiological aspects of female athletes and fitness enthusiasts. Results: A total of 195 active compounds were extracted from the 10 herbs constituting YSGTKL. Additionally, 8,905 common targets associated with RSA were identified from multiple comprehensive databases, with a specific focus on their relevance to female fitness and athletic populations. Subsequently, 432 DEGs were identified through the analysis of GEO datasets within this unique demographic, with 13 overlapping genes extracted from the integrated datasets. The resultant drug-compound-gene-disease network comprised 10 herbs, 123 compounds, and 13 pivotal targets, all tailored to the specific context of female fitness and athletic populations. These identified genes exhibited enrichment in several disease-related signaling pathways pertinent to this demographic. Notably, GF2, linked to MET, IGFBP3, and ERBB3, emerged as the hub genes in the PPI network within the context of female athletes and fitness enthusiasts. Molecular docking analyses were conducted to investigate the interaction between quercetin and IGF2, considering the unique physiological characteristics of this demographic. Importantly, downregulation of IGF2 was observed in villus samples from RSA patients within female fitness and athletic populations compared to normal pregnant women. Furthermore, it was found that quercetin promoted trophoblast cell proliferation, migration, and invasion while concurrently inhibiting IGF2 expression, highlighting its potential relevance for this demographic. Conclusion: This study showcases the utility of network pharmacology in elucidating the effective compounds and mechanisms of action underlying the therapeutic efficacy of the YSGTKL formula in the treatment of RSA, particularly within the unique context of female fitness and athletic populations. [ABSTRACT FROM AUTHOR]

Abstract Background Hematopoietic stem progenitor cells (HSPCs) undergo phenotypical and functional changes during their emergence and development. Although the molecular programs governing the development of human hematopoietic stem cells (HSCs) have been investigated broadly, the relationships between dynamic metabolic alterations and their functions remain poorly characterized. Methods In this study, we comprehensively described the proteomics of HSPCs in the human fetal liver (FL), umbilical cord blood (UCB), and adult bone marrow (aBM). The metabolic state of human HSPCs was assessed via a Seahorse assay, RT‒PCR, and flow cytometry-based metabolic-related analysis. To investigate whether perturbing glutathione metabolism affects reactive oxygen species (ROS) production, the metabolic state, and the expansion of human HSPCs, HSPCs were treated with buthionine sulfoximine (BSO), an inhibitor of glutathione synthetase, and N-acetyl-L-cysteine (NAC). Results We investigated the metabolomic landscape of human HSPCs from the fetal, perinatal, and adult developmental stages by in-depth quantitative proteomics and predicted a metabolic switch from the oxidative state to the glycolytic state during human HSPC development. Seahorse assays, mitochondrial activity, ROS level, glucose uptake, and protein synthesis rate analysis supported our findings. In addition, immune-related pathways and antigen presentation were upregulated in UCB or aBM HSPCs, indicating their functional maturation upon development. Glutathione-related metabolic perturbations resulted in distinct responses in human HSPCs and progenitors. Furthermore, the molecular and immunophenotypic differences between human HSPCs at different developmental stages were revealed at the protein level for the first time. Conclusion The metabolic landscape of human HSPCs at three developmental stages (FL, UCB, and aBM), combined with proteomics and functional validations, substantially extends our understanding of HSC metabolic regulation. These findings provide valuable resources for understanding human HSC function and development during fetal and adult life.

Dietary fat content can reduce the methane production of dairy cows; however, the relevance fatty acid (FA) composition has towards this inhibitory effect is debatable. Furthermore, in-depth studies elucidating the effects of unsaturated fatty acids (UFA) on rumen function and the mechanism of reducing methane (CH4) production are lacking. This study exposed 10 Holstein cows with the same parity, similar milk yield to two total mixed rations: low unsaturated FA (LUFA) and high unsaturated FA (HUFA) with similar fat content. The LUFA group mainly added fat powder (C16:0 > 90%), and the HUFA group mainly replaced fat powder with extruded flaxseed. The experiment lasted 26 d, the last 5 d of which, gas exchange in respiratory chambers was conducted to measure gas emissions. We found that an increase in the UFA in diet did not affect milk production (P > 0.05) and could align the profile of milk FAs more closely with modern human nutritional requirements. Furthermore, we found that increasing the UFA content in the diet lead to a decrease in the abundance of Methanobrevibacter in the rumen (|linear discriminant analysis [LDA] score| > 2 and P 2 and P

Abstract To achieve high power conversion efficiency in perovskite/silicon tandem solar cells, it is necessary to develop a promising wide-bandgap perovskite absorber and processing techniques in relevance. To date, the performance of devices based on wide-bandgap perovskite is still limited mainly by carrier recombination at their electron extraction interface. Here, we demonstrate assembling a binary two-dimensional perovskite by both alternating-cation-interlayer phase and Ruddlesden−Popper phase to passivate perovskite/C60 interface. The binary two-dimensional strategy takes effects not only at the interface but also in the bulk, which enables efficient charge transport in a wide-bandgap perovskite solar cell with a stabilized efficiency of 20.79% (1 cm2). Based on this absorber, a monolithic perovskite/silicon tandem solar cell is fabricated with a steady-state efficiency of 30.65% assessed by a third party. Moreover, the tandem devices retain 96% of their initial efficiency after 527 h of operation under full spectral continuous illumination, and 98% after 1000 h of damp-heat testing (85 °C with 85% relative humidity).

Abstract Metabolomics plays a crucial role in understanding metabolic processes within biological systems. Using specific pulse sequences, NMR-based metabolomics detects small and macromolecular metabolites that are altered in blood samples. Here we proposed a method called spectral editing neural network, which can effectively edit and separate the spectral signals of small and macromolecules in 1H NMR spectra of serum and plasma based on the linewidth of the peaks. We applied the model to process the 1H NMR spectra of plasma and serum. The extracted small and macromolecular spectra were then compared with experimentally obtained relaxation-edited and diffusion-edited spectra. Correlation analysis demonstrated the quantitative capability of the model in the extracted small molecule signals from 1H NMR spectra. The principal component analysis showed that the spectra extracted by the model and those obtained by NMR spectral editing methods reveal similar group information, demonstrating the effectiveness of the model in signal extraction.

Abstract The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

Highlights A systematic review of recent advances of microrobots applied in the musculoskeletal system with an emphasis on design strategies of microrobotic systems for tissue regeneration. The fabrication, motion and control, and image-guided delivery of microrobots in the musculoskeletal system are reviewed based on the up-to-date works. Prospects and challenges for future clinical translation of microrobots in the musculoskeletal system and regenerative medicine are discussed.

Abstract The adsorption behavior of gold thiosulfate ions on the surface of kaolinite was studied using a combination of experimental research and quantum chemical calculations. Under the condition of a stirring time of 30 min, a stirring speed of 500 r·min−1, and a mass ratio of 30% kaolinite in the slurry, when the initial gold concentration of 56.50 mg·L−1,the adsorption rate of gold-thiosulfate ions from a kaolinite-containing solution was 7.44%. The results of Fourier transform infrared spectroscopy (FTIR) and energy dispersive spectroscopy (EDS) showed that the physical and chemical adsorption of kaolinite and gold thiosulfate occurred in solution. Quantum chemical calculations were performed using the CASTEP module in Materials Studio. The adsorption energy of gold thiosulfate on the surface of kaolinite (001) was calculated as − 438.01 kJ·mol−1.The calculated H76–O289 distance was 1.615 Å. Mulliken Charge population analysis and bond population analysis showed that gold thiosulfate ions form relatively stable bonds on the kaolinite surface (001). In the process of thiosulfate immersion, part of gold is adsorbed by kaolinite, which affects the extraction of gold. These results indicate that during the leaching process of gold thiosulfate, kaolinite has the ability to "catch" gold, which affects the leaching efficiency.

Abstract Background Multiple epiphyseal dysplasia-4 (MED-4, MIM 226900) is a rare autosomal recessive disease characterized by disproportionate height and early onset osteoarthritis of the lower limbs. MED-4 is caused by homozygous or compound heterozygous pathogenic variants in the SLC26A2 gene. However, the underlying pathogenic mechanisms in chondrocytes remains unknown. This study aimed to identify the pathogenic variants within a MED-4 family and explore the molecular etiology of this condition in human primary chondrocyte cells. Methods Clinical data were recorded and peripheral blood samples were collected for analysis. Whole exome sequencing (WES) and bioinformatic analyses were performed to determine causative variants. Wild-type SLC26A2 and corresponding mutant expression plasmids were constructed and transfected into human primary chondrocytes. The expression and subcellular distribution of SLC26A2 protein in chondrocytes were detected by immunoblotting and immunofluorescence. Effects of these variants on chondrocytes viability and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay. Expression of genes related to cartilage homeostasis was subsequently analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results We identified two compound heterozygous variants c.1020_1022delTGT(p.Val341del) and c.1262 T > C(p.Ile421Thr) in the SLC26A2 gene in the patients. Mutant SLC26A2Val341del and SLC26A2Ile421Thr proteins were distributed in relatively few cells and were observed only within the nucleus. The viability of chondrocytes with the SLC26A2 variant group was similar to the wild-type (WT) group. However, the protein expressions of SLC26A2Val341del and SLC26A2Ile421Thr were decreased compared with SLC26A2WT. Expression levels of matrix metallopeptidase 13 (MMP13), α-1 chain of type X collagen (COL10A1), and Runt-related transcription factor 2 (RUNX2) were significantly decreased in the variant group. However, aggrecan (ACAN) expression was higher in the variant group than the WT group. Conclusions Overall, our data demonstrate that the variants p.Val341del and p.Ile421Thr in SLC26A2 cause MED-4 and that these two variants promote chondrocyte proliferation while inhibiting chondrocyte differentiation.

IntroductionWith the continuous progress of the automotive industry, the safe driving of intelligent vehicles has received increasing attention. Traditional obstacle avoidance techniques are not accurate enough in dealing with fuzzy information encountered in high-speed driving. Therefore, this study aims to improve the obstacle avoidance ability of intelligent vehicles through fuzzy control theory.MethodsThe study employs fuzzy control theory to enhance the ability of intelligent vehicles to process fuzzy information, thereby improving conventional obstacle avoidance techniques. A combination of visual sensing and ultrasonic detection equipment was used to comprehensively plan the real-time obstacle avoidance routes of the intelligent vehicle.Results and DiscussionThe improved obstacle avoidance technique achieves an accuracy of 96.11%, which is better than the comparison avoidance technique. In the absence of interfering signals, the running time and overshoot were 2.4 s and 7%, respectively, again superior to the comparison technique. The experimental results show that the obstacle avoidance technique proposed in this study can improve the recognition ability of intelligent vehicles on fuzzy information, so as to improve the accuracy of obstacle recognition and provide certain guarantee for the safe driving of intelligent vehicles.

BackgroundThe multifaceted non-pharmaceutical interventions after the outbreak of the COVID-19 pandemic not only limited the spread of SARS-CoV2 but also had an impact on the prevalence of other pathogens.MethodsIn this work, we retrospectively analyzed the epidemiological characteristics of Mycoplasma pneumoniae (MP) in children before and after the COVID-19 pandemic in Shandong, China. From 2019–2023, there were 29,558 visits of pediatric patients (1 month to 15 years old) with respiratory tract infection (RTI) symptoms at a tertiary hospital in Shandong Province, 10,039 of which were positive for MP according to a passive agglutination assay of the serum IgM antibodies. Conduct statistical analysis and epidemiological investigation of the test results categorized by years, months, ages, genders and clinical diagnosis. Utilize the χ2 test to analyze the differences in incidence rates.ResultsCompared to 2019, the number of visits and the positive cases both decreased substantially in 2020, but the positivity rate increased. Both 2021 and 2023 were peak years of MP infection. The peak seasons of MP infection were fall and winter, female patients had higher positivity rate than male patients, and school-age children (>6 years) had higher positivity rate than the children in other age groups. In terms of the clinical manifestation of MP infection, compared to 2019, in 2023, the proportion of bronchopneumonia and upper RTI decreased significantly.ConclusionsThe ongoing surveillance of the epidemiology of MP is critical for effective disease management and provides a basis for diagnosis, treatment, and the corresponding prevention and control strategies. This work for the first time characterized the epidemiology of MP in Shandong before and after the COVID-19 pandemic, thus providing valuable information for monitoring and preventing MP infection in the post-epidemic era.

Eggs, a rich source of protein, vitamins, and minerals, rapidly decline in nutritional quality post-laying due to physicochemical changes, exacerbated by poor storage. Chitosan, a biodegradable antibacterial polysaccharide, has the ability to enhance the preservation of egg when it combined with Slightly acidic hypochlorous water (SAHW). This study investigates the potential of chitosan-SAHW composite films for preserving egg quality by systematically evaluating the films’ properties across different SAHW concentrations. Results showed increased film density and decreased moisture content with SAHW addition. Optimal mechanical properties were observed at 20 mg/L SAHW, while 40 mg/L SAHW films were most effective against microbes. Eggs coated with these films, especially at 20 mg/L and 30 mg/L SAHW, maintained quality significantly better over 49 days, reducing weight loss, preserving the Haugh unit, and stabilizing pH. These findings suggest chitosan-SAHW films effectively extend egg shelf life, warranting further research for broader applications.

BackgroundBreast cancer (BRCA) is the most prevalent type of cancer worldwide. As a highly heterogeneous cancer, it has a high recurrence rate. Since its biological behavior can be regulated by immunity and cuprotosis, so exploring potential therapeutic target to mediate immunity and cuprotosis is of great significance for BRCA therapy.MethodsThe immune-related genes and immune-cuprotosis-related deferentially expressed genes (ICR-DEGs) were identified by mining the TCGA database. Prognostic analysis, differential expression analysis, univariate and lasso regression analyses were used to determine their independent prognostic values. To evaluate the relationship between ICR-DEGs and immune scores, we constructed a prognostic risk model to evaluate immune checkpoints, and then the role of tumor immune microenvironment in BRCA was explored. Furthermore, anti-BRCA function and mechanism of islet amyloid poly-peptide (IAPP) mediated CD8+T cells were verified by means of flow cytometry, ELISA, and subcutaneous transplantation tumor model.ResultsAll results suggested that immune-cuprotosis-related genes were a potential predictor of BRCA’s response to immune checkpoint inhibitors and immunotherapy biomarkers. Thereby downregulation of IAPP reduced cuprotosis of CD8+T or Her2-CAR-T cells to promote the anti-BRCA function both in vitro and in vivo.ConclusionOur research had clarified the function and mechanism of IAPP in CD8+T cells, providing new ideas for improving the diagnosis and treatment of BRCA.