Dynamic multicolor emissions of multimodal phosphors by Mn2+ trace doping in self-activated CaGa4O7.

The manipulation of excitation modes and resultant emission colors in luminescent materials holds pivotal importance for encrypting information in anti-counterfeiting applications. Despite considerable achievements in multimodal and multicolor luminescent materials, existing options generally suffer from static monocolor emission under fixed external stimulation, rendering them vulnerability to replication. Achieving dynamic multimodal luminescence within a single material presents a promising yet challenging solution. Here, we report the development of a phosphor exhibiting dynamic multicolor photoluminescence (PL) and photo-thermo-mechanically responsive multimodal emissions through the incorporation of trace Mn2+ ions into a self-activated CaGa4O7 host. The resulting phosphor offers adjustable emission-color changing rates, controllable via re-excitation intervals and photoexcitation powers. Additionally, it demonstrates temperature-induced color reversal and anti-thermal-quenched emission, alongside reproducible elastic mechanoluminescence (ML) characterized by high mechanical durability. Theoretical calculations elucidate electron transfer pathways dominated by intrinsic interstitial defects and vacancies for dynamic multicolor emission. Mn2+ dopants serve a dual role in stabilizing nearby defects and introducing additional defect levels, enabling flexible multi-responsive luminescence. This developed phosphor facilitates evolutionary color/pattern displays in both temporal and spatial dimensions using readily available tools, offering significant promise for dynamic anticounterfeiting displays and multimode sensing applications.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases.

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

Colchicine Blocks Abdominal Aortic Aneurysm Development by Maintaining Vascular Smooth Muscle Cell Homeostasis.

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models. Mechanistically, colchicine increased global mRNA stability by inhibiting the METTL14/YTHDC1-mediated m6A modification, resulting in increased sclerostin (SOST) expression and consequent inactivation of the WNT/ß-catenin signaling pathway in vascular SMCs from mouse AAA lesions and in cultured human aortic SMCs. Moreover, human and mouse AAA lesions all showed increased m6A methylation, decreased SOST expression, and skewed synthetic SMC de-differentiation phenotype, compared to those without AAA. This study uncovers a novel mechanism of colchicine in slowing AAA development by using the METTL14/SOST/WNT/ß-catenin axis to control vascular SMC homeostasis in mouse aortic vessels and in human aortic SMCs. Therefore, use of colchicine may benefit AAA patients in clinical practice.

Probiotics are beneficial for liver cirrhosis: a systematic review and meta-analysis of randomized control trials.

Introduction: Gut dysbiosis may play a pivotal role in the pathogenesis of cirrhosis and the severity of complications. Numerous studies have investigated the probiotics as treatments for cirrhosis. However, there is still a lack of definitive evidence confirming the beneficial effects of probiotics on cirrhosis. Methods: Databases including PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials that compared the effects of probiotic intervention and control treatments, including placebo, no treatment, and active control, on cirrhosis, published from inception to February 2024. Outcomes included hepatic encephalopathy (HE) reversal, safety and tolerability of probiotics, liver function, quality of life, and other cirrhotic-related outcomes. A meta-analysis was conducted to synthesize evidence. Results: Thirty studies were included. The quantitative synthesis results showed that compared with the control group, probiotics significantly reverse minimal hepatic encephalopathy (MHE) (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.03 to 2.32) and improve HE (RR 1.94, 95% CI 1.24 to 3.06). Additionally, probiotics demonstrated higher safety and tolerability by causing a lower incidence of serious adverse events (RR 0.71, 95% CI 0.58 to 0.87). Probiotics could potentially improve liver function by reducing the Model for End-Stage Liver Disease (MELD) scores (standardized mean difference [SMD] -0.57, 95% CI -0.85 to -0.30), and displayed favorable changes in quality of life (SMD 0.51, 95% CI 0.27 to 0.75) and gut flora (SMD 1.67, 95% CI 1.28 to 2.06). Conclusion: This systematic review and meta-analysis offers compelling evidence that probiotics are beneficial for cirrhosis by demonstrating reversal of HE, potential for liver function improvements, enhancements in quality of life, and regulation of gut dysbiosis. Furthermore, the apparent safety profile suggests that probiotics are a promising intervention for treating cirrhosis. Clinical trial registration number: CRD42023478380.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

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EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2.

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.

Multiple-polarization-sensitive photodetector Based on a plasmonic metasurface.

On-chip polarization-sensitive photodetectors are highly desired for ultra-compact optoelectronic systems. It has been demonstrated that polarization-sensitive photodetection can be realized using intrinsic chiral and anisotropy materials. However, these photodetectors can only realize the detection of either circularly polarized light (CPL) or linear polarized light (LPL) and are not applicable to multiple-polarization-sensitive photodetection. Herein, we experimentally demonstrate a metasurface-integrated semiconductor to realize multiple-polarization-sensitive photodetection at visible wavelengths. This device is composed of a MoSe2 monolayer on an H-shaped plasmonic nanostructure. The geometric chirality and anisotropy of the H-shaped nanostructure result in CPL and LPL resolved optical responses. By integrating a plasmonic metasurface with monolayer MoSe2, we converted polarization-sensitive optical absorption to the polarization-sensitive photocurrent of the device through the photoconductive effect. Polarization-sensitive photocurrent responses to both CPL and LPL are systematically investigated, which demonstrate a high photocurrent circular dichroism (CD) of 0.35 at a wavelength of 810 nm and photocurrent linear polarization (LP) of 0.4 at a wavelength of 633 nm. Our results provide a potential pathway to realize multiple-polarization-sensitive applications in medicine analysis, biology, and remote sensing.

Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays.

Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an enzyme or enzyme substrate; or as the final stage in any procedure that involves a capture reagent when an enzyme reaction is used as the indicator. Rapid mixing and precise timing are however difficult to achieve in point-of-care devices designed for small sample volumes and fast time to result. By using centrifugal microfluidics and transposing the reaction surface from a chamber to a single mm-scale bead we demonstrate an elegant and easily manufacturable solution. Reagents (which may be, for example, an enzyme, enzyme substrate, antibody or antigen) are immobilised on the surface of a single small bead (typically 1-2 mm in diameter) contained in a cylindrical reaction chamber subjected to periodically changing rotational accelerations which promote both mixing and uniform mass-transfer to the bead surface. The gradient of Euler force across the chamber resulting from rotational acceleration of the disc, dΩdisc/dt, drives circulation of fluid in the chamber. Oscillation of Euler force by oscillation of rotational acceleration with period, T, less than that of the hydrodynamic relaxation time of the fluid, folds the fluid streamlines. Movement of the bead in response to the fluid and the changing rotational acceleration provides a dynamically changing chamber shape, further folding and expanding the fluid. Bead rotation and translation driven by fluid flow and disc motion give uniformity of reaction over the surface. Critical parameters for mixing and reaction uniformity are the ratio of chamber radius to bead radius, rchamber/rbead, and the product Trchamber(dΩdisc/dt), of oscillation period and Euler force gradient across the fluid. We illustrate application of the concept using the reaction of horse radish peroxidase (HRP) immobilised on the bead surface with its substrate tetramethylbenzidine (TMB) in solution. Acceleration from rest to break a hydrophobic valve provided precise timing for TMB contact with the bead. Solution uniformity from reaction on the surface of the bead in volumes 20-50 uL was obtained in times of 2.5 s or less. Accurate measurement of the amount of surface-bound HRP by model fitting to the measured kinetics of colour development at 10 s intervals is demonstrated.

Investigating pigeon circovirus infection in a pigeon farm: molecular detection, phylogenetic analysis and complete genome analysis.

BACKGROUND: Pigeon circovirus infections in pigeons (Columba livia domestica) have been reported worldwide. Pigeons should be PiCV-free when utilized as qualified experimental animals. However, pigeons can be freely purchased as experimental animals without any clear guidelines to follow. Herein, we investigated the status quo of PiCV infections on a pigeon farm in Beijing, China, which provides pigeons for experimental use. RESULTS: PiCV infection was verified in at least three types of tissues in all forty pigeons tested. A total of 29 full-length genomes were obtained and deposited in GenBank. The whole genome sequence comparison among the 29 identified PiCV strains revealed nucleotide homologies of 85.8-100%, and these sequences exhibited nucleotide homologies of 82.7-98.9% as compared with those of the reference sequences. The cap gene displayed genetic diversity, with a wide range of amino acid homologies ranging from 64.5% to 100%. Phylogenetic analysis of the 29 full-genome sequences revealed that the PiCV strains in this study could be further divided into four clades: A (17.2%), B (10.4%), C (37.9%) and D (34.5%). Thirteen recombination events were also detected in 18 out of the 29 PiCV genomes obtained in this study. Phylogenetic research using the rep and cap genes verified the recombination events, which occurred between clades A/F, A/B, C/D, and B/D among the 18 PiCV strains studied. CONCLUSIONS: In conclusion, PiCV infection, which is highly genetically varied, is extremely widespread on pigeon farms in Beijing. These findings indicate that if pigeons are to be used as experimental animals, it is necessary to evaluate the impact of PiCV infection on the results.

First-principles study of the mechanical and thermodynamic properties of aluminium-doped magnesium alloys.

Magnesium-aluminum (Mg-Al) alloys are widely used in aerospace, automobile and medical equipment owing to their advantages of easy casting, high strength-to-mass ratio and good biocompatibility. The structural, mechanical, electronic and thermodynamic properties of MgxAly alloys (x + y = 16, x = 1, 2,…, 15) with varying Al-doping contents were studied using the first-principles method. In this work, the structures of MgxAly alloys were constructed by replacing Mg atoms in a supercell with Al atoms. The lattice parameters of the Al-doped MgxAly alloys decrease with an increasing Al content because of the smaller atomic size of Al than that of Mg. The calculated formation energies show that Mg11Al5, Mg5Al3 and Mg9Al7 have prominent structural stability. The analyses of the mechanical properties reveal that the doping of Al improves the ductility of MgxAly alloys. The elastic moduli increase with an increasing Al content, and Mg9Al7 has a notable ability to resist deformation, while Mg11Al5 and Mg5Al3 have better plasticity. The calculated results of their electronic properties reveal that Mg11Al5, Mg5Al3 and Mg9Al7 are good conductors without magnetism. Furthermore, CDD analyses show that the inner layer charges of Al atoms migrated to the outer layer, and the charges of Mg atoms accumulated significantly in the outer region of Al atoms. The Debye temperature of Mg9Al7 is higher than that of Mg11Al5 and Mg5Al3, indicating that it has better thermodynamic stability. Our findings would be helpful for the design of Mg-Al alloys with excellent mechanical and thermodynamic performances.

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Compilation of a self-management assessment scale for postoperative patients with aortic dissection.

Objective: The aim of this research was to compile a self-management assessment scale for patients with aortic dissection (AD). The questionnaire is useful in making the patient aware of the need for post-operative care in order to contribute to improving the outcome and quality of life. Methods: The initial version of the "postoperative self-management assessment scale for patients with aortic dissection" was developed using the Delphi expert consultation method based on qualitative research results, consultation of self-management-related literature, reference to the existing self-management scale, and self-efficacy theory, combined with the disease characteristics of AD. By using the convenience sampling method, a total of 201 patients with AD who had undergone surgery were selected as the research participants. The initial version of the scale was used for follow-up investigation, and the scale entries were evaluated and exploratory factor analysis carried out to form the formal version of the "postoperative self-management assessment scale for patients with aortic dissection." A total of 214 patients with AD after surgery were selected as the research participants. The formal version of the scale was used for follow-up investigation, and its reliability and validity were evaluated. Results: The formal version of the scale had 6 dimensions and 35 entries. The Cronbach's α coefficient for the total scale was 0.908, the split-half reliability was 0.790, and the test-retest reliability after 2 weeks was 0.471. The content validity index of the total scale was 0.963. Exploratory factor analysis yielded six common factors, and the cumulative contribution rate of variance was 66.303%. Confirmatory factor analysis showed that except for the incremental fit index, Tucker-Lewis index, and comparative fit index >0.85, slightly lower than 0.90, χ 2/df <3, root mean square of approximation <0.08, parsimonious goodness-of-fit index, and parsimonious normed fit index >0.50; all other model fitting requirements were satisfied, indicating that the model fitting was acceptable. Conclusion: We compiled the postoperative self-management assessment scale for patients with AD, which has demonstrated excellent reliability and validity and can be used as a tool to evaluate the postoperative self-management level in patients with aortic dissection.

Clinical significance of miR-9-5p in NSCLC and its relationship with smoking.

Purpose: Dysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study. Patients and methods: A total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database. Results: miR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121). Conclusion: Upregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

Novel approach for identifying VOC emission characteristics based on mobile monitoring platform data and deep learning: Application of source apportionment in a chemical industrial park.

Refined volatile organic compound (VOC) emission characteristics are crucial for accurate source apportionment in chemical industrial parks. The data from mobile monitoring platforms in chemical industrial parks contain pollution information that is not intuitively displayed, requiring further excavation. A novel approach was proposed to identify VOC emission characteristics using the class activation map (CAM) technology of convolutional neural network (CNN), which was applied on the mobile monitoring platform data (MD) derived from a typical fine chemical industrial park. It converts a large amount of monitoring data with high spatiotemporal complexity into simple and interpretable characteristic maps, effectively improving the identification effect of VOC emission characteristics, supporting more accurate source apportionment of VOC pollution around the park. Using this method, the VOC emission characteristics of eight key factories were identified. VOC source apportionment in the park was conducted for one day using a positive matrix factorization (PMF) model and seven combined factor profiles (CFPs) were calculated. Based on the identified VOC emission characteristics, the main pollution sources and their contributions to surrounding schools and residential areas were determined, revealing that one pesticide factory (named LKA) had the highest contribution ratio. The source apportionment results indicated that the impact of the chemical industrial park on the surrounding areas varied from morning to afternoon, which to some extent reflected the intermittent production methods employed for fine chemicals.

[Effect of Polyethylene Microplastics on the Microbial Community of Saline Soils].

Mulching to conserve moisture has become an important agronomic practice in saline soil cultivation, and the effects of the dual stress of salinity and microplastics on soil microbes are receiving increasing attention. In order to investigate the effect of polyethylene microplastics on the microbial community of salinized soils, this study investigated the effects of different types (chloride and sulphate) and concentrations (weak, medium, and strong) of polyethylene (PE) microplastics (1% and 4% of the dry weight mass of the soil sample) on the soil microbial community by simulating microplastic contamination in salinized soil environments indoors. The results showed that:PE microplastics reduced the diversity and abundance of microbial communities in salinized soils and were more strongly affected by sulphate saline soil treatments. The relative abundance of each group of bacteria was more strongly changed in the sulphate saline soil treatment than in the chloride saline soil treatment. At the phylum level, the relative abundance of Proteobacteria was positively correlated with the abundance of fugitive PE microplastics, whereas the relative abundances of Bacteroidota, Actinobacteriota, and Acidobacteria were negatively correlated with the abundance of fugitive PE microplastics. At the family level, the relative abundances of Flavobacteriaceae, Alcanivoracaceae, Halomonadaceae, and Sphingomonasceae increased with increasing abundance of PE microplastics. The KEGG metabolic pathway prediction showed that the relative abundance of microbial metabolism and genetic information functions were reduced by the presence of PE microplastics, and the inhibition of metabolic functions was stronger in sulphate saline soils than in chloride saline soils, whereas the inhibition of genetic information functions was weaker than that in chloride saline soils. The secondary metabolic pathways of amino acid metabolism, carbohydrate metabolism, and energy metabolism were inhibited. It was hypothesized that the reduction in metabolic functions may have been caused by the reduced relative abundance of the above-mentioned secondary metabolic pathways. This study may provide a theoretical basis for the study of the effects of microplastics and salinization on the soil environment under the dual pollution conditions.

Unveiling synergy of strain and ligand effects in metallic aerogel for electrocatalytic polyethylene terephthalate upcycling.

Recently, there has been a notable surge in interest regarding reclaiming valuable chemicals from waste plastics. However, the energy-intensive conventional thermal catalysis does not align with the concept of sustainable development. Herein, we report a sustainable electrocatalytic approach allowing the selective synthesis of glycolic acid (GA) from waste polyethylene terephthalate (PET) over a Pd67Ag33 alloy catalyst under ambient conditions. Notably, Pd67Ag33 delivers a high mass activity of 9.7 A mgPd-1 for ethylene glycol oxidation reaction (EGOR) and GA Faradaic efficiency of 92.7 %, representing the most active catalyst for selective GA synthesis. In situ experiments and computational simulations uncover that ligand effect induced by Ag incorporation enhances the GA selectivity by facilitating carbonyl intermediates desorption, while the lattice mismatch-triggered tensile strain optimizes the adsorption of *OH species to boost reaction kinetics. This work unveils the synergistic of strain and ligand effect in alloy catalyst and provides guidance for the design of future catalysts for PET upcycling. We further investigate the versatility of Pd67Ag33 catalyst on CO2 reduction reaction (CO2RR) and assemble EGOR//CO2RR integrated electrolyzer, presenting a pioneering demonstration for reforming waste carbon resource (i.e., PET and CO2) into high-value chemicals.

The Nrf2/ARE pathway as a potential target to ameliorate atrazine-induced endocrine disruption in granulosa cells.

Atrazine (ATR) is widely used worldwide as a commercial herbicide, Diaminochlorotriazine (DACT) is the main metabolite of ATR in the organism. Both of them disrupt the production of steroids and induce abnormal reproductive development. The granulosa cells (GCs) are important for growth and reproduction of animals. However, the toxicity of ATR on the GCs of birds is not well clarified. To evaluate the effect of the environmental pollutant ATR on bird GCs. The quail GCs were allotted into 7 groups, C (The medium of M199), A20 (20 µM ATR), A100 (100 µM ATR), A250 (250 µM ATR), D20 (20 µM DACT), D100 (100 µM DACT) and D200 (200 µM DACT). The results demonstrated that ATR reduced the viability of GCs, disrupted mitochondrial structure (including mitochondrial cristae fragmentation and the mitochondrial morphology disappearance) and decreased mitochondrial membrane potential. Meanwhile, ATR interfered with the expression of key factors in the steroid synthesis pathway, inducing the secretion of the sex hormones E2 and P in GCs. which in turn induced apoptosis. Furthermore, the Nrf2/ARE pathway as a potential target to ameliorate ATR-induced endocrine disruption in GCs for proper reproductive functions. Our research provides a new perspective for understanding the effects of ATR on reproductive functions in birds.

The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection.

During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.

The SP1/SIRT1/ACLY signaling axis mediates fatty acid oxidation in renal ischemia-reperfusion-induced renal fibrosis.

BACKGROUND: Renal ischemia-reperfusion is the primary cause of acute kidney injury (AKI). Clinically, most patients who experience ischemia-reperfusion injury eventually progress gradually to renal fibrosis and chronic kidney disease (CKD). However, the underlying mechanism for AKI to CKD transition remain absent. Our study demonstrated that the downregulation of sirtuin 1 (Sirt1)-mediated fatty acid oxidation (FAO) facilitates IRI-induced renal fibrosis. METHODS: The IRI animal model was established, and ribonucleic acid (RNA) sequencing was used to explore potential differentially expressed genes (DEGs) and pathways. The SIRT1 knockout mice were generated, and a recombinant adeno-associated virus that overexpresses SIRT1 was injected into mice to explore the function of SIRT1 in renal fibrosis induced by renal IRI. In vitro, hypoxia/reoxygenation (H/R) was used to establish the classical model of renal IRI and overexpression or knockdown of SIRT1 to investigate the SIRT1 function through lentiviral plasmids. The underlying molecular mechanism was explored through RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assay. RESULTS: RNA sequencing analysis and western blot demonstrated that the expression of SIRT1 was significantly decreased in IRI mice. Overexpression of SIRT1 improved renal function and reduced lipid deposition and renal fibrosis. On the contrary, knockout of SIRT1 aggravated kidney injury and renal fibrosis. RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assay mechanistically revealed that SIRT1 impairs the acetylation of histone H3K27 on the promoter region of ACLY, thereby impeding FAO activity and promoting renal fibrosis. Additionally, SP1 regulated FAO by directly modulating SIRT1 expression. CONCLUSION: Our findings highlight that downregulation of SIRT1-modulated FAO facilitated by the SP1/SIRT1/ACLY axis in the kidney increases IRI, suggesting SIRT1 to be a potential therapeutic target for renal fibrosis induced by renal IRI.