Specnuezhenide ameliorates hepatic fibrosis via regulating SIRT6-Mediated inflammatory signaling cascades.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustrum lucidum W.T. Aiton is a traditional Chinese medicine that has long been used with high hepatoprotective therapeutic and condition value. Specnuezhenide (SP), the standard prominent secoiridoid compound of Fructus Ligustri Lucidi may ameliorate hepatic inflammation in chronic liver diseases. AIM OF THE STUDY: Regulating inflammation through SIRT6-P2X7R axis has caused the emergence of novel molecular mechanism strategies for reversing hepatic fibrosis. This study focused on the mechanism of SP in modulating the liver inflammatory microenvironment in hepatic fibrosis. MATERIALS AND METHODS: C57BL/6 mice with hepatic fibrosis were stimulated with thioacetamide (TAA) prior to administration of SP. Hepatic stellate cells (HSCs) or normal mouse primary hepatocytes were exposed to transforming growth factor-ß (TGF-ß) treatment. Meanwhile, normal mouse bone marrow-derived macrophages (BMDMs) were treated with lipopolysaccharide/adenosine triphosphate (LPS/ATP), aiming to obtain the conditioned medium. HSCs and hepatocytes were transfected with SIRT6 knockdown vector (siRNA-SIRT6) to estimate the impact of SP on the SIRT6-P2X7R/NLRP3 signaling pathway. RESULTS: SP suppressed the HSCs extracellular matrix (ECM) deposition as well as pro-inflammatory cytokine levels induced by the medium of BMDMs or TGF-ß. In addition, SP also significantly up-regulated SIRT6, inhibited P2X7R-NLRP3 inflammasome in HSCs and hepatocytes, and functioned as MDL-800 (a SIRT6 agonist). SP reduced the hepatocytes pyroptosis and further prevented the occurrence of inflammatory response in the liver. SP could inhibit the activation of BMDMs and impede IL-1ß and IL-18 from entering extracellular regions. Moreover, deficiency of SIRT6 in HSCs or hepatocytes reduced SP's regulation of P2X7R suppression. For TAA-treated mice, SP mitigated histopathological changes, ECM accumulation, EMT process, and NETs formation in hepatic fibrosis. CONCLUSIONS: Therefore, SP decreased inflammatory response via SIRT6-P2X7R/NLRP3 pathway and suppressed fibrillogenesis. These findings supported SP as the novel candidate to treat hepatic fibrosis.

Adaptation of Ustilago maydis to phenolic and alkaloid responsive metabolites in maize B73.

The adaptation of pathogenic fungi to plant-specialized metabolites is necessary for their survival and reproduction. The biotrophic fungus Ustilago maydis can cause maize smut and produce tumors in maize (Zea mays), resulting in reduced maize yield and significant economic losses. Qualitative analysis using UPLC-MS/MS revealed that the infection of maize variety B73 with U. maydis resulted in increased levels of phytohormones, phenolics, and alkaloids in maize seedling tissues. However, correlation analysis showed that nearly all compounds in the mechanical damage group were significantly negatively correlated with the shoot growth indexes of maize B73. The correlation coefficients of 2-hydroxy-7-methoxy-1,4-benzoxazin-3-one (HMBOA) and maize B73 shoot length and shoot weight were r = -0.56 (p < 0.01) and r = -0.75 (p < 0.001), respectively. In the inoculation group, these correlations weakened, with the correlation coefficients between HMBOA and maize B73 shoot length and shoot weight being r = 0.02 and r = -0.1, respectively. The correlation coefficients between 6-methoxy-2-benzoxazolinone (MBOA) and the shoot weight were r = -0.73 (p < 0.001) and r = -0.15 in the mechanical damage group and inoculation group, respectively. These findings suggest that increased concentrations of these compounds are more positively associated with mechanical damage than with U. maydis infection. At high concentrations, most of these compounds had an inhibitory effect on U. maydis. This study investigated the ability of U. maydis to regulate various compounds, including phytohormones, phenolic acids, and alkaloids in maize B73, providing evidence that U. maydis has adapted to the specialized metabolites produced by maize B73.

E-selectin in vascular pathophysiology.

Selectins are a group of Ca2+-dependent, transmembrane type I glycoproteins which attract cell adhesion and migration. E-selectin is exclusively expressed in endothelial cells, and its expression is strongly enhanced upon activation by pro-inflammatory cytokines. The interaction of E-selectin with its ligands on circulating leukocytes captures and slows them down, further facilitating integrin activation, firm adhesion to endothelial cells and transmigration to tissues. Oxidative stress induces endothelial cell injury, leading to aberrant expression of E-selectin. In addition, the elevated level of E-selectin is positively related to high risk of inflammation. Dysregulation of E-selectin has been found in several pathological conditions including acute kidney injury (AKI), pulmonary diseases, hepatic pathology, Venous thromboembolism (VTE). Deletion of the E-selectin gene in mice somewhat ameliorates these complications. In this review, we describe the mechanisms regulating E-selectin expression, the interaction of E-selectin with its ligands, the E-selectin physiological and pathophysiological roles, and the therapeutical potential of targeting E-selectin.

HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Puerarin Attenuates Insulin Resistance by Inhibiting Endoplasmic Reticulum Stress and Suppresses Inflammation by Modulating the JNK and IKKß/NF-κB Pathways in Epididymal White Adipose Tissue of Mice on a High-Fat Diet.

SCOPE: Obesity is associated with insulin resistance (IR), which is characterized by endoplasmic reticulum (ER) stress in multiple organs. ER stress in adipose tissue causes metabolic disturbances and activates inflammatory signaling pathways. Puerarin, an isoflavone extracted from Pueraria lobata, exhibits antioxidant, anti-inflammatory, and antidiabetic effects. This study explores the potential mechanisms underlying puerarin's role in mitigating insulin resistance in high-fat diet (HFD)-induced obese mice. METHODS AND RESULTS: In this study, insulin resistant in mice is induced by a high-fat diet, followed by treatment with puerarin. The results demonstrate that puerarin effectively attenuates insulin resistance, including weight loss, improvement of glucose tolerance and insulin sensitivity, and activation of insulin signaling pathway. Additionally, puerarin administration suppresses ER stress by down-regulation of ATF6, ATF4, CHOP, GRP78 expressions in epididymal white adipose tissue (eWAT), along with decreased phosphorylation IRE1α, PERK, and eIF2α. Furthermore, puerarin exerts anti-inflammatory effects by inhibiting JNK and IKKß/NF-κB pathways, leading to reduction of TNF-α and IL-6. CONCLUSION: These findings suggest that puerarin mitigates insulin resistance by inhibiting ER stress and suppressing inflammation through the JNK and IKKß/NF-κB pathways. This highlights the promising clinical application of puerarin in the treatment of insulin resistance.

Association of chrononutrition patterns with biological aging: evidence from a nationally representative cross-sectional study.

Previous studies mostly focused on the benefits of caloric restriction and fasting on longevity. However, whether the timing and frequency of eating affect aging remains unclear. Here, we investigated the associations between chrononutrition patterns and biological aging, and explored whether and to what extent dietary inflammation mediated this association. 16 531 adults aged 20 to 84 years from the National Health and Nutrition Examination Survey were collected. Chrononutrition patterns were determined with two 24-hour dietary recalls. Phenotypic age was calculated to reflect the biological aging status. The dietary inflammatory index (DII) was used to assess the dietary inflammation. After adjustment of the survey weight and multiple covariates including total energy intake, participants in the third tertile of the time of the first meal (mean 10 : 26) exhibited more advanced biological age (ß 0.64; 95% CI, 0.26-1.00) and a higher incidence of accelerated aging (odds ratio (OR) 1.25; 95% CI, 1.06-1.47) compared to those of the first tertile (mean 6 : 14). Higher eating frequency was associated with delayed biological aging in both multivariable linear (ß -0.31; 95% CI, -0.44 to -0.19) and logistic regression model (OR 0.90; 95% CI, 0.85-0.95). Furthermore, we found that DII rather than metabolic factors mediated the inverse association between eating frequency and biological aging (mediation proportion 24.67%; 95% CI, 19.83%-32.00%). Our findings demonstrated the association between chrononutrition patterns and biological aging among the US general population and the potential role of dietary inflammation in this association, suggesting that modifying chrononutrition patterns may be a practical and cost-effective strategy for combating aging.

Pannonibacter tanglangensis sp. nov., a New Species Isolated from Pond Sediment.

Two bacterial strains (XCT-34T and XCT-53) isolated from sediment samples of an artificial freshwater reservoir were analyzed using a polyphasic approach. The two isolates are aerobic, Gram-stain-negative, oxidase-negative, catalase-positive, motile with polar flagella, rod-shaped, and approximately 1.4-3.4 × 0.4-0.9 µm in size. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences showed that the two strains formed a distinct branch within the evolutionary radiation of the genus Pannonibacter, closest to Pannonibacter carbonis Q4.6T (KCTC 52466). Furthermore, lower than threshold average nucleotide identity values (ANI, 85.7-86.4%) and digital DNA-DNA hybridization values (dDDH, 22.3-30.5%) of the two strains compared to the nearest type strains also confirmed that they represented a novel species. Genomic analyses, including annotation of the KEGG pathways, prediction of the secondary metabolism biosynthetic gene clusters and PHI phenotypes, supported functional inference and differentiation of the strains from the closely related taxa. Results of chemotaxonomic and physiological studies revealed that their distinct phenotypic characteristics distinguished them from existing Pannonibacter species. Thus, the two strains are considered to represent a novel species of Pannonibacter, for which the name of Pannonibacter tanglangensis sp. nov. is proposed, with XCT-34T (= KCTC 82332T = GDMCC 1.1947T) as the respective type strain.

Three-dimensional cultured human umbilical cord mesenchymal stem cells attenuate pulmonary fibrosis by improving the balance of mitochondrial fusion and fission.

Pulmonary fibrosis is a kind of fibrotic interstitial pneumonia with poor prognosis. Aging, environmental pollution, and coronavirus disease 2019 are considered as independent risk factors for pulmonary fibrogenesis. Consequently, the morbidity and mortality striking continues to rise in recent years. However, the clinical therapeutic efficacy is very limited and unsatisfactory. So it is necessary to develop a new effective therapeutic approach for pulmonary fibrosis. Human umbilical cord mesenchymal stem cells (hucMSCs) are considered as a promising treatment for various diseases because of their multiple differentiation and immunomodulatory function. The key bottleneck in the clinical application of hucMSCs therapy is the high-quality and large-scale production. This study used FloTrix miniSpin bioreactor, a three-dimensional (3D) cell culture system, for large-scale expansion of hucMSCs in vitro, and proved 3D cultured hucMSCs inhibited the differentiation of fibroblasts into myofibroblasts and myofibroblasts proliferation and migration, leading to slow down the development of pulmonary fibrosis. Further mechanistic studies clarified that hucMSCs reduced the amount of binding between circELP2 and miR-630, resulting in blocking YAP/TAZ translocation from cytoplasm to nucleus. This condition inhibited mitochondrial fusion and promoted mitochondrial fission, and ultimately improved fusion/fission balance and cellular homeostasis. To sum up, this work clarified the anti-fibrosis and mechanism of hucMSCs cultured from the 3D FloTrix miniSpin bioreactor. We hope to provide new ideas and new methods for the clinical transformation and industrialization of hucMSCs therapy.

Insulin receptor isoform B is required for efficient proinsulin processing in pancreatic ß cells.

The insulin receptor (INSR, IR) has two isoforms, IRA and IRB, through alternative splicing. However, their distinct functions in vivo remain unclear. Here we generated ß cell-specific IRB knockout (KO) mice (ßIRBKO). The KO mice displayed worsened hyperinsulinemia and hyperproinsulinemia in diet-induced obesity due to impaired proinsulin processing in ß cells. Mechanistically, loss of IRB suppresses eukaryotic translation initiation factor 4G1 (eIF4G1) by stabilizing the transcriptional receptor sterol-regulatory element binding protein 1 (SREBP1). Moreover, excessive autocrine proinsulin in ßIRBKO mice enhances the activity of extracellular signal-regulated kinase (ERK) through the remaining IRA to further stabilize nuclear SREBP1, forming a feedback loop. Collectively, our study paves the way to dissecting the isoform-specific function of IR in vivo and highlights the important roles of IRB in insulin processing and protecting ß cells from lipotoxicity in obesity.

OTAMatch: Optimal Transport Assignment with PseudoNCE for Semi-supervised Learning.

In semi-supervised learning (SSL), many approaches follow the effective self-training paradigm with consistency regularization, utilizing threshold heuristics to alleviate label noise. However, such threshold heuristics lead to the underutilization of crucial discriminative information from the excluded data. In this paper, we present OTAMatch, a novel SSL framework that reformulates pseudo-labeling as an optimal transport (OT) assignment problem and simultaneously exploits data with high confidence to mitigate the confirmation bias. Firstly, OTAMatch models the pseudo-label allocation task as a convex minimization problem, facilitating end-to-end optimization with all pseudo-labels and employing the Sinkhorn-Knopp algorithm for efficient approximation. Meanwhile, we incorporate epsilon-greedy posterior regularization and curriculum bias correction strategies to constrain the distribution of OT assignments, improving the robustness with noisy pseudo-labels. Secondly, we propose PseudoNCE, which explicitly exploits pseudo-label consistency with threshold heuristics to maximize mutual information within self-training, significantly boosting the balance of convergence speed and performance. Consequently, our proposed approach achieves competitive performance on various SSL benchmarks. Specifically, OTAMatch substantially outperforms the previous state-of-the-art SSL algorithms in realistic and challenging scenarios, exemplified by a notable 9.45% error rate reduction over SoftMatch on ImageNet with 100K-label split, underlining its robustness and effectiveness.

Effects of Remifentanil Pretreatment on Sufentanil-induced Cough Suppression During the Induction of General Anesthesia.

PURPOSE: The aim of this study was to evaluate the effect of remifentanil pretreatment on sufentanil-induced cough during general anesthesia induction. DESIGN: This experimental research was conducted as a single-center, randomized, parallel-group trial. METHODS: A total of 120 patients scheduled for elective surgery were equally randomized into two groups (remifentanil and control). The incidence and severity of coughing in both groups were recorded after sufentanil administration during general anesthesia induction. The mean arterial pressure, heart rate, and pulse oxygen saturation were recorded at T1 (before the injection of remifentanil or normal saline), T2 (1 minute after remifentanil administration), T3 (before intubation), and T4 (1 minute after intubation). Additionally, the incidences of adverse events, including dizziness, nausea, apnea, truncal rigidity, bradycardia, or other adverse effects were also recorded. FINDINGS: The incidence of sufentanil-induced cough in the remifentanil group was significantly decreased when compared with the control group (5.0% vs 35.0%, respectively; P < .001). No statistical differences were found in mean arterial pressure, heart rate, pulse oxygen saturation, and the incidences of other side effects between the two groups at T1, T2, T3, and T4 (P > .05). CONCLUSIONS: Pretreatment with remifentanil at a dose of 0.5 mcg/kg can effectively and safely suppress the incidence and severity of sufentanil-induced coughing, providing a reference for medication during general anesthesia induction.

Realistic Nanoplastics Induced Pulmonary Damage via the Crosstalk of Ferritinophagy and Mitochondrial Dysfunction.

The smaller size fraction of plastics may be more substantially existing and detrimental than larger-sized particles. However, reports on nanoplastics (NPs), especially their airborne occurrences and potential health hazards to the respiratory system, are scarce. Previous studies limit the understanding of their real respiratory effects, since sphere-type polystyrene (PS) nanoparticles differ from NPs occurring in nature with respect to their physicochemical properties. Here, we employ a mechanical breakdown method, producing NPs directly from bulk plastic, preserving NP properties in nature. We report that among four relatively high abundance NP materials PS, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polyethylene (PE) with a size of 100 nm, PVC induced slightly more severe lung toxicity profiles compared to the other plastics. The lung cytotoxicity of NPs is higher than that of commercial PS NPs and comparable to natural particles silicon dioxide (SiO2) and anatase titanium dioxide (TiO2). Mechanistically, BH3-interacting domain death agonist (Bid) transactivation-mediated mitochondrial dysfunction and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy or ferroptosis are likely common mechanisms of NPs regardless of their chemical composition. This study provides relatively comprehensive data for evaluating the risk of atmospheric NPs to lung health.

Serum 25-hydroxyvitamin D concentrations, vitamin D receptor polymorphisms, and risk of infections among individuals with type 2 diabetes: a prospective cohort study.

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited. OBJECTIVES: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association. METHODS: This study included 19,851 participants with T2D from United Kingdom Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders. RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-y. Compared with those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections, and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall < 0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall < 0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction > 0.050). CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.

Global, regional, and national burden of premenstrual syndrome, 1990-2019: an analysis based on the Global Burden of Disease Study 2019.

STUDY QUESTION: What is the burden of premenstrual syndrome (PMS) at the global, regional, and national levels across 21 regions and 204 countries and territories? SUMMARY ANSWER: Over the past few decades, the global prevalent cases of PMS have grown significantly from 652.5 million in 1990 to 956.0 million in 2019, representing a 46.5% increase. WHAT IS KNOWN ALREADY: PMS, which affects almost half of reproductive women worldwide, has substantial social, occupational, academic, and psychological effects on women's lives. However, no comprehensive and detailed epidemiological estimates of PMS by age and socio-demographic index (SDI) at global, regional, and national levels have been reported. STUDY DESIGN, SIZE, DURATION: An age- and SDI-stratified systematic analysis of the prevalence and years lived with disability (YLD) of PMS by age and SDI across 21 regions and 204 countries and territories has been performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: The prevalence and YLD of PMS from 1990 to 2019 were retrieved directly from the Global Burden of Diseases (GBD) 2019 study. The number, rates per 100 000 persons, and average annual percentage changes (AAPCs) of prevalence and YLD were estimated at the global, regional, and national levels. MAIN RESULTS AND THE ROLE OF CHANCE: Globally, the prevalent cases of PMS increased by 46.5% from 652.5 million in 1990 to 956.0 million in 2019; in contrast, however, the age-standardized prevalence rate was approximately stable at 24 431.15/100 000 persons in 1990 and 24 406.51/100 000 persons in 2019 (AAPC, 0[95% CI: -0.01 to 0.01]). Globally, the YLD was 8.0 million in 2019 and 5.4 million in 1990, with a sizable increase over the past 30 years. The age-standardized YLD rate was stable (AAPC 0.01, P = 0.182), at 203.45/100 000 persons in 1990 and 203.76/100 000 persons in 2019. The age-standardized burden estimates were the highest in the low-middle SDI regions and the lowest in the high SDI regions. Peaks in burden rate estimates were all observed in the 40-44 years age group. Regional age-standardized burden estimates were the highest in South Asia and the lowest in Western Sub-Saharan Africa. The national age-standardized burden estimates were the highest in Pakistan and the lowest in Niger. LIMITATIONS, REASONS FOR CAUTION: The accuracy of the results depended on the quality and quantity of the GBD 2019 data. Fortunately, the GBD study endeavoured to retrieve data globally and applied multiple models to optimize the completeness, accuracy, and reliability of the data. In addition, the GBD study took the country as its basic unit and neglected the influence of race. Further study is warranted to compare differences in PMS burden associated with race. Finally, no data are available on the aetiology and risk information related to PMS, which might help us to better understand the trends and age distribution of PMS and help local governments formulate more detailed policies and comprehensive interventions. WIDER IMPLICATIONS OF THE FINDINGS: Although the age-standardized prevalence/YLD rate has been stable over the past 30 years, the absolute number of prevalent cases and YLD grew significantly worldwide from 1990 to 2019. Public health-related policies should be implemented to reduce the prevalence and alleviate the symptoms of PMS. Lifestyle changes and cognitive-behavioral therapy are critical in helping to reduce the burden of PMS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (grant number 2022YFC2704100) and the National Natural Science Foundation of China (No. 82001498, No. 82371648). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Detection of acetaminophen and P-aminophenol simultaneously by an electrochemical sensor based on Fe-NC derivatives attached with Ti3C2 QDs.

In this paper, Ti3C2 QDs and Fe-ZIF-8 were synthesized by a straightforward hydrothermal method. Fe-ZIF-8 was pyrolyzed at high temperatures to obtain Fe-nanoclusters (Fe-NC). Then Fe-NC is mixed with Ti3C2 QDs to form a new composite material (Ti3C2 QDs/Fe-NC), and its microstructure and composition were analyzed by technology. The proposed material can detect acetaminophen (PA) and P-aminophenol (4-AP) simultaneously with excellent detection performance. With the best conditions, the linear ranges and detection limits were 0.50-210.00 µM, 0.03 µM (S/N = 3) and 0.50-150.00 µM, 0.06 µM (S/N = 3) for PA and 4-AP, respectively. The sensor has lower detection limits and wider linear ranges, and can successfully detect 4-AP and PA in river water and acetaminophen tablets at the same time, showing potential practical application prospects. Especially, this study reports the modification of MOF derivatives with Ti3C2 QDs for the first time, which expands the application scope of Quantum Dots and MOF derivatives.

Albiflorin ameliorates thioacetamide-induced hepatic fibrosis: The involvement of NURR1-mediated inflammatory signaling cascades in hepatic stellate cells activation.

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-ß), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.

Bibliometric analysis and global trends in uterus transplantation.

AIM: The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. METHODS: The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to December 15, 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. RESULTS: A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, which is followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility, respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. CONCLUSIONS: UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1.

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review.

The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a).

Environmental cadmium exposure perturbs systemic iron homeostasis via hemolysis and inflammation, leading to hepatic ferroptosis in common carp (Cyprinus carpio L.).

Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, it is still largely unknown whether and how Cd at environmentally relevant concentrations affects iron metabolism. Here, we studied the effects of environmental Cd exposure (5 and 50 µg/L) on iron homeostasis and possible mechanisms in common carp. The data revealed that Cd elevated serum iron, transferrin saturation and iron deposition in livers and spleens, leading to the disruption of systemic iron homeostasis. Mechanistic investigations substantiated that Cd drove hemolysis by compromising the osmotic fragility and inducing defective morphology of erythrocytes. Cd concurrently exacerbated hepatic inflammatory responses, resulting in the activation of IL6-Stat3 signaling and subsequent hepcidin transcription. Notably, Cd elicited ferroptosis through increased iron burden and oxidative stress in livers. Taken together, our findings provide evidence and mechanistic insight that environmental Cd exposure could undermine iron homeostasis via erythrotoxicity and hepatotoxicity. Further investigation and ecological risk assessment of Cd and other pollutants on metabolism-related effects is warranted, especially under the realistic exposure scenarios.