Glucose and HODEs regulate Aspergillus ochraceus quorum sensing through the GprC-AcyA pathway.

Aspergillus ochraceus is the traditional ochratoxin A (OTA)-producing fungus with density-dependent behaviors, which is known as quorum sensing (QS) that is mediated by signaling molecules. Individual cells trend to adapt environmental changes in a "whole" flora through communications, allowing fungus to occupy an important ecological niche. Signals perception, transmission, and feedback are all rely on a signal network that constituted by membrane receptors and intracellular effectors. However, the interference of density information in signal transduction, which regulates most life activities of Aspergillus, have yet to be elucidated. Here we show that the G protein-coupled receptor (GPCR) to cAMP pathway is responsible for transmitting density information, and regulates the key point in life cycle of A. ochraceus. Firstly, the quorum sensing phenomenon of A. ochraceus is confirmed, and identified the density threshold is 103 spores/mL, which represents the low density that produces the most OTA in a series quorum density. Moreover, the GprC that classified as sugar sensor, and intracellular adenylate cyclase (AcyA)-cAMP-PKA pathway that in response to ligands glucose and HODEs are verified. Furthermore, GprC and AcyA regulate the primary metabolism as well as secondary metabolism, and further affects the growth of A. ochraceus during the entire life cycle. These studies highlight a crucial G protein signaling pathway for cell communication that is mediated by carbohydrate and oxylipins, and clarified a comprehensive effect of fungal development, which include the direct gene regulation and indirect substrate or energy supply. Our work revealed more signal molecules that mediated density information and connected effects on important adaptive behaviors of Aspergillus ochraceus, hoping to achieve comprehensive prevention and control of mycotoxin pollution from interrupting cell communication.

Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.

MiR-421 mediates PM2.5-induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells.

OBJECTIVE: PM2.5 is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM2.5 induced an increased release of miR-421 from the bronchial epithelium. However, the role of miR-421 in PM2.5-induced endothelial injury remains elusive. MATERIALS AND METHODS: We utilized a subacute PM2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM2.5-induced endothelial injury. RESULTS: Our findings reveal that inhibition of miR-421 attenuated PM2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM2.5-induced endothelial injury. CONCLUSIONS: Our results indicate that PM2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM2.5-induced vascular endothelial injury.

Hypoxia-treated adipose mesenchymal stem cell-derived exosomes attenuate lumbar facet joint osteoarthritis.

BACKGROUND: Lumbar facet joint osteoarthritis (LFJ OA) is a common disease, and there is still a lack of effective disease-modifying therapies. Our aim was to determine the therapeutic effect of hypoxia-treated adipose mesenchymal stem cell (ADSC)-derived exosomes (Hypo-ADSC-Exos) on the protective effect against LFJ OA. METHODS: The protective effect of Hypo-ADSC-Exos against LFJ OA was examined in lumbar spinal instability (LSI)-induced LFJ OA models. Spinal pain behavioural assessments and CGRP (Calcitonin Gene-Related Peptide positive) immunofluorescence were evaluated. Cartilage degradation and subchondral bone remodelling were assessed by histological methods, immunohistochemistry, synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR), and 3D X-ray microscope scanning. RESULTS: Hypoxia enhanced the protective effect of ADSC-Exos on LFJ OA. Specifically, tail vein injection of Hypo-ADSC-Exos protected articular cartilage from degradation, as demonstrated by lower FJ OA scores of articular cartilage and less proteoglycan loss in lumbar facet joint (LFJ) cartilage than in the ADSC-Exo group, and these parameters were significantly improved compared to those in the PBS group. In addition, the levels and distribution of collagen and proteoglycan in LFJ cartilage were increased in the Hypo-ADSC-Exo group compared to the ADSC-Exo or PBS group by SR-FTIR. Furthermore, Hypo-ADSC-Exos normalized uncoupled bone remodelling and aberrant H-type vessel formation in subchondral bone and effectively reduced symptomatic spinal pain caused by LFJ OA in mice compared with those in the ADSC-Exo or PBS group. CONCLUSIONS: Our results show that hypoxia is an effective method to improve the therapeutic effect of ADSC-Exos on ameliorating spinal pain and LFJ OA progression.

A Novel Pathway for Porcine Epidemic Diarrhea Virus Transmission from Sows to Neonatal Piglets Mediated by Colostrum.

The mechanisms of colostrum-mediated virus transmission are difficult to elucidate because of the absence of experimental animal models and the difficulties in tissue sample collection from mothers in the peripartum period. Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that has catastrophic impacts on the global pig industry. PEDV primarily infects neonatal piglets by multiple routes, especially 1- to 2-day-old neonatal piglets. Here, our epidemiological investigation and animal challenge experiments revealed that PEDV could be vertically transmitted from sows to neonatal piglets via colostrum, and CD3+ T cells in the colostrum play an important role in this process. The results showed that PEDV colonizing the intestinal epithelial cells (IECs) of orally immunized infected sows could be transferred to CD3+ T cells located just beneath the IECs. Next, PEDV-carrying CD3+ T cells, with the expression of integrin α4ß7 and CCR10, migrate from the intestine to the mammary gland through blood circulation. Arriving in the mammary gland, PEDV-carrying CD3+ T cells could be transported across mammary epithelial cells (MECs) into the lumen (colostrum), as illustrated by an autotransfusion assay and an MECs/T coculture system. The PEDV-carrying CD3+ T cells in colostrum could be interspersed between IECs of neonatal piglets, causing intestinal infection via cell-to-cell contact. Our study demonstrates for the first time that colostrum-derived CD3+ T cells comprise a potential route for the vertical transmission of PEDV. IMPORTANCE The colostrum represents an important infection route for many viruses. Here, we demonstrate the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sows to neonatal piglets via colostrum. PEDV colonizing the intestinal epithelial cells could transfer the virus to CD3+ T cells located in the sow intestine. The PEDV-carrying CD3+ T cells in the sow intestine, with the expression of integrin α4ß7 and CCR10, arrive at the mammary gland through blood circulation and are transported across mammary epithelial cells into the lumen, finally leading to intestinal infection via cell-to-cell contact in neonatal piglets. Our study not only demonstrates an alternative route of PEDV infection but also provides an animal model of vertical transmission of human infectious disease.

Highly Efficient Luminescence from a Red Thermally Activated Delayed Fluorescence Emitter with Flexible Conformation of Ancillary Groups.

Robust scaffolds were typically applied in thermally activated delayed fluorescence (TADF) molecules to suppress the non-radiative decay, trigger the fast spin-flipping, and enhance the light out-coupling efficiency. Herein, we disclosed for the first time the positive effect of flexible conformation of ancillary groups on the photophysical properties of TADF emitter. The red TADF emitter Ph-TPA with flexible conformation demonstrated small excited-state structural distortion and low reorganization energy compared to the counterpart Mc-TPA with a rigid macrocycle. Consequently, Ph-TPA showed an excellent photoluminescent quantum yield (PLQY) of 92 % and a state-of-the-art external quantum efficiency (EQE) of 30.6 % at 630 nm. This work could deepen our understanding of structure-property relationships of organic luminophores and help us to rationalize the design of efficient TADF materials.

Association between serum ß2-microglobulin levels and the risk of all-cause and cardiovascular disease mortality in chinese patients undergoing maintenance hemodialysis.

BACKGROUND: The association between serum ß2-microglobulin (ß2M) levels and the risk of all-cause and cardiovascular disease (CVD) mortality and the incidence of cardiovascular events (CVEs) in patients undergoing maintenance hemodialysis (MHD) is inconclusive. Furthermore, no study has been performed in China on the significance of serum ß2M levels in MHD patients. Therefore, this study investigated the aforementioned association in MHD patients. METHODS: In this prospective cohort study, 521 MHD patients were followed at Dalian Municipal Central Hospital affiliated with Dalian University of Technology from December 2019 to December 2021. The serum ß2M levels were categorized into three tertiles, and the lowest tertile served as the reference group. Survival curves were calculated by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Sensitivity analysis was performed by excluding patients with CVD at baseline. RESULTS: During the follow-up period of 21.4 ± 6.3 months, there were 106 all-cause deaths, of which 68 were caused by CVD. When excluding CVD patients at baseline, there were 66 incident CVEs. Kaplan-Meier analysis revealed that the risk of all-cause and CVD mortality in the highest tertile of serum ß2M levels was significantly higher than that in the lowest tertile (P < 0.05), but not for the CVEs (P > 0.05). After adjusting for potential confounders, serum ß2M levels were positively associated with the risk of all-cause (HR = 2.24, 95% CI = 1.21-4.17) and CVD (HR = 2.54, 95% CI = 1.19-5.43) mortality, and a linear trend was evident (P < 0.05). Besides, the results of sensitivity analysis were consistent with the main findings. However, we didn't observed the significant association between serum ß2M levels and CVEs (P > 0.05). CONCLUSION: The serum ß2M level may be a significant predictor of the risk of all-cause and CVD mortality in MHD patients. Further studies are needed to confirm this finding.

Designing Nonconventional Luminescent Materials with Efficient Emission in Dilute Solutions via Modulation of Dynamic Hydrogen Bonds.

Nonconventional luminescent materials (NLMs) which do not contain traditional aromatic chromophores are of great interest due to their unique chemical structures, optical properties, and their potential applications in various areas, such as cellular imaging and chemical sensing. However, most reported NLMs show weak or no emission in dilute solutions, which severely limits their applications. In this work, dynamic hydrogen bonds were utilized to design NLMs with efficient emission in dilute solutions. To further validate the results, polymers P1 and P2 were successfully prepared and investigated. It was found that the luminescence quantum efficiency of P1 and P2 at a concentration of 0.1 mg/mL in water solution was 8.9 and 0.6%, respectively. The high efficiency can be attributed to the fact that polymer P1 has more intra- or intermolecular dynamic hydrogen bonds and other short interactions than P2 in dilute solutions, allowing P1 to achieve the through-space conjugation effect to increase the degree of system conjugation, restrict molecular motion, and decrease nonradiative transitions, which can effectively improve luminescence. In addition, polymer P2 exhibits the characteristics of clustering-triggered emission, excitation wavelength-dependent and concentration-dependent fluorescence properties, excellent photobleaching resistance, low cytotoxicity, and selective recognition of Fe3+. The present study investigates the manipulation of luminescence properties of NLMs in dilute solutions through the modulation of dynamic hydrogen bonds. This approach can serve as a semi-empirical technique for designing and building innovative NLMs in the times ahead.

Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. METHODS: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples. RESULTS: Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-African American; 67% in TCGA-European American; 63% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes. CONCLUSION: This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.

Serum total indoxyl sulfate levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study.

BACKGROUND: The association between serum total indoxyl sulfate (tIS), and cardiovascular disease (CVD) and all-cause mortality is a matter of debate. In the current study we sought to determine the association, if any, between serum tIS, and all-cause and CVD-associated mortality in patients on maintenance hemodialysis (MHD). METHODS: A prospective cohort study was conducted involving 500 MHD patients at Dalian Municipal Central Hospital from 31 December 2014 to 31 December 2020. Serum tIS levels were measured at baseline and classified as high (≥44.16 ng/ml) or low (< 44.16 ng/ml) according to the "X-tile" program. Besides, the associations between continuous serum tIS and outcomes were also explored. Predictors were tested for colinearity using variance inflation factor analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Restricted cubic spline model was performed to assess dose-response relationships between tIS concentration and all-cause and CVD mortality. RESULTS: During a 58-month median follow-up period, 224 deaths (132 CVD deaths) were documented. After adjustment for potential confounders, the serum tIS level was positively associated with all-cause mortality (HR = 1.02, 95% = 1.01-1.03); however, we did not detect a significant association when tIS was a dichotomous variable. Compared with the MHD population with a serum tIS level < 44.16 ng/ml, the adjusted HR for CVD mortality among those with a serum tIS level ≥ 44.16 ng/ml was 1.76 (95% = 1.10-2.82). Furthermore, we also noted the same association when the serum tIS level was a continuous variable. CONCLUSION: The serum tIS level was associated with higher risk of all-cause and CVD mortality among MHD patients. Further prospective large-scale studies are required to confirm this finding.

Ultraviolet Response in Coplanar Silicon Avalanche Photodiodes with CMOS Compatibility.

Highly sensitive ultraviolet (UV) photodetectors are highly desired for industrial and scientific applications. However, the responsivity of silicon photodiodes in the UV wavelength band is relatively low due to high-density Si/SiO2 interface states. In this paper, a coplanar avalanche photodiode (APD) was developed with a virtual guard ring design. When working in Geiger mode, it exhibited a strong UV response. The responsivity of 4 × 103 A/W (corresponding to a gain of 8 × 106) at 261 nm is measured under the incident power of 0.6 µW with an excess bias of 1.5 V. To the best of our knowledge, the maximum 3-dB bandwidth of 1.4 GHz is the first report ever for a Si APD when working in the Geiger mode in spite of the absence of an integrated CMOS read-out circuit.

PEDV infection in neonatal piglets through the nasal cavity is mediated by subepithelial CD3+ T cells.

Porcine epidemic diarrhea virus (PEDV) primarily infects neonatal piglets causing catastrophic effects on the global pig farming industry. PEDV infects piglets through the nasal cavity, a process in which dendritic cells (DCs) play an important role. However, neonatal piglets have fewer nasal DCs. This study found that subepithelial CD3+ T cells mediated PEDV invasion through the nasal cavity in neonatal piglets. PEDV could replicate in the nasal epithelial cells (NECs) isolated from the nasal cavity of neonatal piglets. Infection of NECs with PEDV could induce antiviral and inflammatory cytokines at the late stage. The infected NECs mediated transfer of virus to CD3+ T cells distributed in the subepithelial of the nasal cavity via cell-to-cell contact. The infected CD3+ T cells could migrate to the intestine via blood circulation, causing intestinal infection in neonatal piglets. Thus, the findings of this study indicate the importance of CD3+T cells in the dissemination of PEDV from the nasal cavity to the intestinal mucosa in neonatal piglets.

Antiviral activity of interleukin-11 as a response to porcine epidemic diarrhea virus infection.

Interleukin-11 (IL-11), a well-known anti-inflammatory factor, provides protection from intestinal epithelium damage caused by physical or chemical factors. However, little is known of the role of IL-11 during viral infections. In this study, IL-11 expression at mRNA and protein levels were found to be high in Vero cells and the jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, while IL-11 expression was found to be positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) was found to suppress PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 was found to inhibit viral infection by preventing PEDV-mediated apoptosis of cells by activating the IL-11/STAT3 signaling pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggest that IL-11 is a newfound PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential of IL-11 to be used as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Heat-Killed Saccharomyces boulardii Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis by Restoring the Intestinal Barrier, Reducing Inflammation, and Modulating the Gut Microbiota.

Ulcerative colitis (UC) is a global intestinal disease, and conventional therapeutic drugs often fail to meet the needs of patients. There is an urgent need to find efficient and affordable novel biological therapies. Saccharomyces boulardii has been widely used in food and pharmaceutical research due to its anti-inflammatory properties and gut health benefits. However, there is still a relatively limited comparison and evaluation of different forms of S. boulardii treatment for UC. This study aimed to compare the therapeutic effects of S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan on UC, to explore the potential of heat-killed S. boulardii as a new biological therapy. The results demonstrate that all three treatments were able to restore body weight, reduce the disease activity index (DAI), inhibit splenomegaly, shorten colon length, and alleviate histopathological damage to colonic epithelial tissues in DSS-induced colitis mice. The oral administration of S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan also increased the levels of tight junction proteins (Occludin and ZO-1), decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the serum, and suppressed the expressions of TNF-α, IL-1ß, and IL-6 mRNA in the colon. In particular, in terms of gut microbiota, S. boulardii, heat-killed S. boulardii, and S. boulardii ß-glucan exhibited varying degrees of modulation on DSS-induced dysbiosis. Among them, heat-killed S. boulardii maximally restored the composition, structure, and functionality of the intestinal microbiota to normal levels. In conclusion, heat-killed S. boulardii showed greater advantages over S. boulardii and S. boulardii ß-glucan in the treatment of intestinal diseases, and it holds promise as an effective novel biological therapy for UC. This study is of great importance in improving the quality of life for UC patients and reducing the burden of the disease.

Cobalt catalyzed ethane dehydrogenation to ethylene with CO2: Relationships between cobalt species and reaction pathways.

TiO2, ZrO2 and a series of TiO2-ZrO2 (TxZ1, x means the atomic ratio of Ti/Zr = 10, 5, 1, 0.2 and 0.1) composite oxide supports were prepared through co-precipitation, and then 3 wt% Co was loaded through wetness impregnation methods. The obtained 3 wt% Co/TiO2 (3CT), 3 wt% Co/ZrO2 (3CZ) and 3 wt% Co/TxZ1 (3CTxZ1) catalysts were evaluated for the oxidative ethane dehydrogenation reaction with CO2 (CO2-ODHE) as a soft oxidant. 3CT1Z1 catalyst exhibits excellent catalytic properties, with C2H4 yield, C2H6 conversion and CO2 conversion about 24.5 %, 33.8 % and 18.0 % at 650 °C, respectively. X-Ray Diffraction (XRD), in-situ Raman, UV-vis diffuse reflectance spectra (UV-vis DRS), H2 temperature-programmed reduction (H2-TPR), Electron paramagnetic resonance (EPR) and quasi in-situ X-ray Photoelectron Spectroscopy (XPS) have been utilized to thoroughly characterize the investigated catalysts. The results revealed that 3CT1Z1 produced TiZrO4 solid solution with more metal defect sites and oxygen vacancies (Ov), promoting the formation of Co2+-TiZrO4 structure. Furthermore, the presence of Ov and Ti3+can facilitate the high dispersion and stabilization of Co2+, as well as suppressing the severe reduction of Co2+, leading to superior ethane oxidative dehydrogenation activity. Besides, less Co0 is beneficial to ODHE reaction, because of its promotion effects for reverse water gas shift reaction; however, more Co0 results in dry reforming reaction (DRE). This work will shed new lights for the design and preparation of highly efficient catalysts for ethylene production.

Monophenyl luminescent material with dual-state emission and pH sensitivity for cell imaging.

Dual-state emission (DSE) luminescent materials are a newly discovered category of luminescent materials that exhibit efficient light emission in multiple states, including dilute solutions, highly concentrated solutions, aggregated states and solid states. These materials effectively address the aggregation-caused quenching (ACQ) observed in traditional organic luminescent materials with large conjugated planes, as well as the limitations of aggregation-induced emission (AIE) materials, which typically do not emit light in dilute solutions. The design and development of DSE luminescent materials for organelle imaging applications has attracted considerable interest. In this context, this study presents the design and synthesis of a novel luminescent compound, DMSS-AM, characterised by intramolecular hydrogen bonding and a D-π-A structure. As a monophenyl luminescent material, DMSS-AM exhibits DSE properties with fluorescence quantum yields of 22.1% in solution and 14.0% in the solid state. In particular, it exhibits unique pH-responsive properties, facilitating the targeted detection of lysosomal pH changes. Confocal laser scanning microscopy imaging of cells demonstrated that DSE emitters at both low and high concentrations do not affect image quality for bio-imaging applications. This advance is expected to significantly broaden the applicability of DSE luminescent materials in future applications.

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies.

OBJECTIVE: This study aims to investigate the effects of natural products on animal models of premature ovarian failure (POF). METHODS: We conducted comprehensive literature searches and identified relevant studies that examined the protective effects of natural products on experimental POF. We extracted quantitative data on various aspects such as follicular development, ovarian function, physical indicators, oxidative stress markers, inflammatory factors, and protein changes. The data was analyzed using random-effects meta-analyses, calculating pooled standardized mean differences and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic, and bias was estimated using the SYRCLE tool. RESULTS: Among the 879 reviewed records, 25 articles met our inclusion criteria. These findings demonstrate that treatment with different phytochemicals and marine natural products (flavonoids, phenols, peptides, and alkaloids, etc.) significantly improved various aspects of ovarian function compared to control groups. The treatment led to an increase in follicle count at different stages, elevated levels of key hormones, and a decrease in atretic follicles and hormone levels associated with POF. This therapy also reduced oxidative stress (specifically polyphenols, resveratrol) and apoptotic cell death (particularly flavonoids, chrysin) in ovarian granulosa cells, although it showed no significant impact on inflammatory responses. The certainty of evidence supporting these findings ranged from low to moderate. CONCLUSIONS: Phytochemicals and marine natural product therapy (explicitly flavonoids, phenols, peptides, and alkaloids) has shown potential in enhancing folliculogenesis and improving ovarian function in animal models of POF. These findings provide promising strategies to protect ovarian reserve and reproductive health. Targeting oxidative stress and apoptosis pathways may be the underlying mechanism.

Global burden and epidemiological prediction of polycystic ovary syndrome from 1990 to 2019: A systematic analysis from the Global Burden of Disease Study 2019.

OBJECTIVE: To comprehensively assess the global, regional and national burden of polycystic ovary syndrome (PCOS) in incidence, prevalence, and years lived with disability (DLYs) based on the Global Burden of Disease Study (GBD) 2019. METHODS: This was a cross-sectional descriptive study. Data on PCOS incidence, prevalence, and DLYs from 1990 to 2019 were obtained from the GBD study 2019. According to the commonwealth income, WHO region, and the sociodemographic index, the estimates were demonstrated along with the estimated annual percentage change (EAPC). The EAPC data were analyzed by four levels of hierarchical clustering and displayed in the world map. The Autoregressive Integrated Moving Average (ARIMA) and Bayesian age-period-cohort (BAPC) model was used to predict the PCOS burden in the next 20 years. RESULTS: From 1990 to 2019, the number of PCOS incidence in one year increased from 1.4 million in 1990 to 2.1 million in 2019 (54.3%). Only the EAPC estimates of incidence in the Region of the Americas decreased, and their aged-standardized incidence rate (ASIR) values were the highest in 1990 and 2019. There was no significant correlation between human development index (HDI) and EAPC. However, when HDI < 0.7, EAPC of incidence and prevalence was positively correlated with HDI, and when HDI > 0.7, EAPC of incidence and prevalence was negatively correlated with HDI. Countries with the middle level HDI have the highest increasing trend of ASIR and age-standardized prevalence rate (ASPR). The 10 to 19 years old group had the highest incidence counts of PCOS globally. Besides, the ARIMA and BAPC model showed the consistent increasing trend of the burden of PCOS. CONCLUSION: In order to better promote the early diagnosis and treatment, expert consensus and diagnosis criteria should be formulated according to the characteristics of different ethnic groups or regions. It is necessary to emphasize the early screening and actively develop targeted drugs for PCOS.

Local delivery of EGFR+NSCs-derived exosomes promotes neural regeneration post spinal cord injury via miR-34a-5p/HDAC6 pathway.

Spinal cord injury (SCI) causes severe axon damage, usually leading to permanent paraparesis, which still lacks effective regenerative therapy. Recent studies have suggested that exosomes derived from neural stem cells (NSCs) may hold promise as attractive candidates for SCI treatment. Epidermal Growth Factor Receptor positive NSC (EGFR+NSC) is a subpopulation of endogenous NSCs, showing strong regenerative capability in central nervous system disease. In the current study, we isolated exosomes from the EGFR+NSCs (EGFR+NSCs-Exos) and discovered that local delivery of EGFR+NSCs-Exos can effectively promote neurite regrowth in the injury site of spinal cord-injured mice and improve their neurological function recovery. Using the miRNA-seq, we firstly characterized the microRNAs (miRNAs) cargo of EGFR+NSCs-Exos and identified miR-34a-5p which was highly enriched in EGFR+NSCs derived exosomes. We further interpreted that exosomal miR-34a-5p could be transferred to neurons and inhibit the HDAC6 expression by directly binding to its mRNA, contributing to microtubule stabilization and autophagy induction for aiding SCI repair. Overall, our research demonstrated a novel therapeutic approach to improving neurological functional recovery by using exosomes secreted from a subpopulation of endogenous NSCs and providing a precise cell-free treatment strategy for SCI repair.