Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods.

STUDY QUESTION: Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles? SUMMARY ANSWER: The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO2) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy. WHAT IS KNOWN ALREADY: Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods. STUDY DESIGN SIZE DURATION: This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study. PARTICIPANTS/MATERIALS SETTING METHODS: Daily average levels of six air pollutants (fine particulate matter (PM2.5), inhalable particulate matter (PM10), SO2, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations. MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO2 in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79-0.99). Among these pollutants, SO2 (33.40%) and NO2 (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m2 and those under 35 years old. LIMITATIONS REASONS FOR CAUTION: Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health. STUDY FUNDING/COMPETING INTERESTS: This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Composition and micromorphological determination of blue honeysuckle fruit (Lonicera caerulea L.) cuticular wax and its effects on fruit post-harvest quality.

The chemical composition and structure of the cuticular wax in blue honeysuckle fruit were investigated using gas chromatography-mass spectrometry (GC-MS) and scanning electron microscopy (SEM). The results revealed that the cuticular wax was dense and uniform, taking on a tubular form. A total of 158 wax components were identified, including alkanes, terpenes, ketones, alcohols, fatty acids, and esters. The wax was found to be particularly rich in alkanes. After storage, the wax content decreased, whereas an increase in 1-undecanol. The destruction or reduction of cuticular wax resulted in a more rapid decline in storage quality, loss of nutrients, and a decrease in antioxidant phytochemicals. Meanwhile, wax metabolizing enzyme activity and gene expression increased. This study presents a deeper understanding of blue honeysuckle fruit cuticular wax composition and aids to developing effective measures to delay its postharvest fruit quality deterioration.

The association of early pregnancy dyslipidemia with preterm birth in twin pregnancies: a retrospective cohort study.

BACKGROUND: Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear. METHODS: This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies. RESULTS: A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB < 37 weeks was significantly higher in the dyslipidemia group compared to the group without dyslipidemia (64.5% vs. 50.4%, P = 0.003). After adjusting for confounding factors, dyslipidemia was positively associated with PTB < 37 weeks (adjusted odds ratio: 1.71; 95% confidence interval: 1.13-2.58). However, these associations varied depending on the chorionicity and mode of conception of the twins. The positive associations between early pregnancy dyslipidemia and PTB < 37 weeks remained significant only in spontaneously conceived (SC) or dichorionic diamniotic (DCDA) twin pregnancies. No statistically significant associations were observed between dyslipidemia and the other secondary outcomes. CONCLUSION: Early pregnancy dyslipidemia was positively associated with PTB < 37 weeks in twin pregnancies, and this association remained significant in SC or DCDA twin pregnancies. Comprehensive lipid profile assessment in the first trimester may be beneficial for patients' monitoring and implementing interventions to mitigate adverse pregnancy outcomes.

Silk protein: A novel antifungal and edible coating for strawberry preservation.

In this study, an antimicrobial component, silk protease inhibitors (SPIs), was extracted from discarded silkworm cocoons, and a suitable degumming method for obtaining regenerated silk fibroin (SF) was screened. An edible antimicrobial coating was prepared by mixing SPIs with SF for evaluation of potential in strawberries preservation. Results demonstrated that SPI could effectively inhibit mycelial growth and spore germination. The alkaline protease method exhibited the highest degumming rate of 24.4 %. The SPI-SF coating exhibited excellent mechanical properties, high water vapor permeability, and easy washability. Within 10 days, seedlings treatment with SPI-SF coating solution showed a germination rate of 94.3 %, and exhibited good biocompatibility with HepG2 cells. Coating with SPI-SF led to increase in the storage period of strawberries to 10-14 days, concurrent with considerable reduction in decay rate at room temperature. Conclusively, this study demonstrates the potential of SPI-SF edible coating in strawberries preservation.

Shiitake mushroom-derived extracellular nanovesicles: Preparation, characterization, and inhibition of Caco-2 cells.

In this study, Shiitake mushroom-derived extracellular nanovesicles (SMDENVs) were isolated from fresh Shiitake mushrooms by ultracentrifugation and sucrose gradient ultracentrifugation. The morphological characteristics of SMDENVs were investigated via Transmission Electron Microscopy and Laser Scanning Confocal Microscopy. SMDENVs were spherical, hollow, and uniform in size, with an average diameter of 177.6 ± 51.4 nm. Based on the analysis of lipidomics and proteomics, 383 lipids species and 1290 proteins were identified in SMDENVs. Compared with the conventional liposomes, SMDENVs demonstrated higher stability in different environmental conditions. Furthermore, we observed that SMDENVs were cytocompatible and inhibited the proliferation of Caco-2 cells. SMDENVs could be phagocytized by Caco-2 cells in a time-dependent manner. Further, SMDENVs also inhibited the proliferation of Caco-2 cells in a dose-dependent manner, and the half-maximal inhibitory concentration (IC50) was 236.2 ± 3.2 µg/mL. Additionally, SMDENVs induced cellular apoptosis by increasing the levels of reactive oxygen species and decreasing the mitochondrial membrane potential.

Microbial dysbiosis in systemic lupus erythematosus: a scientometric study.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Mounting evidence suggests microbiota dysbiosis augment autoimmune response. This study aims to provide a systematic overview of this research field in SLE through a bibliometric analysis. Methods: We conducted a comprehensive search and retrieval of literature related to microbial researches in SLE from the Web of Science Core Collection (WOSCC) database. The retrieved articles were subjected to bibliometric analysis using VOSviewer and Bibliometricx to explore annual publication output, collaborative patterns, research hotspots, current research status, and emerging trends. Results: In this study, we conducted a comprehensive analysis of 218 research articles and 118 review articles. The quantity of publications rises annually, notably surging in 2015 and 2018. The United States and China emerged as the leading contributors in microbial research of SLE. Mashhad University of Medical Sciences had the highest publication outputs among the institutions. Frontiers in Immunology published the most papers. Luo XM and Margolles A were the most prolific and highly cited contributors among individual authors. Microbial research in SLE primarily focused on changes in microbial composition, particularly gut microbiota, as well as the mechanisms and practical applications in SLE. Recent trends emphasize "metabolites," "metabolomics," "fatty acids," "T cells," "lactobacillus," and "dietary supplementation," indicating a growing emphasis on microbial metabolism and interventions in SLE. Conclusion: This study provides a thorough analysis of the research landscape concerning microbiota in SLE. The microbial research in SLE mainly focused on three aspects: microbial dysbiosis, mechanism studies and translational studies (microbiota-based therapeutics). It identifies current research trends and focal points, offering valuable guidance for scholars in the field.

Topical ophthalmic instillation of engineered hMSCs-derived exosomes: A novel non-invasive therapeutic strategy for ocular posterior-segment disorder.

Due to the presence of protective mechanisms and blood-ocular barriers in the eye, drugs aimed at treating posterior segment ophthalmic disorder have to be administrated mostly through periocular or intravitreal injection. In the current study, we sought to investigate whether topical ophthalmic instillation of human mesenchymal stem cells (hMSCs)-derived exosomes can prevent and treat experimental autoimmune uveitis (EAU), a posterior segment ophthalmic disease induced in animals and considered a model of human autoimmune diseases of the eye. Our studies reveal that topical ophthalmic instillation of hMSCs-derived exosomes can effectively ameliorate EAU. More importantly, we demonstrate that exosomes modified by trans-activator of transcription peptide (TAT) were more effective than naive exosomes in penetrating ocular barrier and preventing/treating EAU. Taken together, these results indicate that topical ophthalmic instillation of TAT-peptide modified exosomes represents a novel non-invasive therapeutic strategy for posterior-segment ophthalmic disorders.

A novel function of benzoic acid to enhance intestinal barrier defense against PEDV infection in Piglets.

The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth promoter, exhibits the potential to enhance the gut health of piglets by modulating intestinal morphometry and tight junction dynamics. However, the extent to which BA regulates the intestinal mucus barrier through its impact on stem cells remains inadequately elucidated. Therefore, this study was conducted to investigate the effects of BA on the intestinal barrier and the differentiation of intestinal stem cells, employing in vivo piglet and in vitro intestinal organoid models. Our investigation revealed a significant increase in the number of goblet cells within the small intestine, as well as the strengthening of the mucus barrier in vivo following oral treatment with BA, providing partial protection against PEDV infection in piglets. Additionally, in vitro cultivation of enteroids with BA led to a notable increase in the number of MUC2+ GCs, indicating the promotion of GC differentiation by BA. Furthermore, transcriptome analysis revealed an upregulation of the number of GCs and the expression of cell vesicle transport-related genes during BA stimulation, accompanied by the downregulation of the Wnt and Notch signaling pathways. Mechanistically, MCT1 facilitated the transport of BA, subsequently activating the MAPK pathway to mediate GC differentiation. Overall, this study highlights a novel function for BA as a feed additive in enhancing the intestinal mucus barrier by promoting intestinal GC differentiation, and further prevents viral infection in piglets.

Examining starch metabolism in lotus roots (Nelumbo nucifera Gaertn.) during post-harvest storage at different temperatures.

This study explores the impact of postharvest storage temperatures (4 °C and 25 °C) on starch metabolism and textural attributes of glutinous lotus root. While starch metabolism is a well-known factor influencing texture, changes in powdery and sticky qualities have remained unexplored. Our research reveals that storing lotus roots at 4 °C delays water dissipation, amylopectin reduction, and the decline in textural elements such as hardness, adhesiveness, springiness, gumminess, and resilience. Lower temperatures postpone amylopectin reduction and sugar interconversion, thereby preserving the sticky texture. Additionally, they suppress starch formation, delay starch metabolism, and elevate the expression of genes involved in starch metabolism. The correlation between gene expression and root texture indicates the critical role of gene regulation in enzyme activity during storage. Overall, low-temperature storage extends lotus root preservation by regulating metabolite content, enzyme activities, and the corresponding genes involved in starch metabolism, preserving both intrinsic and external root quality.

Streptomyces albipurpureus sp. nov., a novel actinobacterium with antimicrobial activity isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don.

A novel actinobacterium, designated strain CWNU-1T, was isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don and examined using a polyphasic taxonomic approach. The organism developed pale blue aerial mycelia that was simply branched and terminated in open or closed coils of three or more volutions on International Streptomyces Project 3 agar. Spores were ellipsoidal to cylindrical with wrinkled surfaces. The strain showed high 16S rRNA gene sequence similarity to Streptomyces kurssanovii NBRC 13192T (98.8 %), Streptomyces xantholiticus NBRC 13354T (98.7 %) and Streptomyces peucetius JCM 9920T (98.6 %). The phylogenetic result based on 16S rRNA gene and genome sequences clearly demonstrated that strain CWNU-1T formed an independent phylogenetic lineage. On the basis of orthologous average nucleotide identity, CWNU-1T was most closely related to Streptomyces inusitatus NBRC 13601T with 79.3 % identity. The results of the digital DNA-DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with S. inusitatus NBRC 13601T (25.3 %). With reference to phenotypic characteristics, phylogenetic data, orthologous average nucleotide identity and digital DNA-DNA hybridization results, strain CWNU-1T was readily distinguished from its most closely related strains and classified as representing a novel species, for which the name Streptomyces albipurpureus sp. nov. is proposed. The type strain is CWNU-1T (=CGMCC 4.7758T=MCCC 1K07402T=JCM 35391T).

Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study.

Background: Nephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few have harnessed genetic methodologies to establish causal relationships. Methods: Through Mendelian randomization (MR) in two substantial cohorts, spanning large sample sizes, we evaluated over 100 plasma circulating metabolites and 263 drugs to discern their causal effects on nephritis risk. The primary analytical tool was the inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny of GSE115857 (IgA nephropathy, 86 samples) and GSE72326 (lupus nephritis, 238 samples) unveiled anomalies in lipid metabolism and immunological characteristics in nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken to verify the instrumental variables' (IVs) assumptions. Results: Unique lipoprotein-related molecules established causal links with diverse nephritis subtypes. Notably, docosahexaenoic acid (DHA) emerged as a protective factor for acute tubulointerstitial nephritis (ATIN) (OR1 = 0.84, [95% CI 0.78-0.90], p1 = 0.013; OR2 = 0.89, [95% CI 0.82-0.97], p2 = 0.007). Conversely, multivitamin supplementation minus minerals notably increased the risk of ATIN (OR = 31.25, [95% CI 9.23-105.85], p = 0.004). Reduced α-linolenic acid (ALA) levels due to lipid-lowering drugs were linked to both ATIN (OR = 4.88, [95% CI 3.52-6.77], p < 0.001) and tubulointerstitial nephritis (TIN) (OR = 7.52, [95% CI 2.78-20.30], p = 0.042). While the non-renal drug indivina showed promise for TIN treatment, the use of digoxin, hydroxocobalamin, and liothyronine elevated the risk of chronic tubulointerstitial nephritis (CTIN). Transcriptome analysis affirmed that anomalous lipid metabolism and immune infiltration are characteristic of IgA nephropathy and lupus nephritis. The robustness of these causal links was reinforced by sensitivity analyses and leave-one-out tests, indicating no signs of pleiotropy. Conclusion: Dyslipidemia significantly contributes to nephritis development. Strategies aimed at reducing plasma low-density lipoprotein levels or ALA supplementation may enhance the efficacy of existing lipid-lowering drug regimens for nephritis treatment. Renal functional status should also be judiciously considered with regard to the use of nonrenal medications.

The dual function of calcium ion in fruit edible coating: Regulating polymer internal crosslinking state and improving fruit postharvest quality.

The edible coating is proved to be a convenient approach for fruit preservation. Among these published explorations, naturally sourced macromolecules and green crosslinking strategies gain attention. This work centers on edible coatings containing Ca2+ as crosslinker for the first time, delving into crosslinking mechanisms, include alginate, chitosan, Aloe vera gel, gums, etc. Additionally, the crucial functions of Ca2+ in fruit's quality control are also elaborated in-depth, involving cell wall, calmodulin, antioxidant, etc. Through a comprehensive review, it becomes evident that Ca2+ plays a dual role in fruit edible coating. Specifically, Ca2+ constructs a three-dimensional dense network structure with polymers through ionic bonding. Moreover, Ca2+ acts directly with cell wall to maintain fruit firmness and serve as a second messenger to participate secondary physiological metabolism. In brief, coatings containing Ca2+ present remarkable effects in preserving fruit and this work may provide guidance for Ca2+ related fruit preservation coatings.

Simulated gastrointestinal digestion of walnut protein yields anti-inflammatory peptides.

The impact of the simulated gastrointestinal digestion process on walnut protein and the potential anti-inflammatory properties of its metabolites was studied. Structural changes induced by digestion, notably in α-Helix, ß-Turn, and Random Coil configurations, were unveiled. Proteins over 10,000 Da significantly decreased by 35.6 %. Antioxidant activity in these metabolites paralleled increased amino acid content. Molecular docking identified three walnut polypeptides-IPAGTPVYLINR, FQGQLPR, and VVYVLR-with potent anti-inflammatory properties. RMSD and RMSF analysis demonstrated the stable and flexible interaction of these polypeptides with their target proteins. In lipopolysaccharide (LPS)-induced inflammation in normal human colon mucosal epithelial NCM460 cells, these peptides decreased 5-hydroxytryptamine (5-HT), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) expression, while mitigating cell apoptosis and inflammation. Our study offers valuable insights into walnut protein physiology, shedding light on its potential health benefits.

Telemedicine Trends and Lessons Learned During the COVID-19 Pandemic-World Trade Center Health Program, 2020-2021.

The World Trade Center (WTC) Health Program, a limited federal health care program for eligible people exposed to the terrorist attacks on September 11, 2001, expanded telemedicine services during the COVID-19 pandemic (2020-2021). We analyzed service use trends from January 2020 through December 2021 to describe how the program implemented telemedicine services. About three-quarters (75%) of telemedicine visits were for mental health-related services. In the second quarter of 2020 (April-June), the number of telemedicine visits per 1000 members (n = 367) increased, exceeding in-person visits (n = 152) by 1.4-fold. The number of telemedicine visits per 1000 members decreased gradually during the rest of the study period but still represented 38% of total visits by the end of 2021. Changes in telemedicine visits were offset by comparable changes for in-person visits, such that the rate of total visits was essentially constant during the study period. Multivariate logistic regression models showed differences in telemedicine visit rates by member type and by demographic characteristics. Survivor members (vs responder members), those self-identified as non-Hispanic Other races (vs non-Hispanic White), those with preferred language not English (vs preferred language English), and those not living in the New York metropolitan area (vs living in the New York metropolitan area) were less likely to use telemedicine. Implementing telemedicine services in the WTC Health Program during the COVID-19 pandemic underscored the importance of extensive collaboration among partners, the capacity to rapidly develop necessary technical guidance, and the flexibility to address frequent regulatory guidance updates in a timely fashion. These lessons learned may guide similar health care providers posed with time-sensitive disruptions of in-person services.

Opioid prescriptions among the World Trade Center Health Program population.

BACKGROUND: The World Trade Center Health Program (Program) provides limited health care to those directly affected by the 9/11 terrorist attacks. Because of physical/mental trauma arising from the 9/11 attacks, Program members might be at high risk of opioid use. To prevent prescription opioid overuse, in 2018 the Program implemented various measures to improve opioid prescribing and expand access to non-opioid pain management among Program members. However, the characteristics of opioid prescriptions dispensed among this population has never been described. METHODS: Administrative and claims data from 07/01/2011 to 09/30/2022 were used to describe opioid prescriptions dispensed during 2013-2021. RESULTS: From 2013-2021, 108,285 members were Program-enrolled for ≥ 10 months, 4,053 (3.7%) had 22,938 outpatient opioid prescriptions, of which, 62.1% were for cancer-related pain, 11.1% for hospice/end of life care, 4.8% for surgery pain, and 9.8% for acute/chronic pain. Among members with Program-paid diagnostic/treatment claims (n = 70,721), the proportion with opioid prescriptions for cancer/hospice/end of life care increased from 0.5% in 2013 to 1.6% in 2018 (p = 0.010), then decreased to 1.1% in 2021 (p = 0.070), and the proportion for non-cancer surgery/acute/chronic pain decreased from 0.6% in 2013 to 0.23% in 2021 (p = 0.0005). Among members prescribed opioids without cancer/hospice/sickle cell disease, the proportion who started with long-acting opioids or had opioid prescriptions from ≥ 4 prescribers were below 6.5% annually; the proportion receiving a high-dose (≥ 90 morphine milligram equivalents per day [MED]), or with concurrent opioids and benzodiazepines use, or who started opioids with MED ≥ 50 or with long duration (≥ 7 days' supply) were above 10% annually, but decreased since 2017. CONCLUSIONS: Prevalence of outpatient opioid prescriptions paid by the Program was very low and prescriptions were primarily dispensed for cancer/hospice/end of life care. Although Program efforts to improve opioid prescribing coincided with improvements in outcomes, ongoing surveillance is needed.

NF-κB c-Rel Is a Potential Therapeutic Target for Acute Corneal Transplant Rejection.

Purpose: The purpose of this study was to determine the role of nuclear factor kappa B (NF-κB) c-Rel during acute corneal transplant rejection and whether targeting c-Rel can reduce corneal transplant rejection. Methods: Allogeneic corneal transplantation was performed in wild-type and c-Rel-deficient mice. Corneal graft survival rate, opacity, neovascularization, and edema were evaluated by slit-lamp microscopy. Adeno-associated virus 6 (AAV6) expressing c-Rel-specific small hairpin RNA (AAV6-shRel) and the small-molecule compound pentoxifylline (PTXF) were used to reduce c-Rel expression. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory cytokines. c-Rel expression was determined by quantitative RT-PCR and western blot. The effect of c-Rel inhibition on corneal transplant rejection was examined using a mouse model of acute allogeneic corneal transplantation. Tear production and corneal sensitivity were measured to determine the potential toxicity of AAV6-shRel and PTXF. Results: The expression of c-Rel and its inflammatory targets was increased in both mice and patients with corneal transplant rejection. Loss of c-Rel reduced corneal transplant rejection in mouse. Both AAV6-shRel and PTXF were able to downregulate the expression of c-Rel and its inflammatory targets in vitro. Treatment with AAV6-shRel or PTXF reduced corneal transplant rejection in mouse and downregulated the expression of inflammatory cytokines in peripheral blood mononuclear cells from patients with corneal transplant rejection. Treatment with AAV6-shRel or PTXF displayed no side effects on tear production or corneal sensitivity. Conclusions: Increased expression of c-Rel is a risk factor for acute corneal transplant rejection, and targeting c-Rel can efficiently reduce corneal transplant rejection.

Melatonin treatment delays the softening of blueberry fruit by modulating cuticular wax metabolism and reducing cell wall degradation.

The effects of postharvest melatonin (MT) treatment on cuticular wax and cell wall metabolism in blueberry fruit (Vaccinium spp.) were evaluated. The results revealed that MT treatment maintained the cuticular wax rod-like structure and delayed wax degradation. The gas chromatography-mass spectrometry analysis results revealed that MT application changed the cuticular wax composition in blueberries, and 25 metabolic components were screened. The metabolic regulation of wax quality in blueberry fruit may therefore be influenced by MT. Additionally, MT slowed down pectin and cellulose degradation by reducing the activities of cell wall degrading enzymes like pectin methyl esterase polygalacturonase, ß-galactosidase, and cellulose in the later stages of storage. It also downregulated the transcriptional expression of related genes like VcPE, VcPG, VcBG6, and VcGAL1. Thus, MT prevented softening and senescence by postponing the degradation of the cell wall in postharvest blueberry fruit.

The Invasion of Galinsoga quadriradiata into High Elevations Is Shaped by Variation in AMF Communities.

Mountain ranges have been previously suggested to act as natural barriers to plant invasion due to extreme environmental conditions. However, how arbuscular mycorrhizal fungi (AMF) affect invasion into these systems has been less explored. Here, we investigated how changes in AMF communities affect the performance of Galinsoga quadriradiata in mountain ranges. We performed a greenhouse experiment to study the impact of inoculations of AMF from different elevations on the performance and reproduction of invaders and how competition with native plants changes the effects of invader-AMF interactions. We found strong evidence for a nuanced role of AMF associations in the invasion trajectory of G. quadriradiata, with facilitative effects at low elevations and inhibitory effects at high elevations. Galinsoga quadriradiata performed best when grown with inoculum collected from the same elevation but performed worst when grown with inoculum collected from beyond its currently invaded range, suggesting that AMF communities can help deter invasion at high elevations. Finally, the invasive plants grown alone experienced negative effects from AMF, while those grown in competition experienced positive effects, regardless of the AMF source. This suggests that G. quadriradiata lowers its partnerships with AMF in stressful environments unless native plants are present, in which case it overpowers native plants to obtain AMF support during invasion. Finally, our results indicate that invader-AMF interactions can inhibit invasive range expansion at high elevations, and biotic interactions, in addition to harsh environmental conditions, make high-elevation mountain ranges natural barriers against continued invasion.

Immune podocytes in the immune microenvironment of lupus nephritis (Review).

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder caused by the loss of tolerance to endogenous nuclear antigens such as double­stranded DNA, leading to the proliferation of T cells and subsequent activation of B cells, which results in serious organ damage and life­threatening complications such as lupus nephritis. Lupus nephritis (LN) develops as a frequent complication of SLE, accounting for >60% of SLE cases, and is characterized by proteinuria and heterogeneous histopathological findings. Glomerular injury serves a role in proteinuria as podocyte damage is the leading contributor. Numerous studies have reported that podocytes are involved in the immune response that promotes LN progression. In LN, immune complex deposition stimulates dendritic cells to secrete inflammatory cytokines that activate T cells and B cells. B cells secrete autoantibodies that attack and damage the renal podocytes, leading to renal podocyte injury. The injured podocytes trigger inflammatory cells through the expression of toll­like receptors and trigger T cells through major histocompatibility complexes and CD86, thereby participating in the local immune response and the exacerbation of podocyte injury. Based on the existing literature, the present review summarizes the research progress of podocytes in LN under the local immune microenvironment of the kidney, explores the mechanism of podocyte injury under the immune microenvironment, and evaluates podocytes as a potential therapeutic target for LN.