First Report of Exserohilum rostratum Causing Brown Spot on Spartina alterniflora in China.

Spartina alterniflora Loisel, a perennial grass, has become an invasive species in China's coastal wetlands (Zhang et al. 2018). In July 2021, brown spot symptoms were observed on S. alterniflora in a coastal wetland (21°45'48″N, 108°44'00″E) in Beihai City, Guangxi Province, China. The disease affected approximately 50% of the plants in the surveyed area (0.2 ha) and was also observed in other regions of Beihai. It caused brown lesions with a gray or whitish center on the leaves and stems of S. alterniflora. As the disease developed, it ultimately led to leaf shedding and plant death. To isolate the causal agent, 18 fragments (~ 5 mm) from six symptomatic plants (3 leaf pieces per plant) were surface sterilized with 1% NaOCl solution for 2 min and rinsed three times with sterilized water. Subsequently, the tissues were placed on potato dextrose agar (PDA) medium supplemented with chloramphenicol (0.1 g/liter) and incubated at 28°C for three days. The hyphal tips were transferred onto fresh PDA to obtain pure cultures. A total of 25 isolates were obtained, 20 of which shared similar morphologies, while the remaining five exhibited distinct morphological characteristics and were non-pathogenic to S. alterniflora. Three isolates (MC16.1.3, MC16.6.2, and MC16.8.3) were randomly selected from the 20 for further investigation. The colonies on PDA were flat with dense aerial mycelia. The colony margins were entire, light brown in the centre, white to grey at the margin; reverse dark brown in the centre, gray at the margin. Conidia were straight to slightly curved, light olive-brown to dark olive-brown, septate, measured 33.5 to 79.1 µm × 10.4 to 18.7 µm (average 52.9 × 14.4 µm, n = 100), with a distinctly protruding hilum swelled from the basal cell. For molecular identification, the genomic DNA was extracted from mycelium on PDA using the CTAB method (Guo et al. 2000). The internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and translation elongation factor 1 alpha (TEF1-α) genes were amplified and sequenced with the primer pairs ITS1/ITS4 (White et al. 1990), GPD1/GPD2 (Berbee et al. 1999), and EF1-983/EF1-2218 (Rehner et al. 2005), respectively. A BLAST analysis revealed that the ITS (OR516787-9), GAPDH (OR523686-8), and TEF-α (OR523683-5) had 99.1 to 99.7% identity with those of E. rostratum strains BRIP 11417 (LT837836, LT882553, and LT896656) and CBS 128061 (KT265240, LT715900, and LT896658) (Hernández-Restrepo et al. 2018). Based on the concatenated sequences, a phylogenetic tree generated by PhyloSuite software (Zhang et al., 2020) through Bayesian inference (BI) and Maximum Likelihood (ML) methods placed the isolates within E. rostratum. These morphological characteristics and molecular analyses confirmed the pathogen as E. rostratum (Hernández-Restrepo et al. 2018; Kaboré et al. 2022). To confirm pathogenicity, a conidial water suspension (~ 1 × 106 conidia/ml) of each of the three strains was inoculated on nine healthy S. alterniflora plants that had been grown for six months. Control plants were treated with sterile water. All plants were then enclosed in plastic bags and incubated in a greenhouse at 28°C. Six days after inoculation, the plants exhibited symptoms similar to those observed in nature. The control plants developed no symptoms. These experiments were replicated three times with similar results. To fulfill Koch's postulates, E. rostratum was consistently re-isolated from symptomatic tissue and confirmed by morphology and sequencing, whereas no fungus was isolated from the control plants. In recent years, S. alterniflora has posed a serious threat to the indigenous biodiversity of wetland ecosystems (Zhang et al. 2018). To our knowledge, this is the first report of E. rostratum causing brown spot on S. alterniflora worldwide.

Interceed combined with bone marrow mesenchymal stem cells improves endometrial receptivity of intrauterine adhesion.

Background: This study aimed to investigate the impact of intrauterine adhesions (IUA) therapy and endometrial receptivity by implanting autologous bone marrow mesenchymal stem cells (BMSCs) into the Interceed and subsequently placing them in the uterine cavity of rats. Methods: Fifty rats were divided into 5 groups according to the random number table method (10 rats in each group). Following the development of the IUA model through mechanical injury, the animals were categorized into different treatment groups: the IUA model (intrauterine perfusion of saline), Interceed therapy (intrauterine placement of Interceed), BMSCs therapy (intrauterine perfusion of BMSCs), BMSCs + Interceed therapy (intrauterine placement of BMSCs + Interceed), and a control group (intrauterine perfusion of saline). The Hematoxylin-eosin (HE) staining technique was employed to identify and assess the pathological alterations in the endometrium. Additionally, it facilitated the quantification of endometrial glands and the determination of endometrial thickness. Masson staining was used to detect fibrosis in rat uterus. The number of microvascular density (MVD) was detected by immunohistochemistry (IHC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the levels of leukemia inhibitory factor (LIF), integrin ανß3, and vascular endothelial growth factor (VEGF) in uterine tissue. Male and female rats were combined in cages for reproductive and conception evaluation. Results: In comparison to the control, the number of endometrial glands in the IUA model was significantly reduced, and the degree of endometrial thinning and fibrosis was significantly increased (p < 0.05). Compared with the IUA model, the number of endometrial glands did not exhibit any significant alterations in endometrial thickness and MVD number. The expressions of LIF, integrin ανß3, and VEGF in the uterine tissue were not significantly improved with Interceed therapy, resulting in no significant improvement in the pregnancy rate (p > 0.05). The number of endometrial glands, endometrial thickness, and MVD in the BMSCs therapy group were significantly increased. Moreover, the expressions of LIF, integrin ανß3, and VEGF in uterine tissue exhibited a significant increase, leading to a comparatively higher pregnancy rate (p < 0.05). In the BMSCs + Interceed therapy group, the number of endometrial glands, endometrial thickness, and MVD were significantly increased, and the expressions of LIF, integrin ανß3, and VEGF in uterine tissue were significantly increased as well, along with a corresponding rise in the pregnancy rate (p < 0.05). Conclusion: The intrauterine placement of Interceed combined with BMSCs in IUA rats can thicken the damaged endometrium, increase the number of glands, promote endometrial angiogenesis, improve endometrial receptivity, and increase the rate of pregnancy in IUA rats.

Effect of Salvia sclarea L. extract on growth performance, antioxidant capacity, and immune function in lambs.

The aim of this experiment is to explore the effects of salvia sclarea extract on the growth performance, apparent nutrient digestibility, antioxidant capacity, and immune function of lambs. Sixty female lambs (Chinese Merino sheep) aged 2 months and weighing 20 ± 2 kg were selected and randomly divided into five groups of twelve lambs in each. While the control group (CK) received only basal feed, the experimental group was supplemented with different concentrations of salvia sclarea extract in the basal feed at 0.04 mL/kg (group CL1), 0.08 mL/kg (group CL2), 0.12 mL/kg (group CL3), and 0.16 mL/kg (group CL4). The feeding period was 85 days, including 15 days of pre-feeding and 70 days of regular feeding. Body weight and feed intake were recorded during the test period, and blood was collected at the end of the test for the determination of immune and antioxidant indices. The results showed that the average daily gain and average daily feed intake of lambs were significantly increased in CL3 group compared to CK group (p < 0.05). Also, the apparent nutrient digestibility of crude protein and neutral detergent fiber was significantly increased (p < 0.05). The Dry matter, acid detergent fiber and Ether extract were not significantly different (p > 0.05). The serum levels of superoxide dismutase, catalase, glutathione peroxidase, and antioxidant capacity were significantly higher in the CL2, CL3, and CL4 groups compared to CK group, while malondialdehyde levels were significantly lower (p < 0.05). The serum levels of immune globulin A, immune globulin G, immune globulin M, interferon-γ, and interleukin-10 were significantly higher and the levels of tumor necrosis factor-α and interleukin-1ß were significantly lower in the CL2, CL3, and CL4 groups (p < 0.05). In conclusion, the addition of salvia sclarea extract to the ration promotes growth performance and nutrient digestion in lambs. Improvement of immune response by increasing immunoglobulin and cytokine concentrations. And it enhances the antioxidant status by increasing the antioxidant enzyme activity in lambs. Introduction: This study aimed to explore the effects of Salvia sclarea extract on the growth performance, apparent nutrient digestibility, antioxidant capacity, and immune function of the lambs. Methods: Sixty female lambs (Chinese Merino sheep) aged 2 months and weighing 20 ± 2 kg were selected and randomly divided into five groups of 12 lambs each. The control group (CK) received only basal feed, whereas the experimental group was supplemented with different concentrations of salvia sclarea extract in the basal feed at 0.04, 0.08, 0.12, and 0.16 mL/kg (CL1, CL2, CL3, and CL4, respectively). The feeding period was 85 days, including 15 days of pre-feeding and 70 days of regular feeding. Body weight and feed intake were recorded during the test period, and blood was collected at the end of the test to determine immune and antioxidant indices. Results: The results showed that the average daily weight gain and feed intake of the lambs were significantly higher in the CL3 group than in the CK group (p < 0.05). In addition, the apparent nutrient digestibility of crude protein and neutral detergent fiber increased significantly (p < 0.05). The dry matter, acid detergent fiber, and ether extract were not significantly different (p > 0.05). Serum levels of superoxide dismutase, catalase, and glutathione peroxidase and antioxidant capacity were significantly higher in the CL2, CL3, and CL4 groups than in the CK group, whereas malondialdehyde levels were significantly lower (p < 0.05). The serum levels of immune globulin immune globulin A, immune globulin G, immune globulin M, interferon-γ, and interleukin-10 were significantly higher and the levels of tumor necrosis factor-α and interleukin-1ß were significantly lower in the CL2, CL3, and CL4 groups (p < 0.05). Discussion: In conclusion, the addition of the S. sclarea extract to the diet promoted growth performance and nutrient digestion in lambs. Immune response was improved by increasing Ig and cytokine concentrations. It enhances antioxidant status by increasing antioxidant enzyme activity in lambs.

Occupational well-being in medical workers in Inner Mongolia after the Normalized Epidemic Prevention and Control Strategy: A cross-sectional study.

Little is known about the status of occupational well-being among the Chinese medical workers after the implementation of Normalized Epidemic Prevention and Control strategy as most studies are performed during the COVID-19 pandemic. This study was designed to investigate the occupational well-being among the medical workers in our city in the COVID-19 after the release of Normalized Epidemic Prevention and Control Strategy since May 7, 2020 in mainland China. We included the medical workers involved in the front-line of COVID-19 that were randomly selected from 7 hospitals in Inner Mongolia Autonomous Region, China. The occupational well-being among medical workers was evaluated using the modified occupational well-being scales and the symptom Checklist-90 (SCL-90) scale. Then Logistic regression analysis was given to identify the risk factors that may affect the occupational well-being among the medical workers. Our data showed that hospital type (p < 0.01), hospital grade (p < 0.01), marital status (p < 0.01) and monthly income (p < 0.01) were independent risk factors for the occupational well-being among the medical workers. Obsessive-compulsive disorder, somatization, phobic anxiety, depression and interpersonal sensitivity were risk factors for poor occupational well-being. Therefore, attention should be given to the occupational well-being of the medical workers. Meanwhile, appropriate measurements are necessary to improve their working quality.

Spectrum-effect relationship between ultra-performance liquid chromatography fingerprints and melanogenic effect of Vernonia anthelmintica effective part.

The fingerprint of Vernonia anthelmintica effective part (VAEP) from 15 different producing areas was established, followed by cluster analysis and principal component analysis. The relationship between the fingerprint and the melanogenesis-promoting activity of VAEP was then analyzed using the grey correlation degree and the orthogonal partial least square method. The characteristic peaks reflecting the pharmacodynamic effect of VAEP were identified as vernodalin, 3,5-O-dicaffeoyl quinic acid (3,5-diCQA), and butin. Based on the distribution characteristics of these components in plants from different habitats and the verification of results from the spectrum-effect relationship, vernodalin and 3,5-diCQA can be used as characteristic components for quality control and pharmacodynamic assessment of V. anthelmintica products. This research establishes a theoretical foundation for planting areas and provides a scientific evaluation of the melanogenesis-promoting effect of V. anthelmintica.

Phenotypic heterogeneity unveils a negative correlation between antibiotic resistance and quorum sensing in Pseudomonas aeruginosa clinical isolates.

Colonization of Pseudomonas aeruginosa in the lung environments frequently leads to the enrichment of strains displaying enhanced antibiotic resistance and reduced production of quorum-sensing (QS) controlled products. However, the relationship between the emergence of QS deficient variants and antibiotic resistance remains less understood. In this study, 67 P. aeruginosa strains were isolated from the lungs of 14 patients with chronic obstructive pulmonary disease, followed by determining their genetic relationship, QS-related phenotypes and resistance to commonly used antibiotics. The integrity of P. aeruginosa QS system was checked by DNA sequencing. The relationship between the QS system and antibiotic resistance was then assessed by correlation analyses. The function of the LasR protein and bacterial virulence were evaluated through homology modeling and nematode-infection assay. The influence of antibiotic on the development of extracellular protease production ability of P. aeruginosa was tested by an evolutionary experiment. The results showed that P. aeruginosa clinical strains displayed abundant diversity in phenotype and genotype. The production of extracellular proteases was significantly negatively correlated with antibiotic resistance. The strains with enhanced antibiotic resistance also showed a notable overlap with the mutation of lasR gene, which is the core regulatory gene of P. aeruginosa QS system. Molecular docking and Caenorhabditis elegans infection assays further suggested that P. aeruginosa with impaired LasR protein could also have varying pathogenicity. Moreover, in vitro evolution experiments demonstrated that antibiotic-mediated selective pressure, particularly from Levofloxacin contributed to the emergence of extracellular protease-negative strains. Therefore, this study provides evidence for the connection of P. aeruginosa QS system and antibiotic resistance, and holds significance for developing targeted strategies to address antibiotic resistance and improving the management of antibiotic-resistant infections in chronic respiratory diseases.

Identification and functional characterization of a novel heterozygous splice­site mutation in the calpain 3 gene causes rare autosomal dominant limb­girdle muscular dystrophy.

Limb-girdle muscular dystrophies are a group of extremely heterogenous neuromuscular disorders that manifest with gradual and progressive weakness of both proximal and distal muscles. Autosomal dominant limb-girdle muscular dystrophy (LGMDD4) or calpainopathy is a very rare form of myopathy characterized by weakness and atrophy of both proximal and distal muscles with a variable age of onset. LGMDD4 is caused by germline heterozygous mutations of the calpain 3 (CAPN3) gene. Patients with LGMDD4 often show extreme phenotypic heterogeneity; however, most patients present with gait difficulties, increased levels of serum creatine kinase, myalgia and back pain. In the present study, a 16-year-old male patient, clinically diagnosed with LGMDD4, was investigated. The proband had been suffering from weakness and atrophy of both of their proximal and distal muscles, and had difficulty walking and standing independently. The serum creatine kinase levels (4,754 IU/l; normal, 35-232 IU/l) of the patient were markedly elevated. The younger sister and mother of the proband were also clinically diagnosed with LGMDD4, while the father was phenotypically normal. Whole exome sequencing identified a heterozygous novel splice-site (c.2440-1G>A) mutation in intron 23 of the CAPN3 gene in the proband. Sanger sequencing confirmed that this mutation was also present in both the younger sister and mother of the proband, but the father was not a carrier of this mutation. This splice-site (c.2440-1G>A) mutation causes aberrant splicing of CAPN3 mRNA, leading to the skipping of the last exon (exon 24) of CAPN3 mRNA and resulting in the removal of eight amino acids from the C-terminal of domain IV of the CAPN3 protein. Hence, this splice site mutation causes the formation of a truncated CAPN3 protein (p.Trp814*) of 813 amino acids instead of the wild-type CAPN3 protein that consists of 821 amino acids. This mutation causes partial loss of domain IV (PEF domain) in the CAPN3 protein, which is involved in calcium binding and homodimerization; therefore, this is a loss-of-function mutation. Relative expression of the mutated CAPN3 mRNA was reduced in comparison with the wild-type CAPN3 mRNA in the proband, and their younger sister and mother. This mutation was also not present in 100 normal healthy control individuals of the same ethnicity. The present study reported the first case of CAPN3 gene-associated LGMDD4 in the Chinese population.

A training program for improving the capacity of infection high-throughput sequencing and diagnosis in China.

BACKGROUND: Infectious diseases are a serious threat to human especially since the COVID-19 outbreak has proved the importance and urgency of their diagnosis and treatment again. Metagenomic next-generation sequencing (mNGS) has been widely used and recognized in clinical and carried out localized testing in hospitals. Increasing the training of mNGS detection technicians can enhance their professional quality and more effectively realize the application value of the hospital platform. METHODS: Based on the initial theoretical understanding and practice of the mNGS platform for localization construction, we have designed a training program to enhance the ability of technicians to detect pathogens by utilizing mNGS, and hence to conduct training practices nationwide. RESULTS: Until August 30, 2022, the page views of online classes have reached 51,500 times and 6 of offline small-scale training courses have been conducted. A total of 67 trainees from 67 hospitals have participated in the training with a qualified rate of 100%. After the training course, the localization platform of 1 participating hospital has been put into use, 2 have added the mNGS localization platform for admission, among which 3 have expressed strong intention of localization. CONCLUSIONS: This study focuses on the training procedures and practical experience of the project which is the first systematic standardized program of mNGS in the world. It solves the training difficulties in the current industry, and effectively promotes the localization construction and application of mNGS in hospitals. It has great development potential in the future and is worth further promotion.

AgrA directly binds to the promoter of vraSR and downregulates its expression in Staphylococcus aureus.

Staphylococcus aureus is an important human pathogen and vancomycin is widely used for the treatment of S. aureus infections. The global regulator agr is known as a well-described virulence regulator. Previous studies have found that agr-dysfunction strains are more likely to develop into vancomycin-resistant strains, but the mechanism for this phenomenon remains unknown. VraSR is a two-component regulatory system related to vancomycin resistance. In this study, we found that the expression levels of vraR were higher in agr-dysfunction clinical strains than in the agr-functional strains. We knocked out agr in a clinical strain, and quantitative reverse transcription PCR and ß-galactosidase activity assays revealed that agr repressed transcription of vraR. After vancomycin exposures, population analysis revealed larger subpopulations displaying reduced susceptibility in agr knockout strain compared with wild-type strain, and this pattern was also observed in agr-dysfunction clinical strains compared with the agr-functional strains. Electrophoretic mobility experiment demonstrated binding of purified AgrA to the promoter region of vraR. In conclusion, our results indicated that the loss of agr function in S. aureus may contribute to the evolution of reduced vancomycin susceptibility through the downregulation of vraSR.

A cytosine analogue 5-azacitidine improves the accumulation of licochalcone A in licorice Glycyrrhiza inflata.

Licochalcone A (LCA) is a characteristic compound of Glycyrrhiza inflata with anti-inflammatory, antioxidant and antitumor activities. However, G. inflata produces LCA in low quantities that does not meet the market demand. In this study, we found that DNA methylation inhibitor 5-azacitidine (5-azaC) successfully improved the LCA contents in G. inflata seedlings. Transcriptome analysis revealed a series of differentially expressed genes (DEGs), including transcription factors such as MYB, ERF, WRKY, and some structural genes related to flavonoid biosynthesis. However, whole genome bisulfite sequencing (BS-seq) results showed little effect of the 5-azaC treatment on the alteration of DNA methylation on these genes, indicating the possibility that 5-azaC acts as a stimulus, but not an epigenetic modulation factor to improve the LCA content in G. inflata. Additionally, we applied the 5-azaC treatment to field plants and hairy roots and successfully increased the LCA contents in both cases. This research demonstrates the feasibility of 5-azaC treatments in future applications to improve plant production of LCA.

Environmental and economic assessments of industry-level medical waste disposal technologies - A case study of ten Chinese megacities.

Medical waste (MW) is exploding due to the COVID-19 pandemic, posing a significant environmental threat, and leading to the urgent requirement for affordable and environmentally friendly MW disposal technologies. Prior research on individual MW disposal plants is region-specific, applying these results to other regions may introduce bias. In this study, major MW disposal technologies in China, i.e., incineration technologies (pyrolysis incineration and rotary kiln incineration), and sterilization technologies (steam sterilization, microwave sterilization, and chemical disinfection) with residue landfill or incineration were analyzed from an industry-level perspective via life cycle assessment (LCA), life cycle costing (LCC) and net present value (NPV) methods. Life cycle inventories and economic cost data for 4-5 typical companies were selected from 128 distinct enterprises and academic sources for each technology. LCA results show that microwave sterilization with residue incineration has the lowest environmental impact, emitting only 480 kg CO2 eq. LCC and NPV analyses indicate that steam sterilization with landfilling is the most economical, yielding revenues of 1,210 CNY/t and breaking even in the first year. Conversely, pyrolysis and rotary kiln incineration break even between the 4th and 5th years. Greenhouse gas emissions from the MW disposal in ten cities with the largest MW production in 2020 increased by 7% over 2019 to 43,800 tons and other pollutants increased by 6% to 12%. Economically, Shanghai exhibits the highest cost-effectiveness, while Nanjing delivers the lowest. It can be observed that the adoption of optimal environmental technologies has resulted in a diminution of greenhouse gas emissions by 279,000 tons and energy conservation of 1.76 billion MJ.

PC71BM as Morphology Regulator for Highly Efficient Ternary Organic Solar Cells with Bulk Heterojunction or Layer-by-Layer Configuration.

The ternary strategy is one of the effective methods to regulate the morphology of the active layer in organic solar cells (OSCs). In this work, the ternary OSCs with bulk heterojunction (BHJ) or layer-by-layer (LbL) active layers are prepared by using the polymer donor PM6 and the non-fullerene acceptor L8-BO as the main system and the fullerene acceptor PC71BM as the third component. The power conversion efficiencies (PCEs) of BHJ OSCs and LbL OSCs are increased from 17.10% to 18.02% and from 17.20% to 18.20% by introducing PC71BM into the binary active layer, respectively. The in situ UV-vis absorption spectra indicate that the molecular aggregation and crystallization process can be prolonged by introducing PC71BM into the PM6:L8-BO or PM6/L8-BO active layer. The molecular orientation and molecular crystallinity in the active layer are optimized by introducing the PC71BM into the binary BHJ or LbL active layers, which can be confirmed by the experimental results of grazing incidence wide-angle X-ray scattering. This study demonstrates that the third component PC71BM can be used as a morphology regulator to regulate the morphology of BHJ or LbL active layers, thus effectively improving the performance of BHJ and LbL OSCs.

EBV-Positive Intravascular Large B-Cell Lymphoma of the Small Intestine: A Case Report and Literature Review.

Intravascular large B-cell lymphoma (IVLBCL) is a rare lymphoma that affects the brain, skin, and bone marrow. We describe the case of a 75-year-old man who was admitted to the hospital after 4 h of stomach aches. A thorough physical examination indicated stomach discomfort and skin discoloration. Laboratory tests revealed thrombocytopenia and elevated lactate dehydrogenase levels. A computed tomography scan of the abdomen revealed that the small intestine wall was thickened, edematous, and necrotic. The necrotic small bowel was surgically removed, revealing many little round, homogenous, and unusual cells in the mesenteric vein. In-situ hybridization revealed that these cells were positive for PAX5, CD20, CD79a, CD10, and BCL2, as well as Epstein-Barr virus-encoded small RNA. After 1 week of hospitalization without treatment, the patient was diagnosed with IVLBCL and died of multiple organ dysfunction syndrome. IVLBCL is a rare illness that affects the small intestine and possibly the gastrointestinal system. It has an insidious start, a fast development, and a dismal prognosis. Knowing its clinicopathologic traits helps in understanding the illness, making an early diagnosis, and preventing rapid worsening.

Astragalus polysaccharide alleviates polycystic ovary syndrome by reducing insulin resistance and oxidative stress and increasing the diversity of gut microbiota.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is frequently accompanied by insulin resistance, oxidative stress (OS), and dyslipidemia. Astragalus polysaccharide (APS)-as a water-soluble heteropolysaccharide-can lower blood sugar and lipid and exert anti-aging effects and thus has been proven to be beneficial to various types of metabolic diseases. However, specific mechanisms of the action of APS on PCOS are yet to be studied. METHODS: Herein, BALB/C female mice aged 3 weeks were randomly divided into three groups (10 mice/group): oil + PBS group, DHEA + PBS group, and DHEA + APS group. Changes in the estrous cycle, ovarian tissue sections, serum levels of the hormone, blood glucose, blood lipid, and OS were studied. The intestinal microbiome was sequenced and Spearman correlation analysis was used to analyze the correlation between serum metabolic indexes and microflora. RESULTS: The results revealed that APS treatment ameliorated insulin resistance, OS, and dyslipidemia in PCOS mice. The results of 16S rDNA sequencing indicated that there were significant differences in the composition and diversity of intestinal microorganisms between DHEA and APS treatments. Firmicutes, Lachnospiraceae, Bacilli, Lactobacillaceae, and Lachnospiraceae_NK4A13_group were abundant in the oil + PBS group. Bacteroidota and Muribaculaceae were enriched in the DHEA + PBS group, while Rikenellaceae, Odoribacter, and Marinifilaceae were enriched in the DHEA + APS group. Furthermore, Spearman correlation analysis showed that there were close interactions and correlations between intestinal bacteria and indicators of blood glucose, blood lipids, steroid hormones, and OS in PCOS mice. CONCLUSIONS: Overall, the study showed that APS improved PCOS in mice by correcting serum metabolic disorders and increasing microbiome diversity, which may provide insight into understanding the pathogenesis and be a beneficial intervention for PCOS.

Selective homing of brain-derived reconstituted lipid nanoparticles to cerebral ischemic area enables improved ischemic stroke treatment.

Lipid nanoparticles (LNPs) hold great promise as carriers for developing drug delivery systems (DDSs) aimed at managing ischemic stroke (IS). Previous research has highlighted the vital role played by the lipid composition and biophysical characteristics of LNPs, influencing their interactions with cells and tissues. This understanding presents an opportunity to engineer LNPs tailored specifically for enhanced IS treatment. We previously introduced the innovative concept of reconstituted lipid nanoparticles (rLNPs), which not only retain the advantages of conventional LNPs but also incorporate lipids from the originating cell or tissue. Brain-derived rLNPs (B-rLNPs) exhibit significantly superior accumulation within the cerebral ischemic region when compared to liver-derived rLNPs (L-rLNPs). The homing effect of B-rLNPs was then employed to construct 3-n-butylphthalide (NBP) loaded DDS (B-rLNPs/NBP) for the treatment of IS. Our results demonstrated that compared with free NBP, B-rLNPs/NBP can significantly reduce infarct volume, neurological deficits, blood-brain barrier (BBB) leakage rate, brain water content, neutrophil infiltration, alleviate pathological structures, and improve the motor function in MCAO/R model. We also proved that B-rLNPs/NBP showed further reinforced protective effects on the same model than free NBP through the regulation of TLR4/MyD88/NF-κB (anti-inflammation) and Bax/Bcl-2 (anti-apoptosis) pathways. This study offers a promising tool towards improved IS treatment.

25(OH)D3 improves granulosa cell proliferation and IVF pregnancy outcomes in patients with endometriosis by increasing G2M+S phase cells.

BACKGROUND: The 25-hydroxyvitamin D3 (25 (OH) D3) is crucial for follicular development. This study aimed to investigate the relationship between the level of 25 (OH) D3 in endometriosis patients, pregnancy outcomes of in vitro fertilization (IVF), and the underlying mechanism. METHODS: The 25 (OH) D3 levels in serum and follicular Fluid (FF) samples were detected using enzyme-linked immunosorbent assay (ELISA). Clinical features and pregnancy outcomes of endometriosis patients were also compared between the deficient group (< 20 ug/ml) and the adequate group (≥ 20 ug/ml). The effects of 25 (OH) D3 on the proliferation and cell cycle of human ovarian granulosa cells were respectively detected by CCK-8 assay and flow cytometry (FCM). The differentially expressed genes (DEGs) in granulosa cells of endometriosis and tubal infertility patients were screened from GEO database. The effects of 25 (OH) D3 on the expressions of CDKN2D, PPARA, TGFB2 and THBD were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: The levels of 25 (OH) D3 in serum and FF samples were decreased in endometriosis patients. The deficient group had fewer embryos that can be transferred, lower quality embryos and lower clinical pregnancy rates. Adequate 25 (OH) D3 levels in FF samples was a protective factor for live birth outcome in endometriosis patients. 25 (OH) D3 enhanced the proliferation capacity of granulosa cells (the concentration of 10 nM was the most significant) and increased the proportion of G2M + S phase cells. The expression of CDKN2D was decreased and TGFB2 and THBD were significantly upregulated. CONCLUSIONS: 25 (OH) D3 deficiency may be associated with poor IVF pregnancy outcomes in endometriosis patients. 25 (OH) D3 promotes ovarian granulosa cell proliferation by promoting the ability of cells to divide, and may accelerate cell cycle progression by up-regulating THBD and down-regulating CDKN2D expression.

Research progress in the role of non-coding RNAs and embryo implantation. / éžç¼–ç RNAåœ¨èƒšèƒŽç€åºŠä¸­ä½œç”¨çš„ç ”ç©¶è¿›å±•.

Non-coding RNA (ncRNA) refers to RNA that lack the ability to encode protein. Based on their distinct biological characteristics, ncRNA are mainly classified into microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNA plays a crucial regulatory role in various biological processes. Pregnancy is a highly intricate physiological process that requires successful completion of multiple steps. Embryo implantation, as a key event of pregnancy, which is regulated by numerous factors, including embryo development, endometrial changes, and the maternal-embryo crosstalk. A diverse array of regulatory mechanisms ensures the accomplishment of embryo localization, adhesion, invasion, and ultimately successful implantation. MiRNA, lncRNA, and circRNA are extensively studied ncRNA molecules at present, which play an important role in the physiological and pathological processes associated with embryo implantation through targeting and regulating the expression of multiple cytokine and genes. With advancements in molecular biology technology, it is anticipated that ncRNA will contribute to the prediction and enhancement of clinical pregnancy outcomes from a molecular perspective.

Research progress of Claudin-low breast cancer.

Claudin-low breast cancer (CLBC) is a subgroup of breast cancer discovered at the molecular level in 2007. Claudin is one of the primary proteins that make up tight junctions, and it plays crucial roles in anti-inflammatory and antitumor responses as well as the maintenance of water and electrolyte balance. Decreased expression of claudin results in the disruption of tight junction structures and the activation of downstream signaling pathways, which can lead to tumor formation. The origin of Claudin-low breast cancer is still in dispute. Claudin-low breast cancer is characterized by low expression of Claudin3, 4, 7, E-cadherin, and HER2 and high expression of Vimentin, Snai 1/2, Twist 1/2, Zeb 1/2, and ALDH1, as well as stem cell characteristics. The clinical onset of claudin-low breast cancer is at menopause age, and its histological grade is higher. This subtype of breast cancer is more likely to spread to lymph nodes than other subtypes. Claudin-low breast cancer is frequently accompanied by increased invasiveness and a poor prognosis. According to a clinical retrospective analysis, claudin-low breast cancer can achieve low pathological complete remission. At present, although several therapeutic targets of claudin-low breast cancer have been identified, the effective treatment remains in basic research stages, and no animal studies or clinical trials have been designed. The origin, molecular biological characteristics, pathological characteristics, treatment, and prognosis of CLBC are extensively discussed in this article. This will contribute to a comprehensive understanding of CLBC and serve as the foundation for the individualization of breast cancer treatment.

A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma.

Bladder urothelial carcinoma (BLCA) is one of the most common cancer-related deaths in the world, along with high mortality. Due to the difficult detection of early symptoms, the treatment for this disease is still dissatisfactory. Thus, the current research hotspot is beginning to focus on the immune microenvironment in this disease, aiming to provide guidance for diagnosis and treatment. In this study, the single-cell RNA sequencing data downloaded from the gene expression omnibus database was used to classify the immune cells of BLCA. And the final seven T-cell-related cell clustering genes associated with BLCA prognosis (HSPA2, A2M, JUN, PDGFRB, GBP2, LGALS1, and GAS6) were screened out, and then used for constructing the prognostic model against BLCA based on the Cox and LASSO regression analysis. Satisfactorily, the model could efficiently evaluate the overall survival of BLCA and had the potential to be applied for the clinic treatment. Moreover, we also revealed that the difference in immune infiltration levels and gene mutation might account for the diverse prognosis in BLCA patients. In a word, our findings provided a novel insight for designing efficient immunotherapies for BLCA.

Expression of maize OXS2a in Arabidopsis stunts plant growth but enhances heat tolerance.

As plants encounter various environmental stresses, judicial allocation of resources to stress response is crucial for plant fitness. The plant OXS2 (OXIDATIVE STRESS 2) family has been reported to play important roles in growth regulation and stress response. Here, we report that the maize OXS2 family member ZmOXS2a when expressed in Arabidopsis retards growth including delayed flowering, but improves heat tolerance. ZmOXS2a can be found in the cytoplasm, nucleus and PBs/P bodies (mRNA processing bodies), but heat treatment induces higher accumulation in the PBs. Deletion of ARR (arginine rich region) and TZF (tandem zinc finger) domains for high-affinity RNA-binding reduced PBs accumulation of ZmOXS2a; and unlike ZmOXS2a, expression of this deletion mutant gene affected neither Arabidopsis growth nor heat tolerance. This suggests that ZmOXS2a might be involved in RNA degradation, which would also account for the larger amount of down-regulated genes found in ZmOXS2a expressing lines. Furthermore, 240 of 890 down-regulated genes contain ARE (AU-rich elements) in the mRNA 3'UTR that might be potential targets of ZmOXS2a. Expression of ZmOXS2a also disturbs the response to ABA (abscisic acid) and cytokinin, as GO (gene ontology) analysis shows that 50 and 15 DEGs (differentially expressed genes) are enriched in the GO term for ABA and cytokinin responses, respectively. ZmOXS2a expression lines are more sensitive to ABA, but less sensitive to cytokinin. It is likely that ZmOXS2a promotes the degradation of the mRNA of down-regulated genes containing ARE, which consequently perturbs the hormone pathways that affect stress response-related plant growth.