Establishment of RNAi-Mediated Pest Control Method for Red Imported Fire Ant, Solenopsis invicta.

RNAi plays a crucial role in insect gene function research and pest control field. Nonetheless, the variable efficiency of RNAi across diverse insects and off-target effects also limited its further application. In this study, we cloned six essential housekeeping genes from Solenopsis invicta and conducted RNAi experiments by orally administering dsRNA. Then, we found that mixing with liposomes significantly enhanced the RNAi efficiency by targeting for SiV-ATPaseE. Additionally, we observed a certain lethal effect of this dsRNA on queens by our established RNAi system. Furthermore, no strict sequence-related off-target effects were detected. Finally, the RNAi effect of large-scale bacteria expressing dsRNA was successfully confirmed for controlling S. invicta. In summary, this study established an RNAi system for S. invicta and provided a research template for the future development of nucleic acid drugs based on RNAi.

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

The effect of chlorogenic acid, a potential botanical insecticide, on gene transcription and protein expression of carboxylesterases in the armyworm (Mythimna separata).

Chlorogenic acid (CGA) is a potential botanical insecticide metabolite that naturally occurs in various plants. Our previous studies revealed CGA is sufficient to control the armyworm Mythimna separata. In this study, we conducted a proteomic analysis of saliva collected from M. separata following exposure to CGA and found that differentially expressed proteins (DEPs) treated with CGA for 6 h and 24 h were primarily enriched in glutathione metabolism and the pentose phosphate pathway. Notably, we observed six carboxylesterase (CarE) proteins that were enriched at both time points. Additionally, these corresponding genes were expressed at levels 5.05 to 130.25 times higher in our laboratory-selected resistance strains. We also noted a significant increase in the enzyme activity of carboxylesterase following treatments with varying CGA concentrations. Finally, we confirmed that knockdown of MsCarE14, MsCarE28, and MsCCE001h decreased the susceptibility to CGA in resistance strain, indicating three CarE genes play crucial roles in CGA detoxification. This study presents the first report on the salivary proteomics of M. separata, offering valuable insights into the role of salivary proteins. Moreover, the determination of CarE mediated susceptibility change to CGA provides new targets for agricultural pest control and highlights the potential insecticide resistance mechanism for pest resistance management.

Antibody responses following the surge of SARS-CoV-2 Omicron infection among patients with systemic autoimmune rheumatic diseases.

Objectives: The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs). Methods: To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded. Results: A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs (P < 0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group (P < 0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ. Conclusion: These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection.

The Association of the Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio and Systemic Inflammation Response Index with Short-Term Functional Outcome in Patients with Acute Ischemic Stroke.

Background and Purpose: The aim of this study was to explore the relationship between functional prognosis and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic inflammatory response index (SIRI) in patients with acute ischemic stroke (AIS) at discharge. Methods: A total of 861 patients with AIS were enrolled between January 2019 and December 2021. Blood cell counts were collected on admission. Logistic regression analysis was performed to assess the relationship between NLR, PLR, LMR, SIRI and adverse functional outcomes (modified Rankin scale score of 3-6) at discharge. We also used receiver operating characteristic (ROC) curves to estimate the overall ability of NLR, PLR, LMR and SIRI to judge short-term functional outcomes. Associations between NLR, PLR, LMR, and SIRI with length of hospital stay were analyzed by Spearman correlation test. Results: A total of 194 patients (22.5%) had poor functional outcomes at discharge. Multivariate logistic regression analysis showed that NLR (odds ratio [OR], 1.060; 95% confidence interval [CI] 1.004-1.120, P=0.037), PLR (OR, 1.003; 95% CI 1.000-1.005, P=0.018), LMR (OR, 0.872; 95% CI 0.774-0.981, P=0.023) and SIRI (OR, 1.099; 95% CI 1.020-1.184, P=0.013) were independent factors for poor functional outcome. The odds ratios of the highest versus lowest quartiles of NLR, PLR and SIRI were 2.495 (95% CI 1.394-4.466), 1.959 (95% CI 1.138-3.373) and 1.866 (95% CI 1.106-3.146), respectively. The odds ratio of the lowest versus highest quartile of LMR was 2.300 (95% CI 1.331-3.975). The areas under the curve (AUCs) of the NLR, PLR, LMR, and SIRI to discriminate poor functional prognosis were 0.644, 0.587, 0.628, and 0.651, respectively. NLR, LMR, and SIRI were related with the length of hospital stay (P<0.05). Conclusion: NLR, PLR, LMR, and SIRI were associated with functional outcome at discharge in AIS patients. NLR, LMR and SIRI were related to hospitalization days in patients with AIS.

Biogenesis, Composition and Potential Therapeutic Applications of Mesenchymal Stem Cells Derived Exosomes in Various Diseases.

Exosomes are nanovesicles with a wide range of chemical compositions used in many different applications. Mesenchymal stem cell-derived exosomes (MSCs-EXOs) are spherical vesicles that have been shown to mediate tissue regeneration in a variety of diseases, including neurological, autoimmune and inflammatory, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells due to the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. MSCs-EXOs exhibit cytokine storm-mitigating properties in response to COVID-19. This review discussed the potential function of MSCs-EXOs in a variety of diseases including neurological, notably epileptic encephalopathy and Parkinson's disease, cancer, angiogenesis, autoimmune and inflammatory diseases. We provided an overview of exosome biogenesis and factors that regulate exosome biogenesis. Additionally, we highlight the functions and potential use of MSCs-EXOs in the treatment of the inflammatory disease COVID-19. Finally, we covered a strategies and challenges of MSCs-EXOs. Finally, we discuss conclusion and future perspectives of MSCs-EXOs.

Multiple RNA Profiling Reveal Epigenetic Toxicity Effects of Oxidative Stress by Graphene Oxide Silver Nanoparticles in-vitro.

Introduction: The increasing industrial and biomedical utilization of graphene oxide silver nanoparticles (GO-AgNPs) raises the concern of nanosafety: exposure to the AgNPs or GO-AgNPs increases the generation of reactive oxygen species (ROS), causes DNA damage and alters the expression of whole transcriptome including mRNA, miRNA, tRNA, lncRNA, circRNA and others. Although the roles of different RNAs in epigenetic toxicity are being studied during the last decade, but still we have little knowledge about the role of circle RNAs (circRNAs) in epigenetic toxicity. Methods: Rabbit fetal fibroblast cells (RFFCs) were treated with 0, 8, 16, 24, 32 and 48 µg/mL GO-AgNPs to test the cell viability and 24 µg/mL GO-AgNPs was selected as the experimental dose. After 24 h treatment with 24 µg/mL GO-AgNPs, the level of ROS, malondialdehyde (MDA), superoxide dismutase (SOD), intracellular ATP, glutathione peroxidase (GPx), and glutathione reductase (Gr) were measured in the RFFCs. High-throughput whole transcriptome sequencing was performed to compare the expression of circRNAs, long non-coding RNAs (lncRNA) and mRNA between 24 µg/mL GO-AgNPs-treated RFFCs and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to validate the accuracy of circRNA sequencing data. Bioinformatics analyses were performed to reveal the potential functional roles and related pathways of differentially expressed circRNAs, lncRNA and mRNA and to construct a circRNA-miRNA-mRNA interaction network. Results: We found that 57 circRNAs, 75 lncRNAs, and 444 mRNAs were upregulated while 35 circRNAs, 21 lncRNAs, and 186 mRNAs were downregulated. These differentially expressed genes are mainly involved in the transcriptional mis-regulation of cancer through several pathways: MAPK signaling pathway (circRNAs), non-homologous end-joining (lncRNAs), as well as PPAR and TGF-beta signaling pathways (mRNAs). Conclusion: These data revealed the potential roles of circRNAs in the GO-AgNPs induced toxicity through oxidative damage, which would be the basis for further research to determine their roles in the regulation of different biological processes.

Dingxin recipe â ¢ ameliorates hyperlipidemia injury in SD rats by improving the gut barrier, particularly the SCFAs/GPR43 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. AIM OF THE STUDY: Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR Ⅲ in hyperlipidemia. MATERIALS AND METHODS: The bioactive compounds of DXR Ⅲ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR Ⅲ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. RESULTS: DXR Ⅲ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR Ⅲ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR Ⅲ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR Ⅲ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR Ⅲ and SCFAs upregulated the expression of colon ABCA1. CONCLUSION: DXR Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.

Comparison of ocular trauma between normalized and the COVID-19 epidemic periods in China: a multi-center cross-sectional study.

AIM: To compare the feature of ocular trauma between normalized period and the COVID-19 epidemic period in China, and to provide a profile for eye injuries in special times in future. METHODS: This is a multi-center cross-sectional study with 30 participated hospitals involving the China Ocular Trauma Society members. All hospitalized cases who visited the Ophthalmology Department in participated hospitals with eye injuries during the normalized period (2019) and the COVID-19 epidemic period (2020) were included in this study. Demographic characteristic of cases, date of injury, sites and types of injury were collected. RESULTS: This study involved 13 525 (61 cases with both eyes) injured cases. There were 7269 (53.74%) eye-injured cases and 6256 (46.26%) eye-injured cases in 2019 and 2020 separately. Compared with 2019, the incidence of ocular trauma in retirees, housewives and unemployed increased with year-on-year of 4.96%, 102.67%, and 11.64% among all occupations. In 2020, the incidence of eye injuries decreased in all injury sites except for an increase in home (30.29% year-on-year). The incidence of mechanical eye injuries decreased, while that of non-mechanical eye injuries (chemical/thermal/radiation) increased (47.45% year-on-year). There were 255 (3.51%, 255/7269) and 376 (6.01%, 376/6256) non-mechanical injured cases in 2019 and 2020 (Pearson Chi2=47.33, P<0.001) separately. CONCLUSION: During the COVID-19 epidemic period, the total cases of ocular trauma decrease but the proportion of non-mechanical ocular trauma increase. Penetrating is still the highest proportion among all types of mechanical ocular trauma. From a preventive point of view, protection for retired persons, housewives and unemployed persons should be improved during public health events period.

Risk Factors Analysis and the Establishment of Nomogram Prediction Model of Hidden Blood Loss After Total Hip Arthroplasty for Femoral Neck Fracture in Elderly Women.

Purpose: To investigate the risk factors of increased hidden blood loss (HBL) after total hip arthroplasty (THA) for femoral neck fracture in elderly women and establish the nomogram prediction model for the guidance to reduce HBL in clinic. Patients and Methods: A total of 206 elderly female patients with femoral neck fracture who underwent THA in Northern Jiangsu People's Hospital from January 2019 to November 2021 were included. The demographic and relevant clinical information of the patients were collected. Pearson, independent sample t-test, multiple linear regression and other statistical methods were used for correlation analysis by SPSS 22.0 statistical software. Moreover, the risk factors of postoperative HBL increase in THA patients were obtained and the nomogram prediction model for the guidance to reduce HBL in clinic was established. Results: HBL was 626 ± 400 mL, accounting for 72.8% ± 18.4% of the perioperative total blood loss (TBL) (799 ± 411 mL), while blood loss of HGB was 15.1±10.4 g/L. Multiple linear regression analysis showed that HBL was associated with lower age (regression coefficient = -9.271, P = 0.010), operative time (regression coefficient = 2.653, P = 0.004), preoperative blood calcium (<2.25 mmol/L) (regression coefficient = 232.492, P < 0.001), hypertension (regression coefficient = 150.352, P = 0.002) and osteoporosis (regression coefficient = 276.072, P < 0.001). R software was used to construct the nomogram prediction model and draw the ROC curve and calibration curve. The area under the curve (AUC) is 0.92 and the slope of calibration curve is close to 1. Conclusion: Based on the five independent risk factors including age, operative time, preoperative blood calcium, hypertension and osteoporosis, the nomogram can predict the risk of HBL after THA for femoral neck fracture in elderly women with favorable differentiation and accuracy.

Highly Efficient Conversion of Propargylic Alcohols and Propargylic Amines with CO2 Activated by Noble-Metal-Free Catalyst Cu2 O@ZIF-8.

The cyclization reactions of propargylic alcohols and propargylic amines with CO2 are important in industrial applications, but it was a great challenge that non-noble-metal catalysts catalyzed both reactions under mild conditions. Herein, the catalyst Cu2 O@ZIF-8 was prepared by encapsulating Cu2 O nanoparticles into robust ZIF-8, and it can effectively catalyze the cyclization of both propargylic alcohols and propargylic amines with CO2 into valuable α-alkylidene cyclic carbonates and oxazolidinones with turnover numbers (TONs) of 12.1 and 19.6, which can be recycled at least five times. The mechanisms were further uncovered by NMR, FTIR, 13 C isotope-labeling experiments and DFT calculations, in which Cu2 O and DBU can synergistically activate the C≡C bond and the hydroxy/amino group of substrates. Importantly, it is the first example of a noble-metal-free catalyst that can catalyze both propargylic alcohols and propargylic amines with CO2 simultaneously.

Targeting cyclin-dependent kinase 9 in cancer therapy.

Cyclin-dependent kinase (CDK) 9 associates mainly with cyclin T1 and forms the positive transcription elongation factor b (p-TEFb) complex responsible for transcriptional regulation. It has been shown that CDK9 modulates the expression and activity of oncogenes, such as MYC and murine double minute 4 (MDM4), and it also plays an important role in development and/or maintenance of the malignant cell phenotype. Malfunction of CDK9 is frequently observed in numerous cancers. Recent studies have highlighted the function of CDK9 through a variety of mechanisms in cancers, including the formation of new complexes and epigenetic alterations. Due to the importance of CDK9 activation in cancer cells, CDK9 inhibitors have emerged as promising candidates for cancer therapy. Natural product-derived and chemically synthesized CDK9 inhibitors are being examined in preclinical and clinical research. In this review, we summarize the current knowledge on the role of CDK9 in transcriptional regulation, epigenetic regulation, and different cellular factor interactions, focusing on new advances. We show the importance of CDK9 in mediating tumorigenesis and tumor progression. Then, we provide an overview of some CDK9 inhibitors supported by multiple oncologic preclinical and clinical investigations. Finally, we discuss the perspective and challenge of CDK9 modulation in cancer.

The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota.

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.

A Porous Copper-Organic Framework Assembled by [Cu12] Nanocages: Highly Efficient CO2 Capture and Chemical Fixation and Theoretical DFT Calculations.

A new porous copper-organic framework assembled from 12-nuclear [Cu12] nanocages {[Cu2(L4-)(H2O)2]·4DMA·2H2O}n (1) (H4L = 5,5'-(butane-1,4-diyl)-bis(oxy)-diisophthalic acid) was successfully prepared and structurally characterized. Compound 1 feathering of a 3D framework with two types of 1D nanotubular channels and a large specific surface area can effectively enrich various harmful dyes. Additionally, due to the carbon dioxide (CO2) interactions with open Cu(II) sites and the electron-rich ether oxygen atoms of ligand in 1, it exhibits a highly selective CO2 uptake. Interestingly, 1 can effectively catalyze the cycloaddition reaction of CO2 with various epoxides under mild conditions, which is ascribed to the Lewis acid Cu(II) sites in the framework of 1. Importantly, 1 acting as a heterogeneous catalyst can be recycled at least 10 times without an obvious loss of catalytic activity, and the CO2 cycloaddition mechanism was further uncovered by density functional theory (DFT) calculations. This study can greatly enrich the MOF catalysts system of CO2 conversion and also provide a valuable guidance for the design of efficient MOFs catalysts.

Homozygous variants in SYCP2L cause premature ovarian insufficiency.

BACKGROUND: The genetic causes of the majority of cases of female infertility caused by premature ovarian insufficiency (POI) are unknown. OBJECTIVE: To identify the genetic causes of POI in 110 patients. METHODS: Whole-exome sequencing was performed on 110 patients with POI, and putative disease-causative variants were validated by Sanger sequencing. Bioinformatic and in vitro functional analyses were performed for functional characterisation of the identified candidate disease-causative variants. RESULTS: We identified two homozygous variants (NM_001040274: c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in SYCP2L in two patients, which had co-segregated with POI in these families. Bioinformatic analysis predicted that the two variants are deleterious, and in vitro functional analysis showed that mutant SYCP2L proteins exhibited mislocalisation and loss of function. CONCLUSIONS: SYCP2L is a novel gene found to be responsible for human POI. Our findings provide a potential molecular marker for POI and improve the understanding of the genetic basis of female infertility.

Novel loss-of-function mutation in MCM8 causes premature ovarian insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is one major cause of female infertility, minichromosome maintenance complex component 8 (MCM8) has been reported to be responsible for POI. METHODS: Whole-exome sequencing was performed to identify the genetic variants of women with POI. Sanger sequencing was used to validate the variants in all the family members. Various bioinformatic software was used for the pathogenicity assessment. Reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative PCR, and a chromosomal instability study induced by mitomycin C were performed to analyze the functional effects of the variant. RESULTS: A novel homozygous frameshift mutation (NM_032485.4:c.351_354delAAAG) of MCM8 gene was identified in the patients, segregated with POI in this family. This mutation is predicted to produce truncated MCM8 protein and to be pathogenic. Reverse transcription polymerase chain reaction revealed that the frameshift mutation led to a remarkably reduced level of MCM8 transcript products, and chromosomal instability study showed that the ability of mutant MCM8 to repair DNA breaks was impaired. CONCLUSION: We identified a novel homozygous frameshift mutation in the MCM8 gene in two affected sisters with POI, and functional analysis revealed that this mutation is pathogenic. Our findings enrich the MCM8 mutation spectrum and might help clinicians to make a precise diagnosis, thereby allowing better family planning and genetic counseling.

6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway.

Sepsis-induced liver injury is very common in intensive care units. Here, we investigated the effects of 6-gingerol on sepsis-induced liver injury and the role of the Nrf2 pathway in this process. 6-Gingerol is the principal ingredient of ginger that exerts anti-inflammatory and antioxidant effects. Using cecal ligation and puncture (CLP) to induce polymicrobial sepsis and related liver injury, we found that mice pre-treated with 6-Gingerol showed less incidences of severe liver inflammation and death than untreated CLP groups. 6-Gingerol administration also inhibited the expression of pyroptosis-related proteins, including NOD-like receptor protein 3 (NLRP3), IL-1ß, and caspase-1. Consistent with these findings, 6-gingerol reduced the effects of pyroptosis induced by lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP) in RAW 264.7 cells, as evidenced by IL-1ß and caspase-1 protein levels in the supernatant and propidium iodide (PI) staining. 6-Gingerol was shown to activate the Nrf2 pathway in vivo and in vitro. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of 6-gingerol on pyroptosis in vitro. In summary, these findings suggested that 6-gingerol alleviated sepsis-induced liver injury by inhibiting pyroptosis through the Nrf2 pathway.

In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is a severe clinical syndrome defined by ovarian dysfunction in women less than 40 years old who generally manifest with infertility, menstrual disturbance, elevated gonadotrophins, and low estradiol levels. STAG3 is considered a genetic aetiology of POI, which facilitates entry of REC8 into the nucleus of a cell and plays an essential role in gametogenesis. At present, only six truncated variants associated with POI have been reported; there have been no reports of an in-frame variant of STAG3 causing POI. In this study, two novel homozygous in-frame variants (c.877_885del, p.293_295del; c.891_893dupTGA, p.297_298insAsp) in STAG3 were identified in two sisters with POI from a five-generation consanguineous Han Chinese family. To evaluate the effects of these two variants, we performed fluorescence localization and co-immunoprecipitation analyses using in vitro cell model. The two variants were shown to be pathogenic, as neither STAG3 nor REC8 entered nuclei, and interactions between mutant STAG3 and REC8 or SMC1A were absent. To the best of our knowledge, this is the first report on in-frame variants of STAG3 that cause POI. This finding extends the spectrum of variants in STAG3 and sheds new light on the genetic origins of POI.

X-chromosome inactivation pattern of amniocytes predicts the risk of dystrophinopathy in fetal carriers of DMD mutations.

OBJECTIVE: To predict the risk of dystrophinopathy in fetal carriers of dystrophin gene (DMD) mutations. METHODS: Twenty-three pregnant women, with a total of 25 female fetuses carrying DMD mutations, were recruited. Among them, 13 pregnant women who participated in this study were only used to analyse the incidence of induced abortion after fetuses were diagnosed as dystrophinopathy carriers. Eleven fetal carriers from 10 pregnant women were tested to analyse X-chromosome inactivation (XCI) using amniocytes to assess the risk of dystrophinopathy. Follow-ups were conducted on all cases. RESULTS: Approximately one-third of fetuses were aborted before assessing the risk of dystrophinopathy. XCI analysis of amniocytes showed that 10 fetuses had random XCI patterns, and one fetus exhibited a highly skewed XCI pattern (100:0) with primary expression of the maternal X chromosome that carried the mutant allele. These 11 fetal carriers were born, and follow-up showed that the girl who showed the skewed XCI pattern as a fetus was diagnosed with Duchenne muscular dystrophy (DMD) at the age of four. The others did not present with dystrophinopathy-associated symptoms. CONCLUSIONS: XCI was significantly implicated in symptomatic female carriers of dystrophinopathies, and XCI pattern analysis of amniocytes may be useful in predicting the risk of dystrophinopathy in fetal carriers.