Bioinspired PROTAC-induced macrophage fate determination alleviates atherosclerosis.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.

Analysis of Volatile Aroma Components and Regulatory Genes in Different Kinds and Development Stages of Pepper Fruits Based on Non-Targeted Metabolome Combined with Transcriptome.

Aroma is a crucial attribute affecting the quality of pepper and its processed products, which has significant commercial value. However, little is known about the composition of volatile aroma compounds (VACs) in pepper fruits and their potential molecular regulatory mechanisms. In this study, HS-SPME-GC-MS combined with transcriptome sequencing is used to analyze the composition and formation mechanism of VACs in different kinds and development stages of pepper fruits. The results showed that 149 VACs, such as esters, alcohols, aldehydes, and terpenoids, were identified from 4 varieties and 3 development stages, and there were significant quantitative differences among different samples. Volatile esters were the most important aroma components in pepper fruits. PCA analysis showed that pepper fruits of different developmental stages had significantly different marker aroma compounds, which may be an important provider of pepper's characteristic aroma. Transcriptome analysis showed that many differential genes (DEGs) were enriched in the metabolic pathways related to the synthesis of VACs, such as fatty acids, amino acids, MVA, and MEP in pepper fruits. In addition, we identified a large number of differential transcription factors (TFs) that may regulate the synthesis of VACs. Combined analysis of differential aroma metabolites and DEGs identified two co-expression network modules highly correlated with the relative content of VACs in pepper fruit. This study confirmed the basic information on the changes of VACs in the fruits of several Chinese spicy peppers at different stages of development, screened out the characteristic aroma components of different varieties, and revealed the molecular mechanism of aroma formation, providing a valuable reference for the quality breeding of pepper.

Genome-Wide Identification of WRKY Gene Family and Functional Characterization of CcWRKY25 in Capsicum chinense.

Pepper is renowned worldwide for its distinctive spicy flavor. While the gene expression characteristics of the capsaicinoid biosynthesis pathway have been extensively studied, there are already a few reports regarding transcriptional regulation in capsaicin biosynthesis. In this study, 73 WRKYs were identified in the genome of Capsicum chinense, and their physicochemical traits, DNA, and protein sequence characteristics were found to be complex. Combining RNA-seq and qRT-PCR data, the WRKY transcription factor CA06g13580, which was associated with the accumulation tendency of capsaicinoid, was screened and named CcWRKY25. CcWRKY25 was highly expressed in the placenta of spicy peppers. The heterologous expression of CcWRKY25 in Arabidopsis promoted the expression of genes PAL, 4CL1, 4CL2, 4CL3, CCR, and CCoAOMT and led to the accumulation of lignin and flavonoids. Furthermore, the expression of the capsaicinoid biosynthesis pathway genes (CBGs) pAMT, AT3, and KAS was significantly reduced in CcWRKY25-silenced pepper plants, resulting in a decrease in the amount of capsaicin. However, there was no noticeable difference in lignin accumulation. The findings suggested that CcWRKY25 could be involved in regulating capsaicinoid synthesis by promoting the expression of genes upstream of the phenylpropanoid pathway and inhibiting CBGs' expression. Moreover, the results highlighted the role of CcWRKY25 in controlling the pungency of pepper and suggested that the competitive relationship between lignin and capsaicin could also regulate the spiciness of the pepper.

MYB24 Negatively Regulates the Biosynthesis of Lignin and Capsaicin by Affecting the Expression of Key Genes in the Phenylpropanoid Metabolism Pathway in Capsicum chinense.

The wide application of pepper is mostly related to the content of capsaicin, and phenylpropanoid metabolism and its branch pathways may play an important role in the biosynthesis of capsaicin. The expression level of MYB24, a transcription factor screened from the transcriptome data of the pepper fruit development stage, was closely related to the spicy taste. In this experiment, CcMYB24 was cloned from Hainan Huangdenglong pepper, a hot aromatic pepper variety popular in the world for processing, and its function was confirmed by tissue expression characteristics, heterologous transformation in Arabidopsis thaliana, and VIGS technology. The results showed that the relative expression level of CcMYB24 was stable in the early stage of pepper fruit development, and increased significantly from 30 to 50 days after flowering. Heterologous expression led to a significant increase in the expression of CcMYB24 and decrease in lignin content in transgenic Arabidopsis thaliana plants. CcMYB24 silencing led to a significant increase in the expression of phenylpropanoid metabolism pathway genes PAL, 4CL, and pAMT; lignin branch CCR1 and CAD; and capsaicin pathway CS, AT3, and COMT genes in the placenta of pepper, with capsaicin content increased by more than 31.72% and lignin content increased by 20.78%. However, the expression of PAL, pAMT, AT3, COMT, etc., in the corresponding pericarps did not change significantly. Although CS, CCR1, and CAD increased significantly, the relative expression amount was smaller than that in placental tissue, and the lignin content did not change significantly. As indicated above, CcMYB24 may negatively regulate the formation of capsaicin and lignin by regulating the expression of genes from phenylpropanoid metabolism and its branch pathways.

Effect of Yellowing Duration on the Chemical Profile of Yellow Tea and the Associations with Sensory Traits.

The yellowing process is the crucial step to form the characteristic sensory and chemical properties of yellow tea. To investigate the chemical changes and the associations with sensory traits during yellowing, yellow teas with different yellowing times (0-13 h) were prepared for sensory evaluation and chemical analysis. The intensities of umami and green-tea aroma were reduced whereas sweet taste, mellow taste and sweet aroma were increased under long-term yellowing treatment. A total of 230 chemical constituents were determined, among which 25 non-volatiles and 42 volatiles were the key chemical contributors to sensory traits based on orthogonal partial least squares discrimination analysis (OPLS-DA), multiple factor analysis (MFA) and multidimensional alignment (MDA) analysis. The decrease in catechins, flavonol glycosides and caffeine and the increase in certain amino acids contributed to the elevated sweet taste and mellow taste. The sweet, woody and herbal odorants and the fermented and fatty odorants were the key contributors to the characteristic sensory feature of yellow tea with sweet aroma and over-oxidation aroma, including 7 ketones, 5 alcohols, 1 aldehyde, 5 acids, 4 esters, 5 hydrocarbons, 1 phenolic compound and 1 sulfocompound. This study reveals the sensory trait-related chemical changes in the yellowing process of tea, which provides a theoretical basis for the optimization of the yellowing process and quality control of yellow tea.

The association among apathy, leisure activity participation, and severity of dementia in nursing home residents with Alzheimer's disease: A cross-sectional study.

The purpose of this study was to examine 1) the relationship between apathy and leisure activity participation in nursing home residents with Alzheimer disease (AD) and 2) the moderator effect of the severity of dementia on this relationship. Data were collected from 290 residents with AD using the Apathy Evaluation Scale-informant version (AES-I), Leisure Activities Questionnaire (LAQ), and Clinical Dementia Rating scale (CDR). The multiple linear regression model showed that leisure activity participation (ß=-0.452, p<0.001) was negatively associated with apathy, while the severity of dementia (ß=0.515, p<0.001) was positively associated with apathy. The severity of dementia moderated the effect of leisure activity participation on apathy (ß=-0.108, p=0.015). The results indicate that the effects of leisure activity participation on apathy diminish with the aggravation of AD. The severity of dementia should be considered when designing and delivering leisure activity interventions to manage apathy in nursing home residents with AD.

Potential reservoirs and routes of Cronobacter transmission during cereal growing, processing and consumption.

Cronobacter are opportunistic bacterial pathogens of both infants and adults. We investigated the incidence and distribution of Cronobacter in 1245 samples of cereal and related environments. 39.1% (101/258) rice-related and 46.9% (98/209) wheat-related samples tested positive for Cronobacter, and the positive rate differed notably according to processing method. Cronobacter was found in rice and wheat plants at the tillering, filling and mature stages. Soil, water and swab samples from nearby milling plants were assayed, and results revealed that 6.3% (7/122) of water from paddy fields, 49.1% (28/57) and 62.1% (41/67) of swab samples from rice and wheat flour milling plants were Cronobacter positive. Pulsed-field gel electrophoresis (PFGE) subtyping indicated that some strains had a common profile, which suggested their persistence in the environment, potential transmission routes and cross-contamination in processing. Finally, we surveyed 18 families to evaluate potential risks. None of the families who primarily ate rice cooked with water tested positive for Cronobacter, though of 66.7% families (6/9) whose food staples were produced from wheat flour tested positive. Taken together, our results are important for understanding Cronobacter transmission and will aid in the development of additional control measures to reduce the risk of infection by these opportunistic pathogenic bacteria.

Boceprevir-based triple therapy to rescue HCV genotype 1/HBV dually infected patients refractory to peginterferon plus ribavirin combination therapy in Taiwan.

BACKGROUND/PURPOSE: The role of directly-acting antivirals (DAA)-containing regimens in the treatment of patients dually-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to explore the safety and efficacy of a protease inhibitor, boceprevir, in combination with peginterferon/ribavirin for HCV genotype 1 (HCV-1)/HBV dually-infected patients refractory to prior peginterferon/ribavirin. METHODS: Twelve peginterferon-experienced patients dually-infected with HCV-1/HBV were assigned to receive boceprevir 800 mg, twice a day, plus peginterferon-α 2b 1.5 µg/kg/week and ribavirin 800-1400 mg/day for 36 or 48 weeks. The primary endpoint was HCV sustained virological response (SVR, HCV RNA undetectable 24 weeks after end-of-treatment). RESULTS: Five patients terminated treatment early due to adverse events (one at week 4, one at week 46), virological failures (one non-response and one breakthrough), and patient request (n = 1). Eight patients achieved HCV SVR (66.7% in full-analysis set and 72.7% in modified intention-to-treat population). The HCV SVR rate was 71.4% (5/7) in prior relapsers, 60.0% (3/5) in prior null responder; 75% in non-cirrhotic and 50% in cirrhotic patients. All four patients of prior non-cirrhotic relapsers received 36-week regimen and achieved HCV SVR. There was no HBV-related hepatic flare. All patients experienced at least one adverse event. Two had serious adverse events. CONCLUSION: Boceprevir plus peginterferon/ribavirin is effective in the treatment of HCV-1/HBV dually infected patients' refractory to prior peginterferon/ribavirin combination therapy.

2,3-Dihydro-3ß-methoxy Withaferin-A Protects Normal Cells against Stress: Molecular Evidence of Its Potent Cytoprotective Activity.

2,3-Dihydro-3ß-methoxy withaferin-A (3ßmWi-A) is a natural withanolide that is structurally close to withaferin-A (Wi-A), is cytotoxic to human cancer cells, and is a candidate anticancer natural compound. Using cell-based biochemical, molecular, and imaging assays, we report that Wi-A and 3ßmWi-A possess contrasting activities. Whereas Wi-A caused oxidative stress to normal cells, 3ßmWi-A was well tolerated at even 10-fold higher concentrations. Furthermore, it promoted survival and protected normal cells against oxidative, UV radiation, and chemical stresses. We provide molecular evidence that 3ßmWi-A induces antistress and pro-survival signaling through activation of the pAkt/MAPK pathway. We demonstrate that 3ßmWi-A (i) contrary to Wi-A is safe and possesses stress-relieving activity, (ii) when given subsequent to a variety of stress factors including Wi-A, protects normal cells against their toxicity, and (iii) is a vital compound that may guard normal cells against the toxicity associated with various targeted therapeutic regimes in clinical practice.

[In vitro culture medium for sparse spermatozoa improves human sperm motility].

OBJECTIVE: To investigate whether in vitro culture medium (IVCM) for sparse spermatozoa can improve human sperm motility for the purpose of helping clinicians, laboratorians and patients choose a better strategy of assisted reproduction. METHODS: Semen samples were obtained from 178 males for routine semen examination from March to August 2016, including 151 cases of asthenozoospermia and 27 cases of normal sperm motility. A total of 200 µl was collected from each sample and divided into two equal portions and equal volumes of IVCM (experimental group) and F10 (1×) (control group) were added to the two portions, respectively, followed by 30-minute incubation at 37℃ in an incubator with 5% CO2. Sperm concentration, motility and viability and the percentages of progressively motile, non-progressively motile and immotile sperm were recorded before and after incubation. RESULTS: After activated with IVCM, neither the samples with asthenozoospermia nor those with normal sperm motility showed any statistically significant difference in sperm viability from the baseline or the control group (P>0.05). The rates of progressively and non-progressively motile sperm from the asthenozoospermia males were increased by 14.02% and 4.86% respectively, while that of immotile sperm decreased by 19.01% in the experimental group (P >0.01), and similar results were observed in the semen samples from the men with normal sperm motility. The percentage of reduced immotile viable sperm was positively correlated with that of immotile viable sperm in both the asthenozoospermia patients (r = 0.260, P <0.01) and the men with normal sperm motility (r = 0.679, P <0.01). CONCLUSIONS: IVCM can increase sperm motility without affecting sperm viability in men with either asthenozoospermia or normal sperm motility. The larger the proportion of immotile viable sperm, the higher the percentages of progressively and non-progressively motile sperm in the semen after IVCM activation, and this correlation is more significant in men with normal sperm motility than in asthenozoospermia patients.

Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study.

Background: Several observational studies have documented a potential link between obesity and peripheral artery disease (PAD), although conflicting findings exist. The causal relationship between obesity and PAD continues to be a subject of ongoing debate in the medical community. Objectives: In this study, we employed a bidirectional Mendelian randomization (MR) analysis to explore the potential causal relationship between obesity and the risk of PAD. Methods: To investigate these causal relationships, we conducted bidirectional MR analysis using publicly available genome-wide association study (GWAS) data. Effect estimates were calculated using the random-effects inverse variance-weighted (IVW) method. Results: We identified eight independent single nucleotide polymorphisms (SNPs) associated with obesity in 218,735 samples involving 16,380,465 SNPs, all of which met the genome-wide significance threshold (p < 5 × 10-8). The IVW analysis indicates a significant positive association between genetic obesity and multiple datasets with PAD as the outcome: Queue-1 (GWAS ID: finn-b-I9_PAD) (OR = 1.138, 95% CI: 1.027-1.261, p = 0.013), Queue-2 (GWAS ID: bbj-a-144) (OR = 1.190, 95% CI: 1.019-1.390, p = 0.028), Queue-3 (GWAS ID: ebi-a-GCST90018670) (OR = 1.174, 95% CI: 1.014-1.360, p = 0.032), and Queue-4 (GWAS ID: ebi-a-GCST90018890) (OR = 1.194, 95% CI: 1.099-1.296, p < 0.001). However, we did not observe a significant genetic-level association between obesity and PAD for Queue-5 (GWAS ID: ukb-d-I9_PAD) (OR = 1.001, 95% CI: 1.000-1.002, p = 0.071). Furthermore, we conducted a reverse causal MR analysis to explore the potential reverse causal relationship between obesity and PAD. This comprehensive analysis did not provide evidence of a reverse causal association between these two factors. Conclusions: In summary, our study offers genetic evidence suggesting a possible causal link between obesity and PAD. While we did not find evidence supporting the "obesity paradox", prudent weight management remains crucial, as lower weight does not necessarily guarantee better outcomes. As with any study, caution is required in interpreting the findings. Further research is essential to assess the clinical relevance of weight in preventing PAD, which could inform the development of more precise intervention strategies.

Air Transportation Impact on a Late Preterm Neonate.

BACKGROUND: Neonatal air transportation is a crucial means of moving critically ill or sick neonates to specialized neonatal intensive care units or medical centers for consultation, regardless of distance or geographical limits. Proper preparation and consideration of air transport can help alleviate medical emergencies and ensure safe delivery. However, crewmembers and neonates may face stress during transportation. To date, there are few studies on neonatal air transportation in Taiwan.CASE REPORT: We present the case of a late preterm neonate born with neonatal respiratory distress syndrome and polycythemia, who was also diagnosed with patent ductus arteriosus and mild pulmonary arterial hypertension on echocardiography. Due to disease progression, the neonate underwent endotracheal intubation and was subsequently transported to a medical center in Taiwan via a rotary-wing aircraft at 3 d of age. During takeoff and landing, a temporary oxygen desaturation event occurred. The physiological changes in these patients have seldom been discussed. This case emphasizes the important considerations of neonatal transport in Taiwan.DISCUSSION: The air transport process could be influenced by both the patient's medical condition and environmental factors. In preterm infants with cardiopulmonary conditions, thorough assessment is necessary for ensuring safe transportation.Li S-P, Hsu P-C, Huang C-Y, Wu P-W, Fang H-H. Air transportation impact on a late preterm neonate. Aerosp Med Hum Perform. 2024; 95(4):219-222.

[Insertion efficiency of Tgf2 transposon in the genome of Megalo-brama amblycephala].

To study insertion efficiency of goldfish Tgf2 transposon in the genome of Megalobrama amblycephala, we built Tgf2-Mlyz2-RFP donor plasmid with goldfish Tgf2 transposon left and right arms, and then co-injected with goldfish Tgf2 transposase mRNA into the 1-2 cell stage fertilized eggs of M. amblycephala. In 30 d- and 180 d-stage larval, RFP fluorescence can be observed in back and side muscle of the fish. The rate of RFP fluorescence expression was 48.1%. In adult fish, PCR results demonstrated that integration efficiency of goldfish Tgf2 transposition system was 31.5% in M. am-blycephala genome. RT-PCR analysis showed that RFP RNAs were highly transcribed among all the 12 tissues in three transgenic fishes, while it could be highly detected only in muscle, skin, and kidney in another two individuals. Our results suggested that RFP expression in tissues vaied among different M. amblycephala. By means of the inverse PCR, the copy numbers of Tgf2 transposon were at least 2 in transgenic M. amblycephala. The average copy number of each fish was about 5. Over 50% of flanking sequences at the insertion site have homologous sequence in other vertebrate species. Our data suggest that goldfish Tgf2 transposon can efficiently mediate gene insertion in M. amblycephala, which could been used in transgene and gene trap in M. amblycephala.

Bioflocculation characteristics of bound extracellular polymers substances from Pseudomonas sp. XD-3 and behavior of polysaccharides.

This study aimed to investigate the bioflocculation characteristics of bound extracellular polymers substances (B-EPS), which were extracted from Pseudomonas sp. XD-3. The flocculation efficiency of B-EPS achieved about 80%- 95% with an initial pH of 4-7, kaolin concentrations of 3-7 g L-1, temperature of 25-100 â„ƒ and B-EPS dosage of 9-105 mg L-1. The bioflocculation process of B-EPS conformed to pseudo-second-order kinetic mode, suggesting that the bioflocculation belonged to chemical adsorption process. Enzymatic hydrolysis experiments demonstrated that both polysaccharides and proteins were active components for bioflocculation. The polysaccharides were irregular aggregates with rough and porous surfaces and contained hydroxyl and carboxyl groups, which helped to promote bridging effect. Ribose, glucose and galactose were the main monosaccharides of polysaccharides. The molecular weight of the polysaccharides was relatively small, but the relatively loose configuration exposed more ion bridging sites, thus promoting the bioflocculation. Optimizing the ingredients of culture medium and culture time for B-EPS were effective strategies to increase the yield of flocculation active components. When the conditions were 10% of 2 g L-1 KH2PO4 + 5 g L-1 K2HPO4, 0.05% of Tween-80, citrate as carbon source and 32-48 h of culture time, both proteins and polysaccharides in B-EPS were significantly improved. This study gives an in-deep understanding on the flocculation characteristics of a novel bioflocculant from Pseudomonas sp. XD-3, which is conducive to the widespread application of bioflocculation.

The correlation between clinical features and ultrastructure of testis of non-mosaic Klinefelter's syndrome patients with hypogonadism and androgen deficiency: A case report.

Background: Klinefelter Syndrome (KS) is a sex chromosomal syndrome usually with an extra X chromosome (47, XXY) in males, which has various phenotype (mosaicism 47, XXY/46, XY, or more chromosomes 48, XXXY, 49, XXXXY) and clinical features, including eunuchoid body proportions, abnormally long legs and arm span, gynecomastia, ynecomastia, absent or decreased facial and pubic hair, small hyalinized testes, small penis, below-normal verbal intelligence quotient, and learning difficulties. At present, there are no studies on the correlation between the clinical characteristics of patients with KS and the ultrastructural changes of intracellular organelles in testicular tissue in China. Case presentation: Here we report the ultrastructure manifestation of the testis tissues in a KS patient with hypogonadism and androgen deficiency, to find a relationship between ultrastructural changes of organelles and spermatogenic dysfunction, clinical features, timing of surgery and metabolic abnormalities. It has been shown that the spermatocytes are absent and the ultrastructure of Sertoli cells and Leydig cells is obviously abnormal, which may lead to spermatogenic dysfunction, androgen deficiency, impaired glucose tolerance (IGT), and abdominal fat accumulation. Conclusions: Based on the European Academy of Andrology (EAA) Gudilines on Klinefelter Syndrome, this study conducted a retrospective study on the diagnosis and treatment of one adult patient with KS, aiming to provide a standardized diagnosis and treatment for patients with KS. This study is also highly concerned with the correlation between the ultrastructural changes of target organs and clinical symptoms.

A Teleoperated Robotic System-Assisted Percutaneous Transiliac-Transsacral Screw Fixation Technique.

Transiliac-transsacral screw fixation is challenging in clinical practice as the screws need to break through six layers of cortical bone. Transiliac-transsacral screws provide a longer lever arm to withstand the perpendicular vertical shear forces. However, the screw channel is so long that a minor discrepancy can lead to iatrogenic neurovascular injuries. The development of medical robots has improved the precision of surgery. The present protocol describes how to use a new teleoperated robotic system to execute transiliac-transacral screw fixation. The Robot was operated remotely to position the entry point and adjust the orientation of the sleeve. The screw positions were evaluated using postoperative computed tomography (CT). All the screws were safely implanted, as confirmed using intraoperative fluoroscopy. Postoperative CT confirmed that all the screws were in the cancellous bone. This system combines the doctor's initiative with the Robot's stability. The remote control of this procedure is possible. Robot-assisted surgery has a higher position-retention capacity compared with conventional methods. In contrast to active robotic systems, surgeons have full control over the operation. The robot system is fully compatible with operating room systems and does not require additional equipment.

Effects of L-carnitine Administration on Sperm and Sex Hormone Levels in a Male Wistar Rat Reproductive System Injury Model in a High-Altitude Hypobaric Hypoxic Environment.

The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. L-carnitine can improve the semen microenvironment. However, the role of L-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of L-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg L-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that L-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.

High-grade endometrial stromal sarcoma in cesarean section scar isthmocele - case report.

OBJECTIVE: Cesarean section scar defect isthmocele, the pouchlike defect in the anterior uterine wall of the prior cesarean site. No previous report of malignant neoplasm in the isthmocele have been published. We reported a case of High-grade endometrial stromal sarcoma in isthmocele. CASE REPORT: A 45-year-old patient with gravida 4, parity 2, two previous cesarean section presents of recurrent heavy vaginal bleeding. Curettage and hormone therapy were unsuccessful. She underwent hysteroscopic isthmoplasty. The pathology revealed high-grade sarcoma. Patient was referred to a tertiary medical center and she underwent total hysterectomy with bilateral salpingo-oophorectomy, aortic & pelvic LNs dissection. The final diagnosis was High-grade endometrial stromal sarcoma (HG-ESS) stage IA (pT1a N0) involving isthmocele. CONCLUSION: The presence of this rare tumor in the isthmocele is very interested. We stress the necessity for a high degree of suspicion to diagnose the malignancy in perimenopausal women with isthmocele and persisted abnormal uterine bleeding.

Interactions of circRNAs with methylation: An important aspect of circRNA biogenesis and function (Review).

Circular RNA (circRNA) molecules are noncoding RNAs with unique circular covalently closed structures that contribute to gene expression regulation, protein translation and act as microRNA sponges. circRNAs also have important roles in human disease, particularly tumorigenesis and antitumor processes. Methylation is an epigenetic modification that regulates the expression and roles of DNA and coding RNA and their interactions, as well as of noncoding RNA molecules. Previous studies have focused on the effects of methylation modification on circRNA expression, transport, stability, translation and degradation of circRNAs, as well as how circRNA methylation occurs and the influence of circRNAs on methylation modification processes. circRNA and methylation can also regulate disease pathogenesis via these interactions. In the present study, we define the relationship between circRNAs and methylation, as well as the functions and mechanisms of their interactions during disease progression.

Investigating the Effects of Different Sizes of Silicone Rubber Vacuum Extractors during the Course of Delivery on the Fetal Head: A Finite Element Analysis Study.

During certain clinical situations, some parturients require instruments for operative vaginal delivery, and various designs of vacuum extractors may affect the fetal head. To investigate the biomechanical effects of divergent sizes of silicone rubber vacuum extractors, we employed finite element analysis in this study. First, we constructed computer models for different vacuum extractor sizes (diameters: 40 mm, 50 mm, 60 mm, and 70 mm), flat surface, hemispherical ball, and fetal head shape. A hemispherical ball was the main design for the vacuum extractor model, and the material used for the vacuum extractor was silicone rubber. Next, the settings of 1 mm vacuum extractor displacement and vacuum cap pressure of 60 cmHg were applied. The main observation markers of this study were the respective von Mises stresses on the vacuum extractor and skull by the reaction force on the fixed end. The concluded results revealed that vacuum extractors with larger diameters lead to greater reaction force, stress, and strain on fetal heads. Therefore, this study's biomechanical analytic consequences suggest that clinicians avoid selecting larger vacuum extractors during operative instrumental delivery so that fetal heads will experience less external force, deformation, and resultant complications. It could also provide a practical reference for obstetricians for instrumental vaginal delivery with the vacuum extractor made of silicone rubber.