Flexible ureteroscopic treatment of kidney stones: How do the new laser systems change our concepts?

Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This literature review aims to examine the current state of knowledge on fURS treatment of kidney stones, with a particular focus on the impact of the latest laser technologies on clinical outcomes and patient safety. Methods: We conducted a search of the PubMed/PMC, Web of Science Core Collection, Scopus, Embase (Ovid), and Cochrane Databases for all randomized controlled trial articles on laser lithotripsy in September 2023 without time restriction. Results: We found a total of 22 relevant pieces of literature. Holmium laser has been used for intracavitary laser lithotripsy for nearly 30 years and has become the golden standard for the treatment of urinary stones. However, the existing holmium laser cannot completely powder the stone, and the retropulsion of the stone after the laser emission and the thermal damage to the tissue have caused many problems for clinicians. The introduction of thulium fiber laser and Moses technology brings highly efficient dusting lithotripsy effect through laser innovation, limiting pulse energy and broadening pulse frequency. Conclusion: While the holmium:yttrium-aluminum-garnet laser remains the primary choice for endoscopic laser lithotripsy, recent technological advancements hint at a potential new gold standard. Parameter range, retropulsion effect, laser fiber adaptability, and overall system performance demand comprehensive attention. The ablation efficacy of high-pulse-frequency devices relies on precise targeting, which may pose practical challenges.

Rapid formed temperature-sensitive hydrogel for the multi-effective wound healing of deep second-degree burn with shikonin based scar prevention.

Burns are a significant public health issue worldwide, resulting in prolonged hospitalization, disfigurement, disability and, in severe cases, death. Among them, deep second-degree burns are often accompanied by bacterial infections, insufficient blood flow, excessive skin fibroblasts proliferation and collagen deposition, all of which contribute to poor wound healing and scarring following recovery. In this study, SNP/MCNs-SKN-chitosan-ß-glycerophosphate hydrogel (MSSH), a hydrogel composed of a temperature-sensitive chitosan-ß-glycerophosphate hydrogel matrix (CGH), mesoporous carbon nanospheres (MCNs), nitric oxide (NO) donor sodium nitroprusside (SNP) and anti-scarring substance shikonin (SKN), is intended for use as a biomedical material. In vitro tests have revealed that MSSH has broad-spectrum antibacterial abilities and releases NO in response to near-infrared (NIR) laser to promote angiogenesis. Notably, MSSH can inhibit excessive proliferation of fibroblasts and effectively reduce scarring caused by deep second-degree burns, as demonstrated by in vitro and in vivo tests.

Integrated analyses revealed the potential role and immune link of mitochondrial dysfunction between periodontitis and type 2 diabetes mellitus.

There is a reciprocal comorbid relationship between periodontitis and type 2 diabetes mellitus (T2DM). Recent studies have suggested that mitochondrial dysfunction (MD) could be the key driver underlying this comorbidity. The aim of this study is to provide novel understandings into the potential molecular mechanisms between MD and the comorbidity, and identify potential therapeutic targets for personalized clinical management. MD-related differentially expressed genes (MDDEGs) were identified. Enrichment analyses and PPI network analysis were then conducted. Six algorithms were used to explore the hub MDDEGs, and these were validated by ROC analysis and qRT-PCR. Co-expression and potential drug targeting analyses were then performed. Potential biomarkers were identified using LASSO regression. The immunocyte infiltration levels in periodontitis and T2DM were evaluated via CIBERSORTx and validated in mouse models. Subsequently, MD-related immune-related genes (MDIRGs) were screened by WGCNA. The in vitro experiment verified that MD was closely associated with this comorbidity. GO and KEGG analyses demonstrated that the connection between periodontitis and T2DM was mainly enriched in immuno-inflammatory pathways. In total, 116 MDDEGs, eight hub MDDEGs, and two biomarkers were identified. qRT-PCR revealed a distinct hub MDDEG expression pattern in the comorbidity group. Altered immunocytes in disease samples were identified, and their correlations were explored. The in vivo examination revealed higher infiltration levels of inflammatory immunocytes. The findings of this study provide insight into the mechanism underlying the gene-mitochondria-immunocyte network and provide a novel reference for future research into the function of mitochondria in periodontitis and T2DM.

UHPLC-qTOF-MS-Based Nontargeted Metabolomics to Characterize the Effects of Capsaicin on Plasma and Skin Metabolic Profiles of C57BL/6 Mice-An In vivo Experimental Study.

Background: Capsaicin is the main compound found in chili pepper and has complex pharmacologic effects. This study aimed to elucidate the mechanism of the effect of capsaicin on physiological processes by analyzing changes in metabolites and metabolic pathways. Methods: Female C57BL/6 mice were divided into two groups(n = 10/group) and fed with capsaicin-soybean oil solution(group T) or soybean oil(group C) for 6 weeks. Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was undertaken to assess plasma and skin metabolic profile changes and identify differential metabolites through multivariate analysis. Results: According to the OPLS-DA score plots, the plasma and skin metabolic profiles in the group T and group C were significantly separated. In plasma, 38 significant differential metabolites were identified. KEGG pathway enrichment analysis revealed that the most significant plasma metabolic pathways included pyruvate metabolism and ABC transporters. In skin, seven significant differential metabolites were found. Four metabolic pathways with p values < 0.05 were detected, including sphingolipid metabolism, sphingolipid signaling pathway, apoptosis, and necroptosis. Conclusion: These findings will provide metabolomic insights to assess the physiological functions of capsaicin and contribute to a better understanding of the potential effects of a capsaicin-rich diet on health.

Poling-assisted hydrofluoric acid wet etching of thin-film lithium niobate.

Thin-film lithium niobate (TFLN) has been extensively investigated for a wide range of applications due to continuous advancements in its fabrication methods. The recent emergence of high-fidelity ferroelectric domain poling of TFLN provides an opportunity for achieving a precise pattern control of ferroelectric domains and a subsequent pattern transfer to the TFLN layer using hydrofluoric acid (HF). In this work, we present, to the best of our knowledge, the first demonstration of z-cut TFLN microdisks using a poling-assisted HF wet etching approach. By applying intense electric fields, we are able to induce a domain inversion in the TFLN with a designed microdisk pattern. A HF solution is subsequently utilized to transfer the inverted domain pattern to the TFLN layer with the selective etching of -z LN, ultimately revealing the microdisks.

Traditional Scraping (Gua Sha) Combined with Copper-Curcumin Nanoparticle Oleogel for Accurate and Multi-Effective Therapy of Androgenic Alopecia.

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.

Assessing HIV risk and the social and behavioural characteristics of gay and bisexual men who have recently migrated to Australia: an analysis of national, behavioural surveillance data 2019-2021.

INTRODUCTION: Overseas-born gay and bisexual men (GBM) are overrepresented in HIV diagnoses in Australia. We assessed social and sexual behaviours, and the use of HIV prevention and testing, by region of birth and length of residence in Australia. We sought to identify similarities and differences between recently arrived and non-recently arrived GBM from non-English-speaking countries to improve targeting and engagement with HIV testing and prevention. METHODS: Data were collected in national repeated, behavioural surveillance surveys conducted across Australia during 2019-2021. Logistic regression was used to identify factors that differentiated between recently arrived (<2 years) and non-recently arrived (≥2 years in Australia) GBM from non-English-speaking countries. RESULTS: Among 24,707 participants in 2019-21, 2811 (11.4%) were from high-income English-speaking countries, 714 (2.9%) were recently arrived overseas-born GBM and 3833 (15.5%) were non-recently arrived migrants. Recently arrived GBM were most likely to be born in Asia (36.1%) and Europe (21.1%). Compared with non-recently arrived GBM, recently arrived GBM from non-English-speaking countries were younger (aOR = 0.95, 95% CI = 0.94-0.96, p<0.001), more likely to be students (aOR = 1.43, 95% CI = 1.11-1.85, p = 0.005), less likely to be in full-time employment (aOR = 0.56, 95% CI = 0.46-0.69, p <0.001), more likely to report consistent condom use (aOR = 1.30, 95% CI = 1.01-1.66, p = 0.039), but had lower awareness (aOR = 0.62, 95% CI = 0.48-0.80, p<0.001) and use of pre-exposure prophylaxis (PrEP) (22.8%, vs. 32.3%, χ2 (1, 4185) = 23.78, p<0.001), and similar levels of casual sex with a risk of HIV acquisition or transmission (aOR = 1.29, 95% CI = 0.98-1.69, p = 0.066). Recently arrived GBM reported similar levels of lifetime HIV testing (aOR = 0.97, 95% CI = 0.54-1.74, p = 0.915) and recent HIV testing (OR = 1.03, 95% CI = 0.86-1.22, p = 0.779), but were much less likely to have tested at general practitioners (aOR = 0.53, 95% CI = 0.41-0.68, p<0.001) and more likely to report testing at hospitals (aOR = 3.35, 95% CI = 2.53-4.43, p<0.001), at home (aOR = 2.85, 95% CI = 1.63-4.99, p<0.001), or community-based services (aOR = 1.36, 95% CI = 1.01-1.84, p = 0.043). CONCLUSIONS: Recently arrived GBM from non-English-speaking countries reported similar levels of risk of HIV acquisition to longer-term residents in Australia, but lower levels of PrEP awareness and use, and more reliance on HIV testing services which are free or low cost. It is necessary to enhance access to HIV testing and prevention among recently arrived GBM in Australia.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

Two Novel and Three Recurrent Mutations in the Mevalonate Pathway Genes in Chinese Patients with Porokeratosis.

Purpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK. Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as "disease-causing" (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as "deleterious" (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), "probably damaging" (score = 1) by PolyPhen2, and "disease-causing" (p = 0.999) by Mutation Taster. Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.

Nano-selenium repaired the damage caused by fungicides on strawberry flavor quality and antioxidant capacity by regulating ABA biosynthesis and ripening-related transcription factors.

Recently, studies have shown that pesticides may have adverse effects on the flavor quality of the fruits, but there is still a lack of appropriate methods to repair the damage. This study investigated the effects and mechanism of applying the emerging material, nano­selenium, and two fungicides (Boscalid and Pydiflumetofen) alone or together on the flavor quality and antioxidant capacity of strawberries. The results showed that the two fungicides had a negative impact on strawberry color, flavor, antioxidant capacity and different enzymatic systems. The color damage was mainly attributed to the impact on anthocyanin content. Nano­selenium alleviated the quality losses by increasing sugar-acid ratio, volatiles, anthocyanin levels, enzyme activities and DPPH scavenging ability and reducing ROS levels. Results also showed that these damage and repair processes were related to the regulation of flavor and ripening related transcription factors (including FaRIF, FaSnRK1, FaMYB10, FaMYB1, FaSnRK2.6 and FaABI1), the upregulation of genes on sugar-acid, volatile, and anthocyanin synthesis pathways, as well as the increase of sucrose and ABA signaling molecules. In addition, the application of nano-Se supplemented the selenium content in fruits, and was harmless to human health. This information is crucial for revealing the mechanisms of flavor damage caused by pesticides to strawberry and the repaired of nano­selenium, and broadens the researching and applying of nano­selenium in repairing the damage caused by pesticides.

Effect of acetochlor on the symbiotic relationship between microalgae and bacteria.

In this study, two strains of symbiotic bacteria (SOB-1 and SOB-2) were isolated from Scenedesmus obliquus, and various algal-bacterial mutualistic systems were established under acetochlor (ACT) stress conditions. Following exposure to varying ACT concentrations from 2.0 to 25.0 µg/L, the capacity for co-cultured bacteria to degrade ACT was enhanced in 7 days by up to 226.9% (SOB-1) and 193.0% (SOB-2), compared with axenic algae, although bacteria exposed to higher ACT concentrations exacerbated algal metabolic stress, oxidative states, apoptosis and cellular lysis. ACT reduced carbohydrates in the phycosphere by up to 31.5%; compensatory nutrient plunder and structural damage by bacteria were the potential exploitation pathways determined based on the inhibition of bacterial infection using a glucanase inhibitor. The ACT-induced reduction in algal antimicrobial substances, including fatty acids and phenolics (by up to 58.1% and 56.6%, respectively), also facilitated bacterial exploitation of algae. ACT-dependent interspecific interaction coefficients between algae and bacteria generated from long-term symbiosis cultures implied that bacteria moved from mutualism (0 and 2.0 µg/L ACT) to exploitation (7.9 and 25.0 µg/L ACT). The population dynamic model under incremental ACT-concentration scenarios inferred that theoretical systematic extinction may occur in algal-bacterial systems earlier than in axenic algae. These outcomes provide interspecific insights into the distortion of algal-bacterial reciprocity due to the ecotoxicological effects of ACT.

Perceived HIV risk and factors associated with condom use among women aged 40 and older: A cross-sectional survey.

Objectives: A noticeable increase in HIV-positive cases among women, particularly those of middle and old age, has been observed worldwide. This study aimed to describe women's perceived HIV risk, HIV/Acquired Immunodeficiency Syndrome (AIDS) knowledge, attitude, and sexual behaviors to determine factors associated with condom use among these women in Hunan, China. Methods: A cross-sectional study was conducted from July 2019 to August 2020 among 958 women aged 40 and older in four regions of Hunan, China. We collected data on sociodemographic characteristics, perceived HIV risk, HIV/AIDS knowledge and attitude, condom use, and sexual behaviors. Univariate and multivariate logistic regression were performed to identify factors related to condom use. Results: Out of 958 participants, 60.6% perceived no risk of HIV infection, and 46.8% reported they had never used a condom during their past sexual life. Those who were older, had lower monthly household income for family, had not received HIV education in the past year, were unwilling to use condoms, could not determine condom use during sexual activity, and had more negative attitudes towards HIV/AIDS and HIV-positive people were less likely to use condoms in their past sexual behaviors. Conclusions: In Hunan Province, most women aged 40 and older perceived themselves as having a low or no risk of HIV infection; their rate of condom use was low, and six factors were associated with condom use. It is imperative to strengthen HIV prevention and control programs among women aged 40 and above, particularly focusing on those who may use condoms infrequently or not at all.

Untargeted Plasma Lipidomics Reveal Perturbed Metabolites of Glycerophospholipids, and Sphingolipids in Moderate-to-Severe Acne.

Background: Acne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. The study aimed to explore the plasma lipidome signatures and identify specific lipid biomarkers in moderate-to-severe acne patients. Patients and Methods: Untargeted plasma lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was employed on 30 moderate-to-severe acne patients aged between 16-25 years and 30 healthy controls. Multivariate data analyses were used to identify the distinguishing lipid metabolites. Results: All 1449 species of 37 lipid subclasses were identified from the MS data. There were apparent differences in plasma lipid profiles between acne groups and control groups. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 26 significantly different lipid metabolites were identified. These metabolites consisted mainly of glycerophospholipids (GPs), sphingolipids (SPs), and glycerolipids (GLs). Combining with AUC≥0.800 as the elected criteria, we obtained five differential lipids with good diagnostic performance for acne severity, including 2 sphingomyelins (SM), 1 phosphatidylglycerol (PG), 1 trihexosylceramide (Hex3Cer), and 1 Phosphatidylcholine (PC). Among them, PG (44:0) had the highest AUC values. Conclusion: Our study revealed the plasma lipidome signature of patients with moderate-to-severe acne. The results will provide a novel light into the perturbed lipid metabolism leading to the development of acne.

Glyphosate-based herbicide (GBH) challenged thermoregulation in lizards (Eremias argus), compensatory warming could mitigate this effect.

Chemical pollution and global warming are two major threats to reptiles, and these two factors can interact with each other. Glyphosate have attracted worldwide attention due to their ubiquitous occurrence, yet their impact on reptiles remains unknown. We designed a crossover experiment with different external GBH exposures (control/GBH) x different environmental temperatures (current climate treatment/warmer climate treatment) over 60 days to simulate environmental exposure in the Mongolian Racerunner lizard (Eremias argus). Preferred body temperature and active body temperature data were collected to calculate the accuracy of thermoregulation, while liver detoxification metabolic enzymes, oxidative stress system function, and the non-targeted metabolome of the brain tissue were assessed. Warmer-treated lizards adjusted their physiological levels and behavioral strategies in response to increased ambient temperatures and maintained body temperature homeostasis at moderate thermal perturbations. GBH-treated lizards suffered from oxidative damage to the brain tissue and abnormal histidine metabolism, thus their thermoregulatory accuracy reduced. Interestingly, at elevated ambient temperatures, GBH treatment did not affect on their thermoregulatory, possibly through several temperature-dependent detoxification mechanisms. Importantly, this data suggested that the subtle toxicological effects of GBH may threaten increasingly thermoregulation behavior of E. argus with species-wide repercussions, as climate change and exposure time extension.

Interspecific insights into direct and indirect effects of acetochlor on interactions between daphnids and microalgae: Toxic, trophic, and grazer-infochemical responses.

As the herbicide acetochlor (ACT) affects the plankton food web, this study investigated the effects of ACT and exocrine infochemicals from daphnids (after ACT exposure and/or starvation) on Scenedesmus obliquus growth, as well as the effects of ACT and starvation on life-history traits of Daphnia magna. Filtered secretions from daphnids increased algal ACT tolerance, dependent on different ACT exposure histories and food intake. Endogenous and secretory metabolite profiles of daphnids following ACT and/or starvation appear to be regulated by the fatty acid synthesis pathway and sulfotransferases and were related to energy allocation trade-offs. Oleic acid (OA) and octyl sulfate (OS), screened by secreted and somatic metabolomics, affected algal growth and ACT behavior in the algal culture in opposite ways. Trophic and non-trophic interspecific effects caused by ACT were observed in microalgae-daphnid microcosms, including algal growth inhibition, daphnid starvation, OA down-regulation, and OS up-regulation. Based on these findings, risk assessment of ACT on the freshwater plankton communities should take species interactions into account.

Improvement by application of three nanomaterials on flavor quality and physiological and antioxidant properties of tomato and their comparison.

In recent years, it has been found that the flavor quality of tomato is continuously reduced compared with the original tomato varieties. Studies have found that nanomaterials can improve crop quality, but the differences and related mechanisms among different nanomaterials were not reported. In this study, nano-Se, nano-TiO2 and nano-CeO2 were spraying on tomato, and the effects of the three nanomaterials on the flavor quality and physiological and antioxidant properties of fruits were analyzed and compared. The results showed compared with nano-TiO2 and nano-CeO2, nano-Se showed more obvious positive effects. Nano-Se increased the size and weight of tomato fruits and the levels of soluble sugar, promoted the accumulation of photosynthetic pigment, decreased the content of titratable acid, and also changed the expression of related genes, finally making the fruit sweeter; it also promoted the accumulation of antioxidant substances and nutrients such as lycopene, ascorbic acid, salicylic acid, GSH, SOD and CAT and decreased the content of MDA, H2O2 and OFR thus improving the antioxidant performance of fruits; the contents of volatiles were also increased and the olfactory experience of tomato was improved. Nano-TiO2 and nano-CeO2 also improved the flavor quality and antioxidant properties of tomato, but the degree was lower than nano-Se. This experiment provided references for selecting more appropriate nanomaterials to improve tomato quality, and revealed the effects and mechanisms of different nanomaterials on tomato quality.

Two Novel and a Recurrent ATP2C1 Mutations in Chinese Population with Hailey-Hailey Disease.

Purpose: Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited blistering dermatosis. Pathogenic variants in ATP2C1 have been associated with HHD since 2000. This study aimed to identify the mutations in the ATP2C1 gene in two Chinese pedigrees and two sporadic cases with HHD. Patients and Methods: Two Chinese pedigrees and two sporadic cases were included in this study. Whole-exome sequencing and Sanger sequencing were performed to detect the mutation of the ATP2C1 gene. Predictions of protein structure and function were performed using bioinformatics tools, including Mutation Taster, Polyphen-2, SIFT, and Swiss-Model. Results: In this study, we detected three heterozygous mutations, including novel compound mutations of (c.1840-4delA and c.1840_1844delGTTGC), splice site mutation of c.1570+3A>C, and a previously known nonsense mutation c.1402C>T in the ATP2C1 gene. Combined with our previous study, ten patients with c.1402C>T mutation in the ATP2C1 gene have been identified, and all these patients originated from Jiangxi Province. Conclusion: c.1402C>T mutation in the ATP2C1 gene was considered a regional highly prevalent mutation in the Chinese population with HHD. The results added new variants to the database of ATP2C1 mutations associated with HHD.

Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect the host tissue cells' mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand the role of intestinal flora in ovarian cells inflammation by regulating mRNA m6A modification particularly the inflammatory state in PCOS. The gut microbiome composition of PCOS and Control groups was analyzed by 16S rRNA sequencing, and the short chain fatty acids were detected in patients' serum by mass spectrometry methods. The level of butyric acid was found to be decreased in the serum of the obese PCOS group (FAT) compared to other groups, and this was correlated with increased Streptococcaceae and decreased Rikenellaceae based on the Spearman's rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq and MeRIP-seq methodologies. Cellular experiments demonstrated that the addition of butyric acid led to a decrease in FOSL2 m6A methylation levels and mRNA expression by suppressing the expression of METTL3, an m6A methyltransferase. Additionally, NLRP3 protein expression and the expression of inflammatory cytokines (IL-6 and TNF-α) were downregulated in KGN cells. Butyric acid supplementation in obese PCOS mice improved ovarian function and decreased the expression of local inflammatory factors in the ovary. Taken together, the correlation between the gut microbiome and PCOS may unveil crucial mechanisms for the role of specific gut microbiota in the pathogenesis of PCOS. Furthermore, butyric acid may present new prospects for future PCOS treatments.

A theoretical base for non-invasive prenatal paternity testing.

There is an increasing demand for prenatal paternity testing in the forensic applications, which identify biological fathers before the birth of children. Currently, one of the most effective and safe Non-Invasive Prenatal Paternity Testing (NIPPT) methods is high-throughput Next-Generation Sequencing (NGS)-based SNP genotyping of cell-free DNA in maternal peripheral blood. To the best of our knowledge, nearly all methods being used in such applications are based on traditional postnatal paternity tests and/or statistical models of conventional polymorphism sites. These methods have shown unsatisfactory performance due to the uncertainty of fetal genotype. In this study, we propose a cutting-edge methodology called the Prenatal paternity Test Analysis System (PTAS) for cell-free fetal DNA-based NIPPT using NGS-based SNP genotyping. With the implementation of our proposed PTAS methodology, 63 out of 64 early-pregnancy (i.e., less than seven weeks) samples can be precisely identified to determine paternity, except for one sample that does not meet quality control requirements. Although the fetal fraction of the non-identified sample is extremely low (0.51%), its paternity can still be detected by our proposed PTAS methodology through unique molecular identifier tagging. Paternity of the total 313 samples for mid-to-late pregnancy (i.e., more than seven weeks) can be accurately identified. Extensive experiments indicate that our methodology makes a significant breakthrough in the NIPPT theory and will bring substantial benefits to forensic applications.