Sulfate-mediated Fe(III) mineral reduction accelerates arsenic mobilization by a Desulfovibrio strain isolated from paddy soil.

The biogeochemical cycling of arsenic (As) is often intertwined with iron (Fe) and sulfur (S) cycles, wherein Fe(III)- and sulfate-reducing bacteria (SRB) play a crucial role. Here, we isolated strain DS-1, a strictly anaerobic Fe(III)- and sulfate-reducing bacterium, from As-contaminated paddy soil. Using 16S rRNA gene sequence analysis, strain DS-1 was identified as a member of the genus Desulfovibrio. Strain DS-1 utilized energy derived from ferrihydrite reduction to support its cellular growth. Under anoxic sulfate-reducing conditions, the presence of strain DS-1 significantly increased As mobilization compared to sulfate-free conditions. Mechanistically, SRB-produced sulfide reacts with Fe(III) to form FeS, which disrupts Fe(III) minerals, thereby enhancing As release. These findings highlight the critical role of redox disequilibrium in As mobilization and suggest that SRB-produced sulfide may permeate to the rice rhizosphere, increasing As mobilization through Fe(III) reduction.

Effect of opioid receptor antagonist on mitigating tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-induced apoptolysis in pemphigus pathogenesis.

Pemphigus is a severe autoimmune blistering disease characterized by acantholysis triggered by autoantibodies against desmoglein 1 and 3 (DSG1/3). Apoptosis plays a pivotal role in facilitating acantholysis, yet the precise underlying mechanism remains obscure. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to promote apoptosis and disrupt cell junctions, although its involvement in pemphigus pathogenesis remains ambiguous. Our study observed decreased DSG1/3 expression alongside increased TWEAK/fibroblast growth factor-inducible 14 (Fn14) expression and keratinocyte apoptosis in both lesional and perilesional skin. In vitro experiments revealed that TWEAK-stimulated keratinocytes exhibited enhanced apoptosis, STAT1 phosphorylation, and reduced intercellular DSG1/3 expression. Notably, bulk-RNA sequencing unveiled that CASPASE-3 was responsible for mediating the DSG1/3 depletion, as confirmed by direct interaction with DSG1/3 in a co-immunoprecipitation assay. Naloxone, known for preserving cellular adhesion and preventing cell death, effectively reduced apoptosis and restored DSG1/3 levels in TWEAK-stimulated keratinocytes. The anti-apoptotic properties of naloxone were further validated in a murine pemphigus model. Our findings elucidate that TWEAK facilitates keratinocyte apoptosis by augmenting caspase-3 activity, leading to DSG1/3 depletion and apoptosis in pemphigus. Importantly, naloxone can counter TWEAK-induced apoptosis in pemphigus pathogenesis, offering a potential therapeutic intervention.

Exploring the Diversity and Specificity of Secondary Biosynthetic Potential in Rhodococcus.

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites.

Application of a UV-vis spectrometer to investigate the effect of dissolution media on the diffusivity of small molecules and proteins.

To date, the commonly used methods for diffusion coefficient measurements have some hurdles that prevent them from being widely applied in pharmaceutical laboratories. This study aimed to modify a method developed by di Cagno et al. based on the use of a UV-Vis spectrometer and apply the method to investigate the effect of dissolution media on the diffusivity of small molecules and proteins. A total of five small molecules and two proteins in different aqueous media and polymer solutions were investigated in this study. By attaching a 3D-printed cover with an open slit to a standard UV-Vis cuvette, the incident UV light could only pass through the open slit to measure the local drug concentration. During the diffusion experiment, drug molecules diffused from the cuvette bottom to the slit. According to the concentration measured as a function of time, diffusion coefficient was calculated based on Fick's law of diffusion using the analytical and numerical approaches. As a result, diffusion coefficients could be accurately measured with high reproducibility. The results also suggested that different media could affect the diffusion coefficients of small molecules by < 10% and proteins by < 15%. Since the UV-Vis spectrometer is a routine instrument, this method can potentially be employed by many pharmaceutical laboratories for diffusion coefficient measurements.

Comparative Analysis of Gene Expression Profiles in Ovarian Clear Cell Carcinoma and High-Grade Serous Ovarian Cancer.

OBJECTIVE: To evaluate disparities in gene expression profiles between Ovarian Clear Cell Carcinoma (OCCC) and High-Grade Serous Ovarian Carcinoma (HGSOC). STUDY DESIGN: A descriptive study. Place and Duration of the Study: The Second People's Hospital of Jingdezhen, Jiangxi, China, between 31st December 2017 and December 2023. METHODOLOGY: Basic and clinical diagnostic information, along with genetic test reports, were compiled from all patients within the included groups. Differential gene expression between the two cohorts was scrutinised to elucidate its clinical significance. RESULTS: Comparative analysis revealed nine differentially expressed genes in OCCC relative to HGSOC, with six exhibiting significant disparities (p <0.05). These genes are implicated in pivotal cellular processes including the cell cycle, apoptosis, DNA damage repair, and the PI3K pathway. Notably, aberrant expression patterns, such as overexpression of MET and downregulation of PTEN and SMARCA4, correlated with adverse prognosis and survival outcomes in selected patients. CONCLUSION: Distinctive gene expression profiles between OCCC and HGSOC underscore disparate tumorigenic mechanisms, thereby laying a foundation for the tailored therapeutic interventions. Further elucidation of the identified differentially expressed genes is warranted to delineate their role in OCCC pathogenesis and prognostic significance. KEY WORDS: Ovarian clear cell carcinoma, High-grade serous ovarian cancer, Gene expression profiles, Homologous recombination repair.

flDPnn2: Accurate and Fast Predictor of Intrinsic Disorder in Proteins.

Prediction of the intrinsic disorder in protein sequences is an active research area, with well over 100 predictors that were released to date. These efforts are motivated by the functional importance and high levels of abundance of intrinsic disorder, combined with relatively low amounts of experimental annotations. The disorder predictors are periodically evaluated by independent assessors in the Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiments. The recently completed CAID2 experiment assessed close to 40 state-of-the-art methods demonstrating that some of them produce accurate results. In particular, flDPnn2 method, which is the successor of flDPnn that performed well in the CAID1 experiment, secured the overall most accurate results on the Disorder-NOX dataset in CAID2. flDPnn2 implements a number of improvements when compared to its predecessor including changes to the inputs, increased size of the deep network model that we retrained on a larger training set, and addition of an alignment module. Using results from CAID2, we show that flDPnn2 produces accurate predictions very quickly, modestly improving over the accuracy of flDPnn and reducing the runtime by half, to about 27 s per protein. flDPnn2 is freely available as a convenient web server at http://biomine.cs.vcu.edu/servers/flDPnn2/.

Effect of post-traumatic stress disorder on type 2 diabetes and the mediated effect of obesity: a Mendelian randomization study.

Objective: Whether the role of post-traumatic stress disorder (PTSD) on type 2 diabetes (T2D) is mediated by obesity or other mediating factors is controversial. This study was designed to assess the impact of PTSD on genetic susceptibility to T2D and mediating factors. Methods: The datasets for PTSD, T2D, obesity, hypertension, hyperlipidemia, smoking status, and alcohol consumption were obtained from genome-wide association studies. Mendelian randomization (MR) was used to assess exposure-outcome causality, and inverse variance weighted was used as the primary tool for MR analysis. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were employed to assess horizontal pleiotropy, heterogeneity, and robustness, respectively. Results: The MR analysis showed that PTSD was associated with increased genetic susceptibility to T2D (OR, 1.036; 95% CI, 1.008-1.064; p = 0.011), obesity (OR, 1.033; 95% CI, 1.016-1.050; p < 0.001), and hypertension (OR, 1.002; 95% CI, 1.000-1.003; p = 0.015), but not not with genetic susceptibility to hyperlipidemia, alcohol consumption, and smoking status (p ≥ 0.05). Mediated effect analysis showed that PTSD increased genetic susceptibility to T2D by increasing genetic susceptibility to obesity and hypertension, with obesity accounting for 9.51% and hypertension accounting for 2.09%. MR-Egger intercept showed no horizontal pleiotropy (p ≥ 0.05). Cochran's Q showed no heterogeneity (p ≥ 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion: This MR analysis suggests that PTSD increases the risk of T2D and that this effect is partially mediated by obesity and hypertension. Active prevention and treatment of PTSD can help reduce the risk of T2D.

[Ultrafiltration of Angelicae Sinensis Radix and Astragali Radix inhibits ferroptosis and improves pulmonary fibrosis in rats by regulating Nrf2/xCT/GPX4 signaling pathway].

This study aims to investigate the mechanism of ferroptosis mediated by the nuclear factor-E2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11, also known as xCT)/glutathione peroxidase 4(GPX4) signaling pathway in radiationinduced pulmonary fibrosis and the intervention effect of Angelicae Sinensis Radix(ASR) and Astragali Radix(AR) ultrafiltration extract. Fifty Wistar rats were randomly divided into five groups, with 10 rats in each group. Except for the blank group without radiation, the rats in each group were anesthetized and subjected to a single local chest irradiation of 40 Gy X-rays once to establish a rat model of radiation-induced pulmonary fibrosis. After radiation, the rats in the intervention groups were orally administered with ASR-AR ultrafiltration extract at doses of 0. 12, 0. 24, and 0. 48 g·kg~(-1), respectively, once a day for 30 days. After 30 days of continuous administration, the levels of oxidative stress indicators superoxide dismutase(SOD) activity, reduced glutathione(GSH),malondialdehyde(MDA), and ferrous ion(Fe~(2+)) in lung tissues of each group were detected by colorimetry. Immunofluorescence was used to detect reactive oxygen species(ROS) fluorescence expression in lung tissues. Hematoxylin-eosin(HE) and Masson staining were performed to observe pathological changes in lung tissues. Immunohistochemistry and Western blot were used to detect the expression levels of Nrf2/xCT/GPX4 signaling pathway and fibrotic proteins in lung tissues. The results showed that compared with the results in the blank group, the levels of Fe~(2+) and MDA in the model group increased, while SOD activity and GSH levels decreased,and ROS levels increased. HE and Masson staining results showed that the structure of lung tissue was seriously damaged, the pulmonary interstitium was significantly proliferated, the alveoli collapsed and consolidated severely, and there were more inflammatory cell aggregates and collagen fiber deposits. Transmission electron microscopy showed that the degree of lung tissue damage in the model group was relatively high, with increased, smaller, and disorganized damaged mitochondria, irregular morphology, shallow matrix,most mitochondria ruptured and shortened, mildly expanded, some mitochondria with increased electron density of the matrix, partial mitochondrial outer membrane rupture, and characteristic changes of ferroptosis-specific mitochondria. Immunohistochemistry showed that the expression of transferrin receptor protein 1(TFR1) in lung tissues was significantly increased, while the expression of GPX4,ferritin heavy chain 1(FTH1), Nrf2, and xCT was significantly decreased. Western blot showed that the expression of α-smooth muscle actin(α-SMA) and collagen Ⅰ protein increased. Compared with the model group, the intervention group with ASR-AR ultrafiltration extract significantly improved lipid peroxidation and antioxidant-related indicators, decreased Fe~(2+) levels, alleviated fibrosis, and decreased the expression of TFR1, α-SMA, and collagen Ⅰ proteins in lung tissues, while increased the expression of GPX4, FTH1, Nrf2, and xCT proteins. In summary, ASR-AR ultrafiltration extract has an ameliorative effect on radiation-induced pulmonary fibrosis, and its mechanism may involve the inhibition of ferroptosis by regulating the Nrf2/xCT/GPX4 signaling pathway.

Trends in the Incidence of Hypertensive Disorders of Pregnancy Among the Medicaid Population before and During COVID-19.

Importance: Hypertensive disorders of pregnancy (HDP) are a group of high blood pressure disorders during pregnancy that are a leading cause of maternal and infant morbidity and mortality. Data on the trend in the incidence of HDP among the Medicaid population during coronavirus disease of 2019 (COVID-19) are lacking. Objective: To determine the trends in the annual incidence of HDP among pregnant Medicaid-insured women in Louisiana before and during the COVID-19 pandemic (2016-2021). Methods: A total of 113,776 pregnant women aged 15-50 years were included in this study. For multiparous individuals, only the first pregnancy was used in the analyses. Women with a diagnosis of each type-specific HDP were identified by using the International Classification of Diseases, 10th revision (ICD-10) codes. The annual incidence of HDP was calculated for each race and age subgroup. For each type-specific HDP, the annual age-specific incidence was calculated. Results: The incidence of HDP increased from 10.5% in 2016 to 17.7% in 2021. The highest race/ethnicity-specific incidence of HDP was seen in African American women (19.2%), then White women (13.1%), followed by other women (10.7%). Conclusion and Relevance: HDP remains a very prevalent and significant global health issue, especially in African American women and during the COVID-19 pandemic. Severe HDP substantially increases the risk of mortality in offspring and poses long-term issues for both mother and infant. HDP prevention holds particular relevance for the Medicaid population, given the health care disparities and barriers that impact quality of care, leading to an increased risk for HDP.

Yushaniadezhui (Poaceae, Bambusoideae), a new bamboo species from Yunnan, China.

A new bamboo species, Yushaniadezhui, from Kunming, Yunnan, China is described and illustrated in this paper. The new species used to be misidentified as Y.polytricha. Based on careful comparison of morphological features and molecular phylogeny evidence, we confirmed its identity as a new member of the genus Yushania. Yushaniadezhui resembles Y.maculata, Y.polytricha and Y.weixiensis in several aspects, such as culm height and branch complement structure. However, the glabrous culm leaf sheaths and internodes, the absence of auricles and oral setae on most foliage leaves, except the one-year-old foliage leaves, the pubescence on the adaxial surface of the one-year-old foliage leaves and its limestone habitat preference can readily distinguish this new species from its related taxa. Moreover, we emphasise that individuals from various populations and molecular markers with different inheritance patterns for phylogeny reconstruction should be included in new species discovery, especially in plant groups with complex evolutionary histories.

Serum CD44 levels in early pregnancy and its genetic variants for increased risk of gestational diabetes mellitus in Chinese pregnant women.

This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.

Blood perfusion assessment by near-infrared fluorescence angiography of epiploic appendages in prevention of anastomotic leakage after laparoscopic intersphincteric resection for ultra-low rectal cancer: a case-matched study.

BACKGROUND: The role of intraoperative near-infrared fluorescence angiography with indocyanine green in reducing anastomotic leakage (AL) has been demonstrated in colorectal surgery, however, its perfusion assessment mode, and efficacy in reducing anastomotic leakage after laparoscopic intersphincteric resection (LsISR) need to be further elucidated. AIM: Aim was to study near-infrared fluorescent angiography to help identify bowel ischemia to reduce AL after LsISR. MATERIAL AND METHODS: A retrospective case-matched study was conducted in one referral center. A total of 556 consecutive patients with ultra-low rectal cancer including 140 patients with fluorescence angiography of epiploic appendages (FAEA)were enrolled. Perfusion assessment by FAEA in the monochrome fluorescence mode. Patients were divided into two groups based on perfusion assessment by FAEA. The primary endpoint was the AL rate within 6 months, and the secondary endpoint was the structural sequelae of anastomotic leakage (SSAL). RESULTS: After matching, the study group (n = 109) and control group (n = 190) were well-balanced. The AL rate in the FAEA group was lower before (3.6% vs. 10.1%, P = 0.026) and after matching (3.7% vs. 10.5%, P = 0.036). Propensity scores matching analysis (OR 0.275, 95% CI 0.035-0.937, P 0.039), inverse probability of treatment weighting (OR 0.814, 95% CI 0.765-0.921, P 0.002), and regression analysis (OR 0.298, 95% CI 0.112-0.790, P = 0.015), showed that FAEA was an independent protector factor for AL. This technique can significantly shorten postoperative hospital stay [9 (6-13) vs. 10 (8-13), P = 0.024] and reduce the risk of SSAL (1.4% vs. 6.0%, P = 0.029). CONCLUSIONS: Perfusion assessment by FAEA can achieve better visualization in LsISR and reduce the incidence of AL, subsequently avoiding SSAL after LsISR.

Short-term and long-term outcomes of laparoscopic surgery for locally recurrent rectal cancer: a propensity score-matched cohort study.

BACKGROUND: Radical surgery remains the primary option for locally recurrent rectal cancer (LRRC) as it has the potential to considerably extend the patient's lifespan. At present, the effectiveness of laparoscopic surgery for LRRC remains unclear. METHODS: The clinical data of patients with LRRC who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences between 2015 and 2021 were retrospectively analyzed in this study. Patients were categorized into two groups, namely the open group and the laparoscopic group, based on the surgical method used. Propensity score matching was used to reduce baseline differences. The short-term outcomes and long-term survival between the two groups were compared. RESULTS: Curative surgery was performed on 111 patients who were diagnosed with LRRC. After propensity score matching, a total of 80 patients were included and divided into the laparoscopic group (40 patients) and the open group (40 patients). The laparoscopic group had less intraoperative bleeding (100 vs. 300, P = 0.011), a lower postoperative complication rate (20.0% vs. 42.5%, P = 0.030), a lower incidence of wound infection (0 vs. 15.0%, P = 0.026), and a shorter time to first flatus (2 vs. 3, P = 0.005). The laparoscopic group had higher 3-year overall survival (85.4% vs. 57.5%, P = 0.016) and 3-year disease-free survival (63.9% vs 36.5%, P = 0.029). CONCLUSIONS: In comparison to open surgery, laparoscopic surgery is linked to less bleeding during the operation, quicker recovery after the surgery, and a lower incidence of infections at the surgical site. Moreover, laparoscopic surgery for LRRC might yield superior long-term survival outcomes.

Risk cycling in diabetes and autism spectrum disorder: a bidirectional Mendelian randomization study.

Objective: The relationship between diabetes mellitus (DM) and autism spectrum disorder (ASD) remains controversial. This study aimed to analyze the causal relationship between different types of DM and ASD by bidirectional Mendelian randomization (MR). Methods: Single nucleotide polymorphisms for type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and ASD were obtained from genome-wide association studies. Subsequently, inverse variance weighted, MR-Egger, and weighted median were used to test the exposure-outcome causality. Finally, MR-Egger's intercept, Cochran's Q, and leave-one-out method were used to assess horizontal pleiotropy, heterogeneity, and sensitivity of the results, respectively. Results: The positive analysis showed that T2DM was associated with an increased risk of ASD, whereas neither T1DM nor GDM was associated with the risk of ASD. The reverse analysis showed that ASD was associated with an increased risk of T2DM, while it was not associated with the risk of either T1DM or GDM. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05) for these results. Cochran's Q showed no heterogeneity expect for the results of T1DM on the risk of ASD, and leave-one-out sensitivity analysis showed these results were robust. Conclusion: This MR analysis suggests that T2DM and ASD are reciprocal risk factors and that they may create an intergenerational risk cycling in female patients. Aggressive prevention and treatment of T2DM and ASD help to break the trap of this risk cycling. Additionally, this study does not support a causal relationship between T1DM and ASD, as well as GDM and ASD. And more studies are needed in the future to continue to explore the interactions and underlying mechanisms between different types of DM and ASD.

Clinical application of pulse-gated non-enhanced rapid magnetic resonance imaging in the definitive diagnosis of aortic dissection.

OBJECTIVE: Aortic Dissection (AD) is one of the most fatal acute diseases in cardiovascular diseases, with rapid onset and progression and a high fatality rate. This study aims to investigate the clinical values of non-enhancement peripheral pulse-gating rapid magnetic resonance imaging in deterministic diagnosis of AD. METHODS: Aorta magnetic resonance imaging was performed in 21 healthy volunteers at a 1.5t MR scanner sequences including cardiac-gated and peripheral pulse-gated True-FISP and HASTE were carried out separately. Acquisition Time (TA), Signal to Noise Ratio (SNR), Contrast Noise Ratio (CNR), and entirety of vessel wall blood flow artifacts were measured and compared. A total of 56 AD cases were displayed by non-enhancement peripheral pulse-gating fast MR imaging, and the results were compared with pathological findings or CTA of the aorta. The dissection rupture, tear film, true and false lumen, thrombosis, hydropericardium, and the main branches of AD were evaluated respectively. RESULTS: There were no significant differences in SNR, CNR, entirety of the vessel wall, and blood flow artifact between cardiac-gated and peripheral pulse-gated fast MR imaging. Non-enhancement pulse-gated fast scanning takes less TA time. By the pulse-gated non-enhancement fast MR imaging, the dissection rupture, tear film, true and false cavity, thrombosis, hydropericardium, and the main branches of aortic dissection were shown clearly. Multi-planar and multi-angle scans helped to show the extent of entrapment rupture, whereas partial complex tears or bi-directional tears were slightly less well visualized. CONCLUSION: Non-enhancement peripheral pulse-gated rapid magnetic resonance imaging can be used for deterministic diagnosis of AD.

The Therapeutic Potential of Lactobacillus crispatus for Chronic Endometritis: A Comprehensive Clinical Trial and Experimental Investigation.

Chronic endometritis (CE) is common in patients with infertility, and it is challenging to treat with antibiotics as bacteria often acquire resistance to the antibiotics, which leads to frequent recurrence of the condition. Probiotics, especially Lactobacillus species, are known for their usefulness in treating reproductive infections. This study evaluated Lactobacillus crispatus chen 01 (L. crispatus chen 01) isolated from healthy women who were 22-30 years old and married with children. In vitro experiments showed that L. crispatus chen 01 inhibited pathogens and reduced inflammation in CE mice by downregulating inflammatory proteins (TLR, MyD88, and p65/p-p65; L + Abx vs M, P < 0.01), improving histopathological features, and inhibiting bacterial growth. It also regulated endometrial processes, such as enhancing embryo implantation (BMP2 and Wnt4, L + Abx vs M, P < 0.01) via the Wnt/ß-catenin pathway, leading to increased pregnancy rates (L + Abx vs M, 100% vs 0%) in mice. In clinical trials, L. crispatus chen 01 improved progesterone levels (P = 0.0038), pregnancy rates (C vs Abx + L. c, 76.19% vs 87.18%), and pathological changes in CE patients. The findings from this study identify the administration of L. crispatus chen 01 as a promising intervention for CE that could improve pregnancy rates.

Antagonism of ß-arrestins in IL-4-driven microglia reactivity via the Samd4/mTOR/OXPHOS axis in Parkinson's disease.

Interleukin-4 (IL-4)-exposed microglia acquire neuroprotective properties, but their functions and regulation in Parkinson's disease (PD) are poorly understood. In this study, we demonstrate that IL-4 enhances anti-inflammatory microglia reactivity, ameliorates the pathological features of PD, and reciprocally affects expression of ß-arrestin 1 and ß-arrestin 2 in microglia in PD mouse models. We also show that manipulation of two ß-arrestins produces contrary effects on the anti-inflammatory states and neuroprotective action of microglia induced by IL-4 in vivo and in vitro. We further find that the functional antagonism of two ß-arrestins is mediated through sequential activation of sterile alpha motif domain containing 4 (Samd4), mammalian target of rapamycin (mTOR), and mitochondrial oxidative phosphorylation (OXPHOS). Collectively, these data reveal opposing functions of two closely related ß-arrestins in regulating the IL-4-induced microglia reactivity via the Samd4/mTOR/OXPHOS axis in PD mouse models and provide important insights into the pathogenesis and therapeutics of PD.

Fractional-Order Boosted Hybrid Young's Double-Slit Experimental Optimizer for Truss Topology Engineering Optimization.

Inspired by classical experiments that uncovered the inherent properties of light waves, Young's Double-Slit Experiment (YDSE) optimization algorithm represents a physics-driven meta-heuristic method. Its unique search mechanism and scalability have attracted much attention. However, when facing complex or high-dimensional problems, the YDSE optimizer, although striking a good balance between global and local searches, does not converge as fast as it should and is prone to fall into local optimums, thus limiting its application scope. A fractional-order boosted hybrid YDSE, called FYDSE, is proposed in this article. FYDSE employs a multi-strategy mechanism to jointly address the YDSE problems and enhance its ability to solve complex problems. First, a fractional-order strategy is introduced into the dark edge position update of FYDSE to ensure more efficient use of the search potential of a single neighborhood space while reducing the possibility of trapping in a local best. Second, piecewise chaotic mapping is constructed at the initial stage of the population to obtain better-distributed initial solutions and increase the convergence rate to the optimal position. Moreover, the low exploration space is extended by using a dynamic opposition strategy, which improves the probability of acquisition of a globally optimal solution. Finally, by introducing the vertical operator, FYDSE can better balance global exploration and local exploitation and explore new unknown areas. The numerical results show that FYDSE outperforms YDSE in 11 (91.6%) of cec2022 sets. In addition, FYDSE performs best in 8 (66.6%) among all algorithms. Compared with the 11 methods, FYDSE obtains the optimal best and average weights for the 20-bar, 24-bar, and 72-bar truss problems, which proves its efficient optimization capability for difficult optimization cases.

A Multi-Strategy Improvement Secretary Bird Optimization Algorithm for Engineering Optimization Problems.

Based on a meta-heuristic secretary bird optimization algorithm (SBOA), this paper develops a multi-strategy improvement secretary bird optimization algorithm (MISBOA) to further enhance the solving accuracy and convergence speed for engineering optimization problems. Firstly, a feedback regulation mechanism based on incremental PID control is used to update the whole population according to the output value. Then, in the hunting stage, a golden sinusoidal guidance strategy is employed to enhance the success rate of capture. Meanwhile, to keep the population diverse, a cooperative camouflage strategy and an update strategy based on cosine similarity are introduced into the escaping stage. Analyzing the results in solving the CEC2022 test suite, the MISBOA both get the best comprehensive performance when the dimensions are set as 10 and 20. Especially when the dimension is increased, the advantage of MISBOA is further expanded, which ranks first on 10 test functions, accounting for 83.33% of the total. It illustrates the introduction of improvement strategies that effectively enhance the searching accuracy and stability of MISBOA for various problems. For five real-world optimization problems, the MISBOA also has the best performance on the fitness values, indicating a stronger searching ability with higher accuracy and stability. Finally, when it is used to solve the shape optimization problem of the combined quartic generalized Ball interpolation (CQGBI) curve, the shape can be designed to be smoother according to the obtained parameters based on MISBOA to improve power generation efficiency.

Central Lean Mass Distribution and the Risks of All-Cause and Cause-Specific Mortality in 40,283 UK Biobank Participants.

INTRODUCTION: The purpose of this study was to investigate the association of central lean mass distribution with the risk of mortality. METHODS: This cohort study included 40,283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, with the risk of mortality. RESULTS: The median age of the participants was 65 years, and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95% CI: 1.23-1.94), 1.69 (95% CI: 1.26-2.26), and 1.14 (95% CI: 0.72-1.80) for all-cause, cancer, and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI: 3.3%-40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. CONCLUSION: Trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging and poor diet quality to further increase the risk of death.