Cortical atrophy in early-stage patients with anti-NMDA receptor encephalitis: a machine-learning MRI study with various feature extraction.

Conventional brain magnetic resonance imaging (MRI) of anti-N-methyl-D-aspartate-receptor encephalitis (NMDARE) is non-specific, thus showing little differential diagnostic value, especially for MRI-negative patients. To characterize patterns of structural alterations and facilitate the diagnosis of MRI-negative NMDARE patients, we build two support vector machine models (NMDARE versus healthy controls [HC] model and NMDARE versus viral encephalitis [VE] model) based on radiomics features extracted from brain MRI. A total of 109 MRI-negative NMDARE patients in the acute phase, 108 HCs and 84 acute MRI-negative VE cases were included for training. Another 29 NMDARE patients, 28 HCs and 26 VE cases were included for validation. Eighty features discriminated NMDARE patients from HCs, with area under the receiver operating characteristic curve (AUC) of 0.963 in validation set. NMDARE patients presented with significantly lower thickness, area, and volume and higher mean curvature than HCs. Potential atrophy predominately presented in the frontal lobe (cumulative weight = 4.3725, contribution rate of 29.86%), and temporal lobe (cumulative weight = 2.573, contribution rate of 17.57%). The NMDARE versus VE model achieved certain diagnostic power, with AUC of 0.879 in validation set. Our research shows potential atrophy across the entire cerebral cortex in acute NMDARE patients, and MRI machine learning model has a potential to facilitate the diagnosis MRI-negative NMDARE.

Passively Q-switched 2.3†µm Tm:YVO4 laser using a Cr:ZnS saturable absorber.

A diode-pumped wavelength switchable passively Q-switched 2.3 µm Tm:YVO4 laser was demonstrated in this work. A Cr:ZnS saturable absorber was introduced into the cavity for initiating passive Q-switching. With the increase of the absorbed pump power, the passively Q-switched laser could be switched from the single wavelength of 2366 nm to the dual wavelength of 2290 and 2360 nm. The pulse duration and pulse repetition frequency could be tuned in the ranges of 0.745-1.782 µs and 2.9-43.4 kHz, respectively. The pulse energy and peak power were estimated to be 7.5 µJ and 10 W, respectively, at an absorbed pump power of 12 W.

Endometrial stem cells alleviate cisplatin-induced ferroptosis of granulosa cells by regulating Nrf2 expression.

BACKGROUND: Premature ovarian failure (POF) caused by cisplatin is a severe and intractable sequela for young women with cancer who received chemotherapy. Cisplatin causes the dysfunction of granulosa cells and mainly leads to but is not limited to its apoptosis and autophagy. Ferroptosis has been also reported to participate, while little is known about it. Our previous experiment has demonstrated that endometrial stem cells (EnSCs) can repair cisplatin-injured granulosa cells. However, it is still unclear whether EnSCs can play a repair role by acting on ferroptosis. METHODS: Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were applied to detect the expression levels of ferroptosis-related genes. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EdU) assays were used to evaluate cell viability. Transmission electron microscopy (TEM) was performed to detect ferroptosis in morphology. And the extent of ferroptosis was assessed by ROS, GPx, GSSG and MDA indicators. In vivo, ovarian morphology was presented by HE staining and the protein expression in ovarian tissue was detected by immunohistochemistry. RESULTS: Our results showed that ferroptosis could occur in cisplatin-injured granulosa cells. Ferroptosis inhibitor ferrostatin-1 (Fer-1) and EnSCs partly restored cell viability and mitigated the damage of cisplatin to granulosa cells by inhibiting ferroptosis. Moreover, the repair potential of EnSCs can be markedly blocked by ML385. CONCLUSION: Our study demonstrated that cisplatin could induce ferroptosis in granulosa cells, while EnSCs could inhibit ferroptosis and thus exert repair effects on the cisplatin-induced injury model both in vivo and in vitro. Meanwhile, Nrf2 was validated to participate in this regulatory process and played an essential role.

Mangrovimonas cancribranchiae sp. nov., a novel bacterial species associated with the gills of the fiddler crab Cranuca inversa (Brachyura, Ocypodidae) from Red Sea mangroves.

Two bacteria, UG2_1T and UG2_2, were isolated from the gill tissues of the mangrove fiddler crab Cranuca inversa collected on the east coast of the Red Sea (Thuwal, Saudi Arabia). The cells are Gram-negative, rod-shaped, orange-pigmented, motile by gliding with no flagella, strictly aerobic, and grow at 20-37 °C (optimum, 28-35 °C), at pH 5.0-9.0 (optimum, pH 6.0-7.0), and with 1-11 % (w/v) NaCl (optimum, 2-4 %). They were positive for oxidase and catalase activity. Phylogenetic analysis based on 16S rRNA gene sequences indicated that isolates UG2_1T and UG2_2 belong to the genus Mangrovimonas, showing the highest similarity to Mangrovimonas spongiae HN-E26T (99.4 %). Phylogenomic analysis based on the whole genomes, independently using 49 and 120 concatenated genes, showed that strains UG2_1T and UG2_2 formed a monophyletic lineage in a different cluster from other type strain species within the genus Mangrovimonas. The genome sizes were 3.08 and 3.07 Mbp for UG2_1T and UG2_2, respectively, with a G+C content of 33.8 mol% for both strains. Values of average nucleotide identity and digital DNA-DNA hybridization between the strains and closely related species were 91.0 and 43.5 %, respectively. Chemotaxonomic analysis indicated that both strains had iso-C15 : 0 and iso-C15 : 1 G as dominant fatty acids, and the primary respiratory quinone was identified as MK-6. The major polar lipids comprised phosphatidylethanolamine, one unidentified glycolipid, one unidentified phospholipid, two unidentified aminolipids, and four unidentified lipids. Based on phylogenetic, phylogenomic, genome relatedness, phenotypic, and chemotaxonomical data, the two isolates represent a novel species within the genus Mangrovimonas, with the proposed name Mangrovimonas cancribranchiae sp. nov., and the type strain UG2_1T (=KCTC 102158T=DSM 117025T).

Characterization of the prognostic, diagnostic, and immunological roles of DSCC1 and its genomic alteration and instability in human cancers.

DNA replication and sister chromatid cohesion 1 (DSCC1) exerts various functions including sister chromatid cohesion. DSCC1 overexpression plays an important role in cancer development, such as in colorectal, breast, and hepatocellular cancers. The specific role of DSCC1 in tumor progression remains largely unknown, necessitating a pan-cancer investigation to understand the potential function of DSCC1 in various cancers. In this study, we obtained data on physiological conditions, transcriptional expression, survival prognosis, genomic alteration, genomic instability, enriched pathways, immune infiltration, and immunotherapy from The Cancer Genome Atlas, The Genotype-Tissue Expression, cBioPortal, and other publicly available databases to systematically characterize the oncogenic and immunological roles of DSCC1 in 33 different cancers. We found that DSCC1 expression was upregulated at both mRNA and protein levels in various cancers. Additionally, DSCC1 expression was associated with higher tumor stage and grade in specific cancers. DSCC1 was a potential pan-cancer prognostic biomarker for its close association with patient prognosis and a diagnostic biomarker for its high predictive value in distinguishing tumor tissues from normal tissues. DSCC1 was universally amplified across different cancers and tightly associated with genomic instability. Moreover, DSCC1 had a close relationship with tumor immune cell infiltration; thus, it could be used as a potential biomarker for predicting the response and survival of patients with cancer who receive immune checkpoint blockade treatment. To sum up, our study revealed that DSCC1 is a promising target for tumor therapy.

Association of systemic immunity-inflammation index with metabolic syndrome in U.S. adult: a cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a pathological condition characterized by the abnormal clustering of several metabolic components and has become a major public health concern. We aim to investigate the potential link of Systemic immunity-inflammation index (SII) on MetS and its components. METHODS AND RESULT: Weighted multivariable logistic regression was conducted to assess the relationship between SII and MetS and its components. Restricted cubic spline (RCS) model and threshold effect analysis were also performed. A total of 6,999 U.S. adults were enrolled. Multivariate model found that SII were positively associated with MetS (OR = 1.18;95CI%:1.07-1.30) and hypertension (OR = 1.22; 95CI%:1.12-1.34) in a dose-dependent manner. When SII was converted into a categorical variable, the risk of MetS increased by 36% and the risk of hypertension increased by 53% in the highest quantile of SIIs. The RCS model confirmed linear associations between SII and MetS, as well as a non-linear association between SII and certain components of MetS, including hypertension, hyperglycemia, low HDL, and hyperlipidemia. Meanwhile, the relationship between SII and hypertension presents a J-shaped curve with a threshold of 8.27, above which the risk of hypertension increases. Furthermore, in MetS and hypertension, age, sex, body mass index (BMI), and race were not significantly associated with this positive association based on subgroup analyses and interaction tests(p for interaction > 0.05). CONCLUSIONS: The present study indicated that there was a higher SII association with an increased risk of MetS and hypertension in adults. However, further prospective cohort studies are required to establish a causal relationship between SII and MetS, as well as its components.

Mesoscopic Kinetic Approach of Nonequilibrium Effects for Shock Waves.

A shock wave is a flow phenomenon that needs to be considered in the development of high-speed aircraft and engines. The traditional computational fluid dynamics (CFD) method describes it from the perspective of macroscopic variables, such as the Mach number, pressure, density, and temperature. The thickness of the shock wave is close to the level of the molecular free path, and molecular motion has a strong influence on the shock wave. According to the analysis of the Chapman-Enskog approach, the nonequilibrium effect is the source term that causes the fluid system to deviate from the equilibrium state. The nonequilibrium effect can be used to obtain a description of the physical characteristics of shock waves that are different from the macroscopic variables. The basic idea of the nonequilibrium effect approach is to obtain the nonequilibrium moment of the molecular velocity distribution function by solving the Boltzmann-Bhatnagar-Gross-Krook (Boltzmann BGK) equations or multiple relaxation times Boltzmann (MRT-Boltzmann) equations and to explore the nonequilibrium effect near the shock wave from the molecular motion level. This article introduces the theory and understanding of the nonequilibrium effect approach and reviews the research progress of nonequilibrium behavior in shock-related flow phenomena. The role of nonequilibrium moments played on the macroscopic governing equations of fluids is discussed, the physical meaning of nonequilibrium moments is given from the perspective of molecular motion, and the relationship between nonequilibrium moments and equilibrium moments is analyzed. Studies on the nonequilibrium effects of shock problems, such as the Riemann problem, shock reflection, shock wave/boundary layer interaction, and detonation wave, are introduced. It reveals the nonequilibrium behavior of the shock wave from the mesoscopic level, which is different from the traditional macro perspective and shows the application potential of the mesoscopic kinetic approach of the nonequilibrium effect in the shock problem.

A novel toolbox for precise regulation of gene expression and metabolic engineering in Bacillus licheniformis.

Despite industrial bio-manufacturing progress using Bacillus licheniformis, the absence of a well-characterized toolbox allowing precise regulation of multiple genes limits its expansion for basic research and application. Here, a novel gene expression toolbox (GET) was developed for precise regulation of gene expression and high-level production of 2-phenylethanol. Firstly, we established a novel promoter core region mosaic combination model to combine, characterize and analyze different core regions. Characterization and orthogonal design of promoter ribbons allowed convenient construction of an adaptable and robust GET, gene gfp expression intensity was 0.64%-16755.77%, with a dynamic range of 2.61 × 104 times, which is the largest regulatory range of GET in Bacillus based on modification of promoter P43. Then we verified the protein and species universality of GET using different proteins expressed in B. licheniformis and Bacillus subtilis. Finally, the GET for 2-phenylethanol metabolic breeding, resulting in a plasmid-free strain producing 6.95 g/L 2-phenylethanol with a yield and productivity of 0.15 g/g glucose and 0.14 g/L/h, respectively, the highest de novo synthesis yield of 2-phenylethanol reported. Taken together, this is the first report elucidating the impact of mosaic combination and tandem of multiple core regions to initiate transcription and improve the output of proteins and metabolites, which provides strong support for gene regulation and diversified product production in Bacillus.

FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway.

Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2.

FTO protects human granulosa cells from chemotherapy-induced cytotoxicity.

BACKGROUND: Premature ovarian failure (POF) is a serious problem for young women who receive chemotherapy, and its pathophysiological basis is the dysfunction of granulosa cells. According to previous reports, menstrual-derived stem cells (MenSCs) can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Fat mass- and obesity-associated (FTO) was reported to be associated with oocyte development and maturation. FTO was decreased in POF and may be a biomarker for the occurrence of POF. Knockdown of FTO in granulosa cells promoted cell apoptosis and inhibited proliferation. But the relationship between FTO and ovarian repair was still unclear. This study was aimed at investigating the FTO expression level and the role of FTO in the MenSCs recovering the function of injured granulosa cells. METHOD: First, cisplatin was used to establish a granulosa cell injury model. Then, the MenSCs and injured granulosa cell coculture model and POF mouse model were established in this study to explore the role of FTO. Furthermore, gain- and loss-of-function studies, small interfering RNA transfection, and meclofenamic acid (MA), a highly selective inhibitor of FTO, studies were also conducted to clarify the regulatory mechanism of FTO in granulosa cells. RESULTS: MenSCs coculture could improve the function of injured granulosa cells by increasing the expression of FTO. MenSCs transplantation restored the expression of FTO in the ovaries of POF mice. Overexpression of FTO restored the injured cell proliferation and decreased apoptosis by regulating the expression of BNIP3. Down-regulation of FTO got the opposite results. CONCLUSIONS: In the treatment of MenSCs, FTO has a protective effect, which could improve the viability of granulosa cells after cisplatin treatment by decreasing the expression of BNIP3. Meanwhile, FTO may provide new insight into therapeutic targets for the chemotherapy-induced POF.

Polymorphic distribution and forensic effectiveness study of eight miniSTR in Chinese Uyghur ethnic group.

We obtained the allelic frequencies and forensic efficiency data for eight mini short tandem repeat loci including Penta E, D12S391, D6S1043, D2S1338, D19S433, CSF1PO, Penta D and D19S253 loci from a sample of 128 unrelated Uyghur individuals from China. The amplification products of the eight STR loci are <240 bp in size. A total of 94 alleles were observed and the corresponding allelic frequencies ranged from 0.0039 to 0.3438 in the present study. Observed genotype distributions for each locus do not show deviations from Hardy-Weinberg equilibrium expectations. The combined power of discrimination, combined power of exclusion and combined matching probability of the eight STR loci equaled to 0.999999999963373, 0.9997770 and 3.6627 × 10(-11), respectively. Because of the small fragment length of PCR products and the high degree of polymorphisms, the eight STR loci are highly beneficial for the forensic analysis of degraded DNA samples which are commonly observed in forensic cases. The STR data of the Uyghur group were compared with the previously published population STR data of other groups from different ethnic or areas, and significant differences were observed among these groups at some loci.

FTO attenuates the cytotoxicity of cisplatin in KGN granulosa cell-like tumour cells by regulating the Hippo/YAP1 signalling pathway.

Premature ovarian failure (POF) is a devastating condition for women under 40 years old. Chemotherapy, especially the use of cisplatin, has been demonstrated to promote the apoptosis of granulosa cells in primary and secondary follicles, leading to POF. Our previous studies demonstrated that fat mass- and obesity-associated (FTO) plays an essential role in protecting granulosa cells from cisplatin-induced cytotoxicity. Various studies have suggested that the Hippo/YAP signalling pathway plays a significant role in regulating cell apoptosis and proliferation. Additionally, YAP1 is the main downstream target of the Hippo signalling pathway and is negatively regulated by the Hippo signalling pathway. However, whether the Hippo/YAP signalling pathway is involved in the protective effect of FTO on granulosa cells has not been determined. In this study, we found that after cisplatin treatment, the apoptosis of granulosa cells increased in a concentration-dependent manner, accompanied by the downregulation of FTO and YAP1. Furthermore, overexpression of FTO decreased cisplatin-induced granulosa cell apoptosis, inhibited the Hippo/YAP kinase cascade-induced phosphorylation of YAP1, and promoted the entry of YAP1 into the nucleus. The downstream targets of YAP1 (CTGF, CYR61, and ANKRD1) were also increased. Si-RNA-mediated downregulation of FTO promoted cisplatin-induced granulosa cell apoptosis, activated the Hippo/YAP kinase cascade, and inhibited the YAP1 entry into the nucleus. These effects were completely reversed by the small molecule inhibitor of YAP1-verteporfin (VP). Taken together, these data suggested that FTO-YAP1 plays a positive role in regulating the proliferation of injured granulosa cells induced by cisplatin.

Microfluidic-based multifunctional microspheres for enhanced oral co-delivery of probiotics and postbiotics.

Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics (Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects. In vivo studies shown that the integrated multifunctional microspheres can significantly reduce intestinal inflammation, repair intestinal barrier function, enhance probiotic colonization in the intestine, and modulate disordered intestinal flora, demonstrating enhanced therapeutic effects in a mouse model of colitis. This work reveals that microfluidic-based smart droplet microspheres can provide a versatile platform for advanced microbial therapies.

Field-Free Spin-Orbit Torque Magnetization Switching in a Perpendicularly Magnetized Semiconductor (Ga,Mn)As Single Layer.

Current-induced spin-orbit torque (SOT) in a perpendicularly magnetized single layer has a strong potential to switch the magnetization using an extremely low current density, which is generally 2-3 orders of magnitude smaller than that required for conventional metal bilayer systems. However, an in-plane external magnetic field has to be applied to break the symmetry and achieve deterministic switching. To further enhance the high-density integration and accelerate the practical application of highly efficient SOT magnetic random-access memory (SOT-MRAM) devices, field-free SOT magnetization switching in a ferromagnetic single layer is strongly needed. In a spin-orbit ferromagnet (a ferromagnet with strong spin-orbit interaction) with crystal inversion asymmetry and a multi-domain structure, the internal Dzyaloshinskii-Moriya effective fields are considered to induce field-free switching. Here, combined with strong spin-orbit coupling and a tilted anisotropy axis induced by a nonuniform Mn distribution and a possible magnetocrystalline anisotropy resulting from a slight substrate tilting, we successfully achieve magnetization switching in a spin-orbit ferromagnet (Ga,Mn)As single layer by utilizing SOT without applying any external magnetic field. Our findings help to deeply elucidate the SOT switching mechanism and can advance the development of a highly efficient MRAM with better scalability.

Bioinspired Confined Assembly of Cellulosic Cholesteric Liquid Crystal Bubbles.

Construction of biomimetic models for structural color evolution not only gives new photonic phenomena but also provide cues for biological morphogenesis. Here, a novel confined self-assembly method is proposed for the generation of hydroxypropyl cellulose (HPC)-based cholesteric liquid crystals (CLCs) microbubbles. The assembly process relies on the combination of droplet microfluidics, solvent extraction, and a volume confined environment. The as-prepared HPC structural color microbubbles have a transparent shell, an orderly arranged cholesteric liquid crystal (CLC) middle layer, and an innermost bubble core. The size of the microbubble, shell thickness, and the color of the CLC layer can be adjusted by altering the microfluidic parameters. Intriguingly, benefited from the compartmentalization effect provided by droplet microfluidics, microbubbles with multiple cores of different color combinations are generated under precise control. The self-assembled CLCs microbubbles have bright structural color, suspending ability, and good temperature-sensitive characteristics, making them ideal underwater sensors. The present confined assembly approach will shed light on creating novel photonic structures and the HPC microbubble will find widespread applications in multifunctional sensing, optical display, and other related fields are believed.

Glucose Responsive Coacervate Protocells from Microfluidics for Diabetic Wound Healing.

The hyperglycemic pathophysiological environment in diabetic wounds is a major obstacle that impedes the healing process. Glucose-responsive wound healing materials are a promising approach to address this challenge. In this study, complex coacervate-based protocells are introduced for diabetic wound healing. By employing a microfluidic chip with an external mechanical vibrator, uniform coacervate microdroplets are generated via electrostatic interactions between diethylaminoethyl-dextran and double-stranded DNA. The spontaneous assembly of a phospholipid membrane on the droplet surface enhances its biocompatibility. Glucose oxidase and copper peroxide nanodots are integrated into microdroplets, enabling a glucose-responsive cascade that produces hydroxyl radicals as antibacterial agents. These features contribute to efficient antibacterial activity and wound healing in diabetic mice. The present protocells facilitate intelligent wound management, and the design of cascade catalytic coacervates can contribute to the development of various smart vehicles for drug delivery.

Antibiotic resistance gene distribution in Shine Muscat grapes and health risk assessment of streptomycin residues in mice.

Antibiotic residues and antibiotic resistance genes (ARGs) in fruits and vegetables pose public health risks via the food chain, attracting increased attention. Antibiotics such as streptomycin, used directly on seedless grapes or introduced into vineyard soil through organic fertilizers. However, extensive data supporting the risk assessment of antibiotic residues and resistance in these produce remains lacking. Utilizing metagenomic sequencing, we characterized Shine Muscat grape antibiotic resistome and mobile genetic elements (MGEs). Abundant MGEs and ARGs were found in grapes, with 174 ARGs on the grape surface and 32 in the fruit. Furthermore, our data indicated that soil is not the primary source of these MGEs and ARGs. Escherichia was identified as an essential carrier and potential transmitter of ARGs. In our previous study, streptomycin residue was identified in grapes. Further short-term exposure experiments in mice revealed no severe physiological or histological damage at several environment-related concentrations. However, with increased exposure, some ARGs levels in mouse gut microbes increased, indicating a potential threat to animal health. Overall, this study provides comprehensive insights into the resistance genome and potential hosts in grapes, supporting the risk assessment of antibiotic resistance in fruits and vegetables.

FGF2 promotes the proliferation of injured granulosa cells in premature ovarian failure via Hippo-YAP signaling pathway.

Young women undergoing anticancer treatment are at risk of premature ovarian failure (POF). Endometrial-derived stem cells (EnSCs) have demonstrated significant therapeutic potential for treating ovarian insufficiency, although the underlying mechanisms remain to be fully understood. This study aims to further investigate the therapeutic effects of EnSCs, particularly through the paracrine action of fibroblast growth factor 2 (FGF2), on POF. The findings show that exogenous FGF2 enhances the survival of ovarian granulosa cells damaged by cisplatin. FGF2 stimulates the proliferation of these damaged cells by suppressing the Hippo signaling pathway and activating YAP expression. In vivo experiments also revealed that FGF2 treatment significantly improves ovarian reserve and endocrine function in mice with POF. These results suggest that FGF2 can boost the proliferative capacity of damaged ovarian granulosa cells through the Hippo-YAP signaling pathway, providing a theoretical foundation for using EnSCs and FGF2 in clinical treatments for POF.

Predictors of successful salvage microdissection testicular sperm extraction (mTESE) after failed initial TESE in patients with non-obstructive azoospermia: A systematic review and meta-analysis.

BACKGROUND: There has been no systematic review and meta-analysis to analyze and summarize the predictive factors of successful sperm extraction in salvage microdissection testicular sperm extraction. OBJECTIVES: We aimed to investigate the factors predicting the result of salvage microdissection testicular sperm extraction in patients with non-obstructive azoospermia who failed the initial microdissection testicular sperm extraction or conventional testicular sperm extraction. MATERIALS AND METHODS: We conducted a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library for literature that described the characteristics of patients with non-obstructive azoospermia who underwent salvage microdissection testicular sperm extraction after failing the initial microdissection testicular sperm extraction or conventional testicular sperm extraction published prior to June 2022. RESULTS: This meta-analysis included four retrospective studies with 332 patients with non-obstructive azoospermia who underwent a failed initial microdissection testicular sperm extraction and three retrospective studies with 177 non-obstructive azoospermia patients who underwent a failed conventional testicular sperm extraction. The results were as follows: among non-obstructive azoospermia patients whose first surgery was microdissection testicular sperm extraction, younger patients (standard mean difference: -0.28, 95% confidence interval [CI]: -0.55 to -0.01) and those with smaller bilateral testicular volume (standard mean difference: -0.55, 95% CI: -0.95 to -0.15), lower levels of follicle-stimulating hormone (standard mean difference: -0.86, 95% CI: -1.18 to -0.54) and luteinizing hormone (standard mean difference: -0.68, 95% CI: -1.16 to -0.19), and whose testicular histological type was hypospermatogenesis (odds ratio: 3.52, 95% CI: 1.30-9.53) were more likely to retrieve spermatozoa successfully, while patients with Sertoli-cell-only syndrome (odds ratio: 0.41, 95% CI: 0.24-0.73) were more likely to fail again in salvage microdissection testicular sperm extraction. Additionally, in patients who underwent salvage microdissection testicular sperm extraction after a failed initial conventional testicular sperm extraction, those with testicular histological type of hypospermatogenesis (odds ratio: 30.35, 95% CI: 8.27-111.34) were more likely to be successful, while those with maturation arrest (odds ratio: 0.39, 95% CI: 0.18-0.83) rarely benefited. CONCLUSION: We found that age, testicular volume, follicle-stimulating hormone, luteinizing hormone, hypospermatogenesis, Sertoli-cell-only syndrome, and maturation arrest were valuable predictors of salvage microdissection testicular sperm extraction, which will assist andrologists in clinical decision-making and minimize unnecessary injury to patients.

Endometrial stem cell-derived exosomes repair cisplatin-induced premature ovarian failure via Hippo signaling pathway.

Stem cells have been documented as a new therapeutic method for ovarian injuries such as premature ovarian failure (POF). However, effects of exosomes (Exos) derived from human endometrial stem cells (EnSCs) on diminished ovarian failure remain to be carefully elucidated. Our study aims to investigate the mechanisms of EnSC-Exos in the recovery of the cisplatin-induced granulosa cell injury model in vitro or POF mouses model in vivo and whether the Hippo signaling pathway is involved in the regulation. In this study, we established successful construction of the cisplatin-induced granulosa cell injury model and evaluated Hippo signaling pathway activation in cisplatin-damaged granulosa cells (GCs). Furthermore, laser scanning confocal microscope and immunofluorescence demonstrated that EnSC-Exos can be transferred to cisplatin-damaged GCs to decrease apoptosis. In addition, the enhanced expression of YAP at the protein level as well as YAP/TEAD target genes, such as CTGF, ANKRD1, and the increase of YAP into the nucleus in immunofluorescence staining after the addition of EnSC-Exos to cisplatin-damaged GCs confirmed the suppression of Hippo signaling pathway. While in vivo, EnSC-Exos successfully remedied POF in a mouse model. Collectively, our findings suggest that chemotherapy-induced POF was associated with the activating of Hippo signaling pathway. Human EnSC-Exos significantly elevated the proliferation of ovarian GCs and the ovarian function by regulating Hippo signaling pathway. These findings provide new insights for further understanding of EnSC-Exos in the recovery of ovary function.