Sphingolipids in prostate cancer prognosis: integrating single-cell and bulk sequencing.

BACKGROUND: Stratifying patient risk and exploring the tumor microenvironment are critical endeavors in prostate cancer research, essential for advancing our understanding and management of this disease. METHODS: Single-cell sequencing data for prostate cancer were sourced from the pradcellatlas website, while bulk transcriptome data were obtained from the TCGA database. Dimensionality reduction cluster analysis was employed to investigate heterogeneity in single-cell sequencing data. Gene set enrichment analysis, utilizing GO and KEGG pathways, was conducted to explore functional aspects. Weighted gene coexpression network analysis (WGCNA) identified key gene modules. Prognostic models were developed using Cox regression and LASSO regression techniques, implemented in R software. Validation of key gene expression levels was performed via PCR assays. RESULTS: Through integrative analysis of single-cell and bulk transcriptome data, key genes implicated in prostate cancer pathogenesis were identified. A prognostic model focused on sphingolipid metabolism (SRSR) was constructed, comprising five genes: "FUS," "MARK3," "CHTOP," "ILF3," and "ARIH2." This model effectively stratified patients into high-risk and low-risk groups, with the high-risk cohort exhibiting significantly poorer prognoses. Furthermore, distinct differences in the immune microenvironment were observed between these groups. Validation of key gene expression, exemplified by ILF3, was confirmed through PCR analysis. CONCLUSION: This study contributes to our understanding of the role of sphingolipid metabolism in prostate cancer diagnosis and treatment. The identified prognostic model holds promise for improving risk stratification and patient outcomes in clinical settings.

Novel Providencia xianensis sp. nov.: A multidrug-resistant species identified in clinical infections.

Providencia genus is known to harbor certain opportunistic pathogens capable of causing human infections. Here, we report two strains of multidrug-resistant bacteria initially identified as Providencia rettgeri by mass spectrometry, but genome analysis revealed their ANI (79.84-84.20%) and dDDH (21.1-25.6%) values to fall below the accepted species threshold for known Providencia species. We therefore propose that these isolates be recognized as a novel species, Providencia xianensis sp. nov. Alarmingly, both strains, isolated from locations far apart, exhibited resistance to last-resort antibiotics, indicating their possible wide distribution, underscoring the urgency for immediate attention and enhanced surveillance for this emerging multidrug-resistant pathogen.

Interfacial Super-Assembly of Vacancy Engineered Ultrathin-Nanosheets toward Nanochannels for Smart Ion Transport and Salinity Gradient Power Conversion.

Ion-selective nanochannel membranes assembled from two-dimensional (2D) nanosheets hold immense promise for power conversion using salinity gradient. However, they face challenges stemming from insufficient surface charge density, which impairs both permselectivity and durability. Herein, we present a novel vacancy-engineered, oxygen-deficient NiCo layered double hydroxide (NiCoLDH)/cellulose nanofibers-wrapped carbon nanotubes (VOLDH/CNF-CNT) composite membrane. This membrane, featuring abundant angstrom-scale, cation-selective nanochannels, is designed and fabricated through a synergistic combination of vacancy engineering and interfacial super-assembly. The membrane shows interlayer free-spacing of ~3.62 Å, which validates the membrane size exclusion selectivity.This strategy, validated by DFT calculations and experimental data, improves hydrophilicity and surface charge density, leading to the strong interaction with K+ ions to benefit the low ion transport resistance and exceptional charge selectivity. When employed in an artificial river water|seawater salinity gradient power generator, it delivers a high-power density of 5.35 W/m2 with long-term durability (20,000s), which is almost 400% higher than that of the pristine NiCoLDH membrane. Furthermore, it displays both pH- and temperature-sensitive ion transport behavior, offering additional opportunities for optimization. This work establishes a basis for high-performance salinity gradient power conversion and underscores the potential of vacancy engineering and super-assembly in customizing 2D nanomaterials for diverse advanced nanofluidic energy devices.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Astaxanthin prevents bone loss in osteoporotic rats with palmitic acid through suppressing oxidative stress.

OBJECTIVES: The study aimed to assess the role of Astaxanthin (ATX) in palmitic acid(PA) -induced bone loss in Ovariectomized(OVX) rats. METHODS: In the OVX rat model, we observed that PA affects bone metabolism and accelerates bone loss. Additionally, treatment with ATX was able to suppress the deleterious effects of PA and a simultaneous decrease in serum MDA levels and an increase in SOD was observed. RESULTS: In addition, rats treated with ATX were observed to have significantly increased bone mass and elevated activity of SIRT1 and SOD2 in bone tissue. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclast differentiation, the ATX intervention was able to significantly restore the restriction of osteogenic differentiation and the up-regulation of osteoclast differentiation with PA therapy. Furthermore, we confirm that PA damage to cells is caused by increased oxidative stress, and that ATX can target and modulate the activity of SIRT1 to regulate the levels of oxidative stress in cells. CONCLUSION: Summarizing, ATX may inhibit PA-induced bone loss through its antioxidant properties via the SIRT1 signaling pathway.

Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

Beyond nothingness in the formation and functional relevance of voids in polymer films.

Voids-the nothingness-broadly exist within nanomaterials and impact properties ranging from catalysis to mechanical response. However, understanding nanovoids is challenging due to lack of imaging methods with the needed penetration depth and spatial resolution. Here, we integrate electron tomography, morphometry, graph theory and coarse-grained molecular dynamics simulation to study the formation of interconnected nanovoids in polymer films and their impacts on permeance and nanomechanical behaviour. Using polyamide membranes for molecular separation as a representative system, three-dimensional electron tomography at nanometre resolution reveals nanovoid formation from coalescence of oligomers, supported by coarse-grained molecular dynamics simulations. Void analysis provides otherwise inaccessible inputs for accurate fittings of methanol permeance for polyamide membranes. Three-dimensional structural graphs accounting for the tortuous nanovoids within, measure higher apparent moduli with polyamide membranes of higher graph rigidity. Our study elucidates the significance of nanovoids beyond the nothingness, impacting the synthesis‒morphology‒function relationships of complex nanomaterials.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Mechanochemically Enabled Metastable Niobium Tungsten Oxides.

Metastable compounds have greatly expanded the synthesizable compositions of solid-state materials and have attracted enormous amounts of attention in recent years. Especially, mechanochemically enabled metastable materials synthesis has been very successful in realizing cation-disordered materials with highly simple crystal structures, such as rock salts. Application of the same strategy for other structural types, especially for non-close-packed structures, is peculiarly underexplored. Niobium tungsten oxides (NbWOs), a class of materials that have been under the spotlight because of their diverse structural varieties and promising electrochemical and thermoelectric properties, are ideally suited to fill such a knowledge gap. In this work, we develop a new series of metastable NbWOs and realize one with a fully cation-disordered structure. Furthermore, we find that metastable NbWOs transform to a cation-disordered cubic structure when applied as a Li-ion battery anode, highlighting an intriguing non-close-packed-close-packed conversion process, as evidenced in various physicochemical characterizations, in terms of diffraction, electronic, and vibrational structures. Finally, by comparing the cation-disordered NbWO with other trending cation-disordered oxides, we raise a few key structural features for cation disorder and suggest a few possible research opportunities for this field.

DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice.

The tumor suppressor p53 is the most common mutated gene in cancer, with the R175H as the most frequent p53 missense mutant. However, there are currently no approved targeted therapies or immunotherapies against mutant p53. Here, we characterized and investigated a monoclonal antibody (mAb) that recognizes the mutant p53-R175H for its affinity, specificity, and activity against tumor cells in vitro. We then delivered DNA plasmids expressing the anti-R175H mAb or a bispecific antibody (BsAb) into mice to evaluate their therapeutic effects. Our results showed that the anti-R175H mAb specifically bound to the p53-R175H antigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells, with no cross-reactivity with wild-type p53. In cultured cells, the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular cytotoxicity. We made a recombinant MC38 mouse cell line (MC38-p53-R175H) that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 alleles. In vivo, administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in mice. The administration of the anti-R175H BsAb plasmid showed no therapeutic effects, yet potent anti-tumor activity was observed in combination with the anti-PD-1 antibody. These results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

Favorable osteogenic activity of vericiguat doped in ß-tricalcium phosphate: In vitro and in vivo studies.

Recently, more and more studies have shown that guanylate cyclase, an enzyme that synthesizes cyclic guanosine monophosphate (cGMP), plays an important role in bone metabolism. Vericiguat (VIT), a novel oral soluble guanylate cyclase stimulator, directly generates cyclic guanosine monophosphate and reduce the death incidence from cardio-vascular causes or hospitalization. Recent studies have shown beneficial effects of VIT in animal models of osteoporosis, but very little is currently known about the effects of VIT on bone defects in the osteoporotic states. Therefore, in this study, ß-tricalcium phosphate (ß-TCP) was used as a carrier to explore the effect of local VIT administration on the repair of femoral metaphyseal bone defects in ovariectomized (OVX) rats. When MC3T3-E1 was cultured in the presence of H2H2, VIT, similar to Melatonin (MT), therapy could increase the matrix mineralization and ALP, SOD2, SIRT1, and OPG expression, reduce ROS and Mito SOX production, RANKL expression, Promote the recovery of mitochondrial membrane potential. In the OVX rat model, VIT increases the osteogenic effect of ß-TCP and better results were obtained at a dose of 5 mg. Local use of VIT can inhibit increased OC, BMP2 and RUNX2 expressions in bone tissue, while decreased SOST and TRAP expressions by RT-PCR and immunohistochemistry. Thereby, VIT stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Mendelian randomization study on causal association of FAM210B with drug-induced lupus.

OBJECTIVE: Due to the complexity of drug-induced lupus (DIL) pathogenesis, more susceptibility factors need to be discovered. FAM210B is a new mitochondrial protein whose function has not been fully elucidated. This study will explore whether there is a correlation between FAM210B and the risk of DIL. METHODS: At first, we extracted three FAM210B genetic variants from the GTEx database (n = 948), and extracted their corresponding genome-wide association study (GWAS) summary statistics from DIL (101 DIL cases and 218691 controls). Then, we performed a Mendelian randomization (MR) study to evaluate the causal association of the expression of FAM210B with DIL using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test. RESULTS: We successfully extracted three FAM210B single-nucleotide polymorphisms (SNPs) (rs116032784, rs34361943 and rs33923703) from the GTEx_Analysis_v8_eQTL data that can reduce FAM210B expression. The results of the MR analysis showed that genetically reduced expression of FAM210B was significantly associated with increased risk of DIL in European ancestry based on the IVW method (ß = 1.037, p = 0.001, odds ratio [OR] = 2.821, 95% confidence interval [CI]:1.495-5.322). CONCLUSION: MR analysis showed a causal relationship between FAM210B expression and the risk of DIL disease. Our results suggested that FAM210B may be a marker that can mark susceptibility of DIL in the future. It provides evidence for the study of DIL, but its specific mechanism of action in DIL needs to be further studied. Key Points •This is the first MR analysis to examine the association between FAM210B and DIL. •The findings of this study suggested that reduced FAM210B expression is associated with the increased risk of DIL. •FAM210B may be a marker that can mark susceptibility of DIL in the future.

A thermoregulation model based on the physical and physiological characteristics of Chinese elderly.

Given the increasing aging population and rising living standards in China, developing an accurate and straightforward thermoregulation model for the elderly has become increasingly essential. To address this need, an existing one-segment four-node thermoregulation model for the young was selected as the base model. This study developed the base model considering age-related physical and physiological changes to predict mean skin temperatures of the elderly. Measured data for model optimization were collected from 24 representative healthy Chinese elderly individuals (average age: 67 years). The subjects underwent temperature step changes between neutral and warm conditions with a temperature range of 25-34 °C. The model's demographic representation was first validated by comparing the subjects' physical characteristics with Chinese census data. Secondly, sensitivity analysis was performed to investigate the influences of passive system parameters on skin and core temperatures, and adjustments were implemented using measurement or literature data specific to the Chinese elderly. Thirdly, the active system was modified by resetting the body temperature set points. The active parameters to control thermoregulation activities were further optimized using the TPE (Tree-structured Parzen Estimator) hyperparameter tuning method. The model's accuracy was further verified using independent experimental data for a temperature range of 18-34 °C for Chinese elderly. By comprehensively considering age-induced thermal response changes, the proposed model has potential applications in designing and optimizing thermal management systems in buildings, as well as informing energy-efficient strategies tailored to the specific needs of the Chinese elderly population.

Cyclosporine a inhibits bone regeneration and induces bone loss in a rat model.

Cyclosporine A (CSA) is an immunosuppressant that has been extensively studied for its side effects on inhibiting osseointegration of titanium implants. However, the impact of CSA on bone healing in postmenopausal osteoporosis remains unknown. Therefore, this study aimed to investigate the effect of CSA on bone repair in an ovariectomized (OVX) rat model through both in vitro and in vivo experiments. We examined the interventions of CSA on osteoblast progenitor cells MC3T3-E1 and assessed their effects on biological function using RT-qPCR, CCK-8 assay, alizarin red staining, and alkaline phosphatase staining. Furthermore, we evaluated the effects of CSA on bone regeneration and bone mass in both OVX rat models and femoral diaphysis bone defect models. The results from the CCK-8 experiment indicated a positive influence of experimental doses of CSA on osteogenic differentiation of MC3T3-E1 cells. ALP expression levels and calcified nodules were also evaluated, suggesting that CSA intervention promoted osteogenic differentiation in MC3T3-E1 cells. Additionally, specific gene expressions including OPN, Runx-2, OC, and Col1a1 were up-regulated after CSA intervention. Biomechanical parameters aligned with histological analysis as well as micro-CT scans confirmed worse bone microstructure and strength following CSA intervention. Our findings preliminarily suggest that whether it is normal or osteoporotic bones, CSA has adverse effects on bone health which are associated with elevated-bone turnover.

MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.

Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/ß-catenin signaling. ß-catenin knockout blocked 2-AG/CB2-induced fatty acid ß-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.

Plasma-derived from human umbilical cord blood restores ovarian function and improves serum reproductive hormones levels in mice with premature ovarian insufficiency (POI) through cytokines and growth factors.

Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-ß (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-ß1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.

Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

Comparative evaluation of double- and single-armed two-suture longitudinal intussusception techniques in microsurgical vasoepididymostomy: An updated systematic review and meta-analysis.

BACKGROUND: This study aimed to compare the outcomes of double-armed two-suture longitudinal intussusception microsurgical vasoepididymostomy (LIVE) and single-armed two-suture LIVE techniques in patients with epididymal obstructive azoospermia (EOA). The main outcomes assessed were patency rates, patency time, semen quality and natural pregnancy rates. METHODS: Data from patients with EOA who underwent two-suture LIVE were obtained from databases including PubMed, EMBASE, and Web of Science. Weighted data were analyzed using a random-effects model, and weighted mean differences were reported. RESULTS: A total of 1574 patients with EOA from 24 studies were included. The overall patency rate was approximately 68% (95% confidence interval [CI]: 63-72%), with a patency time of approximately 4.63 months (95% CI: 4.15-5.12). The sperm concentration reached 26.90 million/ml and the sperm motility was 23.74%. The natural pregnancy rate was 38% (95% CI: 31-46%). The different definitions of patency do not seem to have any meaningful impact when comparing patency rates. There was no significant difference in patency rates, patency time, semen quality and natural pregnancy rates between the double-armed and single-armed LIVE techniques. CONCLUSION: The single-armed LIVE is a potential alternative surgical option when high quality double-needle sutures are not easily accessible.

Superassembled MXene-carboxymethyl chitosan nanochannels for the highly sensitive recognition and detection of copper ions.

Copper ions (Cu2+), as a crucial trace element, play a vital role in living organisms. Thus, the detection of Cu2+ is of great significance for disease prevention and diagnosis. Nanochannel devices with an excellent nanoconfinement effect show great potential in recognizing and detecting Cu2+ ions. However, these devices often require complicated modification and treatment, which not only damages the membrane structure, but also induces nonspecific, low-sensitivity and non-repeatable detection. Herein, a 2D MXene-carboxymethyl chitosan (MXene/CMC) freestanding membrane with ordered lamellar channels was developed by a super-assembly strategy. The introduction of CMC provides abundant space charges, improving the nanoconfinement effect of the nanochannel. Importantly, the CMC can chelate with Cu2+ ions, endowing the MXene/CMC with the ability to detect Cu2+. The formation of CMC-Cu2+ complexes decreases the space charges, leading to a discernible variation in the current signal. Therefore, MXene/CMC can achieve highly sensitive and stable Cu2+ detection based on the characteristics of nanochannel composition. The linear response range for Cu2+ detection is 10-9 to 10-5 M with a low detection limit of 0.095 nM. Notably, MXene/CMC was successfully applied for Cu2+ detection in real water and fetal bovine serum samples. This work provides a simple, highly sensitive and stable detection platform based on the properties of the nanochannel composition.