[Bioinformatic analysis of immune-related transcription factors in diabetic kidney disease].

Objective To identify immune-related transcription factors (TFs) in renal glomeruli and tubules from diabetic kidney disease (DKD) patients by bioinformatics analysis. Methods Gene expression datasets from GEO (GSE30528, GSE30529) and RNA sequencing (RNA-seq) data from the Karolinska Kidney Research Center were used. Gene set enrichment analysis (GSEA) was conducted to examine differences in immune-related gene expression in the glomeruli and tubules (DKD) patients. To identify immune-related genes (IRGs) and TFs, differential expression analysis was carried out using the Limma and DESeq2 software packages. Key immune-related TFs were pinpointed through co-expression analysis. The interaction network between TFs and IRGs was constructed using the STRING database and Cytoscape software. Furthermore, the Nephroseq database was employed to investigate the correlation between the identified TFs and clinical-pathological features. Results When compared to normal control tissues, significant differences in the expression of immune genes were observed in both the glomeruli and tubules of individuals with Diabetic Kidney Disease (DKD). Through differential and co-expression analysis, 50 immune genes and 9 immune-related transcription factors (TFs) were identified in the glomeruli. In contrast, 131 immune response genes (IRGs) and 41 immune-related TFs were discovered in the renal tubules. The protein-protein interaction (PPI) network highlighted four key immune-related TFs for the glomeruli: Interferon regulatory factor 8 (IRF8), lactotransferrin (LTF), CCAAT/enhancer binding protein alpha (CEBPA), and Runt-related transcription factor 3 (RUNX3). For the renal tubules, the key immune-related TFs were FBJ murine osteosarcoma viral oncogene homolog B (FOSB), nuclear receptor subfamily 4 group A member 1 (NR4A1), IRF8, and signal transducer and activator of transcription 1 (STAT1). These identified TFs demonstrated a significant correlation with the glomerular filtration rate (GFR), highlighting their potential importance in the pathology of DKD. Conclusion Bioinformatics analysis identifies potential genes associated with DKD pathogenesis and immune dysregulation. Further validation of the expression and function of these genes may contribute to immune-based therapeutic research for DKD.

Thermal control of photothermal implants inspired by polar bear skin for the treatment of infected bone defects.

Photothermal therapy (PTT) encounters challenges in addressing deep tissue infections, characterized by limited penetration or potential hyperthermal damage to surrounding tissues, initiating undesirable inflammatory cascades. Inspired by polar bear thermal regulation, we present a "bio-based endogenic thermal-adaptive booster" implant coating. This coating integrates a photothermal poly(tannic acid) (pTA) layer, mimicking the "polar bear dark skin", securely linked with anti-inflammatory dexamethasone (Dex), resembling the "secretion", and a red blood cell membrane (RBCM) layer, forming the insulating "transparent fur". The RBCM "fur" demonstrates unexpectedly superior local heat storage, amplifying the photothermal effect of the pTA "skin" by 1.30 times and boosting localized photothermal antibacterial efficiency by 1.30-fold (approximately 99%) compared to those without RBCM. Furthermore, RBCM sustains Dex release and offers additional protection against thermal inflammation, releasing Dex 1.90 times more under NIR irradiation than under non-photothermal conditions. In a rat infectious bone model, the photothermal-boosting implant coating provides a favorable biological interface and achieves a 99.97% photothermal antibacterial ratio, enhancing osseointegration without evident tissue harm, evidenced by a 2.47-fold increase in bone volume fraction and a 2.24-fold reduction in pro-inflammatory cytokines compared to those lacking a RBCM. Insights derived from cell membrane-based thermal-adaptive coatings herald a paradigm shift in efficient and safe PTT.

Consecutive positive nucleic acid tests in COVID-19 patients: a retrospective cohort study in Fangcang hospitals, Shanghai.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) spread rapidly in Shanghai in February 2022. Patients with asymptomatic and mild symptoms were admitted to Fangcang shelter hospitals for centralized quarantine. METHODOLOGY: A total of 5,217 non-severe patients hospitalized in the Longyao Fangcang and Shilong Fangcang hospitals were included in the study. Demographic and clinical characteristics, comorbidity, exposure history, treatment and disease duration were analyzed. Univariate analysis and binomial logistic regression analysis were performed to identify the factors influencing nucleic acid change from positive to negative over 14 days. RESULTS: Consecutive positive nucleic acid test results (days) were significantly associated with advanced age (OR = 1.343, 95% CI 1.143 to 1.578, p < 0.001), smoking (OR = 0.510, 95% CI 0.327 to 0.796, p = 0.003) and vaccination (OR = 0.728, 95% CI 0.641 to 0.827, p < 0.001). However, there was no significant difference between asymptomatic and mild symptomatic patients (p = 0.187). In univariate analysis, comorbidities including diabetes, hypertension, cardiovascular system, malignant tumors, autoimmune diseases and cerebral apoplexy were associated with consecutive positive nucleic acid test results, but there was no significant difference in binomial logistics regression analysis. CONCLUSIONS: Aging and comorbid conditions lead to the prolongation of positive nucleic acid test results for several days. Improving vaccination coverage is beneficial for prevention and control of the epidemic. The management and treatment methods of Shanghai Fangcang shelter hospitals had important referential significance, which can provide valuable guidance for the prevention and control of the COVID-19 epidemic in the future.

Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

Whole-plant silage maize to improve fiber digestive characteristics and intestinal microbiota of Hezuo pigs.

Introduction: Utilizing roughage resources is an effective approach to alleviate the shortage of corn-soybean feed and reducing the costs in the swine industry. Hezuo pig is one group of plateau type local Tibetan pig with strong tolerance to crude feeding. Nevertheless, current research on the roughage tolerance in Hezuo pigs and the microbiological mechanisms behind it is still minimally.This study explored the impact of various ratios of whole-plant silage (WPS) maize on the pH, cellulase activity, short-chain fatty acids (SCFAs), and intestinal microbiota in Hezuo pigs. Methods: Thirty-two Hezuo pigs were randomly divided into four groups (n = 8). The control group received a basal diet, while experimental groups I, II, and III were given diets with incremental additions of 5%, 10%, and 15% air-dried WPS maize, respectively, for 120 days. Results: The findings revealed that compared with the control group, in Group II, the pH of cecum and colon were notably decreased (p < 0.05), while acid detergent fiberdigestibility, the concentration of propionic and isobutyric acid in the cecum, and the concentration of isobutyric acid in the colon were significantly increased (p < 0.05). Also, carboxymethyl cellulase activity in the cecum in group II of Hezuo pigs was significantly higher than that in the other three groups (p < 0.05). Furthermore, the cecum microbiota showed a higher diversity in the group II of Hezuo pigs than that in the control group, as shown by the Simpson and Shannon indices. Specifically, 15 and 24 bacterial species showed a significant difference in relative abundance at the family and genus levels, respectively. Correlation analyses revealed significant associations between bacterial genera and SCFAs concentrations in the cecum. The abundance of Bacteroides and NK4A214_group was positively correlated with amounts of valeric and isovaleric acid but negatively with propionic acid (p < 0.05). The abundance of UCG-010 was positively linked with acetic acid and negatively correlated with butyric acid (p < 0.05). Actinobacillus abundance was positively associated with butyric acid levels (p < 0.05). Discussion: In conclusion, a 10% WPS maize diet improved crude fiber digestibility by lowering cecal and colonic chyme pH, enhancing intestinal cellulase activity, improving SCFA production, and increasing intestinal microbiota diversity.

Isolation, culture, characterization and the functional study of testicular Leydig cells from Hezuo pig.

Testosterone, an important sex hormone, regulates sexual maturation, testicular development, spermatogenesis and the maintenance of secondary sexual characteristics in males. Testicular Leydig cells are the primary source of testosterone production in the body. Hezuo pigs, native to the southern part of Gansu, China, are characterized by early sexual maturity, strong disease resistance and roughage tolerance. This study employed type IV collagenase digestion combined with cell sieve filtration to isolate and purify Leydig cells from the testicular tissue of 1-month-old Hezuo pigs. We also preliminarily investigated the functions of these cells. The results indicated that the purity of the isolated and purified Leydig cells was as high as 95%. Immunofluorescence analysis demonstrated that the isolated cells specifically expressed the 3ß-hydroxysteroid dehydrogenase antibody. Enzyme-linked immunosorbent assay results showed that the testosterone secretion of the Leydig cells cultured in vitro (generations 5-9) ranged between 1.29-1.67 ng/mL. Additionally, the content of the cellular autophagy signature protein microtubule-associated protein 1 light chain 3 was measured at 230-280 pg/mL. Through this study, we established an in vitro system for the isolation, purification and characterization of testicular Leydig cells from 1-month-old Hezuo pigs, providing a reference for exploring the molecular mechanism behind precocious puberty in Hezuo pigs.

Stress reduction through cortical bone thickening improves bone mechanical behavior in adult female Beclin-1+/- mice.

Fragility fractures, which are more prevalent in women, may be significantly influenced by autophagy due to altered bone turnover. As an essential mediator of autophagy, Beclin-1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation, however, the alteration in the local bone mechanical environment in female Beclin-1+/- mice remains unclear. In this study, our aim is to investigate the biomechanical behavior of femurs from seven-month-old female wild-type (WT) and Beclin-1+/- mice under peak physiological load, using finite element analysis on micro-CT images. Micro-CT imaging analyses revealed femoral cortical thickening in Beclin-1+/- female mice compared to WT. Three-point bending test demonstrated a 63.94% increase in whole-bone strength and a 61.18% increase in stiffness for female Beclin-1+/- murine femurs, indicating improved biomechanical integrity. After conducting finite element analysis, Beclin-1+/- mice exhibited a 26.99% reduction in von Mises stress and a 31.62% reduction in maximum principal strain in the femoral midshaft, as well as a 36.64% decrease of von Mises stress in the distal femurs, compared to WT mice. Subsequently, the strength-safety factor was determined using an empirical formula, revealing that Beclin-1+/- mice exhibited significantly higher minimum safety factors in both the midshaft and distal regions compared to WT mice. In summary, considering the increased response of bone adaptation to mechanical loading in female Beclin-1+/- mice, our findings indicate that increasing cortical bone thickness significantly improves bone biomechanical behavior by effectively reducing stress and strain within the femoral shaft.

Natural Underwater Bioadhesive Offering Cohesion Modulation via Hydrogen Bond Disruptor: A Highly Injectable and in Vivo Stable Remedy for Gastric Ulcer Resolution.

Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application.

Vitamin C-regulated CoAl- layered double hydroxide with oxygen vacancies to efficiently activate peroxydisulfate for sulfamethoxazole removal triggered via reactive oxygen and high-valent cobalt species.

In this study, a vitamin C-regulated CoAl-layered double hydroxide with abundant oxygen vacancies was synthesized via a simple hydrothermal process. The resulting CoAl-layered double hydroxide was employed to activate peroxydisulfate for removal of sulfamethoxazole. The effect of the experimental parameters such as pH, catalyst dose and peroxydisulfate concentration on sulfamethoxazole removal was investigated. The current system exhibited excellent catalytic performance for sulfamethoxazole removal in a broad pH range (i.e., pH 3.0-11.0). Under the optimized condition, 94.2% of sulfamethoxazole was degraded within 15 min, accompanied by a 67.6% reduction in chemical oxygen demand. The effective sulfamethoxazole degradation could be attributed to four pathways. Firstly, the ≡ Co2+ in catalyst reacted with peroxydisulfate to generate reactive species, including SO4•-, •OH, O2•- and 1O2, which could degrade sulfamethoxazole. Secondly, the oxygen vacancies could modulate intrinsic electrons, resulted in the surface activation of catalyst and accelerated charge transfer, which was favorable for the degradation of sulfamethoxazole. Thirdly, the presence of vitamin C not only promoted the formation of oxygen vacancies but also expanded the interlayer spacing of layered double hydroxide. A large interlayer spacing facilitated the diffusion of peroxydisulfate and pollutants in the interlayer and improved the utilization efficiency of the active site. Lastly, the high-valent cobalt species exhibited excellent oxidation ability and enhanced the catalyst performance through continuously being employed as an electron acceptor. This study provided a valuable insight for the design and application of Co-based catalysts in peroxydisulfate-based advanced oxidation processes.

Advances in reparative materials for infectious bone defects and their applications in maxillofacial regions.

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects.

The Prognostic Value of Alpha-Fetoprotein Ratio in Patients With Resectable Alpha-Fetoprotein-Negative Hepatocellular Carcinoma.

PURPOSE: This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. CONCLUSION: The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.

Esketamine pretreatment during cesarean section reduced the incidence of postpartum depression: a randomized controlled trail.

BACKGROUND: Postpartum depression (PPD) is a common mental disease in postpartum women, which has received more and more attention in society. Ketamine has been confirmed for its rapid antidepressant effect in women with PPD. We speculate that esketamine, an enantiomer of ketamine, pretreatment during cesarean can also reduce the incidence of PPD. METHODS: All the parturients enrolled in the study were randomly assigned to two groups: the esktamine group (0.2 mg/kg esketamine) and the control group (a same volume of saline). All the drugs were pumped for 40 min started from the beginning of the surgery. The Amsterdam Anxiety and Information Scale (APAIS) scores before the surgery, the Edinburgh postnatal depression scale (EPDS) scores at 4 d and 42 d after surgery, the Pain Numerical Rating Scale (NRS) scores at 6 h, 12 h, 24 h and 48 h post-operation were evaluated, as well as the adverse reactions were recorded. RESULTS: A total of 319 parturients were analyzed in the study. The incidence of PPD (EPDS score > 9) in the esketamine group was lower than the control group at 4 days after surgery (13.8% vs 23.1%, P = 0.0430) but not 42 days after surgery (P = 0.0987). Esketamine 0.2 mg/kg could reduce the NRS score at 6 h,12 h and 24 h after surgery, as well as the use of vasoactive drugs during surgery (P < 0.05). The incidences of maternal dizziness (17.0%), blurred vision (5%), illusion (3.8%) and drowsiness (3.8%) in the esketamine group were higher than those of control group (P < 0.05). CONCLUSIONS: Intraoperative injection of esketamine (0.2 mg/kg) prevented the occurrence of depression (EPDS score > 9) at 4 days after delivery but not 42 days. Esketamine reduced the NRS scores at 6 h, 12 h and 24 h after surgery, but the occurrence of maternal side effects such as dizziness, blurred vision, drowsiness and hallucination were increased. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2100053422) on 20/11/2021.

A Drop-By-Drop Self-Assembled All-Natural Hydrogel as a Desensitizer for Rapid and Enduring Management of Dentin Hypersensitivity.

Dentin hypersensitivity (DH) is a prevalent dental condition arising from the exposure of dentin tubules (DTs), leading to discomfort upon external stimuli. However, achieving swift and profound occlusion of these exposed DTs for immediate and enduring relief remains challenging due to the intricate dentin structure and oral environment. Herein, a pioneering and facile drop-by-drop strategy involving an in situ generated natural supramolecular hydrogel formed by self-assembling silk fibroin (SF) and tannic acid (TA) within the narrow DT space is proposed. When SF and TA aqueous solutions are applied successively to exposed dentin, they penetrate deeply within DTs and coassemble into compact gels, robustly adhering to DT walls. This yields a rapid and compact occlusion effect with an unprecedented depth exceeding 250 µm, maintaining stable occlusion efficacy even under rigorous in vitro and in vivo erosion and friction conditions for no less than 21 days. Furthermore, the biocompatibility and effective occlusion properties are verified through cell studies in simulated oral settings and an in vivo rabbit model. This study, for the first time, demonstrates the translational potential of hydrogel-based desensitizers in treating DH with prompt action, superior occlusion depth and enduring treatment benefits, holding promise as clinical-friendly restorative solutions for delicate-structured biosystems.

A macrophage cell membrane-coated cascade-targeting photothermal nanosystem for combating intracellular bacterial infections.

Current antibacterial interventions encounter formidable challenges when confronting intracellular bacteria, attributable to their clustering within phagocytes, particularly macrophages, evading host immunity and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem, denoted as MM@DAu NPs, which seamlessly integrates cascade-targeting capabilities with controllable antibacterial functions for the precise elimination of intracellular bacteria. MM@DAu NPs feature a core comprising D-alanine-functionalized gold nanoparticles (DAu NPs) enveloped by a macrophage cell membrane (MM) coating. Upon administration, MM@DAu NPs harness the intrinsic homologous targeting ability of their macrophage membrane to infiltrate bacteria-infected macrophages. Upon internalization within these host cells, exposed DAu NPs from MM@DAu NPs selectively bind to intracellular bacteria through the bacteria-targeting agent, D-alanine present on DAu NPs. This intricate process establishes a cascade mechanism that efficiently targets intracellular bacteria. Upon exposure to near-infrared irradiation, the accumulated DAu NPs surrounding intracellular bacteria induce local hyperthermia, enabling precise clearance of intracellular bacteria. Further validation in animal models infected with the typical intracellular bacteria, Staphylococcus aureus, substantiates the exceptional cascade-targeting efficacy and photothermal antibacterial potential of MM@DAu NPs in vivo. Therefore, this integrated cell membrane-based cascade-targeting photothermal nanosystem offers a promising approach for conquering persistent intracellular infections without drug resistance risks. STATEMENT OF SIGNIFICANCE: Intracellular bacterial infections lead to treatment failures and relapses because intracellular bacteria could cluster within phagocytes, especially macrophages, evading the host immune system and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem MM@DAu NPs, which is designed to precisely eliminate intracellular bacteria through a controllable cascade-targeting photothermal antibacterial approach. MM@DAu NPs combine D-alanine-functionalized gold nanoparticles with a macrophage cell membrane coating. Upon administration, MM@DAu NPs harness the homologous targeting ability of macrophage membrane to infiltrate bacteria-infected macrophages. Upon internalization, exposed DAu NPs from MM@DAu NPs selectively bind to intracellular bacteria through the bacteria-targeting agent, enabling precise clearance of intracellular bacteria through local hyperthermia. This integrated cell membrane-based cascade-targeting photothermal nanosystem offers a promising avenue for conquering persistent intracellular infections without drug resistance risks.

Regulatory Effects of the Kiss1 Gene in the Testis on Puberty and Reproduction in Hezuo and Landrance Boars.

Kisspeptin, a neuropeptide encoded by the Kiss1 gene, combines with its receptor Kiss1R to regulate the onset of puberty and male fertility by the hypothalamic-pituitary-gonadal axis. However, little is known regarding the expression signatures and molecular functions of Kiss1 in the testis. H&E staining revealed that well-arranged spermatogonia, spermatocytes, round and elongated spermatids, and spermatozoa, were observed in 4-, 6-, and 8-month-old testes compared to 1- and 3-month-old testes of Hezuo pigs; however, these were not observed in Landrance until 6 months. The diameter, perimeter, and cross-sectional area of seminiferous tubules and the perimeter and area of the tubular lumen increased gradually with age in both pigs. Still, Hezuo pigs grew faster than Landrance. The cloning results suggested that the Hezuo pigs' Kiss1 CDS region is 417 bp in length, encodes 138 amino acids, and is highly conserved in the kisspeptin-10 region. qRT-PCR and Western blot indicated that the expression trends of Kiss1 mRNA and protein were essentially identical, with higher expression levels at post-pubertal stages. Immunohistochemistry demonstrated that the Kiss1 protein was mainly located in Leydig cells and post-pubertal spermatogenic cells, ranging from round spermatids to spermatozoa. These studies suggest that Kiss1 is an essential regulator in the onset of puberty and spermatogenesis of boars.

Melatonin-mediated mitophagy protects against long-term impairments after repeated neonatal sevoflurane exposures.

BACKGROUND: Melatonin is known to have protective effects in aging, neurodegenerative disorders and mitochondria-related diseases, while there is a poor understanding of the effects of melatonin treatment on mitophagy in neonatal cognitive dysfunction after repeated sevoflurane exposures. This study explores the protective effects of melatonin on mitophagy and cognition in developing rats exposed to sevoflurane. METHODS: Postnatal day six (P6) neonatal rats were exposed to 3 % sevoflurane for 2 h daily from P6 to P8. In the intervention groups, rats received 3-Methyladenine (3-MA) intracerebroventricularly from P6 to P8 and melatonin intraperitoneally from P6 to P8 following water drinking once daily from P21 to P41, respectively. Behavioral tests, including open field (OF), novel object recognition (NOR), and fear conditioning (FC) tests, were performed to assess cognitive function during young adulthood. In another experiment, rat brains were harvested for biochemical, histopathological, and electron microscopy studies. RESULTS: Rats exposed to sevoflurane showed disordered mitophagy and mitochondrial dysfunction as revealed by increased mitophagy marker proteins (microtubule-associated protein 1 light chain 3 (LC3) II/I, and parkin), decreased autophagy marker protein (sequestosome 1 (P62/SQSTM1)), electron transport chain (ETC) proteins and ATP levels. Immunofluorescent staining of LC3 was co-localized mostly with a neuronal marker and microglial marker but was not co-localized with a marker for astrocytes in rats exposed to sevoflurane. These rats had poorer performance in the NOR and FC tests than control rats during young adulthood. Melatonin treatment reversed the abnormal expression of mitophagy proteins, mitochondrial energy metabolism, the activity of microglia, and impaired cognition. These ameliorations were blocked by an autophagy inhibitor, 3-MA, except for the activation of microglia. CONCLUSION: We have demonstrated that melatonin inhibits microglial activation by enhancing mitophagy and finally significantly reduces sevoflurane-induced deficits in cognition in neonatal rats. These results suggest that melatonin might be beneficial if considered when the anesthesia must be administered at a very young age.

Differences in survivability and toxic potential among Microcystis colonies of different sizes in sediment.

Microcystis colonies have the ability to persist for extended periods in sediment and function as a "seed bank" for the succeeding summer bloom in water column. The colonial morphology and toxin production ability of Microcystis are important for their population maintenance and life history. However, it is unclear about the influence of the colony morphology and toxic potential of Microcystis colonies on their benthic process. To address this question, we classified field Microcystis samples into three groups based on their size (< 150 µm, 150-300 µm, and > 300 µm) and compared their survivability and toxic potential during culturing in sediment. The results showed that Microcystis colonies in sediments disappeared quickly at 25℃ but survived for long periods at 5℃. The survivability of smaller Microcystis colonies (< 300 µm) was significantly higher than that of larger ones (> 300 µm). The activities of catalase (CAT) were significantly increased in large colonies compared to small colonies at 15℃ and 25℃. Real-time PCR indicated that smaller colonies had higher proportion of potential toxic genotype, and Microcystis colonies cultured at 15℃ and 25℃ showed higher percentage of microcystin-producing genotype. These results indicate that Microcystis colonies survived longer at low temperature and that larger Microcystis colonies are more susceptible to oxidative stress in sediments. The difference of toxic potential of Microcystis colonies of different sizes in sediments may be related to their survival ability in sediments.

Comprehensive analysis reveals potential therapeutic targets and an integrated risk stratification model for solitary fibrous tumors.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs.

Decreased Functional Connectivity of the Core Pain Matrix in Herpes Zoster and Postherpetic Neuralgia Patients.

The purpose of this study was to explore the resting-state functional connectivity (FC) changes among the pain matrix and other brain regions in herpes zoster (HZ) and postherpetic neuralgia (PHN) patients. Fifty-four PHN patients, 52 HZ patients, and 54 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We used a seed-based FC approach to investigate whether HZ and PHN patients exhibited abnormal FC between the pain matrix and other brain regions compared to HCs. A random forest (RF) model was constructed to explore the feasibility of potential neuroimaging indicators to distinguish the two groups of patients. We found that PHN patients exhibited decreased FCs between the pain matrix and the putamen, superior temporal gyrus, middle frontal gyrus, middle cingulate gyrus, amygdala, precuneus, and supplementary motor area compared with HCs. Similar results were observed in HZ patients. The disease durations of PHN patients were negatively correlated with those aforementioned impaired FCs. The results of machine learning experiments showed that the RF model combined with FC features achieved a classification accuracy of 75%. Disrupted FC among the pain matrix and other regions in HZ and PHN patients may affect multiple dimensions of pain processing.

A Bischler-Napieralski and homo-Mannich sequence enables diversified syntheses of sarpagine alkaloids and analogues.

Sarpagine alkaloids offer signicant opportunities in drug discovery, yet the efficient total syntheses and diverse structural modifications of these natural products remain highly challenging due to the architectural complexity. Here we show a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction enables a protecting-group-free, redox economic, four-step access to the tetracyclic sarpagine core from L-tryptophan esters. Based on this advancement, diversified syntheses of sarpagine alkaloids and analogues are achieved in a short synthetic route. The systematic anticancer evaluation indicates that natural products vellosimine and Na-methyl vellosimine possess modest anticancer activity. Intensive structural optimization of these lead molecules and exploration of the structure-activity relationship lead to the identification of analogue 15ai with an allene unit showing a tenfold improvement in anticancer activities. Further mechanism studies indicate compound 15ai exertes antiproliferation effects by inducing ferroptosis, which is an appealing non-apoptotic cell death form that may provide new solutions in future cancer therapies.