Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro.

AIMS: Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs), primarily constituted of α-synuclein (α-Syn). Microglial cells exhibit specific reactivity toward misfolded proteins such as α-Syn. However, the exact clearance mechanism and related molecular targets remain elusive. METHODS: BV2 cells, primary microglia from wild-type and MT1 knockout mice, and primary cortical neurons were utilized as experimental models. The study investigated relevant mechanisms by modulating microglial MT1 expression through small RNA interference (RNAi) and lentiviral overexpression techniques. Furthermore, pathological aggregation of α-Syn was induced using pre-formed fibrils (PFF) α-Syn. Co-immunoprecipitation, immunofluorescence, Western blot (WB), and quantitative real-time PCR were used to elucidate the mechanisms of molecular regulation. RESULTS: In this study, we elucidated the regulatory role of the melatonin receptor 1 (MT1) in the microglial phagocytic process. Following MT1 knockout, the ability of microglial cells to engulf latex beads and zymosan particles decreased, subsequently affecting the phagocytic degradation of fibrillar α-Syn by microglial cells. Furthermore, the loss of MT1 receptors in microglial cells exacerbates the aggregation of α-Syn in neurons induced by pre-formed fibrils (PFF) α-Syn. Mechanistically, MT1 influences the phagocytic function of microglial cells by regulating the Rubicon-dependent LC3-associated phagocytosis (LAP) pathway. CONCLUSION: Taken together, the results suggest the neuroprotective function of microglial cells in clearing α-Syn through MT1-mediated LAP, highlighting the potential key role of MT1 in pathogenic mechanisms associated with α-Syn.

Engineering Interlayer Space and Composite of Square-Shaped V2O5 by PVP-Assisted Polyaniline Intercalation and Graphene for Aqueous Zinc-Ion Batteries.

V2O5 undergoes irreversible phase transition and collapse of layered structure during the Zn2+ insertion/extraction, which severely limits its application as a cathode for aqueous zinc-ion batteries (AZIBs). Herein, a synergistic strategy of conductive polyaniline insertion and graphene composite was proposed to boost the Zn2+ storage performance of the V2O5 cathode. A square-shaped polyaniline (PANI)-intercalated and graphene-composited vanadium oxide (GO/PANI-PVP/V2O5) structure was successfully synthesized via an in situ oxidation/insertion polymerization combined with a hydrothermal method. The results showed that PANI intercalation and the composite of graphene combined with layered V2O5, enabling reversible intercalation of Zn2+/H+. The insertion of conjugated PANI not only increases the lattice spacing of V2O5, providing a channel for rapid transport of Zn2+, but also increases the storage sites for charges through doping/dedoping processes and redox conversion reactions. GO/PANI-PVP/V2O5 delivers an excellent specific capacity (495 mA h g-1 at 0.1 A g-1), wonderful rate capability (208 mA h g-1 at 30 A g-1), and good cycling stability (93% after 4000 cycles). Our results provide a new approach for adjusting the valence states, interlayer spacing, and rational design of organic-inorganic compound materials for different functional materials.

The potential auxiliary effects of Sargassum fusiform polysaccharides on sitagliptin in the treatment of diabetes mellitus.

This work aimed to evaluate the potential positive effects of Sargassum fusiform polysaccharides (SFP) as add-on adjuncts to sitagliptin (SIT) in treating diabetes in rats. The results showed that both SIT and SIT co-administrated with SFP (SIT+SFP) could improve hyperglycemia, glucose tolerance, insulin resistance and hyperlipidemia, and SIT+SFP exhibited better effects in alleviating the levels of blood glucose, glucose tolerance, insulin resistance index, cholesterol, and low-density lipoprotein cholesterol compared to SIT administration. Intestinal flora analysis showed that SIT+SFP treatment significantly restored the beneficial composition of gut flora as compared with SIT administration, such as the increase of Lactobacillus, Romboutsia, Blautia, Bifidobacterium, Bacteroides, Ruminococcaceae_UCG_014 and Ruminococcus_1, and the decrease of Helicobacter, Escherichia-Shigella and Pseudomonas. The fecal metabolite analysis demonstrated that the fecal bile acid and short-chain fatty acid levels in the SIT+SFP group significantly increased compared to SIT treatment. Additionally, mRNA expression results confirmed that the hypoglycemic effects of SIT+SFP were better than those of SIT, which might be attributed to the regulation of blood glucose absorption, inhibition of gluconeogenesis and regulation of cholesterol metabolism. These results suggested that SFP could be used as an auxiliary substance for SIT in treating diabetes mellitus.

Pleasant Odor Decreases Mouse Anxiety-like Behaviors by Regulating Hippocampal Endocannabinoid Signaling.

Anxiety disorder is one of the most common neuropsychiatric disorders, and affects many people's daily activities. Although the pathogenesis and treatments of anxiety disorder have been studied for several decades, the underlying mechanisms remain elusive. Here, we provide evidence that olfactory stimuli with inhaled linalool or 2-phenylethanol decreased mouse anxiety-like behaviors and increased the activities of hippocampal dentate granule cells (DGCs). RNA-sequencing analysis identified retrograde endocannabinoid signaling, which is a critical pathway for mood regulation and neuron activation, is altered in the hippocampus of both linalool- and 2-phenylethanol-exposed mice. Further studies found that selective inhibition of endocannabinoid signaling by injecting rimonabant abolished the activation of DGCs and the anxiolytic effect induced by linalool or 2-phenylethanol. Together, these results uncovered a novel mechanism by which linalool or 2-phenylethanol decreases mouse anxiety-like behaviors and increases DG activity likely through activating hippocampal retrograde endocannabinoid signaling.

Effect of Extraction Methods on Chemical Characteristics and Bioactivity of Chrysanthemum morifolium cv. Fubaiju Extracts.

Chrysanthemum morifolium cv. Fubaiju (CMF) is regarded as one of the three most renowned varieties of white Chrysanthemum in China, and different extraction methods have significant effects on its composition and activities. Therefore, six extractions were used in this study to assess the effects on extracts. The basic chemical composition showed that hot water extract (Hw) had the highest total phenolic content, alkali water immersion-assisted hot water extract (Al) had the highest content of protein, and enzyme-assisted hot water extract (Enz) had the highest content of carbohydrate. The UPLC-Q-Exactive-MS results evinced the presence of 19 small-molecule compounds, including chlorogenic acid, caffeic acid, tuberonic acid glucoside, luteolin-7-O-rutinoside, and other substances. In addition, the antioxidant test found that the Hw exhibited the best 1,1-diphenyl-2-picrylhydrazyl (DPPH) (82.05 ± 1.59 mM TE/mg) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (61.91 ± 0.27 mM TE/mg) scavenging ability. The anti-glycation test demonstrated that Enz possessed the most pronounced inhibitory effect on glycation products, including fructosamine and advanced glycation end products (AGEs). Additionally, the Enz also exhibited the most significant inhibitory effect on the protein oxidation product N'-formylkynurenine. The correlation analysis revealed that there was a close relationship between antioxidant properties and glycation resistance of extracts, and tuberonic acid glucoside, 1,3-di-O-caffeoylquinic acid, 1,4-Dicaffeoylquinic acid, quercetin-7-O-ß-D-glucopyranoside, and isochlorogenic acid B were key small molecule components that affected activities. In summary, the extracts of CMF can be regarded as an excellent antioxidant and anti-glycosylation agent.

Quantitative and qualitative analysis of contrast-enhanced ultrasound for differentiating benign and malignant superficial enlarged lymph nodes.

Background: In many clinical situations, it is critical to exclude or identify abnormally lymph nodes (LNs). The nature of superficial abnormally LNs is closely related to the stage, treatment, and prognosis of the disease. Ultrasound (US) is an important method for examining superficial LNs due to its cheap and safe characteristics. However, it is still difficult to determine the nature of some LNs with overlapping benign and malignant features in images. Contrast-enhanced ultrasound (CEUS) can be used to evaluate the microperfusion status of tissues in real time, and it can improve diagnostic accuracy to a certain extent. Therefore, in this study, we will analyze the correlation between CEUS quantitative parameters and benign and malignant superficial abnormally LNs, to evaluate the efficacy and value of CEUS in distinguishing benign and malignant superficial LNs. Methods: This study retrospectively analyzed 120 patients of abnormal LNs who underwent US and CEUS at the China-Japan Union Hospital of Jilin University from December 2020 to August 2023. All 120 cases of abnormal LNs underwent US-guided coarse needle biopsy, and accurate pathological results were obtained, along with complete US and CEUS images. According to the pathological results, LNs were divided into benign and malignant groups, and the qualitative and quantitative parameters of US and CEUS between the two groups were analyzed. The cutoff value is determined by the receiver operating characteristic (ROC) curve of the subjects, and sensitivity, specificity, and accuracy are applied to evaluate the ability of the cutoff value to distinguish between the two groups. Results: There were a total of 120 LNs, including 36 in the benign group and 84 in the malignant group. The results showed that malignant LNs were usually characterized by the disappearance of lymphatic hilum, round ness index (L/T) <2, irregular morphology, and the manifestation of uneven perfusion (P<0.05). The differences in the quantitative parameters peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in rate (WIR), and wash-out rate (WOR) were statistically significant (P<0.05). The result showed that RT and TTP in the malignant LNs were higher than those in the benign LNs, while the PE, WIR, and WOR were lower. A comparison of the ∆ values showed that the differences in ∆PE, ∆WIR, and ∆fall time (FT) were statistically significant (P<0.05), Among them, the ∆PE and ∆WIR of malignant LNs were higher than those of benign LNs, while the ∆FT was lower than that of benign LNs. Conclusions: Quantitative analysis of CEUS features is valuable in the diagnosis of benign and malignant LNs, and US combined with CEUS helps to improve the accuracy of identifying the nature of LNs.

Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model.

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

Genetic Variability and Evolutionary Dynamics of Papaya Ringspot Virus and Papaya Leaf Distortion Mosaic Virus Infecting Feral Papaya in Hainan Island.

The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence (P=0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors. On these grounds, this review describes the dynamic changes in oxygen levels at the maternal-fetal interface throughout gestation, summarizing current knowledge on how the hypoxic environment sustains a successful pregnancy by regulating retention, differentiation and efferocytosis of decidual macrophages. Additionally, we explore the relationship between spontaneous miscarriages and an abnormal hypoxia-macrophage axis, shedding light on the underlying mechanisms. However, further studies are essential to elucidate these pathways in greater detail and to develop targeted interventions that could improve pregnancy outcomes.

Screening high-efficiency promoter to construct trans-vp28 gene Anabaena sp. PCC7120 against white spot syndrome virus of Litopenaeus vannamei.

This study aimed to select high-quality promoters to construct trans-vp28 gene Anabaena sp. PCC7120 and feed Litopenaeus vannamei to assess the effect of L.vannamei against white spot syndrome virus (WSSV). Transgenic algae were created using five plasmids containing PrbcL, Pcpc560, Ptrc, Ptac, and PpsbA. According to the gene expression efficiency and the growth index of transgenic algae, Pcpc560 was determined to be the most efficient promoter. Shrimps were continuously fed trans-vp28 gene Anabaena sp. PCC7120 for one week and then challenged with WSSV. After the challenge, the transgenic algae group (vp28-7120 group) was continuously immunized [continuous immunization for 0 days (vp28-7120-0d); continuous immunization for 2 days (vp28-7120-2d); continuous immunization for 4 days (vp28-7120-4d)]. After seven days, the daily survival rate of each experimental group was continuously tracked. Following the viral challenge, the hepatopancreas samples were assayed for their levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), thioredoxin peroxidase (TPX), acid phosphatase (ACP), and alkaline phosphatase (AKP) at varying time intervals. In comparison to the positive control group (challenge and no vaccination) and the wild-type group (challenge, fed wild-type Anabaena sp. PCC7120), the vp28-7120 group (challenge, fed trans-vp28 gene Anabaena sp. PCC7120) exhibited a remarkable increase in survival rates, reaching 50 % (vp28-7120-0d), 76.67 % (vp28-7120-2d), and 80 % (vp28-7120-4d). Furthermore, the vp28-7120 group consistently displayed significantly higher activities of SOD, CAT, GSH-Px, ACP, and AKP, while exhibiting notably lower TPX activity, when compared to the control group. These results indicate that the Pcpc560 promoter effectively elevated the expression level of the exogenous vp28 gene and spurred the growth of the trans-vp28 gene Anabaena sp. PCC7120. Consequently, trans-vp28 gene Anabaena sp. PCC7120 significantly bolstered the immunity of L.vannamei. Therefore, utilizing the Pcpc560 promoter to develop trans-vp28 gene Anabaena sp. PCC7120 based oral vaccine is highly beneficial for industrial-scale cultivation, advancing its commercialization prospects.

Protective Effect of Polysaccharides Isolated from Sargassum horneri against H2O2-Induced Oxidative Stress Both In Vitro, in Vero Cells, and In Vivo in Zebrafish.

The extensive outbreak of Sargassum horneri in China has not merely imposed a severe threat to the ecological environment and human life in coastal waters but also impeded the development of waterway transportation and the local economy. Consequently, we isolated polysaccharides from S. horneri, designated as SHP, and evaluated the antioxidant activity of SHP both in vitro and in vivo by investigating the effect of SHP on H2O2-induced African green monkey kidney cells (Vero cells) and zebrafish. The results demonstrated that SHP can enhance the activities of superoxide dismutase, catalase, and glutathione peroxidase in zebrafish. It also effectively inhibits micro malondialdehyde and ROS levels in Vero cells and zebrafish to mitigate the oxidative damage caused by H2O2, thereby achieving the protective effect of SHP on Vero cells and zebrafish. In conclusion, SHP holds the potential as a natural antioxidant. SHP can be contemplated for utilization as a natural antioxidant in the biomedical, cosmetic, and food industries, thereby alleviating the environmental stress caused by S. horneri and achieving resource utilization.

Supramolecular-macrocycle-based functional organic cocrystals.

Supramolecular macrocycles, renowned for their remarkable capabilities in molecular recognition and complexation, have emerged as pivotal elements driving advancements across various innovative research fields. Cocrystal materials, an important branch within the realm of crystalline organic materials, have garnered considerable attention owing to their simple preparation methods and diverse potential applications, particularly in optics, electronics, chemical sensing and photothermal conversion. In recent years, macrocyclic entitles have been successfully brought into this field, providing an essential and complementary channel to create novel functional materials, especially those with multiple functionalities and smart stimuli-responsiveness. In this Review, we present an overview of the research efforts on functional cocrystals constructed with macrocycles, covering their design principles, preparation strategies, assembly modes, and diverse functions and applications. Finally, the remaining challenges and perspectives are outlined. We anticipate that this review will serve as a valuable and timely reference for researchers interested in supramolecular crystalline materials and beyond, catalyzing the emergence of more original and innovative studies in related fields.

Effects of exposure length, cortical and trabecular bone contact areas on primary stability of infrazygomatic crest mini-screws at different insertion angles.

BACKGROUND: The infrazygomatic crest mini-screw has been widely used, but the biomechanical performance of mini-screws at different insertion angles is still uncertain. The aim of this study was to analyse the primary stability of infrazygomatic crest mini-screws at different angles and to explore the effects of the exposure length (EL), screw-cortical bone contact area (SCA), and screw-trabecular bone contact area (STA) on this primary stability. METHODS: Ninety synthetic bones were assigned to nine groups to insert mini-screws at the cross-combined angles in the occlusogingival and mesiodistal directions. SCA, STA, EL, and lateral pull-out strength (LPS) were measured, and their relationships were analysed. Twelve mini-screws were then inserted at the optimal and poor angulations into the maxillae from six fresh cadaver heads, and the same biomechanical metrics were measured for validation. RESULTS: In the synthetic-bone test, the LPS, SCA, STA, and EL had significant correlations with the angle in the occlusogingival direction (rLPS = 0.886, rSCA = -0.946, rSTA = 0.911, and rEL= -0.731; all P < 0.001). In the cadaver-validation test, significant differences were noted in the LPS (P = 0.011), SCA (P = 0.020), STA (P = 0.004), and EL (P = 0.001) between the poor and optimal angulations in the occlusogingival direction. The STA had positive correlations with LPS (rs = 0.245 [synthetic-bone test] and r = 0.720 [cadaver-validation test]; both P < 0.05). CONCLUSIONS: The primary stability of the infrazygomatic crest mini-screw was correlated with occlusogingival angulations. The STA significantly affected the primary stability of the infrazygomatic crest mini-screw, but the SCA and EL did not.

Cavity-Induced Optical Nonreciprocity Based on Degenerate Two-Level Atoms.

We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg = 4 ↔ Fe = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.

A novel AP2/ERF transcription factor, NtERF10, positively regulates plant height in tobacco.

Ethylene response factors have been shown to be involved in the effects of plant developmental processes and to regulate stress tolerance. The aim of this study was to recognize the regulatory mechanisms of ethylene response factors on tobacco plant height. In this study, a gene-edited mutant (ERF10-KO) and wild type (WT) were utilized as experimental materials. Transcriptome and metabolome analyses were used to investigate the regulatory mechanism of NtERF10 gene editing on plant height in tobacco. Here, through the analysis of differentially expressed genes (DEGs), 2051 genes were upregulated and 1965 genes were downregulated. We characterized the different ERF10-KO and WT plant heights and identified key genes for photosynthesis, the plant hormone signal transduction pathway and the terpene biosynthesis pathway. NtERF10 was found to affect the growth and development of tobacco by regulating the expression levels of the PSAA, PSBA, GLY17 and GGP3 genes. Amino acid metabolism was analyzed by combining analyses of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). In addition, we found that members of the bHLH, NAC, MYB, and WRKY transcription factor families have vital roles in regulating plant height. This study not only provides important insights into the positive regulation of the ethylene response factor NtERF10 on plant height during plant growth and development but also provides new research ideas for tobacco molecular breeding.

The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.

Vascular anomalies of the limb and trunk in children: a retrospective comparative study of endoscopic surgery and open surgery.

BACKGROUND: Endoscopic resection has been reported for vascular anomalies (VA) previously. However, there is no study comparing endoscopic resection surgery (ERS) with open resection surgery (ORS) in children. We aimed to compare clinical and cosmetic outcomes between two approaches in pediatric VA. METHODS: Between June 2018 and June 2023, 138 pediatric VA patients undergoing ERS or ORS were retrospectively reviewed. Propensity score matching (PSM) was performed to minimize selection bias. The Scar Cosmesis Assessment and Rating (SCAR) Scale and numerical rating scale (NRS) based on patient satisfaction were used for cosmetic assessment. RESULTS: After PSM for age, depth of lesion, size of lesion, and site of surgery, 72 patients (ERS = 24, ORS = 48) were analyzed. Patients undergoing ERS had longer operative time (164.25 ± 18.46 vs. 112.85 ± 14.26 min; P < 0.001), less estimated blood loss (5.42 ± 2.15 vs. 18.04 ± 1.62 ml; P < 0.001), and shorter median hospital stay (4.50 [3.00-5.00] vs. 6.00 [5.00-6.00] days; P < 0.001). The follow-up time was 8.04 ± 1.23 month for ERS group and 8.56 ± 1.57 month for ORS group. For aesthetic results, the median overall SCAR score in ERS was lower than that in ORS (2 [1-3] vs. 5 [4-5]; P < 0.001), and the subscales of "scar spread," "dyspigmentation," "track marks or suture marks," and "overall impression" were better. The median NRS score was higher (8 [7-8] vs. 6 [5-6]; P < 0.001) and length of scars was shorter (2.18 ± 0.30 vs. 8.75 ± 1.98 cm; P < 0.001) in ERS group than those in ORS group. The incidences of total complications and recurrence showed no significant difference between two groups. CONCLUSIONS: Endoscopic surgery can be a safe and effective option for pediatric VA in the limbs and trunk. It offers the advantages of improving aesthetic outcomes and reducing postoperative wound healing time.

Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism.

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.