Lysosome Positioning Influences mTORC2 and AKT Signaling.

Growth factor signaling is initiated at the plasma membrane and propagated through the cytoplasm for eventual relay to intracellular organelles such as lysosomes. The serine/threonine kinase mTOR participates in growth factor signaling as a component of two multi-subunit complexes, mTORC1 and mTORC2. mTORC1 associates with lysosomes, and its activity depends on the positioning of lysosomes within the cytoplasm, although there is no consensus regarding the exact effect of perinuclear versus peripheral distribution. mTORC2 and its substrate kinase AKT have a widespread distribution, but they are thought to act mainly at the plasma membrane. Using cell lines with knockout of components of the lysosome-positioning machinery, we show that perinuclear clustering of lysosomes delays reactivation of not only mTORC1, but also mTORC2 and AKT upon serum replenishment. These experiments demonstrate the existence of pools of mTORC2 and AKT that are sensitive to lysosome positioning.

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.

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.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

Rational Design of High-Loading Electrodes with Superior Performances Toward Practical Application for Energy Storage Devices.

High-loading electrodes play a crucial role in designing practical high-energy batteries as they reduce the proportion of non-active materials, such as current separators, collectors, and battery packaging components. This design approach not only enhances battery performance but also facilitates faster processing and assembly, ultimately leading to reduced production costs. Despite the existing strategies to improve rechargeable battery performance, which mainly focus on novel electrode materials and high-performance electrolyte, most reported high electrochemical performances are achieved with low loading of active materials (<2 mg cm-2). Such low loading, however, fails to meet application requirements. Moreover, when attempting to scale up the loading of active materials, significant challenges are identified, including sluggish ion diffusion and electron conduction kinetics, volume expansion, high reaction barriers, and limitations associated with conventional electrode preparation processes. Unfortunately, these issues are often overlooked. In this review, the mechanisms responsible for the decay in the electrochemical performance of high-loading electrodes are thoroughly discussed. Additionally, efficient solutions, such as doping and structural design, are summarized to address these challenges. Drawing from the current achievements, this review proposes future directions for development and identifies technological challenges that must be tackled to facilitate the commercialization of high-energy-density rechargeable batteries.

The rice LATE ELONGATED HYPOCOTYL enhances salt tolerance by regulating Na+/K+ homeostasis and ABA signalling.

The circadian clock plays multiple functions in the regulation of plant growth, development and response to various abiotic stress. Here, we showed that the core oscillator component late elongated hypocotyl (LHY) was involved in rice response to salt stress. The mutations of OsLHY gene led to reduced salt tolerance in rice. Transcriptomic analyses revealed that the OsLHY gene regulates the expression of genes related to ion homeostasis and the abscisic acid (ABA) signalling pathway, including genes encoded High-affinity K+ transporters (OsHKTs) and the stress-activated protein kinases (OsSAPKs). We demonstrated that OsLHY directly binds the promoters of OsHKT1;1, OsHKT1;4 and OsSAPK9 to regulate their expression. Moreover, the ossapk9 mutants exhibited salt tolerance under salt stress. Taken together, our findings revealed that OsLHY integrates ion homeostasis and the ABA pathway to regulate salt tolerance in rice, providing insights into our understanding of how the circadian clock controls rice response to salt stress.

Enhancing the performance of mode-pairing quantum key distribution by wavelength division multiplexing.

Mode-pairing quantum key distribution (MP-QKD) holds great promise for the practical implementation of QKD in the near future. It combines the security advantages of measurement device independence while still being capable of breaking the Pirandola-Laurenza-Ottaviani-Banchi bound without the need for highly demanding phase-locking and phase-tracking technologies for deployment. In this work, we explore optimization strategies for MP-QKD in a wavelength-division multiplexing scenario. The simulation results reveal that incorporation of multiple wavelengths not only leads to a direct increase in key rate but also enhances the pairing efficiency by employing our novel pairing strategies among different wavelengths. As a result, our work provides a new avenue for the future application and development of MP-QKD.

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.

Prusogliptin (DBPR108) monotherapy in treatment-naïve patients with type 2 diabetes: A randomized, double-blind, active and placebo-controlled, phase 3 study.

AIM: This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase-4 inhibitor, in individuals with type 2 diabetes who had not been using glucose-lowering agents regularly for the 8 weeks before the screening period. MATERIALS AND METHODS: In this multicentre, randomized, double-blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24-week double-blind treatment period, followed by a 28-week open-label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24. RESULTS: In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 ± 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were -0.63% (0.04%) for DBPR108, -0.60% (0.07%) for sitagliptin and -0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was -0.61% (95% CI -0.77% to -0.44%), and between DBPR108 and sitagliptin was -0.03% (95% CI -0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non-inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were -0.50% (0.97%) for the DBPR108 group, -0.46% (0.96%) for the sitagliptin group and -0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups. CONCLUSIONS: DBPR108 showed superiority to placebo and non-inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment-naïve patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

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.

Effects of antimicrobial peptides from dietary Hermetia illucens larvae on the growth, immunity, gene expression, intestinal microbiota and resistance to Aeromonas hydrophila of juvenile red claw crayfish (Cherax quadricarinatus).

Antimicrobial peptides (AMPs), which are widely present in animals and plants, have a broad distribution, strong broad-spectrum antibacterial activity, low likelihood of developing drug resistance, high thermal stability and antiviral properties. The present study investigated the effects of adding AMPs from Hermetia illucens larvae on the growth performance, muscle composition, antioxidant capacity, immune response, gene expression, antibacterial ability and intestinal microbiota of Cherax quadricarinatus (red claw crayfish). Five experimental diets were prepared by adding 50 (M1), 100 (M2), 150 (M3) and 200 (M4) mg/kg of crude AMP extract from H. illucens larvae to the basal diet feed, which was also used as the control (M0). After an eight-week feeding experiment, it was discovered that the addition of 100-150 mg/kg of H. illucens larvae AMPs to the feed significantly improved the weight gain rate and specific growth rate of C. quadricarinatus. Furthermore, the addition of H. illucens larvae AMPs to the feed had no significant effect on the moisture content, crude protein, crude fat and ash content of the C. quadricarinatus muscle. The addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed also increased the antioxidant capacity, nonspecific immune enzyme activity and related gene expression levels in C. quadricarinatus, thereby enhancing their antioxidant capacity and immune function. The H. illucens larvae AMPs improved the structure and composition of the intestinal microbiota of C. quadricarinatus, increasing the microbial community diversity of the crayfish gut. Finally, the addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed enhanced the resistance of C. quadricarinatus against Aeromonas hydrophila, improving the survival rate of the crayfish. Based on the aforementioned findings, it is recommended that H. illucens larvae AMPs be incorporated into the C. quadricarinatus feed at a concentration of 100-150 mg/kg.

Effects of dietary chitosan oligosaccharide on the growth, intestinal microbiota and immunity of juvenile red claw crayfish (Cherax quadricarinatus).

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.

Effects of dietary astaxanthin on growth performance, muscle composition, non-specific immunity, gene expression, and ammonia resistance of juvenile ivory shell (Babylonia areolate).

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.

Astragaloside IV inhibits idiopathic pulmonary fibrosis through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway.

As the main active ingredient of Astragalus, Astragaloside IV (AS-IV) can ameliorate pulmonary fibrosis. In this experiment, we studied how AS-IV reduces idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) or TGF-ß1 was treated in mice or alveolar epithelial cells to mimic IPF in vivo as well as in vitro. ASV-IV alleviated levels of inflammatory cytokines and fibrosis markers in IPF model. Through detection of autophagy-related genes, ASV-IV was observed to induce autophagy in IPF. Besides, ASV-IV inhibited miR-21 expression in IPF models, and overexpression of miR-21 could reverse the protective potential of ASV-IV on IPF. PTEN was targeted by miR-21 and was up-regulated by ASV-IV in IPF models. In addition, levels of inflammatory cytokines and fibrosis markers, autophagy, as well as the PI3K/AKT/mTOR pathway regulated by ASV-IV could be neutralized after treatment with autophagy inhibitors, miR-21 mimics, or si-PTEN. Our study demonstrates that ASV-IV inhibits IPF through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway, suggesting that ASV-IV could be acted to be a promising therapeutic method for IPF.

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Variations in antibiotic resistomes associated with archaeal, bacterial, and viral communities affected by integrated rice-fish farming in the paddy field ecosystem.

Antibiotic resistance genes (ARGs) serving as a newly recognized pollutant that poses potential risks to global human health, which in the paddy soil can be potentially altered by different agricultural production patterns. To elucidate the impacts and mechanisms of the widely used and sustainable agricultural production pattern, namely integrated rice-fish farming, on the antibiotic resistomes, we applied metagenomic sequencing to assess ARGs, mobile genetic elements (MGEs), bacteria, archaea, and viruses in paddy soil. There were 20 types and 359 subtypes of ARGs identified in paddy soil. The integrated rice-fish farming reduced the ARG and MGE diversities and the abundances of dominant ARGs and MGEs. Significantly decreased ARGs were mainly antibiotic deactivation and regulator types and primarily ranked level IV based on their potential threat to human health. The integrated rice-fish farming decreased the alpha diversities and altered microbial community compositions. MGEs, bacteria, archaea, and virus exhibited significant correlations with ARGs, while integrated rice-fish farming effectively changed their interrelationships. Viruses, bacteria, and MGEs played crucial roles in affecting the ARGs by the integrated rice-fish farming. The most crucial pathway by which integrated rice-fish farming affected ARGs was through the modulation of viral communities, thereby directly or indirectly influencing ARG abundance. Our research contributed to the control and restoration of ARGs pollution from a new perspective and providing theoretical support for the development of clean and sustainable agricultural production.

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.

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.

Exploring treatment and antifungal resistance in an outbreak of tinea caused by Microsporum audouinii.

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. OBJECTIVES: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). METHODS: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. CONCLUSION: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.