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Introduction: Guilingji, a famous traditional Chinese medicine (TCM) formula, has been used to combat aging and male sexual dysfunction in China for centuries. To date, there has been little evidence-based clinical research on the use of Guilingji to treat idiopathic oligo-asthenoteratozoospermia (OAT), and the therapeutic mechanism from a metabolic perspective needs to be investigated further. Methods: This was a multicenter, double-blind, randomized controlled clinical study of 240 patients with idiopathic OAT recruited from four hospitals between January 2020 and January 2022. Patients were randomly assigned in a 1꞉1 ratio to receive oral Guilingji capsules or placebo for 12 weeks. The total progressive motile sperm count (TPMSC) was considered the primary outcome, and the other sperm parameters, seminal plasma parameters and serum hormones were considered the secondary outcome. A nontargeted metabolomics analysis of serum from OAT patients before and after Guilingji administration was performed by HPLC–MS to identify key metabolites. Furthermore, we used a rat model to show spermatogenesis phenotypes to validate the effect of the key metabolites screened from the patients. Results: At weeks 4, 8 and 12, TPMSC and other sperm parameters were significantly improved in the Guilingji group compared with the placebo group (P

AIM: To present the 1-year results of a prospective cohort study investigating the efficacy, potential mechanism, and safety of orthokeratology (ortho-k) with different back optic zone diameters (BOZD) for myopia control in children. METHODS: This randomized clinical study was performed between Dec. 2020 and Dec. 2021. Participants were randomly assigned to three groups wearing ortho-k: 5 mm BOZD (5-MM group), 5.5 mm BOZD (5.5-MM group), and 6 mm BOZD (6-MM group). The 1-year data were recorded, including axial length, relative peripheral refraction (RPR, measured by multispectral refractive topography, MRT), and visual quality. The contrast sensitivity (CS) was evaluated by CSV-1000 instrument with spatial frequencies of 3, 6, 12, and 18 cycles/degree (c/d); the corneal higher-order aberrations (HOAs) were measured by iTrace aberration analyzer. The one-way ANOVA was performed to assess the differences between the three groups. The correlation between the change in AL and RPR was calculated by Pearson's correlation coefficient. RESULTS: The 1-year results of 20, 21, and 21 subjects in the 5-MM, 5.5-MM, and 6-MM groups, respectively, were presented. There were no statistical differences in baseline age, sex, or ocular parameters between the three groups (all P>0.05). At the 1-year visit, the 5-MM group had lower axial elongation than the 6-MM group (0.07±0.09 vs 0.18±0.11 mm, P=0.001). The 5-MM group had more myopic total RPR (TRPR, P=0.014), with RPR in the 15°–30° (RPR 15–30, P=0.015), 30°–45° (RPR 30–45, P=0.011), temporal (RPR-T, P=0.008), and nasal area (RPR-N, P

IntroductionWaardenburg syndrome (WS) is a genetic disorder characterized by hearing loss, hypopigmentation, and distinct facial features. Despite > 60% molecular diagnosis rate for WS patients, pathogenic variants within coding regions are predominant, with few non-coding copy number variations (CNVs) reported.MethodsIn this study, we performed whole genome sequencing (WGS) on 59 undiagnosed WS patients and analyzed the CNVs within the promoter and enhancer regions of the SOX10 gene.ResultsWe identified five novel pathogenic deletions ranging from 448 bp to 70 kb upstream of SOX10. Two deletions were in the enhancer region, while three were in the promoter and 5'UTR region. These CNVs manifested as WS type II in eight patients from five unrelated families, demonstrating phenotypic heterogeneity. Furthermore, analysis of CNV1 within the enhancer region suggested a potential mechanism involving Alu-mediated non-allelic homologous recombination (NAHR).ConclusionOur findings extend the mutation spectrum of the SOX10 gene and elucidate the pathogenic role of CNVs in cis-regulatory elements, particularly variations in enhancer and promoter regions, thereby enhancing clinical gene detection and interpretation of non-coding regions.

Abstract Plot‐scale experiments indicate that functional diversity (FD) plays a pivotal role in sustaining ecosystem functions such as net primary productivity (NPP). However, the relationships between functional diversity and NPP across larger scale under varying climatic conditions are sparsely studied, despite its significance for understanding forest–atmosphere interactions and informing policy development. Hence, we examine the relationships of community‐weighted mean (CWM) and functional dispersion (FDis) of woody plant traits on NPP across China and if such relationships are modulated by climatic conditions at the national scale. Using comprehensive datasets of distribution, functional traits, and productivity for 9120 Chinese woody plant species, we evaluated the distribution pattern of community‐weighted mean and functional dispersion (including three orthogonal trait indicators: plant size, leaf morphology, and flower duration) and its relationships with NPP. Finally, we tested the effects of climatic conditions on community‐weighted mean/functional dispersion–NPP relationships. We first found overall functional diversity–NPP relationships, but also that the magnitude of these relationships was sensitive to climate, with plant size community‐weighted mean promoting NPP in warm regions and plant size functional dispersion promoting NPP in wet regions. Second, warm and wet conditions indirectly increased NPP by its positive effects on community‐weighted mean or functional dispersion, particularly through mean plant size and leaf morphology. Our study provides comprehensive evidence for the relationships between functional diversity and NPP under varying climates at a large scale. Importantly, our results indicate a broadening significance of multidimensional plant functional traits for woody vegetation NPP in response to rising temperatures and wetter climates. Restoration, reforestation actions and natural capital accounting need to carefully consider not only community‐weighted mean and functional dispersion but also their interactions with climate, to predict how functional diversity may promote ecosystem functioning under future climatic conditions.

Abstract Glioblastoma (GBM) is an aggressive intracranial tumour, and current chemotherapy regimens have limited efficacy. Aloperine (ALO), a natural alkaline compound, has shown potential as an antitumor agent. However, the effect of ALO against GBM remains unclear. This study aimed to investigate the function of ALO in treating GBM. U87, A172, and GL261 cell lines were used for in vitro experiments, and GL261 was also used to establish in vivo models. The results showed that ALO inhibited the proliferation of GBM cells by cell cycle arrest and apoptosis. Furthermore, autophagy was found to play a critical role, suggested by observation of autophagosomes under the transmission electron microscopy. It was discovered for the first time that ALO targeted lysosomes directly in glioma cells, tested by fluo-rescence-labelled ALO and organelle-localizing probes. In addition, ALO inhibited late autophagy and induced paraptosis in GBM, verified by classical gene expression changes in qPCR and western blotting. Also, ALO inhibited tumour growth and acted synergistically with temozolomide in intracranial glioma mice models in vivo. Our findings suggest that ALO targets lysosomes to inhibit late autophagy in GBM, inducing cell cycle arrest, paraptosis, and apoptosis. ALO may therefore be a promising therapeutic agent for the treatment of GBM.

Abstract The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.

At present, it is widely believed that a 95–96% average nucleotide identity (ANI) value is equivalent to a 70% digital DNA–DNA hybridization (dDDH) value in the prokaryotic taxonomy. However, in the present study, comparative genome analysis of 29 pairs of Amycolatopsis type strains revealed that a 70% dDDH value did not correspond to a 95–96% ANI based on the MuMmer ultra-rapid aligning tool (ANIm) but approximately corresponded to a 96.6% ANIm value in the genus Amycolatopsis. Based on this corresponding relationship, phenotypic and chemotaxonomical characteristics, as well as phylogenetic analysis, an actinobacterial strain HUAS 11-8T isolated from the rhizosphere soil of Cynara scolymus, was subjected to a polyphasic taxonomic characterization. Based on EzBioCloud alignment, it was found that strain HUAS11-8T had the 16S rRNA gene similarities of 99.78% with A. rhizosphaerae JCM 32589T, 97.8% with A. dongchuanensis YIM 75904T, and

Summary: Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.

Abstract In order to solve the problems of difficult control, poor stability, and low control precision in complex autonomous non‐linear systems, and some sensors have non‐linear errors in special environments. Based on the PSO (Particle Swarm Optimization) algorithm, an PSO‐BP‐PID (Particle Swarm Optimization Back Propagation neural network PID) control method and a sensor error compensation algorithm based on BP (Back Propagation) neural network are designed for optimal temperature and humidity control and sensor error compensation in the autonomous greenhouse system. The error between the average temperature value and the target value after steady state is 0.5°C, and the error between the average humidity value and the target value is 1% RH. The results show that the control method can effectively compensate the non‐linear error of the sensor and improve the performance of the control system in a complex environment, which is suitable for the stable and control of actuators in autonomous systems. The error of temperature and humidity sensor is compensated by BP neural network; PSO (Particle Swarm Optimization) was used to optimize the BP‐PID parameters of the automatic greenhouse system.

Morel‐Lavallée lesion is a closed soft tissue degloving injury usually associated with high‐velocity trauma. It most commonly occurs in the thigh, hip, and pelvis. Because such lesions are prone to a missed or delayed diagnosis, it may present a potential risk of infection at the fracture site once it progresses. Therefore, timely identification and management of Morel‐Lavallée lesion is crucial. Moreover, there are no relevant guidelines for the treatment of Morel‐Lavallée lesion. Based on the above facts, we reviewed the etiology, epidemiology, pathophysiology, clinical presentation, imaging features, treatment, prognosis, and complications of Morel‐Lavallée lesion with the aim of providing a comprehensive overview of Morel‐Lavallée lesion, increasing awareness of this injury among orthopaedic surgeons, and thus providing a management algorithm that can be applied to this injury.

AIM: To compare the accuracy of different intraocular lens(IOL)calculation formulas in cataract patients with axial length longer than 28mm and a history of radial keratotomy(RK).METHODS: Retrospective study. The medical records of 19 cataract patients(29 eyes)after RK and with axial length longer than 28mm who underwent cataract surgery from January 2011 to July 2020 in Beijing Tongren Hospital were analyzed. The absolute error(AE)of the difference among three different formulas was calculated. AE refers to the absolute value between the actual spherical equivalent after cataract surgery and the spherical equivalent predicted by the IOL formula. The AE values of the three formulas and the percentages of eyes with AE≤0.5, 0.75, 1.0, and 2.0D were calculated and compared.RESULTS: The AE values of the three formulas were significantly different(χ2=8.759, P=0.013). The Barrett True-K formula had the smallest median AE, which was only 0.62(0.20, 1.15)D, followed by the Haigis formula 0.76(0.34, 1.26)D, and the Holladay 1(D-K)formula had the largest 1.01(0.49, 1.62)D. The percentages of affected eyes with AE ≤0.5, 0.75, 1.0, and 2.0D for the Barrett True-K formula were 48%, 59%, 69%, and 93%, which were equal to or higher than the other two formulas.CONCLUSION: The Barrett True-K formula is more recommended among the three formulas for cataract patients after RK and with axial length longer than 28 mm.

Abstract Background The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development. Methods MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis. Results MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P

In order to precisely reproduce the precise seeding process of the population in the air-suction seed-metering device, it is necessary to execute accurate modeling of seed particles using the bonded-particle model, in combination with the discrete element method (DEM) and computational fluid dynamics (CFD). Through the repose angle, slope screening, rotating container, and particle sedimentation experiments, in this paper, the influence of the filling accuracy of the bonded-particle model on the flow behavior and mixing characteristics of the seed population was first explored based on EDEM software. The viability of the suggested modeling approach for pelleted vegetable seeds, as described in this study, was confirmed by comparing experimental and simulation outcomes. The surface roughness values obtained from the studies above were utilized to assess the accuracy of the bonded-particle model in filling. Additionally, a mathematical technique for determining the surface roughness was provided. Furthermore, an analysis of the multiple contacts in the bonded-particle model was also performed. The results indicated that the simulation results closely matched the experimental data when the number of sub-spheres in the bonded-particle model was equal to or more than 70, as measured by the standard deviation. In addition, the most optimal modeling scheme for the pelletized vegetable seed bonded-particles, based on the cost of coupling simulation, was found to be the bonded-particle surface roughness (BS) with a value of 0.1. Ultimately, a practical example was utilized to demonstrate the utilization of the pelleted vegetable seed bonded-particle model and the DEM-CFD coupling approach in analyzing the accuracy of the seeding process in the air-suction seed-metering device. This example will serve as a valuable reference point for future field studies.

BackgroundShort sleep duration and poor sleep quality are important risk factors for atherosclerosis. The use of smart bracelets that measure sleep parameters, such as sleep stage, can help determine the effect of sleep quality on lower-extremity atherosclerosis in patients with type 2 diabetes.ObjectiveTo investigate the correlation between sleep disorders and lower-extremity atherosclerosis in patients with type 2 diabetes.MethodsAfter admission, all patients were treated with lower-extremity arterial ultrasound and graded as having diabetic lower-extremity vascular lesions according to the results. A smart bracelet was used to obtain the patient sleep data. The correlation between sleep patterns and diabetic lower-extremity atherosclerosis, diabetic foot, and various metabolic indices was verified.ResultsBetween August 2021 and April 2022, we screened 100 patients with type 2 diabetes, with 80 completing sleep monitoring. Univariate ordered logistic regression analysis indicated that patients with a sleep score below 76 (OR = 2.707, 95%CI: 1.127–6.488), shallow sleep duration of 5.3 h or more (OR=3.040, 95 CI: 1.005–9.202), wakefulness at night of 2.6 times or more (OR = 4.112, 95%CI: 1.513–11.174), and a deep sleep continuity score below 70 (OR = 4.141, 95%CI: 2.460–615.674) had greater risk of high-grade lower limb atherosclerosis. Multivariate ordinal logistic regression analysis revealed that the risk of high-grade lower limb atherosclerosis was higher in patients with 2.6 or more instances of nighttime wakefulness (OR = 3.975, 95%CI: 1.297–12.182) compared with those with fewer occurrences. The sleep duration curve of patients with different grades of diabetic lower-extremity atherosclerosis was U-shaped. According to the results of the one-way analysis of variance, the higher the deep sleep continuity score, the lower the Wagner scale score for diabetic foot (P

ABSTRACT H6 influenza A viruses are enzootic and genetically diverse in both domestic poultry and wild birds, occasionally causing spillovers to mammals, including humans, posing threat to public health. However, the antigenic sites of the hemagglutinin (HA) of H6 are poorly understood. In this study, a panel of murine monoclonal antibodies (MAbs) with different reactivity spectra against HA of H6 was generated and nine key residues of antigenic epitopes in H6 were identified through escape mutants of these MAbs. Of these, residues 139 and 140 belonged to antigenic Sa, residue 89 belonged to antigenic Cb, residue 149 belonged to Ca2, while residue 221 belonged to Ca1 regarding the H1 antigenic sites. However, the other four residues 69, 120, 124, and 246 were not located in the identified antigenic regions of H1. Although most HA variants of the escape mutants had the preference for avian-like receptor, whereas escape mutants m3B9 and m4C2 increased the binding affinity for both avian and human-like receptors, and m1A5 and m6D11 decreased the binding affinity for avian-like receptors. Moreover, a single dose of MAbs 4C2 or 6E3 could fully protect mice against lethal challenge of mouse-adapted A/Eurasian teal/Jiangxi/2018WB0417(H6N2) (MA E-Teal/417) in the prophylactic treatment and also could provide partial protection in the therapeutic treatment. Overall, the generated MAbs and the identified key residues of antigenic epitopes not only provide novel insights into the key markers for monitoring the antigenic variation of H6 but also demonstrate the potential for developing MAb-based passitive treatments for H6. IMPORTANCE Since the escape immunity of influenza A viruses (IAVs) is mainly caused by the continuous antigenic variations in HA, the identification of key antigenic epitopes is crucial for better understanding of the escape immunity and vaccine development for IAVs. The antigenic sites of several HA subtypes, including H1, H3, H5, and H9, have been well characterized, whereas those of H6 subtype are poorly understood. Here, we mapped nine key residues of antigenic epitopes in H6 through escape mutants using a panel of MAbs. Moreover, MAbs 4C2 and 6E3, targeting 140 and 89 residues, respectively, could protect mice against lethal challenge of MA E-Teal/417. These key residues of antigenic epitopes identified here provide the molecular targets for further elucidating the antigenic evolution of H6 and better preparing the vaccine against H6 IAV.

Summary: Parkinson’s disease (PD) is characterized by the irreversible loss of dopaminergic neurons and the accumulation of α-synuclein in Lewy bodies. The oligomeric α-synuclein (O-αS) is the most toxic form of α-synuclein species, and it has been reported to be a robust inflammatory mediator. Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are also genetically linked to PD and neuroinflammation. However, how O-αS and LRRK2 interact in glial cells remains unclear. Here, we reported that LRRK2 G2019S mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-αS on astrocytes both in vivo and in vitro. Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both LRRK2 G2019S and O-αS. We also demonstrated that nuclear factor κB (NF-κB) pathway might be involved in the neuroinflammatory responses. These findings revealed that inhibition of LRRK2 kinase activity may be a viable strategy for suppressing neuroinflammation in PD.

Background and objective Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE. Methods The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test. Results The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P

Abstract In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

AIM: To explore the long-term efficacy, safety, and optical mechanism of orthokeratology with increased compression factor in adolescent myopia control. METHODS: A prospective, double-masked, and randomized clinical trial was performed from May 2016 to June 2020. Subjects aged between 8 and 16y, with myopia (-5.00 to -1.00 D), low astigmatism (≥-1.50 D) and anisometropia (≤1.00 D), were stratified into low (-2.75 to -1.00 D) and moderate (-5.00 to -3.00 D) myopia groups. Then they were randomly assigned to wear either increased compression factor (ICF; 1.75 D) orthokeratology or conventional compression factor (CCF; 0.75 D) orthokeratology. The data were recorded including axial length (AL), spherical equivalent (SE), best corrected visual acuity (BCVA), near visual acuity (NVA), corneal staining (using Efron grading scales), corneal hysteresis (CH), corneal resistance factor (CRF), higher-order aberrations (HOAs, expressed as root mean square, RMSh), and subfoveal choroidal thickness (SFChT) in the 2-year follow-up period. Pearson's correlation coefficient was conducted to analyze the association between the changes in AL and RMSh, SFChT. RESULTS: At the 2-year visit, there were no statistical differences in all the parameters between the ICF group and the CCF group in low myopia subjects (P>0.05). For the moderate myopia subjects, the ICF group had shorter AL elongation (0.23±0.08 vs 0.30±0.11 mm, P=0.015), higher RMSh (1.94±0.50 vs 1.65±0.51 μm, P=0.041), and higher SFChT (279.04±35.72 vs 254.08±29.60 μm, P=0.008) than those in CCF group. The change in AL was negatively correlated with RMSh (r=-0.687, P

Phytoremediation of heavy metal-polluted soils assisted by plant-associated endophytes, is a suitable method for plant growth and manganese (Mn) removal in contaminated soils. This investigation was conducted to evaluate the Mn-resistant endophytic resources of the Mn hyperaccumulator Arabis paniculata and their functions in the phytoremediation of Mn2+ toxicity. This study isolated an endophytic bacterium with high Mn resistance and indole-3-acetic acid (IAA) production form A. paniculata and identified it as Bacillus sp. AP10 using 16 S rRNA gene sequencing analysis. The effects of Bacillus sp. AP10 on the alleviation of Mn2+ toxicity in Arabidopsis thaliana seedlings and the molecular mechanisms were further investigated using biochemical tests and RNA-seq analysis. Under Mn2+ stress, Bacillus sp. AP10 increased the biomass, chlorophyll content and the translocation factor (TF) values of Mn in the aerial parts, while decreased the malondialdehyde (MDA) content of A. thaliana seedlings compared with that of control plants. The differentially expressed genes (DEGs) and enrichment analysis showed that Bacillus sp. AP10 could significantly increase the expression of key genes involved in cell-wall loosening, which may improve plant growth under Mn stress. Superoxide dismutase (SOD)-encoding genes were detected as DEGs after AP10 treatment. Moreover, AP10 regulated the expression of genes responsible for phenylpropanoid pathway, which may promote antioxidant flavonoids accumulation for reactive oxygen species (ROS) scavenging to improve Mn tolerance. The activation of ATP-binding cassette (ABC) transporter gene expression especially ABCB1 after AP10 stimulation, explained the elevation of metal ion binding or transport related to enhanced Mn accumulation in plants. Futhermore, AP10 might alleviate Mn toxicity through enhancing abscisic acid (ABA) responsive gene expression and ABA biosynthesis. These findings provide new insights into the functions and regulatory mechanism of Bacillus sp. AP10 in promoting plant growth, and tolerance, improving Mn accumulation and alleviating Mn2+ toxicity in plants. The application of Bacillus sp. AP10 as potential phytoremediators may be a promising strategy in Mn2+ contaminated fields. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Woven lattice truss sandwich panels (WLTSPs) structure has excellent anti-stripping ability and energy absorption effect. The warp and weft distributions have an effect on the WLTSPs. Foam-filling technique and different heights of WLTSPs were double studied by the testing. Through the compression test and lateral compression test reveal the deformation, damage, failure and energy absorption. In the compression testing, the foam-filling can effectively increase peak force (PF) and energy absorption (EA), especially the weft distribution along the length direction-the specific energy absorption per unit mass of foam (△SEA) is 7.086 J/g. The foam filling transforms the piles from compression-shear coupled damage to progressive damage. In the lateral compression testing, when the WLTSPs at a low height the foam filling leads the load-displacement curve changes from brittleness to ductility. Foam filling improves the PF of PB by up to 459% at the height of 80 mm and restrain the decrease of bearing capacity with the increased height. The failure modes of the WLTSPs includes bending failure to progressive failure, concave, and the end fracture compression.

Diabetes is a significant chronic endocrine/metabolism disorder that can result in a number of life-threatening consequences. According to research, the gut microbiota is strongly linked to the development of diabetes, making it a viable target for diabetes treatment. The intestinal microbiota affects intestinal barrier function, organism immunity, and thus glucose metabolism and lipid metabolism. According to research, a disruption in the intestinal microbiota causes a decrease in short-chain fatty acids (SCFAs), alters the metabolism of bile acids (BAs), branched-chain amino acids (BCAAs), lipopolysaccharide (LPS), and endotoxin secretion, resulting in insulin resistance, chronic inflammation, and the progression to type 2 diabetes mellitus (T2DM). Astragali Radix is a medicinal herb of the same genus as food that has been extensively researched for treating diabetes mellitus with promising results in recent years. Polysaccharides, saponins, flavonoids, and other components are important. Among them, Astragaloside has a role in protecting the cellular integrity of the pancreas and liver, can leading to alleviation of insulin resistance and reducing blood glucose and triglyceride (TC) levels; The primary impact of Astragalus polysaccharides (APS) on diabetes is a decrease in insulin resistance, encouragement of islet cell proliferation, and suppression of islet β cell death; Astragali Radix flavonoids are known to enhance immunity, anti-inflammatory, regulate glucose metabolism and control the progression of diabetes. This study summarizes recent studies on Astragali Radix and its group formulations in the treatment of type 2 diabetes mellitus by modulating the intestinal microbiota.

Abstract The ecology of soil fungi is poorly understood, and recent comprehensive reports on Trichoderma are unavailable for any region, including the Zoige alpine wetland ecological region in China. One hundred soil samples were collected from different soil types and soil layers in Zoige alpine wetland ecological regions. Using the traditional suspension plating method, 80 Trichoderma strains were chosen to analyze species diversity. After a preliminary classification of morphological characteristics and the genes glyceraldehyde-3-phosphate dehydrogenase (gpd), 57 representative strains were selected and eventually identified as seven species via phylogenetic analyses of multilocus sequences based on the genes transcription elongation factor 1 alpha (tef1), encoding RNA polymerase II subunit B (rpb2) and ATP citrate lyase (acl1). Among them, T. harzianum was the dominant species isolated from five soil layers and four soil types, and had the highest isolation frequency (23%) in this zone, while T. polysporum and T. pyramidale were rare species, with isolation frequencies of less than 1%. Our detailed morphological observation and molecular phylogenetic analyses support the recognition of Trichoderma zoigense was described for the first time as a new species, while T. atrobrunneum as a new record for China was found. Our results will be used as a reference for a greater understanding of soil microbial resources, ecological rehabilitation and reconstructions in the Zoige alpine wetland.

AIM: To explore that double steep axial transparent corneal incision can effectively minimize corneal astigmatism and high-order aberration(HOA)in cataract patients with moderate to low degree corneal astigmatism, as well as improve postoperative visual quality.METHODS: A total of 60 cataract patients diagnosed with moderate to low corneal astigmatism in our hospital from October 2020 to July 2021 were randomly divided into group A(normal 135° incision, 30 cases)and group B(double steep axial transparent corneal incision, 30 cases). The uncorrected visual acuity(UCVA), astigmatism, astigmatism vector decomposition, polar keratometry(Polar K), second-order astigmatism, spherical, coma and trefoil aberration within 3mm of the central pupil were compared at 1 and 3mo before and after surgery.RESULTS: UCVA of group A and group B at 1 and 3mo after surgery was significantly higher than that before surgery(P0.05). The corneal astigmatism of group A at 1 and 3mo postoperative were not significantly different from that before surgery(P>0.05).The mean corneal astigmatism of group B was 0.66±0.13 and 0.61±0.12D at 1 and 3mo after surgery, respectively, which was significantly lower than the preoperative value of 1.38±0.24D(P0.05). In group A, CJ0/CJ45 were both significantly different from those at 1 and 3mo before surgery(P0.05). The coma aberration of group B at 3mo after surgery was lower than that before surgery and group A.CONCLUSION: For cataract patients with moderate to low corneal astigmatism, there was no significant difference in postoperative UCVA and HOA between double steep axial transparent corneal incision and normal incision. However, compared with normal incision, double steep axial transparent corneal incision can improve postoperative visual quality by effectively reducing corneal astigmatism and coma aberration.

‘Water circles’ are presented as flexible water cycle diagrams aggregating the flows through a system for a specific region and time period, categorized by flow type and organized by magnitude. Water circles for an entire system and separate storage components can be interpreted as water cycle speedometers and can help compare and communicate different climate and human impacts on different regions, time periods, and storage components. Water circles can facilitate comparisons between hydrological models and other methods for deriving water balances.

As the raw material for tea making, the quality of tea leaves directly affects the quality of finished tea. The quality of fresh tea leaves is mainly assessed by manual judgment or physical and chemical testing of the content of internal components. Physical and chemical methods are more mature, and the test results are more accurate and objective, but traditional chemical methods for measuring the biochemical indexes of tea leaves are time-consuming, labor-costly, complicated, and destructive. With the rapid development of imaging and spectroscopic technology, spectroscopic technology as an emerging technology has been widely used in rapid non-destructive testing of the quality and safety of agricultural products. Due to the existence of spectral information with a low signal-to-noise ratio, high information redundancy, and strong autocorrelation, scholars have conducted a series of studies on spectral data preprocessing. The correlation between spectral data and target data is improved by smoothing noise reduction, correction, extraction of feature bands, and so on, to construct a stable, highly accurate estimation or discrimination model with strong generalization ability. There have been more research papers published on spectroscopic techniques to detect the quality of tea fresh leaves. This study summarizes the principles, analytical methods, and applications of Hyperspectral imaging (HSI) in the nondestructive testing of the quality and safety of fresh tea leaves for the purpose of tracking the latest research advances at home and abroad. At the same time, the principles and applications of other spectroscopic techniques including Near-infrared spectroscopy (NIRS), Mid-infrared spectroscopy (MIRS), Raman spectroscopy (RS), and other spectroscopic techniques for non-destructive testing of quality and safety of fresh tea leaves are also briefly introduced. Finally, in terms of technical obstacles and practical applications, the challenges and development trends of spectral analysis technology in the nondestructive assessment of tea leaf quality are examined.

Brucella, a zoonotic facultative intracellular pathogenic bacterium, poses a significant threat both to human health and to the development of the livestock industry. Alanine racemase (Alr), the enzyme responsible for alanine racemization, plays a pivotal role in regulating virulence in this bacterium. Moreover, Brucella mutants with alr gene deletions (Δalr) exhibit potential as vaccine candidates. However, the mechanisms that underlie the detrimental effects of alr knockouts on Brucella pathogenicity remain elusive. Here, initially, we conducted a bioinformatics analysis of Alr, which demonstrated a high degree of conservation of the protein within Brucella spp. Subsequent metabolomics studies unveiled alterations in amino acid pathways following deletion of the alr gene. Furthermore, alr deletion in Brucella suis S2 induced decreased resistance to stress, antibiotics, and other factors. Transmission electron microscopy of simulated macrophage intracellular infection revealed damage to the cell wall in the Δalr strain, whereas propidium iodide staining and alkaline phosphatase and lactate dehydrogenase assays demonstrated alterations in cell membrane permeability. Changes in cell wall properties were revealed by measurements of cell surface hydrophobicity and zeta potential. Finally, the diminished adhesion capacity of the Δalr strain was shown by immunofluorescence and bacterial enumeration assays. In summary, our findings indicate that the alr gene that regulates amino acid metabolism in Brucella influences the properties of the cell wall, which modulates bacterial adherence capability. This study is the first demonstration that Alr impacts virulence by modulating bacterial metabolism, thereby providing novel insights into the pathogenic mechanisms of Brucella spp.

Introduction: The tumor microenvironment (TME) is mainly characterized by abnormally elevated intracellular redox levels and excessive oxidative stress. However, the balance of the TME is also very fragile and susceptible to be disturbed by external factors. Therefore, several researchers are now focusing on intervening in redox processes as a therapeutic strategy to treat tumors. Here, we have developed a liposomal drug delivery platform that can load a Pt(IV) prodrug (DSCP) and cinnamaldehyde (CA) into a pH-responsive liposome to enrich more drugs in the tumor region for better therapeutic efficacy through enhanced permeability and retention effect.Methods: Using the glutathione-depleting properties of DSCP together with the ROS-generating properties of cisplatin and CA, we synergistically altered ROS levels in the tumor microenvironment to damage tumor cells and achieve anti-tumor effects in vitro.Results: A liposome loaded with DSCP and CA was successfully established, and this liposome effectively increased the level of ROS in the tumor microenvironment and achieved effective killing of tumor cells in vitro.Conclusion: In this study, novel liposomal nanodrugs loaded with DSCP and CA provided a synergistic strategy between conventional chemotherapy and disruption of TME redox homeostasis, leading to a significant increase in antitumor effects in vitro.

Objective The modified Stoppa combined with iliac fossa approach has gained increasing popularity. Although early clinical outcomes have been satisfactory, extensive long‐term clinical outcomes are relatively scarce. The purpose of this study was to evaluate the medium‐ and long‐term outcomes of this approach for complex acetabular fractures. Methods This was a retrospective study involving 57 patients with complex acetabular fractures from January 2009 to January 2016. All fractures were treated with the modified Stoppa combined with iliac fossa approach. Follow‐up was at least 5 years. Primary outcome measures, including quality of reduction and clinical outcomes, were recorded by an independent observer. Secondary outcome measures included time to surgery, surgical time, intraoperative blood loss, and perioperative complications. Results Fifty‐seven patients (range, 18–80 years) included 46 males and 11 females. There were 32 cases on the left side and 25 cases on the right side. The most common associated injury was pulmonary contusion. According to the Judet–Letournel classification, there were 27 both‐column fractures, 16 anterior column with posterior hemitransverse fractures and 14 T‐type fractures. The average time from injury to surgery was 7.3 days. The average intraoperative blood loss and transfusion were 750.9 ml and 564.3 ml, respectively. All fractures healed within 6 months after surgery. The average follow‐up time was 7.7 years, and there was no loss of follow‐up. The quality of reduction was graded as anatomical in 23 cases (40.4%), imperfect in 22 cases (38.6%), and poor in 12 cases (21.0%). According to grading system of Merle d’ Aubigne and Postel, clinical outcomes at 1 year follow‐up were excellent in 17 cases (29.8%), good in 25 cases (43.9%), fair in four cases (7.0%), and poor in 11 cases (19.3%). The excellent and good rate was 73.7% and the difference was not statistically significant compared with the clinical outcomes at the last follow‐up. Intraoperative complications included four cases of obturator nerve injury and two cases of vascular injury. Postoperative complications included one case of wound delayed healing, two cases of deep vein thrombosis, two cases of avascular necrosis of femoral head, three cases of heterotopic ossification and five cases of post‐traumatic arthritis. Only one of these patients underwent reoperation for femoral head necrosis. Conclusions The modified Stoppa combined with iliac fossa approach can achieve satisfactory reduction quality and hip function. It might be a valuable alternative to the ilioinguinal approach for the surgical management of acetabular fractures.

Beginning in May 2022, a rising number of monkeypox cases were reported in non–monkeypox-endemic countries in the Northern Hemisphere. We adapted 2 published quantitative PCRs for use as a dual-target monkeypox virus test on widely used automated high-throughput PCR systems. We determined analytic performance by serial dilutions of monkeypox virus reference material, which we quantified by digital PCR. We found the lower limit of detection for the combined assays was 4.795 (95% CI 3.6–8.6) copies/mL. We compared clinical performance against a commercial manual orthopoxvirus research use only PCR kit by using clinical remnant swab samples. Our assay showed 100% positive (n = 11) and 100% negative (n = 56) agreement. Timely and scalable PCR tests are crucial for limiting further spread of monkeypox. The assay we provide streamlines high-throughput molecular testing for monkeypox virus on existing broadly established platforms used for SARS-CoV-2 diagnostic testing.

AIM:To discuss the efficacy and safety of orthokeratology with reducing back optic zone diameter(5mm-BOZD)compared with conventional back optic zone diameter(6mm-BOZD)in the treatment of adolescent myopia.METHODS: A prospective randomized controlled trial was performed. There were 100 cases with 100 eyes of adolescent myopia(all right eye data were taken)selected from April 2016 to January 2019, the spherical degree was -1.00--5.00D. Then they were randomly divided into the two groups. The experimental group wore 5mm-BOZD orthokeratology, and the control group wore 6mm-BOZD orthokeratology. Their axis length(AL), spherical equivalent(SE), relative peripheral refraction(RPR), best corrected visual acuity(BCVA), uncorrected near visual acuity(NVA), Efron grading was applied to record the anterior segment of the eyes, corneal hysteresis(CH), corneal resistance factor(CRF), corneal-compensated intraocular pressure(IOPcc), average noninvasive Keratograph tear breakup time(NIKBUTav)and higher order aberration(RMSh) were compared between the two groups during the 1a treatment period.RESULTS: After 1a of treatment, the AL in experimental group increased 0.05±0.05mm,while it increased 0.15±0.05mm(t=-8.949, P0.05).CONCLUSION:Reducing back optic zone diameter orthokeratology can correct adolescent myopia safely and more effectively during the observation period.

Abstract Background Venous thromboembolism has been a major public health problem and caused a heavy disease burden. Venous thromboembolism clinical decision support system was proved to have a positive influence on the prevention and management of venous thromboembolism. As the direct users, nurses' acceptance of this system is of great importance to support the successful implementation of it. However, there are few relevant studies to investigate nurses' acceptance and the associated factors are still unclear. Objective To investigate the determinant factors of nurses' acceptance of venous thromboembolism clinical decision support system with the modified Unified Theory of Acceptance and Use of Technology. Methods We designed a questionnaire based on the modified Unified Theory of Acceptance and Use of Technology and then a cross-sectional survey was conducted among nurses in a tertiary hospital in Nanjing, China. Statistically, a Structural Equation Modeling -Partial Least Squares path modeling approach was applied to examine the research model. Results A total of 1100 valid questionnaires were recycled. The modified model explained 74.7%, 83.0% and 86% of the variance in user satisfaction, behavioral intention and user behavior, respectively. The results showed that performance expectancy (β = 0.254, p = 0.000), social influence (β = 0.136, p = 0.047), facilitating conditions (β = 0.245, p = 0.000), self-efficacy (β = 0.121, p = 0.048) and user satisfaction (β = 0.193, p = 0.001) all had significant effects on nurses' intention. Although effort expectancy (β = 0.010, p = 0.785) did not have a direct effect on nurses' intention, it could indirectly influence nurses' intention with user satisfaction as the mediator (β = 0.296, p = 0.000). User behavior was significantly predicted by facilitating conditions (β = 0.298, p = 0.000) and user intention (β = 0.654, p = 0.001). Conclusion The research enhances our understanding of the determinants of nurses' acceptance of venous thromboembolism clinical decision support system. Among these factors, performance expectancy was considered as the top priority. It highlights the importance of optimizing system performance to fit the users' needs. Generally, the findings in our research provide clinical technology designers and administrators with valuable information to better meet users' requirements and promote the implementation of venous thromboembolism clinical decision support system.

The mulberry (Mori Fructus), which is rich in many nutrients needed by the human body, serves as both food and medicine. Polysaccharides, which are considered to be important pharmacological components of mulberry, have received a lot of study for their structure and biological activity. In this study, six mulberry fruit polysaccharides (MFPs) were extracted by different extraction methods, and their physicochemical structures, antioxidant, and hypoglycemic biological activities were investigated and compared. According to the findings, MFP-III exhibited the best α-glucosidase and α-amylase inhibition, whereas MFP-IV had the strongest scavenging activity against DPPH and ABTS. Scanner electron microscopy (SEM) and high-performance liquid chromatography (HPLC) analysis showed that the apparent morphology and monosaccharide content of MFP were significantly impacted by the different extraction techniques. The results of experiments using Congo red, Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), thermogravimetric analysis (TG), and the Congo red experiment showed that the MFP functional groups, glycosidic bonds, triple helix structure, and thermal stability were not significantly different between the extraction methods. According to the aforementioned research, various extraction methods had different effects on the chemical composition and biological activity of mulberry polysaccharides. This information can provide a scientific basis for selecting suitable extraction methods to obtain mulberry polysaccharides with ideal biological activity.

A higher prevalence of depression occurs in patients with lung cancer, while poor prognosis of lung cancer is often associated with depression. Excessive inflammatory response is one of the factors in the presumptive etiology of depression, and the inflammatory microenvironment also plays a key role in tumor genesis, which may indicate a common factor between the lung and the brain. Recently, a new hypothesis, called lung-brain axis, has been proposed because critical pulmonary disorders, such as acute lung injury and acute respiratory distress syndrome appear to be responsible for mood disorder and poor cognitive outcomes. Thus, lung cancer and depression might influence each other through the lung-brain axis. Findings throughout the literature suggest that activation of the interleukin (IL)-6 pathway can activate glial M1 and A1 phenotype activity, which triggers the activity of indoleamine 2,3-dioxygenase (IDO), thereby depleting tryptophan and reducing 5-hydroxytryptamine (5-HT) synthesis. The activation of IL-6 can also inhibit the expression of the 5-HT transporter through the IL-6-JAK/STAT signaling pathway. These changes are major neuropathological aspects of depression. The pathway, as mentioned above, can also promote lung cancer since increased IDO inhibits T lymphocyte proliferation and induces lymphocyte apoptosis. Therefore, the up-regulation of IDO caused by IL-6 may be the common cause for both the development of depression and lung cancer. The purpose of this review is to analyze the inflammatory mechanism and the role of the lung-brain axis in these two disease entities. The review aims to confirm the hypothesis of the lung-brain axis and promote our understanding of the interaction between the lung and the brain.

BackgroundEpicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated.MethodsTo identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining.ResultsCompared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ+ effector memory T lymphocytes (TEM) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients.ConclusionEAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ+ TEM and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue.

Summary: Ovarian granulosa cells (GCs) in the follicle are the important mediator of steroidogenesis and foster oocyte maturation. Evidences suggested that the function of GCs could be regulated by S-palmitoylation. However, the role of S-palmitoylation of GCs in ovarian hyperandrogenism remains elusive. Here, we demonstrated that the protein from GCs in ovarian hyperandrogenism phenotype mouse group exhibits lower palmitoylation level compared with that in the control group. Using S-palmitoylation-enriched quantitative proteomics, we identified heat shock protein isoform α (HSP90α) with lower S-palmitoylation levels in ovarian hyperandrogenism phenotype group. Mechanistically, S-palmitoylation of HSP90α modulates the conversion of androgen to estrogens via the androgen receptor (AR) signalling pathway, and its level is regulated by PPT1. Targeting AR signaling by using dipyridamole attenuated ovarian hyperandrogenism symptoms. Our data help elucidate ovarian hyperandrogenism from perspective of protein modification and provide new evidence showing that HSP90α S-palmitoylation modification might be a potential pharmacological target for ovarian hyperandrogenism treatment.

Nitrogen content is one of the essential elements in citrus leaves (CL), and many studies have been conducted to determine the nutrient content in CL using hyperspectral technology. To address the key problem that the conventional spectral data-denoising algorithms directly discard high-frequency signals, resulting in missing effective signals, this study proposes a denoising preprocessing algorithm, complete ensemble empirical mode decomposition with adaptive noise joint sparse representation (CEEMDAN–SR), for CL hyperspectral data. For this purpose, 225 sets of fresh CL were collected at the Institute of Fruit Tree Research of the Guangdong Academy of Agricultural Sciences, to measure their elemental nitrogen content and the corresponding hyperspectral data. First, the spectral data were preprocessed using CEEMDAN–SR, Stein’s unbiased risk estimate and the linear expansion of thresholds (SURE–LET), sparse representation (SR), Savitzky–Golay (SG), and the first derivative (FD). Second, feature extraction was carried out using principal component analysis (PCA), uninformative variables elimination (UVE), and the competitive adaptive re-weighted sampling (CARS) algorithm. Finally, partial least squares regression (PLSR), support vector regression (SVR), random forest (RF), and Gaussian process regression (GPR) were used to construct a CL nitrogen prediction model. The results showed that most of the prediction models preprocessed using the CEEMDAN–SR algorithm had better accuracy and robustness. The prediction models based on CEEMDAN–SR preprocessing, PCA feature extraction, and GPR modeling had an R2 of 0.944, NRMSE of 0.057, and RPD of 4.219. The study showed that the CEEMDAN–SR algorithm can be effectively used to denoise CL hyperspectral data and reduce the loss of effective information. The prediction model using the CEEMDAN–SR+PCA+GPR algorithm could accurately obtain the nitrogen content of CL and provide a reference for the accurate fertilization of citrus trees.