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Abstract Background There are differences in the research results regarding which edge design of occlusal veneers can achieve the best long-term success rate as a relatively new fixed prosthesis restoration method. Further research is needed. The three-dimensional finite element method was used to conduct stress analysis on occlusal veneers of maxillary first permanent molars with different thicknesses and margin preparation designs. The aim of this study was to provide mechanical research evidence and a reference for exploring standardized clinical protocols for the design of occlusal veneer restorations of maxillary first molars. Method A 3Shape (Intraoral Scanner) was used to scan the maxillary first molar teeth in vitro, after which 3D printing was carried out. Three different edge designs were applied to identical teeth: straight-beveled finishing line(SFL), chamfer finishing line(CFL), and standard cuspal inclination(SCI). Preparation was carried out with a thickness of 0.5 mm. Using the surface deformation feature, the occlusal veneer was thickened to 0.5 mm and 1.0 mm, and periodontal ligaments were added. They were then placed into the upper and lower jaws and dental arches. Finite element analysis was performed after applying bite force dispersion to the loading area on the mandible following dynamic contact. Results (1) As the thickness increased, the maximum Von Mises stress in the occlusal veneers SFL and CFL also increased, while the SCI exhibited the opposite trend. (2). The trend of the maximum Von Mises stress in the adhesive layer decrease gradually with increasing thickness of the occlusal veneer. The stresses of the SFL and CFL is concentrated primarily at the edge position below the functional cusp, resulting in relatively low adhesive stress. However, in the SCI group, the maximum stress at the edge of the adhesive layer exceeds the maximum shear strength of commonly used adhesives. Conclusions Under the experimental conditions, the mechanical properties of the maximum Von Mises stress in the SFL, CFL, and SCI occlusal veneers meet clinical needs. Incorporating the minimally invasive concept of tooth preservation, a thickness of 1.0 mm are optimal for glass ceramic occlusal veneers on maxillary first molars.

Currently, the hierarchical structure is one of the most effective means to enhance the strength and plasticity of metal materials, since the strain localization can be effectively delayed by the coordination of the unique microstructure. In this study, a hierarchical structure of Mg-15Gd-1Zn-0.4Zr (GZ151K) alloys containing grain, twin, and precipitation structural units was prepared by ultrasonic surface rolling process (USRP) and recrystallization annealing (RU). The results showed that the stress gradient generated by USRP formed a twin gradient structure, which will activate the twin-assisted precipitation (TAP) effect and twin-induced recrystallization (TIR) effect during RU. Then, the twin gradient structure transformed into a twin-precipitation gradient structure, and finally into a hierarchical structure with grain-twin-precipitation as the increasement of recrystallization degree. Besides, the dual gradient structure with twin and precipitation structural units had the highest strength and microhardness owing to the precipitation strengthening. However, the hierarchical structure with grain, twin, and precipitation structural units exhibited the most excellent combination of strength and plasticity under grain refinement and precipitation strengthening.

Abstract Background Understanding the release characteristics of soil colloids is a prerequisite for studying the co-transport of colloids and pollutants in subsurface environment. As a crucial agricultural management measure, fertilization not only alters the material composition of farmland soil, but also significantly regulates the properties and release patterns of soil colloids. This study systematically investigated the regulatory mechanism of short-term cattle manure fertilization on the macroscopic release and microscopic properties of soil colloids with different particle sizes, providing a theoretical foundation for subsequent research on the fate and transport of agricultural non-point source pollutants. Results The colloids in natural agricultural soil primarily consist of inorganic components. Graded extraction of the colloids has revealed that the combined proportion of colloids with particle sizes of 1–2 μm and 0.45–1 μm accounts for approximately 80.5%. Applying cattle manure inhibits the release of soil colloids, and the content of large particle size (1–2 μm) components increases. The content of organic colloids is increased due to the high total organic carbon (TOC) in cattle manure, particularly those with a particle size less than 1 μm. The characterization of organic colloid components revealed a significant increase in aromatic carbon and oxygen-containing functional groups, while the aliphatic content decreased. The response sequence regarding changes in functional groups within organic colloids induced by fertilization was as follows: –CH3, –CH2 > C–O > –OH > C=C. Fertilization promotes the release of 1:1-type inorganic mineral colloids, increasing the content of poorly crystalline minerals. The retention of aromatic carbon and oxygen-containing functional groups by poorly crystalline mineral colloids served as the primary mechanism leading to their increased content levels. Changes in environmental factors significantly impacted the release and properties of soil colloids. Conditions such as low cationic valence, high ionic strength, and high pH promoted the release of soil colloids. Conclusions The short-term fertilization resulted in a reduction in the release of soil colloids and brought about significant alterations in their particle size composition and properties. The findings of this study provide valuable insights into understanding the impact of fertilization-induced colloid release on the environmental behavior of agricultural non-point source pollutants.

This paper presents a trajectory tracking control scheme for underactuated surface vessels (USVs) with input delay. Firstly, the underactuated surface vessel system is transformed into a fully actuated system using differential flatness theory. To estimate the unknown nonlinear terms introduced in the transformation process, a fuzzy neural network (FNN) is employed. Secondly, to conserve control resources and communication bandwidth, the controller of the system under prescribed performance is designed using the backstepping method. This method updates the controller according to an event-triggered condition that is designed using a Lyapunov function. Finally, theoretical proof and simulation experiments are conducted to demonstrate the convergence and effectiveness of the proposed method.

Abstract Renal tubular epithelial cells (TECs) undergo an energy‐related metabolic shift from fatty acid oxidation to glycolysis during chronic kidney disease (CKD) progression. However, the mechanisms underlying this burst of glycolysis remain unclear. Herein, a new critical glycolysis regulator, the transcription factor forkhead box protein K1 (FOXK1) that is expressed in TECs during renal fibrosis and exhibits fibrogenic and metabolism‐rewiring capacities is reported. Genetic modification of the Foxk1 locus in TECs alters glycolytic metabolism and fibrotic lesions. A surge in the expression of a set of glycolysis‐related genes following FOXK1 protein activation contributes to the energy‐related metabolic shift. Nuclear‐translocated FOXK1 forms condensate through liquid‐liquid phase separation (LLPS) to drive the transcription of target genes. Core intrinsically disordered regions within FOXK1 protein are mapped and validated. A therapeutic strategy is explored by targeting the Foxk1 locus in a murine model of CKD by the renal subcapsular injection of a recombinant adeno‐associated virus 9 vector encoding Foxk1‐short hairpin RNA. In summary, the mechanism of a FOXK1‐mediated glycolytic burst in TECs, which involves the LLPS to enhance FOXK1 transcriptional activity is elucidated.

Abstract Mercury (Hg), a potent neurotoxin posing risks to human health, is cycled through vegetation uptake, which is susceptible to climate change impacts. However, the extent and pattern of these impacts are largely unknown, obstructing predictions of Hg’s fate in terrestrial ecosystems. Here, we evaluate the effects of climate change on vegetation elemental Hg [Hg(0)] uptake using a state-of-the-art global terrestrial Hg model (CLM5-Hg) that incorporates plant physiology. In a business-as-usual scenario, the terrestrial Hg(0) sink is predicted to decrease by 1870 Mg yr−1 in 2100, that is ~60% lower than the present-day condition. We find a potential decoupling between the trends of CO2 assimilation and Hg(0) uptake process by vegetation in the 21st century, caused by the decreased stomatal conductance with increasing CO2. This implies a substantial influx of Hg into aquatic ecosystems, posing an elevated threat that warrants consideration during the evaluation of the effectiveness of the Minamata Convention.

Model-Free Adaptive Control (MFAC) is a control strategy that eliminates the need for prior knowledge of the system model by leveraging online data to learn the system dynamics and design controllers. This paper offers a comprehensive exploration of the significance of control theory in unmanned surface vessels (USVs), with a particular focus on data-driven approaches. It provides a comprehensive overview of various MFAC algorithms proposed for USVs in diverse scenarios, including neural network-based MFAC, reinforcement learning-based MFAC, and fuzzy logic-based MFAC. The objective of this review is to provide a profound understanding of the latest advancements in MFAC technologies and serve as a guiding resource for further developments in the field.

Traditional antibacterial agents are often observed to be ineffective because bacteria evolved to strains with greater antibiotic resistance. Here, vigorous chitosan‐stabilized PtAu nanoparticles (CSPA) with multienzyme‐like activity are successfully fabricated, which serve an effective artificial nanozyme to enhance antibacterial activity for mixed bacterial infection wound treatment. Ultrasmall size CSPA exhibits excellent hydrophilicity and biocompatibility, possesses strong oxidase‐ and peroxidase‐like activity generating a substantial amount of ROS (O2−, 1O2, ·OH) to cause oxidative damage to bacteria, also demonstrates nicotinamide adenine dinucleotide dehydrogenase‐like activity disrupting the bacterial respiratory chains, and subsequently impedes adenosine triphosphate production. CSPA exhibits favorable broad‐spectrum antibacterial activity at very low concentrations, prevents bacterial resistance, and completely inhibits bacterial biofilm formation. Antibacterial Mechanism of CSPA by the transcriptomics is further revealed that CSPA can induce bacterial oxidative stress, hinder bacterial energy metabolism, and disrupt the synthesis and function of bacterial cell walls and cell membranes. In vivo, CSPA inhibits the mixed bacterial population at the wound site and promotes wound healing in rats. This study introduces a novel antibacterial approach, providing important insight into the antibacterial mechanism of CSPA nanozymes and promoting the advancement of nanocatalytic materials in biomedical applications.

Improving energy utilization efficiency is a crucial means to achieve energy conservation, emission reduction, and green development. At present, to establish a high-quality development framework and satisfy the growing need for a better life among all its people, China must steadfastly pursue the path of green development. Although China’s substantial economic scale and achievements in ecological civilization construction provide favorable conditions for green transformation, there remains a significant gap compared to developed countries in the application of green and clean technologies. Confronted with technological bottlenecks, leveraging emerging technologies such as industrial robots from the new round of scientific and technological revolutions to improve the green total factor energy efficiency (GTFEE) is of critical importance to China’s green development. This study explores the potential impact of industrial robots on enhancing China’s GTFEE. It begins by reviewing the current research landscape in this field, highlighting its shortcomings, and theorizing potential impact pathways of industrial robots. Subsequently, the paper analyzes data from 2010 to 2019 on the usage of industrial robots and GTFEE across 276 cities at the prefectural level or above in China. Through empirical regression models that incorporate control variables and interaction terms, the study investigates the specific impacts of industrial robots on energy efficiency and their mechanisms of action. The results indicate that industrial robots significantly enhance the GTFEE of Chinese cities, especially in the Northeastern region. Industrial robots notably improve the GTFEE in resource-based cities, old industrial bases, and low-carbon pilot cities. Additionally, robots indirectly boost GTFEE by increasing labor productivity. Enhanced levels of green innovation and environmental regulations also positively moderate the effectiveness of industrial robots in improving energy efficiency. The findings of this research can assist local government agencies in coordinating and implementing policies that are conducive to green development, making better use of industrial robots to serve the people, and are of significant importance for promoting the transformation of China’s economy and society towards high-quality development.

IntroductionThe finding that familiarity can support associative memory by unitizing the to -be-learned items into a novel representation has been widely accepted, but its effects on overall performance of associative memory and recollection are still controversial.MethodsThe current study aims to elucidate these discrepancies by identifying potential moderating factors through a combined approach of meta-analysis and behavioral experiment.ResultsResults consistently showed that changes in the level of unitization and age groups were two important moderators. Specifically, unitization enhanced younger and older adults’ associative memory and its supporting processes (i.e., familiarity and recollection) when the level of unitization between studied and rearranged pairs was changed. However, when this level remained constant, unitization exhibited no impact on associative memory and familiarity in younger adults, but showed an enhanced effect in older adults. Furthermore, results revealed a marked group difference between younger and older adults in associative memory when the unitization level of noncompound words remained unaltered. Upon breaking this condition, the group difference was reduced by enhancing familiarity or recollection.DiscussionThese findings not only clarify some of the inconsistencies in the literature concerning the impact of unitization on associative memory, but also suggest that unitization is a beneficial strategy for reducing group difference in associative memory, with its effectiveness varying according to the level of unitization changes.

The aim of this study was to present current research trends on the synergistic use of radiotherapy and immunotherapy (IRT) for cancer treatment. On March 1, 2023, we conducted a literature search for IRT papers using the Web of Science database. We extracted information and constructed two databases – the Core Database (CD) with 864 papers and Generalized Database (GD) with 6344 papers. A bibliometric analysis was performed to provide insights into the research landscape, to identify emerging trends and highly cited papers and journals in the field of IRT. The CD contained 864 papers that were collectively cited 31,818 times. Prominent journals in this area included the New England Journal of Medicine, Lancet Oncology, and the Journal of Clinical Oncology. Corresponding authors from the USA contributed the most publications. In recent years, lung cancer, melanoma, stereotactic radiotherapy, immune checkpoint inhibitors, and the tumor microenvironment emerged as hot research areas. This bibliometric analysis presented quantitative insights into research concerning IRT and proposed potential avenues for further exploration. Moreover, researchers can use our findings to select appropriate journals for publication or identify prospective collaborators. In summary, this bibliometric analysis provides a comprehensive overview of the historical progression and recent advancements in IRT research that may serve as inspiration for future investigations.

Abstract Background The sedative dexmedetomidine has been shown to reduce mortality in adult patients with severe sepsis, but it is not known whether children benefit. This study explored the effects of dexmedetomidine on the outcomes of children with severe sepsis with mechanical ventilation. Methods In this retrospective cohort study, children with severe sepsis requiring mechanical ventilation from 2016 to 2020 were categorized as dexmedetomidine and non-dexmedetomidine group. The propensity score matching was performed to match cases in both groups. The primary outcome was 28-day mortality, and the secondary outcomes were acute kidney injury, ventilator-free days, lengths of PICU and hospital stays. The Kaplan-Meier method and was the log-rank test used to estimate the 28-day mortality rate and assess between-group differences. Results In total, 250 patients were eligible patients: 138 in the dexmedetomidine group and 112 in the non-dexmedetomidine group. After 1:1 propensity score matching, 61 children in each group. dexmedetomidine group showed more lower 28-day mortality (9.84% vs. 26.23%, P = 0.008). During the 7-day observation period after PICU admission, the dexmedetomidine group showed significantly lower neurological and renal sub-scores at day 7 and serum creatinine level at day 3 and day 7. There were no statistical differences in the incidence of acute kidney injury, ventilator-free days, lengths of PICU and hospital stays between the two groups. Conclusions dexmedetomidine treatment in children with severe sepsis is associated with better outcomes and should therefore be considered for the sedation strategy.

In recent years, bat-associated pathogens, such as 2019 novel coronavirus, have been ravaging the world, and ectoparasites of bats have received increasing attention. Penicillidia jenynsii is a member of the family Nycteribiidae which is a group of specialized ectoparasites of bats. In this study, the complete mitochondrial genome of P. jenynsii was sequenced for the first time and a comprehensive phylogenetic analysis of the superfamily Hippoboscoidea was conducted. The complete mitochondrial genome of P. jenynsii is 16 165 base pairs (bp) in size, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes and 1 control region. The phylogenetic analysis based on 13 PCGs of the superfamily Hippoboscoidea known from the NCBI supported the monophyly of the family Nycteribiidae, and the family Nycteribiidae was a sister group with the family Streblidae. This study not only provided molecular data for the identification of P. jenynsii, but also provided a reference for the phylogenetic analysis of the superfamily Hippoboscoidea.

IntroductionSlow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear.MethodsPseudo-germ-free rats were constructed after 6 days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX + STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX + STC rats were randomly divided into three groups: Control → ABX + STC, STC → ABX + STC, and STC + TBD → ABX + STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis.ResultsAfter treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria.ConclusionOur study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota.

Abstract Mitochondria are multifaceted and dynamic organelles regulating various important cellular processes from signal transduction to determining cell fate. As dynamic properties of mitochondria, fusion and fission accompanied with mitophagy, undergo constant changes in number and morphology to sustain mitochondrial homeostasis in response to cell context changes. Thus, the dysregulation of mitochondrial dynamics and mitophagy is unsurprisingly related with various diseases, but the unclear underlying mechanism hinders their clinical application. In this review, we summarize the recent developments in the molecular mechanism of mitochondrial dynamics and mitophagy, particularly the different roles of key components in mitochondrial dynamics in different context. We also summarize the roles of mitochondrial dynamics and target treatment in diseases related to the cardiovascular system, nervous system, respiratory system, and tumor cell metabolism demanding high‐energy. In these diseases, it is common that excessive mitochondrial fission is dominant and accompanied by impaired fusion and mitophagy. But there have been many conflicting findings about them recently, which are specifically highlighted in this view. We look forward that these findings will help broaden our understanding of the roles of the mitochondrial dynamics in diseases and will be beneficial to the discovery of novel selective therapeutic targets.

Abstract Background The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) — polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. Results In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP — CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. Conclusion These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.

Objective: Our study aimed to reveal the possible molecular mechanisms of CD2 and CD27 in influencing the tumor microenvironment of breast cancer (BC) brain metastasis based on the TCGA (The Cancer Genome Atlas) and SRA (Sequence Read Archive) databases. Methods: We calculated the proportions of tumor-infiltrating immune cells and the immune and stromal cell scores in 1222 BC samples from the TCGA-BRCA dataset, followed by identification of candidate DEGs. We further screened for BC brain metastasis-related DEGs in the BC brain metastasis dataset SUB12911144 from the SRA database. Finally, we established a mouse breast cancer brain metastasis model for in vivo validation. Results: We further screened two immune-regulatory DEGs (CD2 and CD27). GSEA analysis showed that the downregulation of CD2 and CD27 expression was closely related to the activation of nitrogen metabolism pathways. CIBERSORT algorithm analysis showed a correlation between the expression of 16 types of tumor-infiltrating immune cells and CD2 and 19 types of tumor-infiltrating immune cells and CD27. In addition, CD2 and CD27 expression were negatively associated with the proportion of M2 macrophages. In vivo experimental results demonstrated that overexpression of CD2/CD27 could suppress the M2 polarization of macrophages and inhibit breast cancer brain metastasis. Conclusion: In the tumor microenvironment, overexpression of CD2/CD27 inhibited the activation of nitrogen metabolism pathways and suppressed M2 polarization of macrophages, thereby preventing brain metastasis of breast cancer.

In recent years, the world has witnessed an alarming rise in extreme events, posing significant challenges to the survival and growth of enterprises. In response, adopting a green development strategy has emerged as an imperative for businesses to bolster their resilience. It is crucial to recognize that not all enterprises possess the same level of resilience, thereby highlighting the disparities in their ability to withstand adversity. Consequently, scholars have been fervently engaging in discussions and research to identify the most effective paths of green development, enabling enterprises to enhance their resilience and adeptly navigate through crises. This study employs questionnaires to scrutinize the influence of environmental regulation, environment social and government performance, and technological innovation on enterprise resilience by constructing structural equations that encompass both external constraints and internal corporate management. The findings demonstrate that environmental regulations can stimulate technological innovation for the purpose of promoting sustainable development, thereby bolstering enterprise resilience; By incorporating environment social and government principles into their operations, enterprises can instil a culture of environmental consciousness and proactively incentivize innovative solutions, ultimately enhancing their capacity to adapt swiftly and recover from crises; The practice of environmental regulation and the incorporation of environment social and government concepts serve as a catalyst for enterprises to engage in technological innovation, thereby promoting technological advancement and enhancing corporate resilience.

Phthiridium szechuanum is a bat surface parasite under the family Nycteribiidae that prefers to roost in the hair of bats to feed on their blood. In this study, the complete mitochondrial genome of P. szechuanum was studied for the first time using Illumina sequencing technology. The mitochondrial genome was 14,896 bp in size and was predicted to encode 37 genes including 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. Phylogenetic trees were constructed using the IQ-TREE web server and phylogenetic analysis was performed using the maximum likelihood method, and P. szechuanum was found to be phylogenetically closest to Basilia ansifera. These data will provide a molecular biological approach to the species identification of P. szechuanum and provide a new reference for further studies on the population genetics and phylogeny of the family Nycteribiidae.

Species of the family Nycteribiidae are blood-sucking ectoparasites that parasitize bats. To further enrich the molecular data of species in the family Nycteribiidae, the complete mitochondrial genome of Nycteribia parvula was sequenced for the first time in this study. The complete mitochondrial genome of N. parvula is 16,060 base pairs (bp) in size, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a control region. The nucleotide contents of A, T, G, and C are respectively 40.86%, 42.19%, 6.51%, and 10.44%. The phylogenetic analysis based on 13 PCGs supports the monophyly of the family Nycteribiidae, and N. parvula is the closest relative to Phthiridium szechuanum.

Abstract Objectives Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis. Methods 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated. Results The patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p

Abstract Background Coronavirus disease 2019 (COVID-19) systemic symptoms and sequelae have been studied extensively, but less is known about the characterization, duration, and long-term sequelae of ocular symptoms associated with COVID-19 infection. The purpose of this study was to analyze the frequency, spectrum, and duration of ocular symptoms in participants with COVID-19 infection treated in inpatient and outpatient settings. Methods A retrospective electronic survey was distributed to NIH employees and the public who reported testing positive for SARS-CoV-2. The anonymous survey collected information on demographics, past ocular history, systemic COVID-19 symptoms, and ocular symptoms. Results A total of 229 (21.9% male and 78.1% female, mean age 42.5 ± 13.9) survey responses were included. Ocular symptoms were reported by 165 participants with a mean of 2.31 ± 2.42 symptoms. The most commonly reported ocular symptoms were light sensitivity (31.0%), itchy eyes (24.9%), tearing (24.9%), eye redness (24.5%), and eye pain (24.5%). Participants with ocular symptoms had a higher number of systemic symptoms compared to participants without ocular symptoms (mean 9.17 ± 4.19 vs 6.22 ± 3.63; OR: 1.21; 95% CI: 1.11 – 1.32; p

Adipogenesis involves complex interactions between transcription and metabolic signalling. Exploration of the developmental characteristics of intramuscular adipocyte will provide targets for enhancing beef cattle marbling without increasing obesity. Few reports have compared bovine perirenal and intramuscular adipocyte transcriptomes using the combined analysis of transcriptomes and lipid metabolism to explore differences in adipogenic characteristics. We identified perirenal preadipocytes (PRA) and intramuscular preadipocytes (IMA) in Qinchuan cattle. We found that IMA were highly prolific in the early stages of adipogenesis, while PRA shows a stronger adipogenic ability in the terminal differentiation. Bovine perirenal and intramuscular adipocytes were detected through the combined analysis of the transcriptome and metabolome. More triglyceride was found to be upregulated in perirenal adipocytes; however, more types and amounts of unsaturated fatty acids were detected in intramuscular adipocytes, including eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA). Furthermore, differentially expressed genes in perirenal and intramuscular adipocytes were positively correlated with the eicosanoid, phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), and sphingomyelin contents. Associated differential metabolic pathways included the glycerolipid and glycerophospholipid metabolisms. Our research findings provide a basis for the screening of key metabolic pathways or genes and metabolites involved in intramuscular fat production in cattle.

Human patients carrying genetic mutations in RNA binding motif 20 (RBM20) develop a clinically aggressive dilated cardiomyopathy (DCM). Genetic mutation knockin (KI) animal models imply that altered function of the arginine-serine-rich (RS) domain is crucial for severe DCM. To test this hypothesis, we generated an RS domain deletion mouse model (Rbm20ΔRS). We showed that Rbm20ΔRS mice manifested DCM with mis-splicing of RBM20 target transcripts. We found that RBM20 was mis-localized to the sarcoplasm in Rbm20ΔRS mouse hearts and formed RBM20 granules similar to those detected in mutation KI animals. In contrast, mice lacking the RNA recognition motif showed similar mis-splicing of major RBM20 target genes but did not develop DCM or exhibit RBM20 granule formation. Using in vitro studies with immunocytochemical staining, we demonstrated that only DCM-associated mutations in the RS domain facilitated RBM20 nucleocytoplasmic transport and promoted granule assembly. Further, we defined the core nuclear localization signal (NLS) within the RS domain of RBM20. Mutation analysis of phosphorylation sites in the RS domain suggested that this modification may be dispensable for RBM20 nucleocytoplasmic transport. Collectively, our findings revealed that disruption of RS domain–mediated nuclear localization is crucial for severe DCM caused by NLS mutations.

Ferroptosis has emerged as a therapeutic tactic to trigger cancer cell death driven by abnormal accumulation of reactive oxygen species (ROS). However, a single ferroptosis treatment modality is often limited. In this work, a combination therapy of ferroptosis and immunotherapy for cancer was proposed. Specifically, a versatile nanodrug was designed for the multiple treatment of hepatocellular carcinoma (HCC) by loading dihydroartemisinin (DHA) on Fe3+-doped MnO2 nanosheets (Fe-MnO2/DHA). Firstly, Fe-MnO2/DHA was degraded by glutathione (GSH) in the tumor microenvironment (TME) to release Fe2+, Mn2+ and DHA, leading to aberrant ROS accumulation due to Fenton/Fenton-like reaction. Secondly, breakage of endoperoxide bridge from DHA was caused by Fe2+ to further induce oxidative stress. Thirdly, the depleted GSH promoted the inactivation of glutathione peroxidase 4 (GPX4), resulting in lipid peroxide (LPO) accumulation. The resulting LPO and ROS could induce ferroptosis and apoptosis of liver cancer cells. Furthermore, Fe-MnO2/DHA mediated three-pronged stimulation of oxidative stress, resulting in high levels of targeted immunogenic cell death (ICD). It could enhance the infiltration of CD4+ T and CD8+ T cells, and promote macrophage polarization. DHA also acted as an immunomodulator to inhibit regulatory T cells (Tregs) for systemic antitumor. Overall, Fe-MnO2/DHA presents a multi-modal therapy for HCC driven by ferroptosis, apoptosis and immune activation, significantly advancing synergistic cancer treatment.

Summary: Renal tubular epithelial cells (TECs) undergoing partial epithelial-mesenchymal transition (pEMT) during renal fibrosis has been recognized as a featuring and detrimental event. However, the mechanism for redirecting the cell fate of pEMT remains unclear. Here we mapped the temporal expression trajectories of a series of EMT-related molecules in renal fibrosis. It revealed a unique expression profile of N-cadherin of initial rising and late dropdown, which is distinct from that of other mesenchymal markers. The transcription factor Foxk1, which serves as a negative regulator of the N-cadherin gene, was induced by TGF-β1 but was tightly regulated in the presence of JNK-associated leucine zipper protein (JLP). The loss of JLP resulted in Foxk1 induction, leading to N-cadherin downregulation and compromised cell viability. We propose a novel axis consisting of JLP/Foxk1/N-cadherin in shaping the EMT program and suggest JLP as the checkpoint of the EMT continuum during renal fibrosis progression.

Retinal diseases are a serious and widespread ophthalmic disease that seriously affects patients’ vision and quality of life. With the aging of the population and the change in lifestyle, the incidence rate of retinal diseases has increased year by year. However, traditional diagnostic methods often require experienced doctors to analyze and judge fundus images, which carries the risk of subjectivity and misdiagnosis. This paper will analyze an intelligent medical system based on focal retinal image-aided diagnosis and use a convolutional neural network (CNN) to recognize, classify, and detect hard exudates (HEs) in fundus images (FIs). The research results indicate that under the same other conditions, the accuracy, recall, and precision of the system in diagnosing five types of patients with pathological changes under color retinal FIs range from 86.4% to 98.6%. Under conventional retinopathy FIs, the accuracy, recall, and accuracy of the system in diagnosing five types of patients ranged from 70.1% to 85%. The results show that the application of focus color retinal FIs in the intelligent medical system has high accuracy and reliability for the early detection and diagnosis of diabetic retinopathy and has important clinical applications.

Background: Peritoneal dialysis-related peritoneal fibrosis is the leading cause of peritoneal ultrafiltration failure. Multitude factors and pathological processes have been implicated in peritoneal fibrosis development and progression, whereas the intrinsic anti-fibrotic mechanism has rarely been explored. JNK-associated leucine zipper protein (JLP) has been recently found possessing powerful anti-fibrotic merits of overall antagonizing TGF-β-induced profibrotic effects. Objectives: We wondered whether JLP is expressed in the peritoneum, and if so, whether it exerts the anti-fibrotic effects similar to those in the kidney. Method: Here, we examined and confirmed JLP expression in peritoneum tissue of mice. Then, we established a peritoneal fibrosis model in Jlp wild-type and Jlp global deficient mice and observed the different effects of Jlp on peritoneal fibrosis progression. In vitro studies were performed on peritoneal mesothelial HMrSV5 cells with or without Jlp knockdown to investigate the underlying mechanism by which Jlp exerts anti-fibrotic effects. Results: We found that the expression of JLP decreased in a high-glucose peritoneal dialysis solution (HGPDS)-induced peritoneal fibrosis mouse model and in HGPDS-treated peritoneal mesothelial cell HMrSV5. JLP deletion exacerbated HGPDS-induced peritoneal fibrosis in peritoneal fibrosis mice, and knockdown of JLP resulted in an increased profibrotic response to HGPDS stimulation in HMrSV5 cells, which was associated with epithelial-to-mesenchymal transition, elevated autophagy, and apoptosis, as well as enhanced TGF-β1/Smad signaling activation. Conclusions: Our findings revealed a new anti-fibrotic factor of Jlp involved in peritoneal fibrosis induction and shed light on novel therapeutic targets in peritoneal ultrafiltration failure.

Summary: Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by Chiloscyllium plagiosum immunization. The functional vNARs were selected by phage display panning strategy from the shark immune library. One of the isolated vNARs, AM2H10, could specifically bind to tetrameric M2 instead of monomeric M2e (the ectodomain of M2 protein). Furthermore, AM2H10 blocked ion influx through amantadine-sensitive and resistant M2 channels. Our findings indicated the possibility of developing functional shark nanobodies against various influenza viruses by targeting the M2 protein.

To solve the problems of low hiding capacity and weak detection resistance, a method of coverless information hiding based on synonyms expansion and label delivery mechanism was proposed.To begin the proposed method, the secret information were divided into several keywords, then those keywords were embedded in different carrier texts respectively.Considering the interchangeability of synonyms in Chinese, using the word similarity calculation method based on HowNet,it was possible to filter synonyms which met the contextual semantics.For the purpose of increasing hiding capacity, various keywords or their synonyms were embedded in the same carrier text as much as possible.At the same moment, when recording the positional parameters of the secret information in each carrier text, those parameters were converted into a binary sequence in a fixed format, which was used to generate carrier text.Finally, the carrier texts and generated text were sent to the receiver.Comparison of the results with those of other studies confirm that the proposed method not only makes great improvement in hiding capacity and detection resistance, but also reduces the overhead of establishing and maintaining databases by using small text database.

ObjectiveNoonan syndrome (NS), an autosomal dominant disease known as a RASopathy, is caused by germline mutations in mitogen-activated protein kinase pathway genes. A RIT1 gene mutation has been found to cause NS. The present study summarizes RIT1 gene mutation sites and associated clinical phenotypes.MethodsWe retrospectively analyzed the clinical characteristics of a case of NS caused by RIT1 mutation in our hospital, and searched the PubMed database, China National Knowledge Infrastructure (CNKI) database and Wanfang database with the keywords Noonan syndrome and RIT1. Studies published between May 1, 2014 and July 1, 2021 were retrieved. By reviewing the abstracts and full text of the studies, we screened NS cases associated with RIT1 mutation in children 0–18 years of age. The clinical characteristics of these cases were summarized.ResultsA total of 41 cases were analyzed, including 13 boys and 28 girls. There were 14 premature cases. The age at diagnosis was 4 days to 18 years, and 10 cases were diagnosed at 0–1 years of age. Common amino acid substitution positions included 57 (13/41), 95 (7/41), 82 (8/41), and 90 (4/41). A total of 63.63% cases had abnormal prenatal examination results, manifesting mainly as fetal neck edema, polyhydramnios and cardiac malformation. With respect to abnormal conditions after birth, 70–80% of patients had typical developmental malformations of the face, neck and thorax; 19/35 patients had abnormal lymphatic development; and a portion of patients had short stature and motor development disorders. A total of 87.80% (36/41) patients had cardiac dysplasia, among which hypertrophic cardiomyopathy (HCM) accounted for 58.53%. A total of 84.62% of patients carrying the p.A57G mutation had HCM, but no HCM was found in patients with the p.G95A mutation. A total of 34.15% of patients had pulmonary artery or pulmonary valve stenosis (PVS). In patients with the p.M90I mutation, 75% had PVS. Patients with concurrent HCM and PVS accounted for 19.51 and 48.78% of patients had supraventricular tachycardia.ConclusionA RIT1 gene mutation causing NS was associated with a high rate of abnormal prenatal examination findings. Most patients had typical NS craniofacial deformities, and some have short stature and motor development disorders. The cardiac deformity rate was high, and HCM was common. Some patients had supraventricular arrhythmias. Heart abnormalities showed high heterogeneity, given the various mutation loci.

Dendrobium catenatum is a high-value medicinal plant that is predominantly found in high mountain areas, thriving amidst cliffs and rock crevices. However, its wild resources face constant threats from adverse environmental conditions, especially drought stress. Fatty acyl-CoA reductase (FAR) is crucial in plant drought resistance, but there is a lack of research on FAR genes in D. catenatum. In this study, the FAR family genes were identified from the D. catenatum genome. Their genomic characteristics were investigated using bioinformatics techniques, and their expression patterns in different tissues and under 20% PEG8000 conditions mimicking drought stress were analyzed using quantitative real-time RT-PCR (RT-qPCR). Seven DcFAR genes were identified from the D. catenatum genome. The encoded amino acids range between 377 and 587 aa, with molecular weights between 43.41 and 66.15 kD and isoelectric points between 5.55 and 9.02. Based on the phylogenetic relationships, the FAR family genes were categorized into three subgroups, each with similar conserved sequences and gene structures. The cis-acting elements of the promoter regions were assessed, and the results reveal that the DcFAR upstream promoter region contains multiple stress-related elements, suggesting its potential involvement in abiotic stress responses. The RT-qPCR results show distinct expression patterns of DcFAR genes in various plant tissues. It was observed that the expression of most DcFAR genes was upregulated under drought stress. Among them, the expression levels of DcFAR2, DcFAR3, DcFAR5, and DcFAR7 genes under drought stress were 544-, 193-, 183-, and 214-fold higher compared to the control, respectively. These results indicate that DcFAR2/3/5/7 might play significant roles in D. catenatum drought tolerance. This research offers insight into the function of DcFAR genes and provides theoretical support for breeding drought-resistant D. catenatum varieties.

F-box protein is a key protein of the SCF E3 ubiquitin ligase complex, responsible for substrate recognition and degradation through specific interactions. Previous studies have shown that F-box proteins play crucial roles in Cryptococcus sexual reproduction. However, the molecular mechanism by which F-box proteins regulate sexual reproduction in C. neoformans is unclear. In the study, we discovered the AICAR transformylase/IMP cyclohydrolase Ade16 as a substrate of Fbp1. Through protein interaction and stability experiments, we demonstrated that Ade16 is a substrate for Fbp1. To examine the role of ADE16 in C. neoformans, we constructed the iADE16 strains and ADE16OE strains to analyze the function of Ade16. Our results revealed that the iADE16 strains had a smaller capsule and showed growth defects under NaCl, while the ADE16OE strains were sensitive to SDS but not to Congo red, which is consistent with the stress phenotype of the fbp1Δ strains, indicating that the intracellular protein expression level after ADE16 overexpression was similar to that after FBP1 deletion. Interestingly, although iADE16 strains can produce basidiospores normally, ADE16OE strains can produce mating mycelia but not basidiospores after mating, which is consistent with the fbp1Δmutant strains, suggesting that Fbp1 is likely to regulate the sexual reproduction of C. neoformans through the modulation of Ade16. A fungal nuclei development assay showed that the nuclei of the ADE16OE strains failed to fuse in the bilateral mating, indicating that Ade16 plays a crucial role in the regulation of meiosis during mating. In summary, our findings have revealed a new determinant factor involved in fungal development related to the post-translational regulation of AICAR transformylase/IMP cyclohydrolase.

Abstract Background The biosynthesis of milk fat affects both the technological properties and organoleptic quality of milk and dairy products. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that inhibit the expression of their mRNA targets and are involved in downstream signaling pathways that control several biological processes, including milk fat synthesis. miR-34b is a member of the miR-34 miRNA cluster, which is differentially expressed in the mammary gland tissue of dairy cows during lactation and dry periods. Previous studies have indicated miR-34b is a potential candidate gene that plays a decisive role in regulating milk fat synthesis; therefore, it is important to focus on miR-34b and investigate its regulatory effect on the biosynthesis of milk fat in bovine mammary epithelial cells (BMECs). Results In this study, elevated miR-34b levels reduced milk fat synthesis, upregulated 1,999 genes, and downregulated 2,009 genes in BMECs. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes suggested that miR-34b may play an inhibitory role in milk fat synthesis via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway by reducing phosphorylation levels. Notably, the mTOR activator MHY1485 rescued the inhibitory effect of miR-34b. Furthermore, we demonstrated that retinoic acid-induced protein 14 (RAI14) is a target of miR-34b via TargetScan and immunofluorescence assays. RAI14 mRNA and protein levels were significantly decreased by the miR-34b mimic and increased by the miR-34b inhibitor. Moreover, the reduction in RAI14 levels led to the inhibition of the Akt/mTOR signaling pathway. Conclusions Overall, our results identified a miR-34b-RAI14-Akt/mTOR regulatory network, while also providing a theoretical basis for the molecular breeding of dairy cows.

Abstract Background Secondary lung injury is the most common non-neurological complication after traumatic brain injury (TBI). Lung-protective ventilation (LPV) has been proven to improve perioperative oxygenation and lung compliance in some critical patients. This study aimed to investigate whether intraoperative LPV could improve respiratory function and prevent postoperative complications in emergency TBI patients. Methods Ninety TBI patients were randomly allocated to three groups (1:1:1): Group A, conventional mechanical ventilation [tidal volume (VT) 10 mL/kg only]; Group B, small VT (8 mL/kg) + positive end-expiratory pressure (PEEP) (5 cmH2O); and Group C, small VT (8 mL/kg) + PEEP (5 cmH2O) + recruitment maneuvers (RMs). The primary outcome was the incidence of total postoperative pulmonary complications; Secondary outcomes were intraoperative respiratory mechanics parameters and serum levels of brain injury markers, and the incidence of each postoperative pulmonary and neurological complication. Results Seventy-nine patients completed the final analysis. The intraoperative PaO2 and dynamic pulmonary compliance of Groups B and C were higher than those of Group A (P = 0.028; P = 0.005), while their airway peak pressure and plateau pressure were lower than those of group A (P = 0.004; P = 0.005). Compared to Group A, Groups B and C had decreased 30-day postoperative incidences of total pulmonary complications, hypoxemia, pulmonary infection, and atelectasis (84.0 % vs. 57.1 % vs. 53.8 %, P = 0.047; 52.0 % vs. 14.3 % vs. 19.2 %, P = 0.005; 84.0 % vs. 50.0 % vs. 42.3 %, P = 0.006; 24.0 % vs. 3.6 % vs. 0.0 %, P = 0.004). Moreover, intraoperative hypotension was more frequent in Group C than in Groups A and B (P = 0.007). At the end of surgery, the serum levels of glial fibrillary acidic protein and ubiquitin carboxyl-terminal hydrolase isozyme L1 in Group B were lower than those in Groups A and C (P = 0.002; P

Condition-dependent acoustic signals that potentially reveal information about the signaler’s physical or physiological condition are common and important in the animal kingdom. Given the negative effects of parasites on the health and fitness of their hosts, it is reasonable to expect animal acoustic signals to reflect detailed information concerning parasite infection. However, despite previous studies having verified the potential of sexually selected vocalizations to provide information on parasitism based on the correlations between call acoustic properties and parasitism in some animal taxa, less is known about whether acoustic signals used in a non-sexual context also reflect parasite infection especially for highly vocal bats. We thus investigated the relationships between the acoustic properties of distress calls and echolocation pulses and the infestation intensity of gamasid mites and bat flies in Chinese horseshoe bats (Rhinolophus sinicus) to determine whether acoustic signals potentially contain information about parasite infection. We found that bats infected with more gamasid mites uttered significantly shorter echolocation pulses, suggesting that echolocation pulses may contain information on the intensity of mite infection. Additionally, bats infected with more gamasid mites emitted distress calls with narrower bandwidth, while bats with more bat flies emitted calls with longer pause duration. These results suggest that distress calls may not only reflect a signaler’s parasite infection intensity but also may provide information concerning infection with specific parasites. In short, our findings suggest that acoustic signals of bats potentially reflect detailed information about parasite infection.

A simple method has been developed for the synthesis of ­3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one and ­3-aryl-quinoxalin-2(1H)-one derivatives through C–H activation of quinoxalin-2(1H)-ones by peroxides and iodide. In this protocol, the per­oxide (TBPB) serves as both the radical initiator and aryl source, realizing arylation of quinoxalin-2(1H)-one in a one-step reaction. The methodology has the advantages of being a metal-free strategy and having broad functional group tolerance.

In order to solve the movement dysfunction problem of the lower limbs caused by the decline of muscle strength of the lower limbs， bone and joint diseases， cardiovascular and cerebrovascular diseases， spinal cord injury， etc.， such as the inability to independently complete the basic life actions such as walking， standing， sitting， etc.， a mobile assisted robot structure design scheme with the functions of assisted walking， assisted seating， assisted moving is proposed. According to the size distribution of human body， the size of structural components is calculated. In order to ensure that the mechanism has enough structural strength， the finite element simulation analysis of key components is carried out. On this basis， human-machine coupling system model is established， and kinematics simulation of human-machine coupling is completed. Hardware system design scheme of mobile assisted robot is proposed. Electrical system connection is built， and hardware circuit design is completed. In order to verify the correctness of the theoretical results， the experimental prototype is manufactured and related experiments are carried out.

Flavonoids are considered to be critical metabolites in regulating plant responses to abiotic stress. Chalcone synthase (CHS) catalyzes the first key step in the flavonoid biosynthesis pathway. However, there is no in-depth information on the sequence and functional analysis of CHS genes in Dendrobium catenatum. In this study, a total of 14 DcCHS genes were identified, encoding proteins of 349–504 amino acids in length, a protein molecular weight ranging between 39.08 and 56.56 kDa, and isoelectric points from 5.64 to 9.63. The DcCHS proteins were then divided into three groups according to their phylogenetic relationships. The members of each group had similar conserved motifs and gene structures. Quantitative real-time RT-PCR (RT-qPCR) analysis revealed that the DcCHS genes exhibited variable expression patterns in the different plant tissues evaluated. Furthermore, six genes were differentially expressed following exposure to abiotic stresses: DcCHS-6, DcCHS-5/-6, DcCHS-13/-14, and DcCHS-6/-8/-9/-13, which were specifically expressed in response to drought, heat, cold, and salt stress, respectively. This is the first genome-wide analysis of the CHS genes in D. catenatum, and our findings can provide essential information for a better understanding of the function of DcCHS genes, thus facilitating further research on D. catenatum stress tolerance.

Infectious bone defects present a major challenge in the clinical setting currently. In order to address this issue, it is imperative to explore the development of bone tissue engineering scaffolds that are equipped with both antibacterial and bone regenerative capabilities. In this study, we fabricated antibacterial scaffolds using a silver nanoparticle/poly lactic-co-glycolic acid (AgNP/PLGA) material via a direct ink writing (DIW) 3D printing technique. The scaffolds’ microstructure, mechanical properties, and biological attributes were rigorously assessed to determine their fitness for repairing bone defects. The surface pores of the AgNPs/PLGA scaffolds were uniform, and the AgNPs were evenly distributed within the scaffolds, as confirmed via scanning electron microscopy (SEM). Tensile testing confirmed that the addition of AgNPs enhanced the mechanical strength of the scaffolds. The release curves of the silver ions confirmed that the AgNPs/PLGA scaffolds released them continuously after an initial burst. The growth of hydroxyapatite (HAP) was characterized via SEM and X-ray diffraction (XRD). The results showed that HAP was deposited on the scaffolds, and also confirmed that the scaffolds had mixed with the AgNPs. All scaffolds containing AgNPs exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). A cytotoxicity assay using mouse embryo osteoblast precursor cells (MC3T3-E1) showed that the scaffolds had excellent biocompatibility and could be used for repairing bone tissue. The study shows that the AgNPs/PLGA scaffolds have exceptional mechanical properties and biocompatibility, effectively inhibiting the growth of S. aureus and E. coli. These results demonstrate the potential application of 3D-printed AgNPs/PLGA scaffolds in bone tissue engineering.

Abstract. Background:. Previous evidences show that acupuncture and moxibustion therapy has positive effects on peripheral facial nerve paralysis (PFP), but there are many acupuncture treatments based on meridian theory, and there are differences in the efficacy of each program. This study will compare the clinical efficacy of different acupuncture treatments for PFP through mesh meta-analysis. Methods:. Randomized controlled trials of acupuncture therapy in the treatment of PFP are going to be retrieved from 8 Science databases including CNKI, Wanfang, VIP and Chinese Biomedical Science, PubMed, Embase, Web of Science and the Cochrane Library from establishment to January 2022. We will use the Cochrane Risk Bias Assessment Tool to assess the quality of the studies and the grading of recommendation assessment, development and evaluation method to assess the strength of the evidence. All data analyses will be performed by Revman5.3, Gemtc 0.14.3, and Stata 14.0. Results:. This study will evaluate the efficacy of different acupuncture treatments for PFP by evaluating clinical efficacy rate, facial nerve function score, facial disability score scale, facial electromyography, adverse reactions, etc, and further explore the mechanism of action of each therapy. Conclusion:. This study will provide a reliable evidence-based basis for selecting the best acupuncture treatment for PFP. Trial registration:. Open science framework registration number: DOI 10.17605/OSF.IO/XQRK9

Gastric cancer, one of the most common malignant tumors of the digestive tract, is devoid of effective treatment owing to its highly invasive ability. Aquaporins (AQPs), transmembrane water channel proteins, has been shown to be involved in the malignancy of gastric cancer. This study aims to investigate the pathophysiological roles of AQP-1 in gastric cancer. We first demonstrated quantitative real-time polymerase chain reaction analysis and found up-regulation of AQP-1 in gastric cancer cell lines. Additionally, silence of AQP-1 inhibited cell proliferation via decrease of proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2). Moreover, migration and invasion of gastric cancer cells were also suppressed by the interference of AQP-1. However, the tumorigenic mechanism of AQP-1 on gastric cancer is yet to be found. We demonstrated western blot analysis and found that knockdown of AQP-1 decreased protein expression of phospho (p)-GRB7 (growth factor receptor-bound protein 7) and led to a remarkable reduction of p-extracellular signal-regulated kinase (ERK) via inactivation of RAS. In general, our findings indicated that AQP-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation, illuminating a novel AQP-1-RAS/ERK molecular axis as regulator in gastric cancer progression and suggesting potential implications in the treatment of gastric cancer.

Abstract Background MicroRNAs (miRNAs) target genes involved in the hyperproliferation of keratinocytes or immune dysfunction of psoriasis. This study prospectively determined the involvement of miR-183-3p in the pathogenesis of psoriasis. Methods Differentially expressed miR-183-3p between psoriatic lesional and non-lesional skin were determined by quantitative RT-PCR and in situ hybridization (ISH). CCK8 and wound healing assays were performed to assess cell viability and migration of human keratinocyte cell line (HaCaT). The target of miR-183-3p was validated by luciferase activity assay. Results Lower miR-183-3p expression was observed in psoriatic lesional skin compared to psoriatic non-lesional skin. MiR-183-3p over-expression inhibited the viability and migration of HaCaT cells, while inhibition of miR-183-3p promoted the viability and migration of HaCaT cells. Moreover, miR-183-3p could bind to the 3′ UTR of GAB1 (growth factor receptor binding 2-associated binding protein 1) and decrease the mRNA and protein expression of GAB1 in HaCaT cells. In addition, higher GAB1 expression was observed in psoriatic lesional skin than psoriatic non-lesional skin. Conclusion MiR-183-3p exhibited inhibition property in the proliferation and migration of HaCaT cells via down-regulation of GAB1, suggesting the potential therapeutic strategy for psoriasis.

The synchrotron radiation technology has recently emerged as a powerful tool to characterize the real-time microstructure evolution during solidification of alloys. Compared with other methods, the synchrotron radiation technology, along with its unique advantages of strong brightness, high energy, excellent resolution, and good monochromaticity, allows for capturing the dendrite evolution behavior of alloys in real time and can be dynamically coordinated with high-resolution CCD (Charge-coupled Device) imaging systems. This paper briefly reviews the recent advances in developing synchrotron radiation for solidification of alloys with low, medium, and high melting points, and under the external electric, magnetic, and ultrasonic fields. Furthermore, a series of microstructural features and behaviors such as dendrite morphology, growth orientation, dendrite fracture, and rotation are described in detail. Finally, the development trends and application prospects of synchrotron radiation technology in alloy solidification are forecasted.

Abstract Background MicroRNA 942-5p (miR-942-5p) has been reported to promote migration and invasion in non-small cell lung cancer (NSCLC), but the underlying mechanism is not completely understood. The interplay between long non-coding RNAs (lncRNAs) and miRNAs plays a crucial role in tumor progression. Methods In the present study, we performed bioinformatic and biochemical analyses to identify miR-942-5p-interacting lncRNAs. The function and clinical significance of the candidate lncRNA(s) in NSCLC were determined. Results We identified LIFR-AS1 as a pivotal miR-942-5p-interacting lncRNA. Overexpression of miR-942-5p caused a reduction of LIFR-AS1 in NSCLC cells. LIFR-AS1 showed the ability to sponge miR-942-5p, leading to derepression of ZNF471. Functionally, LIFR-AS1 overexpression inhibited NSCLC cell migration and invasion, whereas LIFR-AS1 silencing yielded an opposite effect. In vivo studies confirmed that LIFR-AS1 overexpression suppressed lung metastasis of NSCLC cells. Rescue experiments demonstrated that enforced expression of miR-942-5p or depletion of ZNF471 restored the migration and invasion capacity of LIFR-AS1-overexpressing cells. Moreover, overexpression of ZNF471 restrained NSCLC cell invasion. Clinically, LIFR-AS1 downregulation was significantly correlated with TNM stage, lymph node metastasis, and reduced overall survival in NSCLC patients. Conclusions we provide first evidence for the involvement of the LIFR-AS1/miR-942-5p/ZNF471 axis in NSCLC invasion and metastasis. LIFR-AS1 may represent a novel target for the treatment of NSCLC.

In traditional model predictive control (MPC) methods, the power prediction of the state quantity is not only limited by the measurement of the voltage sensor, but also the open-loop control. In order to boost the overall prediction accuracy without AC voltage sensor, an improved sliding mode estimation-model predictive power precision control strategy without AC voltage sensor was proposed. In this paper, the voltage on the network side is dynamically estimated by using sliding mode sigmoid function, and the system stability is proved by the Lyapunov function. On this basis, the active power and reactive power at time k+2 are calculated through the designed rolling optimization prediction link with feedback correction, aiming to reduce power pulse vibration and accurate prediction. The simulation and experimental results show that the proposed control strategy effectively suppresses the influence of grid-side harmonics on the prediction accuracy and improves the overall of the dynamic and static performance of the system.

ABSTRACT Infection of Cryptococcus neoformans is one of the leading causes of morbidity and mortality, particularly among immunocompromised patients. However, currently available drugs for the treatment of C. neoformans infection are minimal. Here, we report SP1, a peptide derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Saccharomyces cerevisiae, efficiently kills C. neoformans and Cryptococcus gattii. SP1 causes damages to the capsule. Unlike many antimicrobial peptides, SP1 does not form pores on the cell membrane of C. neoformans. It interacts with membrane ergosterol and enters vacuole possibly through membrane trafficking. C. neoformans treated with SP1 show the apoptotic phenotypes such as imbalance of calcium ion homeostasis, reactive oxygen increment, phosphatidylserine exposure, and nuclear fragmentation. Our data imply that SP1 has the potential to be developed into a treatment option for cryptococcosis. IMPORTANCE Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic. However, amphotericin B has rather high renal toxicity, and tolerance to these drugs are quicky developed. The peptide SP1 derived from baker’s yeast GAPDH shows antifungal function to kill Cryptococcus neoformans and Cryptococcus gattii efficiently with a high specificity, even for the drug-resistant strains. Our data demonstrate that SP1 induces the apoptosis-like death of Cryptococcus neoformans at low concentrations. The finding of this peptide may shed light on a new direction to treat cryptococcosis.

Objective To systematically evaluate the prognostic factors for mortality in bullous pemphigoid. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were searched to collect literature on the prognostic factors for mortality in bullous pemphigoid. The quality of studies was assessed by Newcastle–Ottawa Quality Assessment Scale. Two researchers extracted relevant data and scored study quality independently. The hazard ratio (HR) was calculated using the random effects model. Study heterogeneity was assessed using both Cochran’s Q test and I2 statistics. The causes of heterogeneity were assessed by subgroup analysis and/ or sensitivity analysis when heterogeneity was significant. When ten or more studies were included as outcome indicators, publication bias was evaluated by funnel plot and Egger’s test. Results Out of a total of 1,546 articles retrieved, 15 studies involving 2,435 patients were included. The meta-analysis showed that the mortality of patients with bullous pemphigoid increased with positive bullous pemphigoid 180 antibody (HR = 1.85, 95%CI: 1.25~2.75, P = 0.002); concomitant dementia (HR = 2.26, 95%CI: 1.43~3.59, PConclusion Positive bullous pemphigoid 180 antibody, dementia, stroke, heart disease and diabetes mellitus were the prognostic factors for mortality in bullous pemphigoid.

Vascular endothelial injury is important in anthracycline-induced cardiotoxicity. Anthracyclines seriously damage the mitochondrial function and mitochondrial homeostasis. In this study, we investigated the damage of epirubicin to vascular endothelial cells and the protective role of metformin from the perspective of mitochondrial homeostasis. We found that epirubicin treatment resulted in DNA double-strand breaks (DSB), elevated reactive oxygen species (ROS) production, and excessive Angiotensin II release in HUVEC cells. Pretreatment with metformin significantly mitigated the injuries caused by epirubicin. In addition, inhibited expression of Mitochondrial transcription factor A (TFAM) and increased mitochondria fragmentation were observed in epirubicin-treated cells, which were partially resumed by metformin pretreatment. In epirubicin-treated cells, knockdown of TFAM counteracted the attenuated DSB formation due to metformin pretreatment, and inhibition of mitochondrial fragmentation with Mdivi-1 decreased DSB formation but increased TFAM expression. Furthermore, epirubicin treatment promoted mitochondrial fragmentation by stimulating the expression of Dynamin-1-like protein (DRP1) and inhibiting the expression of Optic atrophy-1(OPA1) and Mitofusin 1(MFN1), which could be partially prevented by metformin. Finally, we found metformin could increase TFAM expression and decrease DRP1 expression in epirubicin-treated HUVEC cells by upregulating the expression of calcineurin/Transcription factor EB (TFEB). Taken together, this study provided evidence that metformin treatment was an effective way to mitigate epirubicin-induced endothelial impairment by maintaining mitochondrial homeostasis.

JMJD8 is a protein from the JMJD family that only has the JmjC domain. Studies on the function of JMJD8 indicate that JMJD8 is involved in signaling pathways, including AKT/NF-κB, and thus affects cell proliferation and development. Here, we reported the activity of JMJD8 as a non-histone demethylase. We investigated the demethylation of JMJD8 on trimethylated lysine of AKT1 in vivo and in vitro using trimethylated AKT1 short peptide and AKT1 protein, and we tracked the regulation of JMJD8 on AKT1 activity at the cellular level. The results showed that JMJD8, a mini lysine demethylase, altered AKT1 protein function via changing its degree of methylation.