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Abstract LPIN3 has emerged as a key factor in a variety of malignancies, although its precise role in colorectal cancer (CRC) remains unclear. By analyzing the data from The Cancer Genome Atlas, we discovered that the expression pattern of LPIN3 and the relevant makeup of the immune microenvironment were immensely diverse among tumors. LPIN3 is abundantly expressed in CRC and may enhance tumor growth by activating the β-catenin signaling pathway. In addition, we discovered that LPIN3 might reduce tumor antigen presentation signals, hence suppressing CD8+ T cell-mediated cytotoxicity. Furthermore, high expression of LPIN3 predicts decreased CD8+ T cell infiltration and effector function via bioinformatics analysis. Indeed, CD8+ T cell-mediated cytotoxicity as well as CD8+ T cell infiltration and activation in vivo were strengthened by LPIN3 knockdown. To sum up, our results highlight the part that LPIN3 plays in driving the progression of CRC by regulating β-catenin signaling and CD8+ T cell activity.

Abstract Background The gut microbiota plays a pivotal role in ulcerative colitis (UC) development. This study explores the impact of latent tuberculosis infection (LTBI) on the gut microbiota in UC and assesses changes during vedolizumab treatment, investigating prophylactic anti-tuberculosis therapy. Results This cohort study included adult patients with UC receiving vedolizumab treatment at Jinhua Hospital, Zhejiang University from April 2021 to December 2022. Patients were divided into LTBI (n = 24) and non-LTBI (n = 21) groups. Patients in the LTBI group were further subdivided into prophylactic (n = 13) and non-prophylactic (n = 11) groups. Clinical and fecal samples were collected pre- and post-vedolizumab treatment for the LTBI groups and pre-treatment for the non-LTBI group. The gut microbiota was analyzed using 16 S rRNA sequencing. Patients in the non-LTBI group exhibited higher diversity indices. Vedolizumab demonstrated efficacy in the LTBI group, with clinical response and remission rates of 83.3% and 75.0%, respectively. The gut microbiota diversity in the LTBI group increased post-vedolizumab treatment, and receiving prophylactic isoniazid showed no significant difference in vedolizumab treatment response compared to not receiving prophylactic isoniazid. Microbiota changes were similar between groups, with an increase in [Ruminococcus] expression after vedolizumab treatment. Conclusions This cohort study, conducted at a single center, highlights that LTBI can reduce gut microbiota diversity among adult patient with UC. The observed efficacy of vedolizumab treatment in the LTBI group indicates a potential association with microbiota changes. However, mono-isoniazid exhibited limited impact, underscoring the potential of vedolizumab as a promising candidate for prophylactic anti-tuberculosis treatment in the context of UC.

Aiming at the problems of low accuracy and limited adaptability to large baseline scenes and motion blur scenarios in current homography estimation methods, an end-to-end homography estimation methodwith attention mechanism for large baseline scenes was constructed, which utilized unsupervised learning for homography estimation. Firstly, by introducing the SE channel attention module, a homography regression network layer with attention mechanism was constructed, enabling the network to learn the inter-channel correlations of images. Secondly, a binary unsupervised loss construction method based on mask and perceptual loss metrics was proposed to enhance the network′s perception range and adaptability to large baseline scenes. Finally, a Homo-COCO synthetic dataset was created, and data augmentation was used to improve the network model′s robustness to changes in lighting and motion blur, resulting in stronger generalization capabilities in real-world scenes. Extensive comparative and ablation experiments demonstrate that this method outperforms existing methods in terms of accuracy and scene adaptability, showing good precision and adaptability. It can effectively estimate image homography and provide accurate parameter estimation for subsequent computer vision tasks such as image stitching and image correction.

Abstract Trauma is a common cause of cutaneous surgical disease with an increased risk of secondary infection in cat clinics. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing multiple cytokines and growth factors, is known to accelerate the healing of wounds. However, how PRF affects wound healing in the cat trauma model has not been fully investigated. The study aimed to examine the impact of PRF on skin wound healing in the cat trauma model. In this study, PRF from cats was successfully produced for our investigation. The models of feline trauma were effectively established. A total of 18 cats were randomly divided into 3 groups (n = 6): (1) Control group (CON); (2) PRF group; (3) Manuka honey group (MAN, as a positive control). Experiments were performed separately on days 7, 14, 21, and 28. Our results showed that PRF was a safe and efficient method of wound healing that did not influence the cat’s body temperature, respiration rate, and heart rate (HR). PRF accelerated skin wound healing in the cat trauma model based on the rate and histological observation of wound healing. In addition, PRF promoted the production of growth factors and suppressed inflammation during wound healing. PRF accelerated wound healing by increasing the formation of collagen fibers, as shown by Masson-trichrome staining. The outcomes of the PRF and MAN groups were comparable. In conclusion, PRF improves the healing of skin wounds in cats by boosting the synthesis of growth factors, reducing inflammation, and enhancing the synthesis of collagen fibers. Graphical Abstract

Abstract Background Sepsis-associated acute kidney injury (AKI) is a serious complication of systemic infection with high morbidity and mortality in patients. However, no effective drugs are available for AKI treatment. Dexmedetomidine (DEX) is an alpha 2 adrenal receptor agonist with antioxidant and anti-apoptotic effects. This study aimed to investigate the therapeutic effects of DEX on sepsis-associated AKI and to elucidate the role of mitochondrial dynamics during this process. Methods A lipopolysaccharide (LPS)-induced AKI rat model and an NRK-52E cell model were used in the study. This study investigated the effects of DEX on sepsis-associated AKI and the molecular mechanisms using histologic assessment, biochemical analyses, ultrastructural observation, western blotting, immunofluorescence, immunohistochemistry, qRT-PCR, flow cytometry, and si-mRNA transfection. Results In rats, the results showed that administration of DEX protected kidney structure and function from LPS-induced septic AKI. In addition, we found that DEX upregulated the α2-AR/SIRT1/PGC-1α pathway, protected mitochondrial structure and function, and decreased oxidative stress and apoptosis compared to the LPS group. In NRK-52E cells, DEX regulated the mitochondrial dynamic balance by preventing intracellular Ca2+ overloading and activating CaMKII. Conclusions DEX ameliorated septic AKI by reducing oxidative stress and apoptosis in addition to modulating mitochondrial dynamics via upregulation of the α2-AR/SIRT1/PGC-1α pathway. This is a confirmatory study about DEX pre-treatment to ameliorate septic AKI. Our research reveals a novel mechanistic molecular pathway by which DEX provides nephroprotection.

Low-dose damage evolution in commercial purity (99.95 wt%) magnesium has been investigated, under 200 keV electron irradiation at room temperature, up to ∼0.03 displacements per atom. Quantitative defect production and evolution statistics were obtained for two types of prism foils (z = [12¯10], [101¯0]), in samples of as-received and heat-treated (400 °C/1 h) condition. An incubation period was found to produce visible damage in all samples, in correspondence with about ⅓ of the maximum dose. The damage microstructure consisted of basal-plane 16 loops, exclusively; while no voids were observed throughout the course of irradiations. Steady-state accumulation of dislocation loops was found at doses beyond the incubation limit in heat-treated samples. Higher loop number density and large loop average size were confirmed in [12¯10] than in [101¯0]. One-dimensional loop rafts were developed via elastic interaction. In as-received samples, the presence of pre-existing dislocations (on the order of 1014 m−2) gave rise to suppressed build-up of loop population. Saturation of loop growth was confirmed, when loop average size reached ∼20 nm. Underlying mechanisms of foil orientation effect and pre-existing dislocation effect upon microstructure development are discussed. The paper concludes with a brief comparison between electron irradiation and fission neutron irradiation in magnesium, aiming to bring new insights upon displacement damage studies in materials with hexagonal close-packed structure.

BackgroundVirtual reality (VR) serious games, due to their high level of freedom and realism, influence the rehabilitation training of inhibitory control abilities in children with attention-deficit/hyperactivity disorder (ADHD). Although reward feedback has a motivating effect on improving inhibitory control, the effectiveness and differences between various forms of rewards lack empirical research. ObjectiveThis study aimed to investigate the effectiveness of different forms of reward feedback on the inhibitory control abilities of children with attention deficits in a VR serious game environment. MethodsThis study focuses on children who meet the diagnostic criteria for ADHD tendencies, using a 2 (material rewards: coin reward and token reward) × 2 (psychological rewards: verbal encouragement and badge reward) factorial between-subject design (N=84), with a control group (n=15) for pre- and posttest experiments. The experimental group received VR feedback reinforcement training, while the control group underwent conventional VR training without feedback. The training period lasted 0.5 months, with each intervention session lasting 25 minutes, occurring twice daily with an interval of at least 5 hours for 28 sessions. Before and after training, the Swanson, Nolan, and Pelham, Version IV Scale (SNAP-IV) Scale, stop signal task, inhibition conflict task, and Simon task were administered to assess the hyperactivity index and the 3 components of inhibitory control ability. The pretest included the SNAP-IV Scale and 3 task tests to obtain baseline data; the posttest involved repeating the above tests after completing all training. Data were entered and analyzed using SPSS (IBM) software. Independent sample t tests were performed on the experimental and control groups’ pre- and posttest task results to determine whether significant differences existed between group means. Paired sample t tests were also conducted on the SNAP-IV Scale’s pre- and posttest results to assess the intervention effect’s significance. ResultsReward feedback was more effective than no reward feedback in improving behaviors related to attention deficits in children. Material rewards showed significant effects in the Stop-Signal Task (F1=13.04, P=.001), Inhibition Conflict Task (F1=7.34, P=.008), and SNAP-IV test (F1=69.23, P

BackgroundLegionnaires’ disease has a high clinical mortality rate, and early diagnosis and treatment are critical. Increasing evidence shows that metagenomic next-generation sequencing (mNGS) has excellent potential for the early identification of pathogens. To help clinicians better recognize Legionnaires’ disease in its early stage and to illustrate the diagnostic value of mNGS technology, we reviewed and summarized two cases of severe Legionnaires’ disease.Methods and analysisWe selected two patients with severe Legionnaires’ disease who were admitted to our department in recent years. We discuss experience with them and the shortcomings in their treatment by summarizing their medical history, disease evolution, tests, and diagnostic and therapeutic processes.ResultsIn both patients, the diagnosis of Legionnaires’ disease was confirmed through analysis of the bronchoalveolar lavage fluid (BALF). The middle-aged male patient was cured and discharged due to early detection and diagnosis. The elderly immunocompromised patient died due to a delay in diagnosis.ConclusionThis study highlights the importance of the early recognition and diagnosis of severe Legionnaires’ disease and the advantages of mNGS in identifying the pathogen.

BackgroundThe role of cancer-associated pericytes (CAPs) in tumor microenvironment (TME) suggests that they are potential targets for cancer treatment. The mechanism of CAP heterogeneity in esophageal squamous cell carcinoma (ESCC) remains unclear, which has limited the development of treatments for tumors through CAPs. Therefore, a comprehensive understanding of the classification, function, cellular communication and spatial distribution of CAP subpopulations in ESCC is urgently needed.MethodsThis study used large-sample single-cell transcriptome sequencing (scRNA-seq) data to investigate pericytes’ subpopulation characteristics, functions, upstream and downstream regulation and interactions with other components of the TME in the ESCC, and analyzed prognostically in conjunction with Bulk RNA-seq data. In addition, pericyte subpopulations were validated and their spatial distribution in the ESCC TME was observed by multiplex immunofluorescence. Drug prediction and molecular docking was further used to validate the medicinal value of drug targets.ResultsCAPs in the ESCC TME were found to be highly heterogeneous, and we identified six pericyte subtypes: c1_ARHGDIB, c2_BCAM, c3_LUM, c4_SOD2, c5_TYMS, and c6_KRT17, which have commonality in a part of their functions, and each of them has a major function to play, by having different strengths of interaction with different components in the TME. In addition, we found that c4_SOD2 was negatively correlated with prognosis, conversely, c5_TYMS was positively correlated with prognosis. The drug with a better effect on c5_TYMS was docetaxel (binding energy = -8.1, -8.7 kcal/mol); raloxifene may be more effective against c4_SOD2, although raloxifene has a slightly lower binding energy to SOD2 (-6.4 kcal/mol), it has a higher binding energy to PDGFRβ (-8.1 kcal/mol).ConclusionThe present study identified and discovered pericyte subpopulations that were significantly associated with prognosis, which provides new biomarkers for predicting patient prognosis and adds usable targets for immunotherapy, and it is also important for gaining insights into the composition of the TME in ESCC.

ABSTRACT: As the stress-inducible isoform of the heat-shock protein 90 (HSP90), the HSP90AA1 gene encodes HSP90α and plays an important role in heat stress (HS) response. Therefore, this study aimed to investigate the role of the HSP90AA1 gene in cellular responses during HS and to identify functional SNPs associated with thermotolerance in Holstein cattle. For the in vitro validation experiment of acute HS, cells from the Madin-Darby bovine kidney cell line were exposed to 42°C for 1 h, and various parameters were assessed, including cell apoptosis, cell autophagy, and the cellular functions of HSP90α by using its inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). Furthermore, the polymorphisms identified in the HSP90AA1 gene and their functions related to HS were validated in vitro. Acute HS exposure induced cell apoptosis, cell autophagy, and upregulated expression of the HSP90AA1 gene. Inhibition of HSP90α by 17-AAG treatment had a significant effect on the expression of the HSP90α protein and increased cell apoptosis. However, autophagy decreased in comparison to the control treatment when cells were exposed to 42°C for 1 h. Five SNPs identified in the HSP90AA1 gene were significantly associated with rectal temperature and respiration score in Holstein cows, in which the rs109256957 SNP is located in the 3′ untranslated region (3′ UTR). Furthermore, we demonstrated that the 3′ UTR of HSP90AA1 is a direct target of bta-miR-1224 by cell transfection with exogenous microRNA (miRNA) mimic and inhibitor. The luciferase assays revealed that the SNP rs109256957 affects the regulation of bta-miR-1224 binding activity and alters the expression of the HSP90AA1 gene. Heat stress–induced HSP90AA1 expression maintains cell survival by inhibiting cell apoptosis and increasing cell autophagy. The rs109256957 located in the 3′ UTR region is a functional variation and it affects the HSP90AA1 expression by altering its binding activity with bta-miR-1224, thereby associating with the physiological parameters of Holstein cows.

Abstract Background Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. Methods We measured mtDNA and 2’3’-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. Results KD patient serum exhibited increased mtDNA and 2’3’-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. Conclusion These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.

Abstract Lignocellulose was directly used in itaconic acid production by a model filamentous fungus Neurospora crassa. The promoters of two clock control genes and cellobiohydrolase 1 gene were selected for heterologous genes expression by evaluating different types of promoters. The effect of overexpression of different cellulase was compared, and it was found that expression of cellobiohydrolase 2 from Trichoderma reesei increased the filter paper activity by 2 times, the cellobiohydrolase activity by 4.5 times, and that the itaconic acid titer was also significantly improved. A bidirectional cis-aconitic acid accumulation strategy was established by constructing the reverse glyoxylate shunt and expressing the transporter MTTA, which increased itaconic acid production to 637.2 mg/L. The simultaneous optimization of cellulase and metabolic pathway was more conducive to the improvement of cellulase activity than that of cellulase alone, so as to further increase itaconic acid production. Finally, through the combination of fermentation by optimized strains and medium optimization, the titers of itaconic acid using Avicel and corn stover as substrate were 1165.1 mg/L and 871.3 mg/L, respectively. The results prove the potential of the consolidated bioprocessing that directly converts lignocellulose to itaconic acid by a model cellulase synthesizing strain.

Cyclin-dependent kinase 2 (CDK2) is a critical regulator of cell division and has emerged as a promising target for anticancer treatment. In this article, we summarize the structural features of CDK2 inhibitors and corresponding binding modes, in particular the noncompetitive binding modes that offer unique advantages for the development of highly selective inhibitors. In addition, we present an overview of the latest advancements in the development of CDK2 inhibitors and discuss the trend in the field. This review provides valuable insights into the structure–activity relationships of the reported CDK2 inhibitors, inspiring the development of potent and selective CDK2 inhibitors in the future.

Abstract Colorectal cancer is a grievous health concern, we have proved long non-coding RNA LINC00689 is considered as a potential diagnosis biomarker for colorectal cancer, and it is necessary to further investigate its upstream and downstream mechanisms. Here, we show that KLF15, a transcription factor, exhibits the reduced expression in colorectal cancer. KLF15 suppresses the proliferative and metastatic capacities of colorectal cancer cells both in vitro and in vivo by transcriptionally activating LINC00689. Subsequently, LINC00689 recruits PTBP1 protein to enhance the stability of LATS2 mRNA in the cytoplasm. This stabilization causes the suppression of the YAP1/β-catenin pathway and its target downstream genes. Our findings highlight a regulatory network involving KLF15, LINC00689, PTBP1, LATS2, and the YAP1/β-catenin pathway in colorectal cancer, shedding light on potential therapeutic targets for colorectal cancer therapy.

Objective To investigate the expression levels of type 2 inflammatory cytokines, IL-4 and IL-13, in the serum and blister fluid of patients with bullous pemphigoid (BP). Methods The serum or blister fluid was collected from BP patients (49 cases) and healthy individuals (33 cases). ELISA was used to measure the concentrations of IL-4 and IL-13. The expression levels of IL-4 and IL-13 were compared between the BP patients and healthy controls. The correlations of IL-4 and IL-13 with total serum IgE levels, eosinophils, skin erythema score and pruritus severity (NRS) in BP patients were analyzed. Moreover, the associations of BP180 and BP230 IgG antibodies with IL-4, IL-13 and total serum IgE levels, and eosinophils were determined. Results The concentrations of IL-4 and IL-13 in the blister fluid, but not in the serum, were significantly higher in the BP patients than in the healthy controls (P

As an intelligent component, the high-performance MRE vibration isolator has great advantages, such as a wide vibration isolation frequency range and good performance in semi-active vibration reduction applications. In order to develop high-performance MRE devices, Firstly, this paper makes use of the advantages of real-time tracking/away from external excitation frequency of MRE devices, analyzes the working mode of MRE, and designs a shear MRE vibration isolator based on airborne equipment. Secondly, the material selection and magnetic circuit analysis of the MRE are also completed, and the magnetic field in the MRE region is maximized under the same input energy, thus improving the working efficiency of the MRE isolator. Finally, the relationship between magnetic induction intensity and structural size variables is established by the finite element method and the structural dimensionless method. Based on COMSOL multi-physics simulation software (version 6.0), the global optimization is carried out, the results show that the optimal solution satisfying the comprehensive index of optimal vibration isolation performance of the MRE isolator is obtained, then the structural parameters of the isolator are optimized, and its magnetic control performance is improved. The MRE vibration isolator designed in this paper meets the vibration isolation requirements of airborne optical equipment and has certain engineering application value.

Background: In March 2022, a severe outbreak of the SARS-CoV-2 Omicron variant occurred in Shanghai. This study aimed to determine disease severity, clinical features, clinical outcome in hospitalized patients with the Omicron variant and evaluate the effectiveness of one-dose, two-dose, and three-dose inactivated vaccines in reducing viral loads, disease course, ICU admissions and severe diseases. Methods: Retrospective cohort analysis was performed on 5,170 adult patients (≥18 years) identified as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction admitted at Shanghai Medical Center for Gerontology between March 2022 and June 2022. Demographic information, laboratory data, immunization status, clinical characteristics and outcomes were extracted from electronic medical records. Results: Among 5,170 enrolled patients, the median age was 53 years, and 2,861 (55.3 %) were male. 71.0 % were mild COVID-19 cases, and cough (1,137 [22.0 %]), fever (592 [11.5 %]), sore throat (510 [9.9 %]), and fatigue (334 [6.5 %]) were the most common symptoms on the patient’s first admission. The median length of hospital stay was 8.7 ± 4.5 days. In multivariate logistic analysis, booster vaccination can significantly reduce ICU admissions and decrease the severity of COVID-19 outcome when compared with less doses of vaccine (OR = 0.75, 95 %CI, 0.62–0.91, P ≤ 0.005; OR = 0.99, 95 %CI, 0.99–1.00, p

Extreme low-temperature incidents have become more frequent and severe as climate change intensifies. In Huang-Huai-Hai wheat growing area of China, the late spring coldness occurring at the jointing-booting stage (the anther interval stage) has resulted in significant yield losses of winter wheat. This study attempts to develop an economical, feasible, and efficient cultivation technique for improving the low-temperature (LT) resistance of wheat by exploring the effects of twice-split phosphorus application (TSPA) on wheat antioxidant characteristics and carbon and nitrogen metabolism physiology under LT treatment at the anther interval stage using Yannong 19 as the experimental material. The treatments consisted of traditional phosphorus application and TSPA, followed by a –4°C LT treatment and natural temperature (NT) control at the anther interval stage. Our analyses showed that, compared with the traditional application, the TSPA increased the net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of leaves and reduced the intercellular carbon dioxide concentration (Ci). The activity of carbon and nitrogen metabolism enzymes in the young wheat spikes was also increased by the TSPA, which promoted the accumulation of soluble sugar (SS), sucrose (SUC), soluble protein (SP), and proline (Pro) in young wheat spike and reduced the toxicity of malondialdehyde (MDA). Due to the improved organic nutrition for reproductive development, the young wheat spikes exhibited enhanced LT resistance, which reduced the sterile spikelet number (SSN) per spike by 11.8% and increased the spikelet setting rate (SSR) and final yield by 6.0 and 8.4%, respectively, compared to the traditional application. The positive effects of split phosphorus application became more pronounced when the LT treatment was prolonged.

The karyotype of an organism is the set of gross features that characterize the way the genome is packaged into separate chromosomes. It has been known for decades that different taxonomic groups often have distinct karyotypic features, but whether selective forces act to maintain these differences over evolutionary timescales is an open question. In this paper we analyze a database of karyotype features and sperm head morphology in 103 mammal species with spatulate sperm heads and 90 sauropsid species (birds and non-avian reptiles) with vermiform heads. We find that mammal species with a larger head area have more chromosomes, while sauropsid species with longer heads have a wider range of chromosome lengths. These results remain significant after controlling for genome size, so sperm head morphology is the relevant variable. This suggest that post-copulatory sexual selection, by acting on sperm head shape, can influence genome architecture.

IntroductionDeep learning-based methods can promote and save critical time for the diagnosis of pneumonia from computed tomography (CT) images of the chest, where the methods usually rely on large amounts of labeled data to learn good visual representations. However, medical images are difficult to obtain and need to be labeled by professional radiologists.MethodsTo address this issue, a novel contrastive learning model with token projection, namely CoTP, is proposed for improving the diagnostic quality of few-shot chest CT images. Specifically, (1) we utilize solely unlabeled data for fitting CoTP, along with a small number of labeled samples for fine-tuning, (2) we present a new Omicron dataset and modify the data augmentation strategy, i.e., random Poisson noise perturbation for the CT interpretation task, and (3) token projection is utilized to further improve the quality of the global visual representations.ResultsThe ResNet50 pre-trained by CoTP attained accuracy (ACC) of 92.35%, sensitivity (SEN) of 92.96%, precision (PRE) of 91.54%, and the area under the receiver-operating characteristics curve (AUC) of 98.90% on the presented Omicron dataset. On the contrary, the ResNet50 without pre-training achieved ACC, SEN, PRE, and AUC of 77.61, 77.90, 76.69, and 85.66%, respectively.ConclusionExtensive experiments reveal that a model pre-trained by CoTP greatly outperforms that without pre-training. The CoTP can improve the efficacy of diagnosis and reduce the heavy workload of radiologists for screening of Omicron pneumonia.

Abstract Metabolic abnormalities represent one of the pathological features of chronic obstructive pulmonary disease (COPD). Glutamic pyruvate transaminase 2 (GPT2) is involved in glutamate metabolism and lipid synthesis pathways, whilst the exact roles of GPT2 in the occurrence and development of COPD remains uncertain. This study aims at investigating how GPT2 and the associated genes modulate smoking‐induced airway epithelial metabolism and damage by reprogramming lipid synthesis. The circulating or human airway epithelial metabolomic and lipidomic profiles of COPD patients or cell‐lines explored with smoking were assessed to elucidate the pivotal roles of GPT2 in reprogramming processes. We found that GPT2 regulate the reprogramming of lipid metabolisms caused by smoking, especially phosphatidylcholine (PC) and triacylglycerol (TAG), along with changes in the expression of lipid metabolism‐associated genes. GPT2 modulated cell sensitivities and survival in response to smoking by enhancing mitochondrial functions and maintaining lipid and energy homeostasis. Our findings provide evidence for the involvement of GPT2 in the reprogramming of airway epithelial lipids following smoking, as well as the molecular mechanisms underlying GPT2‐mediated regulation, which may offer an alternative of therapeutic strategies for chronic lung diseases.

In order to satisfy the diversified communication requirements of terminal source nodes in power distribution network, it is necessary to optimize the communication orchestration in power distribution unified communication network. Firstly, we construct the joint optimization problem of data transmission delay and energy consumption. Then, the joint optimization problem is modeled as a multi-armed bandit problem, and an adversarial reinforcement learning-based communication orchestration algorithm for power distribution unified communication network is proposed, which uses the historical orchestration information and the perceived adversary between source nodes to dynamically learn the communication orchestration strategy. Finally, the superior performance of the proposed algorithm is verified through simulation.

In order to solve such problems of smart substations as numerous alarm information caused by communication link failure and poor operation efficiency, a fault location method for communication link is proposed with multi-information fusion modeling of smart substation. Firstly, a communication network numbering principle is proposed by traversing the device nodes of SCD. Secondly, by fusing multiple alarm information, the node and link coding rules are formulated, and the node-link mapping relationship and positioning model are established. And then, the adaptive genetic particle swarm algorithm is used to solve the positioning model to achieve accurate positioning of link faults. Finally, taking the secondary network of a 220 kV smart substation as an example, the effectiveness of the proposed method is verified under different link failure scenarios.

Aiming at the problem of low troubleshooting efficiency of communication link faults caused by complex links in smart substation, a deep learning based fault location method for intelligent substation communication link of smart substation is proposed. Firstly, based on the network topology of secondary devices in smart substations, a network connectivity matrix is constructed and used as the benchmark, and a fault feature characterization method is proposed for communication link faults. And then, based on the logical relationship between secondary device connection and operation status, a fault sample set of the whole station is constructed. The improved CNN is applied to build the fault location model of the smart substation communication link. Finally, the fault link is accurately located through the fault bay information preliminarily determined by the background information and the model output results. A 220 kV smart substation is taken for case study and some bays of it are taken to construct the fault sample set, and different fault location methods are compared through result analysis. The comparison results show that the proposed location method has higher accuracy.

Abstract Inflammation resolution is critical for acute lung injury (ALI) recovery. Interleukin (IL)-10 is a potent anti-inflammatory factor. However, its role in ALI resolution remains unclear. We investigated the effects of IL-10 during the ALI resolution process in a murine lipopolysaccharide (LPS)-induced ALI model. Blockade of IL-10 signaling aggravates LPS-induced lung injury, as manifested by elevated pro-inflammatory factors production and increased neutrophils recruitment to the lung. Thereafter, we used IL-10 GFP reporter mice to discern the source cell of IL-10 during ALI. We found that IL-10 is predominantly generated by B cells during the ALI recovery process. Furthermore, we used IL-10-specific loss in B-cell mice to elucidate the effect of B-cell-derived IL-10 on the ALI resolution process. IL-10-specific loss in B cells leads to increased pro-inflammatory cytokine expression, persistent leukocyte infiltration, and prolonged alveolar barrier damage. Mechanistically, B cell-derived IL-10 inhibits the activation and recruitment of macrophages and downregulates the production of chemokine KC that recruits neutrophils to the lung. Moreover, we found that IL-10 deletion in B cells leads to alterations in the cGMP–PKG signaling pathway. In addition, an exogenous supply of IL-10 promotes recovery from LPS-induced ALI, and IL-10-secreting B cells are present in sepsis-related ARDS. This study highlights that B cell-derived IL-10 is critical for the resolution of LPS-induced ALI and may serve as a potential therapeutic target.

Late spring coldness (LSC) is the main limiting factor threatening wheat yield and quality stability. Optimal nutrient management is beneficial in mitigating the harms of LSC by improving wheat root physiology. This study proposed a nutrient management strategy that postponed the application of phosphorus (P) and potassium (K), effectively strengthening wheat’s defense against LSC. This experiment used the winter cultivar “Yannong19” (YN 19) as plant material for two consecutive years (2021–2022 and 2022–2023). Two fertilizer treatments were used: traditional P and K fertilizers application (R1: base fertilizer: jointing fertilizer = 10:0) and postponed P and K fertilizers application (R2: base fertilizer: jointing fertilizer = 5:5); wheat plants at the anther connective formation stage shifted to temperature-controlled phytotrons for normal (T0, 11 °C/4 h) and low temperatures (T1, 4 °C/4 h; T2, −4 °C/4 h) as treatments of LSC. The results showed that under low temperature (LT) treatment, compared with R1, the R2 treatment increased the concentrations of osmotic adjustment substances (soluble sugars and soluble protein contents by 6.2–8.7% and 3.0–8.9%), enhanced activities of antioxidant enzymes (superoxide dismutase, peroxidase and catalase activities by 2.2–9.1%, 6.2–9.7% and 4.2–8.4%), balanced the hormone concentrations (increased IAA and GA3 contents by 2.8–17.5% and 10.4–14.1% and decreased ABA contents by 7.2–14.3%), and reduced the toxicity (malondialdehyde, hydrogen peroxide content and O2·− production rate by 5.7–12.4%, 17.7–22.8% and 19.1–19.1%) of the cellular membranes. Furthermore, the wheat root physiology in R2 significantly improved as the root surface area and dry weight increased by 5.0–6.6% and 4.7–6.6%, and P and K accumulation increased by 7.4–11.3% and 12.2–15.4% compared to R1, respectively. Overall, the postponed application of P and K fertilizers enhanced the physiological function of the root system, maintained root morphology, and promoted the accumulation of wheat nutrients under the stress of LSC.

Summary: This study proposed two kinds of tensegrity hopping robots, which were actuated by push-pull electromagnets and servo motors, respectively. Both tensegrity robots are able to conduct stable and consecutive hopping actions. This paper covers the robots’ structural designs, theoretical modeling of the hopping actuators, and detailed analysis of the robot’s self-righting properties, all of which are validated by corresponding experimental and simulational results. The first hopping robot could hop forward at an average speed of 0.641 body length/s. Although the second robot has a lower moving speed of 0.237 body length/s, its average jumping height of 0.301 m is nearly 2.5 times higher than that of the first robot. Then compared with other tensegrity rolling robots, the proposed two robots show obvious advantages in locomotion performance over their counterparts. Therefore, the proposed robots can have large potential in many fields such as space exploration, urban search, military surveillance, etc.

China's economy has transitioned into a phase of high-quality development, with enhancing its industrial structure becoming a critical objective. We gathered panel data from 30 major provinces in China from 2010 to 2020 and employed the fixed effects model to assess the actual influence of environmental regulations on industrial structure upgrading. Our empirical findings show that the impacts of various environmental regulations on industrial structure upgrading in China are significantly different. Mandatory environmental regulation demonstrates an inverted U-shaped nonlinear correlation with the upgrading level of the entire industrial structure. When the intensity of this regulation is low, it significantly accelerates industrial structure upgrading. As the intensity of this regulation rises, its effect on industrial structure upgrading is inhibitory. In contrast, induced environmental regulation exhibits a nonlinear U-shaped relationship with industrial structure upgrading and shows a nonlinear change trend of first decreasing and then rising. When the intensity of induced environmental regulation reaches a certain critical point and continues to increase, it will change from a negative influence on the upgrading of the industrial structure to a promoting effect. The further discussion of threshold regression and the robustness test also led to similar conclusions. The above research is conducive to the Chinese government's rational use of environmental regulation tools to promote industrial structure upgrading. It is also beneficial to developing countries, allowing them to learn from China's experience to improve the effectiveness of environmental regulation and boost their industrial development.

The government's environmental protection policy can significantly contribute to alleviating resource shortages and curbing environmental pollution, but the impact of various policy instruments implemented by the government on energy efficiency is unclear. Based on the panel data of 30 provinces in China from 2005 to 2021, this paper analyses the impact of environmental regulation and the industrial structure on energy efficiency from the perspective of resource taxes. The U-shaped relationship between environmental regulation and energy efficiency and between the optimization of industrial structure can significantly improve energy efficiency, and the optimization of industrial structure is conducive to weakening the initial inhibitory effect of environmental regulation. In addition, the analysis of regional heterogeneity showed that the impact of environmental regulation was stronger in the central and western regions, while the impact of industrial structure was stronger in the eastern and western regions. The conclusions of this study can help to expand the understanding of the relationship between environmental regulation and industrial structure on energy efficiency, provide policy enlightenment for the realization of green development and high-quality development, and provide Chinese examples and experiences for developing countries to improve energy efficiency.

Abstract Background Dioscorea opposita Thunb, as a dual-purpose edible plant with excellent nutritional and medical value, accumulates abundant bioactive compounds, including polysaccharides. Polysaccharides from D. opposita have been widely recognized and studied due to various biological activities, such as anti-inflammatory and anti-cancer, which are influenced by their complex structures. In recent years, numerous studies have investigated the structures and activities of D. opposita polysaccharides, and the relationships between them. However, the detailed structures remain different because the structures are susceptible to various species, producing areas, growth conditions (weather, soil, temperature, moisture, etc.), and extraction and separation methods. In this study, the structures of purified polysaccharides from D. opposita were determined and the biological activities were preliminarily investigated including anti-inflammatory and anti-tumor activities. Results The crude polysaccharides DOP1 and DOP2 were isolated and purified via DEAE-52 and Sephadex G-100 to obtain two purified polysaccharides fractions (DOP1-1 and DOP2-1), with the molecular weights of 15.63 kDa and 32.32 kDa, respectively. The structures of DOP1-1 and DOP2-1 were analyzed by HPLC, FT-IR, methylation, and 1D (1H, 13C) and 2D (HSQC, COSY, TOCSY, and ROESY) NMR spectra. The results indicated the presence of → 2)-β-Manp-(1 → 4)-α-Glcp-(1 → 2)-β-Manp-(1 → , → 1)-β-Manp-(2 → 1)-α-GalpA-(4 →, and → 2)-β-Manp-(1 → 2)-β-Manp-(1 → in DOP1-1, and the ratio was 2:11:5. The bone structure of DOP2-1 was predicted as → 1)-β-d-Galp-(4 → , along with two main branching structures composed of arabinose of different degrees of polymerization. Preliminary anti-inflammatory and anti-tumor activities were investigated. DOP1-1 and DOP2-1 demonstrated inhibitory effects on macrophages cells (RAW264.7). DOP2-1 exhibited anti-tumor effects against hepatocellular carcinoma (SNU-739 and HepG2). Conclusions The structures and bioactivities of DOP1-1 and DOP2-1 were analyzed to provide a basis for the establishment of structure/function relationships. The polysaccharides derived from Dioscorea opposita could be potentially employed in functional food, health care, and pharmaceutical industries. Graphical Abstract

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Alizarin, a dyestuff from herbs, showed effective inhibition effects on pathogenic bacteria, and thus has been frequently used in the world as the main alternative to antibiotics in the treatment of inflammations and pathogen infections. However, it was unclear whether alizarin played key a role in antibiotic-induced antibiotic-resistant gene (ARG) alterations and impacted microbial community shifts in aquatic environments. In this study, the effects of alizarin or co-exposure of alizarin with antibiotics on the fate of ARGs, class 1 integron-integrase gene (intI1), and microbial populations in lake water were investigated, and the potential hosts for ARGs were analyzed. The results showed that the absolute abundance of 16s rRNA gene, ARGs (tetA, tetC, and qnrS), and intI1 were increased during the treatment of alizarin. The combination of alizarin and antibiotics was superior to alizarin in its ability to promote population growth of bacteria and induce ARGs. Additionally, alizarin more significantly altered the community composition of microorganisms in water, which resulted in differences in bacterial communities and functions. HIGHLIGHTS Relationships among ARGs, intI1, and microbial community were obtained.; Exposure of alizarin promoted the growth of microbial populations.; Alizarin boost the absolute abundance of ARGs and intI1 to a higher extent.; Alizarin contributed obviously to changes in microbial communities and functions.;

In order to study the anti-fatigue effect of the active ingredients of the ginseng, glycyrrhiza root and osmanthus flower extract on mice, and discuss its anti-fatigue mechanism. The Balb/C mice were randomly divided into 4 groups according to their body weight: Control group and three dose groups (30, 150, 300 mg/L−1). The ginseng glycyrrhiza root and osmanthus flower extract was extracted, filtered and concentrated by hot water reflux process, and then formulated as gavage material in proportion. Gavage saline and low, medium and high doses of extract (once a day) 2 mL each time into the stomach of Balb/C mice that have adapted to the environment. A 28-day gavage trial was performed to record changes in body weight of each group of mice per week. After the last gavage, the hepatic glycogen content, blood urea nitrogen, blood lactate content and T-SOD activity and MDA content were measured by weight-bearing swimming test, normal pressure hypoxia test and biochemical method. The results showed that the serum lactate decreased more significantly after swimming in the administered group of mice than the blank group data, and the increase level of serum urea nitrogen decreased significantly compeared with the blank group, and some dose groups with significant differences. The serum T-SOD levels (218.71±8.14, 217.21±7.82, 204.33±7.78 U·mL−1) and liver glycogen levels (11.75±1.02, 12.03±1.21, 11.84±0.67 mg/g) were significantly higher than those in the blank group (121.18±17.58 U·mL−1, 7.91±0.89 mg/g). And the serum MDA levels of mice in the administered group (11.24±1.18, 13.62±0.65, 15.25±0.91 nmol·mL−1) were significantly lower than those in the blank group (21.18±1.62 nmol·mL−1). The administration of the drug significantly prolonged the survival time of mice under weight-bearing swimming and atmospheric pressure anoxic condition. In conclusion, it shows that ginseng glycyrrhiza root and osmanthus flower extract has significant anti-fatigue effect. The mechanism of action may be related to the rich content of saponins, flavonoids and polysaccharides, which can regulate the liver glycogen content and improve the level of oxygen free radical scavenging in mice.

Abstract Objectives Enhanced neuroinflammation is an important mechanism underlying perioperative neurocognitive disorders. Regulatory T cells (Tregs) play a crucial role in regulating systemic immune responses. The present study was aimed to investigate the participation of Tregs in the development of postoperative cognitive dysfunction (POCD). Methods Surgery-associated neurocognitive disorder was induced in 18-month-old mice subjected to internal fixation of tibial fracture. Morris water maze was used to examine mice cognitive function. Splenic Tregs were collected for RNA sequencing and flow cytometry. Levels of inflammatory factors in the circulation and hippocampus were measured by enzyme-linked immunosorbent assay. Protein presences of tight junction proteins were detected by immunofluorescence. Results Surgery of internal fixation of tibial fracture induced cognitive impairment in aged mice, accompanied by elevated plasma levels of inflammatory factors and increased circulating Tregs. Transfusion of Tregs from young mice partially restored the structure of the blood–brain barrier and alleviated POCD in aged mice. Compared with young Tregs, differentially expressed genes in aged Tregs were enriched in tumor necrosis factor (TNF) signaling pathway and cytokine–cytokine receptor interaction. Flow cytometry revealed that aged Tregs had blunted functions under basal and stimulated conditions. Blockade of the CD25 epitope protected the blood–brain barrier structure, reduced TNF-α levels in the hippocampus, and improved surgery-associated cognition in aged mice. Conclusions Blocking peripheral regulatory T cells improves surgery-induced cognitive function in aged mice. Therefore, aged Tregs play an essential role in the occurrence of POCD.

Abstract Background Renal excretion is one of the major routes of nanomaterial elimination from the body. Many previous studies have found that graphene oxide nanosheets are excreted in bulk through the kidneys. However, how the lateral size affects GO disposition in the kidneys including glomerular filtration, active tubular secretion and tubular reabsorption is still unknown. Results The thin, two-dimensional graphene oxide nanosheets (GOs) was observed to excrete in urine through the kidneys, but the lateral dimension of GOs affects their renal clearance pathway and renal injury. The s-GOs could be renal excreted via the glomerular filtration, while the l-GOs were predominately excreted via proximal tubular secretion at a much faster renal clearance rate than the s-GOs. For the tubular secretion of l-GOs, the mRNA level of basolateral organic anion transporters Oat1 and Oat2 in the kidney presented dose dependent increase, while no obvious alterations of the efflux transporters such as Mdr1 and Mrp4 mRNA expression levels were observed, suggesting the accumulation of l-GOs. During the GO renal elimination, mostly the high dose of 15 mg/kg s-GO and l-GO treatment showed obvious kidney injuries but at different renal compartment, i.e., the s-GOs induced obvious glomerular changes in podocytes, while the l-GOs induced more obvious tubular injuries including necrosis of renal tubular epithelial cells, loss of brush border, cast formation and tubular dilatation. The specifically tubular injury biomarkers KIM1 and NGAL were shown slight increase with mRNA levels in l-GO administrated mice. Conclusions This study shows that the lateral size of GOs affected their interactions with different renal compartments, renal excretion pathways and potential kidney injuries.

Calcineurin B-like (CBL) proteins are a class of important Ca2+ receptors that play key roles in plant stress response. CBLs have been shown to participate in responses to abiotic stresses such as drought, salt, and cold in many plant species, including Arabidopsis and rice. However, little is known about their potential functions in the desert halophyte Nitraria tangutorum. Here, we have identified 11 CBL genes distributed across six chromosomes of N. tangutorum and categorized them into four groups through phylogenetic analysis. Synteny analysis showed that they have strong collinear relationships and have undergone purifying selection during their evolution. NtCBL promoter regions contain a variety of cis-acting elements related to hormone and environmental stress responses. Real-time quantitative PCR showed that the expression of NtCBLs differed significantly among various tissues and was upregulated by salt and drought stress. We chose NtCBL1-1 for an in-depth functional characterization and observed that transgenic Arabidopsis plants expressing NtCBL1-1 exhibited increased tolerance to both drought and salt stress. Compared to wild-type Arabidopsis, transgenic lines showed higher germination rates, slower chlorophyll degradation, more soluble proteins, and reduced accumulation of the oxidative stress marker malondialdehyde. These findings indicate that NtCBL1-1 plays a significant role in responding to drought and salt stress, laying the foundation for further investigations into the functional mechanisms of NtCBL genes in N. tangutorum.

In this paper, a novel 4H-SiC deep-trench super-junction MOSFET (Metal-Oxide-Semiconductor Field-Effect Transistor) with a split-gate is proposed and theoretically verified by Sentaurus TCAD simulations. A deep trench filled with P-poly-Si combined with the P-SiC region leads to a charge balance effect. Instead of a full-SiC P region in conventional super-junction MOSFET, this new structure reduces the P region in a super-junction MOSFET, thus helping to lower the specific on-resistance. As a result, the figure of merit (FoM, BV2/Ron,sp) of the proposed new structure is 642% and 39.65% higher than the C-MOS and the SJ-MOS, respectively.

Abstract Background Evidence from previous studies has suggested that ginger extract exhibits the potential as an alternative treatment for Coronavirus disease 2019 (COVID-19). Here, we want to investigate whether ginger supplement improves the clinical manifestation of hospitalized COVID-19 individuals. Methods A total of 227 hospitalized individuals with COVID-19 were randomized to either the control (n = 132) or intervention group (n = 95). The intervention group took ginger supplement orally at the dosage of 1.5 g twice daily, until they were discharged from the hospital. Both groups received the same standard of general medical care during hospitalization, and the length of stay was recorded and compared between groups. Results Among all participants, a significant reduction in hospitalization time (the difference between the treatment and control groups was 2.4 d, 95% CI 1.6–3.2) was detected in response to the ginger supplement. This effect was more pronounced in men, participants aged 60 years or older, and participants with pre-existing medical conditions, relative to their counterparts (P-interactions

Bullous pemphigoid (BP) is one of the common autoimmune blister diseases that mainly affects the elderly. Most bullous pemphigoid patients have obvious symptom of pruritus, accompanied by elevated levels of serum total IgE, peripheral blood eosinophils, and type 2 cytokines such as IL-4 and IL-13. It was found that a variety of Th2-related inflammatory cells and mediators are involved in the pathogenesis of BP, while Th2 cells and type 2 cytokines are the core drivers of type 2 inflammatory response which indicates that type 2 inflammatory response exists in BP patients. At the same time, the successful treatment of bullous pemphigoid with omalizumab and dupilumab further suggests that bullous pemphigoid is closely related to type 2 inflammation.

Abstract Here, we investigate the precoding schemes for the downlink data transmission of a time‐division duplex cell‐free massive multiple‐input multiple‐output (MIMO) system with channel aging, which arises from the user mobility. Closed‐form spectral efficiency (SE) expressions of the downlink with the normalized conjugate beamforming (NCB), and the full‐pilot zero‐forcing (FZF), are derived, which are used for the analytical system performance evaluation. Then, a novel combinatorial precoding scheme with enhanced system SE performance, which adopts either NCB or FZF according to each user channel aging condition, is proposed. Moreover, a pilot allocation strategy is proposed to alleviate the extra interference brought by the combinatorial precoding scheme. Also, a statistical channel cooperative power control is employed to further improve the performance for all the above precoding schemes. Numerical results show that the proposed precoding scheme can substantially improve the average downlink SE.

Abstract Tunicamycin inhibits the first step of protein N-glycosylation modification. However, the physiological, transcriptomic, and N-glycomic effects of tunicamycin on important marine diatom Phaeodactylum tricornutum are still unknown. In this study, comprehensive approaches were used to study the effects of tunicamycin stress. The results showed that cell growth and photosynthesis were significantly inhibited in P. tricornutum under the tunicamycin stress. The soluble protein content was significantly decreased, while the soluble sugar and neutral lipid were dramatically increased to orchestrate the balance of carbon and nitrogen metabolisms. The stress of 0.3 μg ml−1 tunicamycin resulted in the differential expression of ERQC and ERAD related genes. The upregulation of genes involved in ERQC pathway, the activation of anti-oxidases and the differential expression of genes related with ERAD mechanism might be important for maintaining homeostasis in cell. The identification of N-glycans, especially complex-type N-glycan structures enriched the N-glycan database of diatom P. tricornutum and provided important information for studying the function of N-glycosylation modification on proteins. As a whole, our study proposed working models of ERQC and ERAD will provide a solid foundation for further in-depth study of the related mechanism and the diatom expression system.

BackgroundCOVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks.MethodsWe employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing sepsis and sepsis-induced ARDS in the context of COVID-19 infection, as well as co-existing or sequentially occurring infections. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS.ResultsOur investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes.ConclusionOur investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes prospective alternative pathways for targeted therapeutic interventions.

Abstract Background Lung epithelial cells play important roles in lung inflammation and injury, although mechanisms remain unclear. Osteopontin (OPN) has essential roles in epithelial damage and repair and in lung cancer biological behaviours. Telocyte (TC) is a type of interstitial cell that interacts with epithelial cells to alleviate acute inflammation and lung injury. The present studies aim at exploring potential mechanisms by which OPN regulates the epithelial origin lung inflammation and the interaction of epithelial cells with TCs in acute and chronic lung injury. Methods The lung disease specificity of OPN and epithelial inflammation were defined by bioinformatics. We evaluated the regulatory roles of OPN in OPN‐knockdown or over‐expressed bronchial epithelia (HBEs) challenged with cigarette smoke extracts (CSE) or in animals with genome OPN knockout (gKO) or lung conditional OPN knockout (cKO). Acute lung injury and chronic obstructive pulmonary disease (COPD) were induced by smoking or lipopolysaccharide (LPS). Effects of OPN on PI3K subunits and ERK were assessed using the inhibitors. Spatialization and distribution of OPN, OPN‐positive epithelial subtypes, and TCs were defined by spatial transcriptomics. The interaction between HBEs and TCs was assayed by the co‐culture system. Results Levels of OPN expression increased in smokers, smokers with COPD, and smokers with COPD and lung cancer, as compared with healthy nonsmokers. LPS and/or CSE induced over‐production of cytokines from HBEs, dependent upon the dysfunction of OPN. The severity of lung inflammation and injury was significantly lower in OPN‐gKO or OPN‐cKO mice. HBEs transferred with OPN enhanced the expression of phosphoinositide 3‐kinase (PI3K)CA/p110α, PIK3CB/p110β, PIK3CD/p110δ, PIK3CG/p110γ, PIK3R1, PIK3R2 or PIK3R3. Spatial locations of OPN and OPN‐positive epithelial subtypes showed the tight contact of airway epithelia and TCs. Epithelial OPN regulated the epithelial communication with TCs, and the down‐regulation of OPN induced more alterations in transcriptomic profiles than the up‐regulation. Conclusion Our data evidenced that OPN regulated lung epithelial inflammation, injury, and cell communication between epithelium and TCs in acute and chronic lung injury. The conditional control of lung epithelial OPN may be an alternative for preventing and treating epithelial‐origin lung inflammation and injury.

Abstract Background Describing the pattern of pediatric eye diseases is necessary for appropriate eye care in children. This study explored the spectrum and characteristics of pediatric ophthalmic diseases in a typical tertiary ophthalmology hospital in China. Methods A retrospective study was conducted at a tertiary ophthalmology hospital between 2010 and 2019 in Guangzhou, China. This study included 44,552 inpatients who were younger than 18 years old. Demographic and diagnostic data were collected from the electronic medical record system. Multiphase regression analysis was used to estimate trends in the annual percentages of ten common ophthalmic diseases. Results From 2010 to 2019, 44,552 inpatients met the inclusion criteria. The majority were male (61.9%), aged 7 to 12 years (30.3%) and self-paying (56.6%). The top ten conditions were refractive error (41.2%), strabismus (36.1%), cataract (13.6%), trauma (11.8%), congenital ptosis (8.8%), tumor (8.1%), amblyopia (7.1%), glaucoma (7.0%), entropion and trichiasis of eyelid (7.0%), and retinal detachment (6.5%). The annual percentage changes (APCs) for refractive error, strabismus, and retinal detachment were 9.3% (95% CI, 8.1–10.5%), 4.7% (95% CI, 3.8–5.6%) and − 2.8% (95% CI, − 5.1% to − 0.4%) respectively. For trauma, the average APC (AAPC = -9.2%, (95% CI, − 12.1% to − 6.2%) decreased gradually from 2010 to 2015 (APC = -4.2% (95% CI, − 8.8-0.7%)) and decreased rapidly from 2015 to 2019 (APC = -15.1% (95% CI, − 21.0% to − 8.7%)). Conclusions Pediatric ophthalmic diseases are common in China. Preventive strategies and health education aimed at the prevention of refractive error, strabismus, and entropion and trichiasis of eyelid will be crucial in reducing the burden of pediatric ophthalmic diseases on health care systems and human development.

Understanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery, tissue engineering, therapeutics, etc. GO has been shown to accumulate in the liver after entering the body, and thus, understanding the GO–liver interaction will facilitate the development of safer bio-applications. In this study, the hepatic clearance of two types of PEGylated GOs with different lateral sizes (s-GOs: ~70 nm and l-GOs: ~300 nm) was carefully investigated. We found that GO sheets across the hepatic sinusoidal endothelium, which then may be taken up by the hepatocytes via the Disse space. The hepatocytes may degrade GO into dot-like particles, which may be excreted via the hepatobiliary route. In combination with ICP-MS, LA-ICP-MS, and synchrotron radiation FTIR techniques, we found that more s-GO sheets in the liver were prone to be cleared via hepatobiliary excretion than l-GO sheets. A Raman imaging analysis of ID/IG ratios further indicated that both s-GO and l-GO generated more defects in the liver. The liver microsomes may contribute to GO biotransformation into O-containing functional groups, which plays an important role in GO degradation and excretion. In particular, more small-sized GO sheets in the liver were more likely to be cleared via hepatobiliary excretion than l-GO sheets, and a greater clearance of s-GO will mitigate their hepatotoxicity. These results provide a better understanding of the hepatic clearance of soft NMs, which is important in the safer-by-design of GO.

The basic region/leucine zipper motif (bZIP) transcription factor (TF) family is one of the most important gene families in plants, regulating the plant growth, development, reproduction, as well as stress responses. It was well known that some bZIP TFs in higher plants can regulate polysaccharide metabolism. However, bZIP TFs in microalgae and their function on the polysaccharide metabolism are still unknown. In this study, bioinformatic and molecular methods were carried out to analyze bZIP TFs in the diatom Phaeodactylum tricornutum (Pt). As a result, a total of twenty-two PtbZIP genes were identified and subsequently classified into seven distinct clades based on phylogenetic relationships, conserved motifs, and gene structures. The number of introns varied from zero to three among the PtbZIP genes. All PtbZIP genes were randomly distributed to 16 chromosomes, and each containing one or two PtbZIP domains. Among the 22 identified PtbZIP genes, PtbZIP12 and PtbZIP13 genes were identified as a putative pair of duplicated genes. Furthermore, it was observed that laminarin content increased during the day and decreased during the night. It was proposed that the 12 PtbZIPs showing the same circadian rhythms could positively affect the accumulation of laminarin, while the 10 PtbZIP genes with the opposite expression pattern might have a negative effect on the laminarin metabolism. Based on these findings, a regulatory mechanism for laminarin biosynthesis was proposed in P. tricornutum. The results of this study provide valuable information for further analysis of bZIP TFs functions and laminarin metabolism in microalgae, which may be useful for optimizing the mass production of laminarin.

To improve the accuracy of the mechanical fault diagnosis of the operating mechanism and fully exploit the characteristic information in the vibration signal of the high-voltage circuit breaker, a mechanical fault diagnosis method of the operating mechanism of the high-voltage circuit breaker based on the deep self-encoding network is proposed. First, the vibration signal of the switch operating mechanism is extracted, the wavelet packet conversion is performed, and the vibration signal of each frequency band is divided into equal times. The energy of the time–frequency subplane of the vibration signal is then calculated, and the time–frequency energy distribution is used as a switch. Finally, a breaker failure diagnostic model based on the deep self-coding network is established. Pretraining and tuning and a 126 kV high-voltage switch are used to simulate different types of faults and validate the method. Experimental results show that this method can acquire sample failure data and perform failure diagnosis, and the diagnosis accuracy rate reaches 97.5%. The deep self-coding network can fully pierce deep information on the switch vibration signal.