Search

Abstract Lactiplantibacillus plantarum is selective for carbohydrate utilization, which is primarily regulated by the catabolic control protein A (ccpA). To investigate the impact of carbohydrate metabolism on the in vivo colonization of L. plantarum AR113, we constructed a ccpA knockout strain (AR113ΔccpA). In vitro assays showed that AR113ΔccpA had a 0.34 decrease in maximum biomass, and a 2.63 h increase in hysteresis time compared to AR113. In a single administration, there was no significant difference in the number of AR113 and AR113ΔccpA in the mucus layers, and the number of AR113 was approximately 34‐times higher than AR113ΔccpA at 48 h in the intestinal lumen. Notably, the knockout of the ccpA gene did not affect the colonization time of AR113 in the intestine during continuous administration. Therefore, the present work demonstrated that the ccpA did not play a crucial role in the in vivo colonization time of AR113 and provided valuable insights into the role of carbohydrate metabolism in bacterial colonization time in vivo.

Abstract Background The epidemiological distribution of functional mitral regurgitation (FMR) in heart failure (HF) and mildly reduced ejection fraction (HFmrEF) patients and its impact on outcomes remains unclear. We attempt to investigate the prognosis of FMR in patients with HFmrEF. Methods The HF center registry study is a prospective, single, observational study conducted at the Second Affiliated Hospital of Shenzhen University, where 2330 patients with acute HF (AHF) were enrolled and 890 HFmrEF patients were included in the analysis. The patients were stratified into three categories based on the severity of FMR: none/mild, moderate, and moderate-to-severe/severe groups. Subsequently, a comparison of the clinical characteristics among these groups was conducted, along with an assessment of the incidence of the primary endpoint (comprising all-cause mortality and readmission for HF) during a one-year follow-up period. Results The one-year follow-up results indicated that the primary composite endpoint occurrence rates in the three groups were 23.5%, 32.9%, and 36.5%, respectively. The all-cause mortality rates in the three groups were 9.3%, 13.7%, and 16.4% respectively. Survival analysis demonstrated a statistically significant difference in the occurrence rates of the primary composite endpoint and all-cause mortality among the three groups (P

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Abstract Feline panleukopenia virus (FPV) is a single-stranded DNA virus that can infect cats and cause feline panleukopenia, which is a highly contagious and fatal disease in felines. The sequence of FPV is highly variable, and mutations in the amino acids of its capsid protein play crucial roles in altering viral virulence, immunogenicity, host selection, and other abilities. In this study, the epidemiology of FPV was studied using 746 gastrointestinal swab samples derived from cats that presented gastrointestinal symptoms specifically, diarrhea or vomiting during the period spanning from 2018 to 2022. The overall prevalence of FPV-positive patients among these samples was determined to be 45.4%. Capsid (virion) protein 2 (VP2) gene of each FPV-positive sample was sequenced and amplified, yielding 65 VP2 sequences. Among them, six VP2 gene sequences were detected in the majority of the samples test positive for FPV, and these positive samples originated from a diverse range of geographical locations. These isolates were named FPV-6, FPV-10, FPV-15, FPV-251, FPV-271 and FPV-S2. Additionally, the substitution of Ala300Pro (A300P) in VP2 was detected for the first time in feline-derived FPV (FPV-251). FPV-251 isolate, with this substitution in VP2 protein, exhibited stable proliferative capacity in Madin-Darby canine kidney (MDCK) cells and A72 cells. FPV-271 was selected as the FPV control isolate due to its single amino acid difference from VP2 protein of FPV-251 at position 300 (FPV-271 has alanine, while FPV-251 has proline). After oral infection, both FPV-251 and FPV-271 isolates caused feline panleukopenia, which is characterized by clinical signs of enterocolitis. However, FPV-251 can infect dogs through the oral route and cause gastrointestinal (GI) symptoms with lesions in the intestine and mesenteric lymph nodes (MLNs) of infected dogs. This is the first report on the presence of an A300P substitution in VP2 protein of feline-derived FPV. Additionally, FPV isolate with a substitution of A300P at VP2 protein demonstrated efficient replication capabilities in canine cell lines and the ability to infect dogs.

As a new integrity authentication technology, subject-sensitive hashing has the ability to achieve subject-sensitive authentication for high-resolution remote sensing (HRRS) images and can provide a security guarantee for their subsequent use. However, existing research on subject-sensitive hashing focuses on improving the structure of the deep neural network of the algorithm to improve the algorithm's performance, which makes it necessary to reconstruct the training dataset or modify the network structure in the face of different integrity authentication requirements. In this article, we delve into the impact of dropout on subject-sensitive hashing and propose a stepwise-drop mechanism to address the robustness and tampering-sensitivity requirements of subject-sensitive hashing. On this basis, a network named stepwise-drop and transformer-based U-net (SDTU-net) is proposed for subject-sensitive hashing of HRRS images. SDTU-net can use our proposed stepwise-drop mechanism to determine the drop rate of different network layers, which makes it possible to adjust the algorithm performance without changing network structure and training data. Experiments show that our SDTU-net based subject-sensitive hashing has better overall performance compared with existing algorithms, especially at medium and low thresholds. Our approach solves the problem that the existing algorithms cannot balance robustness and tamper sensitivity at low thresholds.

Since the introduction of the feline panleukopenia virus (FPV) vaccine in China in 2011, it has played a crucial role in safeguarding the health of numerous pet cats by preventing FPV infections. However, an observed rise in FPV infections among cats previously vaccinated has prompted our investigation. Our laboratory has identified a specific FPV isolate, FPV-251, which raises concerns about its potential to evade the immune response. To validate this hypothesis, we conducted a correlational study on FPV-251. Ten sera samples were collected from ten cats two months after receiving the vaccine three times. These samples were prepared in the laboratory to assess their ability to neutralize FPV-251. Results indicated that the neutralization titers of the 10 sera ranged from 1:313.7 to 1:1051.0, with an average titer of 1:627.4. Considering the diversity and complexity of clinical practice, we expanded our study to include 86 sera samples collected from cats at the clinic after three-time immunizations. Among these, 8 out of 43 sera collected after one year post three-time immunizations and 5 out of 43 sera collected within one year post three-time immunizations exhibited a neutralization index (NI) of less than 50 against FPV-251. Despite its potential immune evasion capabilities, immunization with inactivated FPV-251 demonstrated effectiveness in providing substantial protection for cats. This was evident from the high levels of sera antibodies against FPV-251 in cats with FPV-251 immunization, as well as their ability to survive and maintain good health after being challenged with FPV-251. Furthermore, sera antibodies from immunized cats displayed the ability to neutralize the other five FPV isolates, indicating a robust cross-protection capacity of the FPV-251 vaccine. Our research findings suggest that although FPV-251 may exhibit certain immune evasion capabilities, it holds significant potential for development into a vaccine to protect pet cats from FPV infection.

Abstract The increasing number of approved nucleic acid therapeutics demonstrates the potential for the prevention and treatment of a broad spectrum of diseases. This trend underscores the significant impact and promise of nucleic acid-based treatments in the field of medicine. Nevertheless, employing nucleic acids as therapeutics is challenging due to their susceptibility to degradation by nucleases and their unfavorable physicochemical characteristics that hinder delivery into cells. Appropriate vectors play a pivotal role in improving nucleic acid stability and delivering nucleic acids into specific cells. The maturation of delivery systems has led to breakthroughs in the development of therapeutics based on nucleic acids such as DNA, siRNA, and mRNA. Non-viral vectors have gained prominence among the myriad of nanomaterials due to low immunogenicity, ease of manufacturing, and simplicity of cost-effective, large-scale production. Here, we provide an overview of the recent advancements in nanomaterials for nucleic acid delivery. Specifically, we give a detailed introduction to the characteristics of polymers, lipids, and polymer-lipid hybrids, and provide comprehensive descriptions of their applications in nucleic acid delivery. Also, biological barriers, administration routes, and strategies for organ-selective delivery of nucleic acids are discussed. In summary, this review offers insights into the rational design of next-generation delivery vectors for nucleic acid delivery.

Abstract The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation.

Abstract To provide a theoretical basis for the prevention and treatment of atherosclerosis (As), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on inducing the lipid deposition and foam cell formation of the vascular smooth muscle cell (VSMC) via C1q/Tumor necrosis factor-related protein9 (CTRP9) promoter region Hypermethylation negative regulating endoplasmic reticulum stress (ERs). Therefore, apolipoprotein E deficient (ApoE−/−) mice were randomly divided into the control [ApoE−/− + normal diet (NC)] and high methionine [ApoE−/− + (normal diet supplemented with 1.7% methionine (HMD)] groups (n = 6 mice/group). Following feeding for 15 weeks, the serum levels of Homocysteine (Hcy), total cholesterol (TC), and triglyceride (TG) were measured using an automatic biochemical analyzer. HE and oil red O staining were performed on the aorta roots to observe the pathological changes. Additionally, immunofluorescence staining was performed to detect the protein expression levels of CTRP9, glucose-regulated protein 78 kD (GRP78), phosphorylated protein kinase RNA-like ER kinase (p-PERK), activating transcription factor 6a (ATF6a), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), sterol regulatory element binding proteins-1c (SREBP1c) and sterol regulatory element binding proteins-2 (SREBP2) in VSMC derived from murine aortic roots. In vitro, VSMC was stimulated with 100 μmol/l Hcy. After transfection of plasmids with overexpression and interference of CTRP9, ERs agonist (TM) and inhibitor (4-PBA) were given to stimulate VSMC cells. HE staining and oil red O staining were used to observe the effect of Hcy stimulation on lipid deposition in VSMC. Additionally, The mRNA and protein expression levels of CTRP9, GRP78, PERK, ATF6a, IRE1α, SREBP1c, and SREBP2 in VSMC were detected by RT-qPCR and western blot analysis, respectively. Finally, The methylation modification of the CTRP9 promoter region has been studied. The NCBI database was used to search the promoter region of the CTRP9 gene, and CpG Island was used to predict the methylation site. After Hcy stimulation of VSMC, overexpression of DNMT1, and intervention with 5-Azc, assess the methylation level of the CTRP9 promoter through bisulfite sequencing PCR (BSP). The results showed that the serum levels of Hcy, TC, and TG in the ApoE−/− + HMD group were significantly increased compared with the ApoE−/− + NC group. In addition, HE staining and oil red O staining showed obvious AS plaque formation in the vessel wall, and a large amount of fat deposition in VSMC, thus indicating that the hyperhomocysteinemia As an animal model was successfully established. Furthermore, CTRP9 were downregulated, while GRP78, p-PERK, ATF6a, p-IRE1α, SREBP1c, SREBP2 was upregulated in aortic VSMC in the ApoE−/− + HMD group. Consistent with the in vivo results, Hcy can inhibit the expression of CTRP9 in VSMC and induce ERs and lipid deposition in VSMC. Meanwhile, the increased expression of CTRP9 can reduce ERs and protect the lipid deposition in Hcy induced VSMC. Furthermore, ERs can promote Hcy induced VSMC lipid deposition, inhibition of ERs can reduce Hcy induced VSMC lipid deposition, and CTRP9 may play a protective role in Hcy induced VSMC lipid deposition and foam cell transformation through negative regulation of ERs. In addition, The CTRP9 promoter in the Hcy group showed hypermethylation. At the same time as Hcy intervention, overexpression of DNMT1 increases the methylation level of the CTRP9 promoter, while 5-Azc can reduce the methylation level of the CTRP9 promoter. Finally, Hcy can up-regulate the expression of DNMT1 and down-regulate the expression of CTRP9. After overexpression of DNMT1, the expression of CTRP9 is further decreased. After 5-Azc inhibition of DNMT1, the expression of DNMT1 decreases, while the expression of CTRP9 increases. It is suggested that the molecular mechanism of Hcy inhibiting the expression of CTRP9 is related to the hypermethylation of the CTRP9 promoter induced by Hcy and regulated by DNMT1. 5-Azc can inhibit the expression of DNMT1 and reverse the regulatory effect of DNMT1 on CTRP9. Overall, the results of the present study suggested that Hcy induces DNA hypermethylation in the CTRP9 promoter region by up-regulating DNMT1 expression, and negatively regulates ERs mediated VSMC lipid deposition and foam cell formation. CTRP9 may potentially be a therapeutic target in the treatment of hyperhomocysteinemia and As.

Diabetic cardiomyopathy (DCM), one of the most serious complications of diabetes mellitus, has become recognized as a cardiometabolic disease. In normoxic conditions, the majority of the ATP production (>95%) required for heart beating comes from mitochondrial oxidative phosphorylation of fatty acids (FAs) and glucose, with the remaining portion coming from a variety of sources, including fructose, lactate, ketone bodies (KB) and branched chain amino acids (BCAA). Increased FA intake and decreased utilization of glucose and lactic acid were observed in the diabetic hearts of animal models and diabetic patients. Moreover, the polyol pathway is activated, and fructose metabolism is enhanced. The use of ketones as energy sources in human diabetic hearts also increases significantly. Furthermore, elevated BCAA levels and impaired BCAA metabolism were observed in the hearts of diabetic mice and patients. The shift in energy substrate preference in diabetic hearts results in increased oxygen consumption and impaired oxidative phosphorylation, leading to diabetic cardiomyopathy. However, the precise mechanisms by which impaired myocardial metabolic alterations result in diabetes mellitus cardiac disease are not fully understood. Therefore, this review focuses on the molecular mechanisms involved in alterations of myocardial energy metabolism. It not only adds more molecular targets for the diagnosis and treatment, but also provides an experimental foundation for screening novel therapeutic agents for diabetic cardiomyopathy.

Influenza virus is one of the main pathogens causing respiratory diseases in humans. Vaccines are the most effective ways to prevent viral diseases. However, the limited protective efficacy of current influenza vaccines highlights the importance of novel, safe, and effective universal influenza vaccines. With the progress of the COVID-19 pandemic, live-attenuated vaccines delivered through respiratory mucosa have shown robustly protective efficacy. How to obtain a safe and effective live-attenuated vaccine has become a major challenge. Herein, using the influenza virus as a model, we have established a strategy to quickly obtain a live-attenuated vaccine by mutating the cleavage site of the influenza virus. This mutated influenza virus can be specifically cleaved by chymotrypsin. It has similar biological characteristics to the original strain in vitro, but the safety is improved by at least 100 times in mice. It can effectively protect against lethal doses of both homologous H1N1 and heterologous H5N1 viruses post mucosal administration, confirming that the vaccine generated by this strategy has good safety and broad-spectrum protective activities. Therefore, this study can provide valuable insights for the development of attenuated vaccines for respiratory viruses or other viruses with cleavage sites.

The skin, as the largest organ, serves as a protective barrier against external stimuli. However, when the skin is injured, wound healing becomes a complex process influenced by physiological conditions, bacterial infections, and inflammation. To improve the process of wound healing, a variety of wound dressings with antibacterial qualities have been created. Electrospun nanofibers have gained significant attention in wound dressing research due to their large specific surface area and unique structure. One interesting method for creating Janus-structured nanofibers is side-by-side electrospinning. This work used side-by-side electrospinning to make cellulose acetate/gelatin Janus nanofibers. Curcumin and zinc oxide nanoparticles were added to these nanofibers. We studied Janus nanofibers’ physicochemical characteristics and abilities to regulate small-molecule medication release. Janus nanofibers coated with zinc oxide nanoparticles and curcumin were also tested for antibacterial activity. The Janus nanofibers with specified physicochemical characteristics were successfully fabricated. Nanofibers released small-molecule medicines in a controlled manner. Additionally, the Janus nanofibers loaded with curcumin exhibited excellent antibacterial capabilities. This research contributes to the development of advanced wound dressings for promoting wound healing and combating bacterial infections.

The premise of effective use of high-resolution remote sensing (HRRS) images is that the data integrity and authenticity of HRRS images must be guaranteed. This paper proposes a new subject-sensitive hashing algorithm for the integrity authentication of HRRS images. This algorithm takes AGIM-net (Attention Gate-based improved M-net) proposed in this paper to extract the subject-sensitive features of the HRRS images, and uses Principal Component Analysis (PCA) based method to compress and encode the extracted features. AGIM-net is an improved U-net based on attention mechanism, adding multi-scale input in the encoder stage to extract rich image features; adding multi-scale output in the decoder stage, and suppressing the features irrelevant to the subject through Attention Gate to improve the robustness of the algorithm. Experiments show that the proposed algorithm has improved robustness compared with existing algorithms, and the tamper sensitivity and security are basically equivalent to the existing algorithms.

Abstract Li+ insertion and extraction inherently impact the switching dynamics and cycling stability of inorganic electrochromic (EC) electrodes. Herein, the extraction of Li+ out of the TiO2 lattice to release the electron is replaced by the charge recombination of the electron with I3− at the TiO2‐electrolyte interface, which avoids the mechanical breakdown of the electrodes and renders self‐bleaching with no applied voltages. A device design of the same two TiO2 nanocrystal (NC) electrodes combined with the redox lithium salt (LiI) electrolyte confers symmetric electrochromism. By applying a forward or reverse bias, the two TiO2 electrodes alternately serve as the electrochromic electrode and exhibit voltage‐controlled gradient coloration, a maximum optical modulation of 90% at 700 nm, and a doubled cycling performance. The microstructure of the TiO2 NC film is characterized by transmission electron microscopy, X‐ray diffraction, X‐ray photoelectron spectroscopy, and Brunauer–Emmett–Teller methods. The electrochemical and electrochromic properties of the device are investigated using cyclic voltammetry, chronoamperometry, electrochemical impedance spectroscopy, and Mott–Schottky method.

Programming and computational thinking (CT) have been progressively incorporated into early childhood education to prepare children for the digital age. However, little is known about the content knowledge (CK) and pedagogical knowledge (PK) possessed by early childhood teachers in this domain. To address this gap, we conducted a case study of an early childhood teacher in China who had experience developing and implementing an unplugged programming and CT curriculum. The triangulation of data sources was established to collect evidence from videotaped observations, interviews, and lesson plans. For the CK, analysis of these findings revealed that the teacher had a more robust understanding of CT concepts (e.g., sequences, conditionals, and loops) compared to CT practices (e.g., decomposition, debugging) and CT perspectives (e.g., perseverance, choices of conduct). In terms of PK, the teacher could apply the general pedagogical knowledge but was relatively weak in using content-specific pedagogical knowledge. As the first endeavor to investigate an early childhood teacher’s CK and PK in teaching programming and CT, this study provides significant implications for improving teachers’ professional knowledge and teaching effectiveness in this burgeoning area.

As agroecology deteriorates, agricultural production is threatened by the combined stressors of exposure to environmental pollutants and pathogenic microbes. Proper agronomic practices for crop growth management and fertilization require understanding plant tolerance strategies. Both rice blast and heavy metals substantially impair rice crops, while silicon (Si) is an effective amendment to alleviate the combined stressors. Herein, this study was conducted to investigate the rice physiology and pathology perspective on the mechanism of Si alleviation against both lead (Pb) toxicity and Magnaporthe oryzae infection, utilizing pot experiments with inoculation of the virulent Magnaporthe oryzae strain. Exogenous Si reduced the phyto-availability and plant absorption of Pb, resulting in a 73.5% reduction in exchangeable Pb concentration in soil and a 40.23% reduction in rice plants. Furthermore, Si addition boosted the plant antioxidant system by increasing the activities of related enzymes, as the activities of catalase, superoxide dismutase, and polyphenol oxidase were significantly improved while the activity of peroxidase in rice panicles decreased. As a result, an improvement in dry matter quantity by 19.19% was observed compared to treatments without Si application, and the panicle blast severity (PBS) was reduced by 0.4–37.52%. Notwithstanding the interaction between the combined stressors, this study revealed that the speciation of Pb formation in the rhizosphere was the primary contributor to the alleviation of abiotic stresses, whereas the regulation of oxidative stress by enzymatic antioxidants played a dominant role in alleviating Magnaporthe oryzae colonization and impairments. The regulation process may reveal the mechanism of siliceous fertilizer functioning in the paddy system. Thereby the role of exogenous Si in anti-fungal, heavy metal toxicology, and plant physiology needs further study to fully elucidate the role of Si amendment, which is proposed to be considered from the perspective of soil chemistry and plant physiology.

The helical cruciform fuel (HCF) rod assembly is a new type of fuel for the lead-bismuth (LBE) fast reactor. It can be self-positioned and realize a coolant mixing without wrapped wire or grid spacer. This kind of fuel assembly can not only realize the function of the traditional wire-wrapped fuel assembly, but also omit the wire -wrapped structure, which provides a satisfactory prospect for the development of LBE reactor. In this study, the coolant mixing in the LBE cooled reactor with HCF assembly was analyzed numerically. The influence of the Reynolds number and different coolant mediums were investigated. Advantages and disadvantages of the HCF assembly were analyzed and compared with the wire-wrapped fuel.

Abstract To efficiently combat viral infectious diseases, it is important to develop broadly applicable countermeasures, and efficient antiviral systems can be developed by elaborating the relationship of antiviral efficiency with the interactions between antiviral agents and viruses. In the present study, conjugated polymer (CP)-based photodynamic therapy was used to inhibit RNA virus infections. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudotyped virus composed of an SARS-CoV-2 envelope coated with the S protein and luciferase RNA genome was employed to assess antiviral efficiency. Three cationic CPs with different backbone structures, fluorene-co-phenylene (PFP), thiophene (PMNT), and phenylene vinylene (PPV), exhibit different photoinactivation effects. The highly efficient photoinactivation of PPV and PMNT is derived from the complete photodegradation of spike proteins, nucleocapsid proteins and nucleic acids of SARS-CoV-2 after binding to the viral spike proteins. Although PFP showed the highest efficiency in the photodegradation of spike proteins due to its strong binding affinity, ineffective viral inhibition was observed, which occurred because the viral gene was partially damaged under light irradiation and the process of delivering the viral gene to cells received assistance. This work preliminarily reveals the effect of CP-virus interactions on their photoinactivation activity and should be beneficial for further research on the development of highly efficient antiviral PDT agents.

With the operation of wireless sensor networks (WSNs), energy-constrained sensor nodes and inadequate energy constraint methods are becoming obsolete, as they reduce the efficiency of data transmission. The appearance of edge computing (EC) and causality graph provide a new opportunity for energy fault analysis and assessment in WSNs. As a result, by selecting a reliable data transmission path and averaging the energy consumption, we present an energy fault and consumption optimization (EFCO) algorithm for solving the energy hole and consumption balance (EHCB) problem in wireless sensor networks with edge computing (ECWSNs). Specifically, we first build a novel four-layer network architecture by using edge computing technology and causality graph theory. Then, the energy fault cost (EFC) in ECWSNs is formulated as an optimization problem that is constrained by the energy allocation of relay nodes. Furthermore, we propose a causal reasoning algorithm to deduce the single-value fault status probability of relay nodes. Finally, we utilize version 2 of a network simulator (NS-2) to evaluate the fault derivation and energy allocation efficiency of the EFCO algorithm in ECWSNs.

Soil salinity affects approximately 20% of the world’s arable land, presenting a significant challenge for studying the mechanisms by which plants adapt to saline environments. Cyclocarya paliurus, an invaluable research model due to its ecological and medicinal significance, is primarily concentrated in central and southern China. Nevertheless, Cyclocarya paliurus faces challenges from environmental factors such as soil salinization, which adversely impacts its growth, subsequently affecting the yield and quality of its bioactive compounds. The NAC gene family, a critical group of plant-specific transcription factors, plays pivotal roles in responding to abiotic stresses. However, there has not yet been any studies on NAC genes under salt stress in Cyclocarya paliurus. In this study, we identified 132 NAC genes within the Cyclocarya paliurus genome. Our analysis of the conserved structures and gene organization revealed a high degree of conservation in the proteins of the CpNAC gene family. Cis-element analysis unveiled the participation of these genes in a variety of biological processes, including light responses, phytohormone responses, cell cycle responses, and abiotic stress responses. Under salt stress conditions, the expression of 35 CpNAC genes changed significantly, indicating a response to salt treatment. Furthermore, we provided additional evidence for the identification of the NAC gene family and revealed their potential positive regulatory role in signal transduction by conducting a transcriptional activation activity analysis of CpNAC132(D) and CpNAC040, which are homologous to Arabidopsis thaliana NAC062/91 and NAC103, respectively. This research not only advances our comprehension of the salt stress adaptation in Cyclocarya paliurus but also provides robust support for future investigations into plant responses to environmental stress and the cultivation of salt-tolerant crops.

In this paper, we establish a structural inequality of the ∞-subLaplacian ▵0,∞ in a class of the semi-simple Lie group endowed with the horizontal vector fields X1,…,X2n. When 1

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

Abstract Background In football matches, passing is an important means of organizing attacks, creating shots, changing tactics, and achieving tactical objectives and is a frequently used technique. The purpose of the study was to explore the relevant factors that affect passes in the Chinese Super League (CSL) in different game contexts. Methods A total of 1,440 matches (2,880 samples) of 24 teams participating in the CSL in the 2014–2019 seasons were selected as the research object, and a mixed linear model was constructed to analyse the influencing factors of passes. Results (a) The passing success rate and the total number of forward passes were greatly affected by the stage of the season; (b) except for the passing success rate in the 30 m attack area, all other pass indicators in the home matches were significantly higher than those in the away matches; (c) the number of passes in the 30 m attack area was mainly affected by the team level (table position quartile); the higher the team level, the greater the number of passes in the 30 m attack area; (d) all passing indices for the matches between the first eight and the last eight were significantly greater than the matches between the first eight; (e) the passing success rate in the 30 m attack area in winning matches was higher than that in drawn matches; (f) the number of forward passes was significantly greater in matches won by two or more goals, and the number of defender passes was significantly greater in losing matches. Conclusion The various passing indices of the CSL were affected by different game contexts (including season stage, venue, team level, match type and match outcome), and understanding these influencing factors of passes will help coaches and players better understand football matches.

Background Nephrotic syndrome (NS) is a common chronic kidney disease in children, and has a long treatment cycle with being prone to recurrence and refractoriness. Adverse effects caused by therapeutic drugs and concerns about disease prognosis may all affect the child's physical and mental health, and quality of life. Therefore, it is very necessary to understand the Health-related Quality of Life (HRQOL) of children with nephrotic syndrome. Objective To understand the level of HRQOL in children with nephrotic syndrome. Methods Children (aged 2-18 years) with nephrotic syndrome and their parents were recruited from the Department of Pediatric Nephrology Rheumatism and Immunology, Shengjing Hospital of China Medical University between October 2019 and December 2020. Data were collected on age, gender, disease duration, whether they had frequent relapses, number of relapses, and whether they were prescribed immunosuppressive agents (including cyclophosphamide, tacrolimus, etc.) , place of residence (urban, rural, urban-rural junction areas) . The PedsQL 4.0 core generic scale was used to understand the level of HRQOL (including the child self rating scale and parent report) in children with primary NS. Results A total of 183 questionnaires were distributed, and 174 valid questionnaires were returned, with an effective recovery rate of 95.1%. Among the 174 children, 119 were males and 55 were females. Median age was 6 (4, 11) years. There were 100 children with recurrence (57.5%) , with a median number of 3 (1, 5) recurrences. 54 patients had frequent recurrences and 46 patients had non frequent recurrences. 31 patients were treated with immunosuppressants. The usual place of residence was urban in 86 patients, rural in 63 patients, and urban-rural junctions in 25 patients. The ICC of the concordance analysis between the children's self-rating scale and the parent-reported scale were both greater than 0.75. There were no significant differences in physiological scores, emotional scores, social scores, role scores and total scores between genders (P>0.05) . There were statistically significant differences in physiological scores, emotional scores, social scores and total scores among different ages (P0.05) . There were no significant differences in the physiological scores, emotional scores, social scores, role scores, and total scores among different disease durations (P>0.05) . There were no significant differences in the physiological score, emotional score, social score, role score and total score between children with and without frequent recurrence (P>0.05) . The emotional scores, social scores, and total scores were significantly different between children who used immunosuppressants and those who did not use (P0.05) . Conclusion The scores of children with NS in physical, emotional, social, and role functioning were reduced. When treating the disease, clinicians need to focus on the children's physical, psychological and social adaptability, and intervene in time to improve their quality of life.

Abstract Objective To compare efficacy and safety of fecal microbiota transplantation (FMT) with glucocorticoid as induction therapy in ulcerative colitis (UC). Methods The patients with active mild to moderate UC were recruited into the single-center, prospective cohort study. The patients were treated with either FMT (FMT group) or glucocorticoids (GCs group). Patients received FMT administration for 3 days. The primary outcome was clinical and endoscopic remission at week 12. Inflammatory parameters were assessed by routine blood tests. Safety was assessed by adverse events recorded. The serum levels of TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10 IL-8, IL-12p70, IL-13, IL-17A and IL-23 following FMT were measured by Luminex multiplex assay. Results Of the 122 patients, 62 patients were treated with FMT and 60 with glucocorticoids. 34 patients in FMT group (54.8%) and 29 in GCs group (48.3%) reached the primary outcome (p = 0.30). The incidence of adverse events in GCs group (35/60, 58.3%) was significantly higher than that in FMT group (14/62, 22.6%) and two serious adverse events were observed following GCs. Patients in FMT group were stratified into responders (RE) and non-responders (NR) groups. The level of TNF-α and IL-6 decreased significantly in RE group, while IL-10 decreased significantly in NR group. Conclusion FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events. The modification of serum TNF-α, IL-6 and IL-10 might be related to the efficacy of FMT in UC. Trial registration This study was registered with ClinicalTrials.gov (NCT02435160). Registered on 6 April, 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT02435160&cntry=&state=&city=&dist=

Abstract Background Duck plague virus (DPV), belonging to herpesviruses, is a linear double-stranded DNA virus. There are many reports about the outbreak of the duck plague in a variety of countries, which caused huge economic losses. Recently, increasing reports revealed that multiple long non-coding RNAs (lncRNAs) can possess great potential in the regulation of host antiviral immune response. Furthermore, it remains to be determined which specific molecular mechanisms are responsible for the DPV-host interaction in host immunity. Here, lncRNAs and mRNAs in DPV infected duck embryonic fibroblast (DEF) cells were identified by high-throughput RNA-sequencing (RNA-seq). And we predicted target genes of differentially expressed genes (DEGs) and formed a complex regulatory network depending on in-silico analysis and prediction. Result RNA-seq analysis results showed that 2921 lncRNAs were found at 30 h post-infection (hpi). In our study, 218 DE lncRNAs and 2840 DE mRNAs were obtained in DEF after DPV infection. Among these DEGs and target genes, some have been authenticated as immune-related molecules, such as a Macrophage mannose receptor (MR), Anas platyrhynchos toll-like receptor 2 (TLR2), leukocyte differentiation antigen, interleukin family, and their related regulatory factors. Furthermore, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis, we found that the target genes may have important effects on biological development, biosynthesis, signal transduction, cell biological regulation, and cell process. Also, we obtained, the potential targeting relationship existing in DEF cells between host lncRNAs and DPV-encoded miRNAs by software. Conclusions This study revealed not only expression changes, but also the possible biological regulatory relationship of lncRNAs and mRNAs in DPV infected DEF cells. Together, these data and analyses provide additional insight into the role of lncRNAs and mRNAs in the host's immune response to DPV infection.

IntroductionIn the elder population, both low hemoglobin (Hb)/anemia and osteoporosis (OP) are highly prevalent. However, the relationship between Hb and OP is still poorly understood. This study was to evaluate the correlation between Hb and OP in Chinese elderly population.MethodsOne thousand and sisty-eight individuals aged 55–85 years were enrolled into this cross-sectional study during June 2019–November 2019. Data on the demographics and clinical characteristics were recorded. Detections of complete blood count, liver/kidney function, glucose metabolism and lipid profile, and thoracolumbar X-ray were performed, and bone mineral density (BMD) at lumbar spine 1–4, femur neck, and total hip was measured by dual-energy X-ray absorptiometry (DXA). Univariate and multivariate linear regression analyses were employed to evaluate the correlation between Hb with BMD T-score. Logistic regression analysis was performed to access the correlation between different Hb levels and the odds ratio (OR) for OP.ResultsCompared with non-OP group, OP patients had lower level of Hb. Univariate linear regression analysis indicated Hb level was positively related to the BMD of lumbar spine 1–4, femur neck and total hip, and this relationship remained after adjusting confounding variables [gender, age, body mass index (BMI), diabetes mellitus (DM) and morphological vertebral fracture]. Logistic regression analysis showed the ORs for OP decreased with the increase of Hb. Compared with the subjects with the lowest quartile of Hb, the OR for OP in the highest quartile group was 0.60 (0.41–0.89) after adjusting for gender, age and BMI, and the OR for OP was 0.62 (0.41–0.92) after further adjustment for gender, age, BMI, DM, and lipid indexes.DiscussionIn conclusion, Lower Hb level is related to lower BMD in the elderly population. However, whether Hb level could be used to predict the risk of OP needs to be further determined in more longitudinal clinical studies.

Environmental stresses can disrupt protein structure, resulting in unfolded or misfolded proteins, thereby triggering endoplasmic reticulum (ER) stress. The unfolded protein response (UPR), particularly as activated by Arabidopsis AtbZIP60 gene, is pivotal for counteracting ER stress and ensuring cell survival. The medicinal plant, Cyclocarya paliurus, known for its wealth of beneficial compounds, is threatened by environmental stresses, limiting the exploration of its therapeutic potential. In order to better exploit and utilize its value, it is necessary to understand the signal pathway of environmental stresses. Here, we identify a homolog of AtbZIP60 in C. paliurus, termed CpbZIP11, which can be upregulated by tunicamycin. The conserved double stem-loop structure in its mRNA is spliced under environmental stresses. This splicing event results in a novel CpbZIP11 mRNA variant, leading to the production of a nuclear-localized CpbZIP11 protein with transcriptional activation activity in yeast. We further delve into the study of evolutionary lineage and motif conservation of CpbZIP11 homologs across various plant groups. This research illuminates the stress adaptation mechanisms in C. paliurus and deepens our understanding of the bZIP evolution, which endows versatility for the understanding of this transcription factor.

Abstract Karst tiankengs are rare natural habitats, having a local microclimate different from surrounding regions. A contrast study on plant communities at the inside and outside of the primitive tiankeng was carried out by performing the qualitative analysis of species compositions of arborous and shrub layers. We found that plant communities in the primitive tiankeng belong to the subtropical moist evergreen broad-leaf forest, whereas those outside the tiankeng belong to subtropical semi-moist needle-broadleaved mixed forest. Trapped habitat of primitive karst tiankeng protects the plant communities significantly different from those in external karst ecosystems, so karst tiankeng has the great value in the plant species protection. Although the trapped habitat decreases plant species abundance inside tiankeng to some extent, highly diverse shrub species are present in the inside-tiankeng plant communities, and the primitive karst tiankeng plays an important role in the plant diversity protection. The primitive karst tiankeng is an important refugia for plant not only as a plant species protection library, but a plant diversity protection library. When implementing measures for the reduction of damages to biodiversity due to global climate changes and human activities, more attention should be paid to the primitive karst tiankeng as a small ecological refugia and biodiversity protection library.

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Inflammatory bowel disease (IBD) results from a complex interplay between genetic predisposition, environmental factors, and gut microbes. The role of N6-methyladenosine (m6A) methylation in the pathogenesis of IBD has attracted increasing attention. m6A modification not only regulates intestinal mucosal immunity and intestinal barrier function, but also affects apoptosis and autophagy in intestinal epithelial cells. Additionally, m6A modification participated in the interaction between gut microbes and the host, providing a novel direction to explore the molecular mechanisms of IBD and the theoretical basis for specific microorganism-oriented prevention and treatment measures. m6A regulators are expected to be biomarkers for predicting the prognosis of IBD patients. m6A methylation may be utilized as a novel target in the management of IBD. This review focused on the recent advances in how m6A modification causes the initiation and development of IBD, and provided new insights into optimal prevention and treatment measures for IBD.

In recent years, the role of video games in enhancing brain plasticity and learning ability has been verified, and this learning transfer is known as the “learning to learn” effect of video game training. At the same time, against the background of healthy lighting, the influence of non-visual effects of light environment on the human rhythmic system has been gradually confirmed. As a special operation form of Visual Display Terminal (VDT) operation, video game training has a high dependence on VDT equipment and the VDT screen, and the background usually has a huge difference in brightness. Compared with the light environment of ordinary operation space, the light environment of VDT operation space is more complex. This complex light environment's non-visual effects cause human emotions, alertness, fatigue, cognitive ability, and other changes, which may affect the efficiency of the “learning to learn” effect of video game training. This article focuses on the impact of the light environment in the VDT workspace on the “learning to learn” effect of video game training. It first traces the factors that trigger the “learning to learn” effect of video game training, that is, the improvement of people's attention, perception, and cognitive ability. Then, the influencing mechanism and the evaluation method of the VDT workspace space light environment on the human rhythm system are discussed based on the basic theory of photobiological effect. In addition, the VDT display lighting light time pattern, photophysical properties, regulation, and protection mechanism on the human rhythm system are studied to demonstrate the VDT workspace light environment's special characteristics. Finally, combined with the progress of artificial lighting technology and the research results of health lighting, given the “learning to learn” effect of video game training, some thoughts on the design of the light environment of the workplace and future research directions are presented.

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.

Abstract Immunotherapy has become the standard of care for non-small cell lung cancer (NSCLC), either in combination or monotherapy. However, there are still some patients who cannot benefit from it. Immunization strategies for NSCLC are based on the expression of PD-L1 on tumor cells and TMB, and although these indicators have a certain predictive effect, their predictive performance is not good. Therefore, clinicians must make adjustments to recognize markers. This is a review article that summarized immunotherapeutic biomarkers according to the “seed-soil-environment”, generalizes primary resistance to immunotherapy, and summarizes the integration of markers.

Abstract Aim To assess the effects of health locus of control‐based education programme (HLCEP) on self‐management, health locus of control and glycated haemoglobin (HbA1c) among type 2 diabetes mellitus (T2DM). Design Quasi‐experimental study. Methods The study recruited 120 T2DM participants from May–September 2020. The control group received one‐week in‐hospital care and 12‐week follow‐up. The intervention group received additional HLCEP. The self‐management and the health locus of control were measured by using the Summary of Diabetes Self‐care Activities and the Multidimensional Health Locus of Control at baseline and the 4th and 12th week after discharge. The HbA1c was collected at baseline and the 12th week after discharge. The generalized estimating equation analysis was performed to assess the intervention effects. Results The intervention group has statistically significantly higher scores on the overall level of self‐management, dietary management, foot care, medication management and internal health locus of control, while a lower HbA1c level than the control group.

Lung cancer is the most lethal malignancy around the world and non-small cell lung cancer (NSCLC) accounts for 80% of all cases. Most of the NSCLC patients has “driver gene mutations” and targeted therapy achieved a relatively good efficacy, but some patients progressed or relapsed after treatment. Previous studies demonstrated that immune checkpoint inhibitor could improve the prognosis of advanced-stage NSCLC and prolong the survival time. However, the efficacy of immune therapy varies in NSCLC patients with different immune and molecular features. The efficacy of immune therapy was controversial in NSCLC patients with driver gene mutation. The present review will summarize the immune characteristics of NSCLC patients with driver mutation and the directions of immunotherapy for patients with driver mutation.

Detecting traces of patients with novel coronavirus pneumonia (COVID-19) is a prerequisite for avoiding the virus’s rapid spread. However, too much patient privacy data uploaded to the cloud centre will overwhelm the network and cause user information security not to be guaranteed. In this paper, we propose a personal prediction method for COVID-19 infections by perceiving the information of worn biosensors and monitoring equipment in a body area network (BAN). Edge computing and blockchain technology are introduced to solve the problems of user privacy protection and perceptual data transmission and storage. We first construct an edge body area network (EBAN) and characterize the edge blockchain cost’s maximization function by considering the bandwidth, storage space, and energy consumption constraints. Then we build a blockchain without redundant perception information and select effective transmission paths by using the edge blockchain construction efficiency maximization (EBCEM) algorithm. Finally, we use the network simulator (NS-2) to simulate the performance of the EBCEM algorithm and compare it with the excellent assignment game algorithm (AGA) in terms of the effective requester ratio (ERR), effective provider ratio (EPR), edge blockchain construction success ratio (EBCSR), and average storage usage ratio (ASUR) in the EBAN.

New technologies such as Internet, cloud computing, artificial intelligence (AI) and blockchain have greatly promoted the innovation of financial industry structure and paradigm, improved the efficiency of financial services and brought the spillover of the financial technology (FinTech) risk. The existing financial regulation methods cannot meet the needs of the development of FinTech, therefore, there is an urgent need to improve the trust mechanism. Blockchain can effectively solve the problems of security and trust in FinTech. This paper will explore the expression method of trust index in blockchain, and build based on blockchain a multi-dimensional trust index system and evaluation mechanism (MDTEM) for FinTech. Firstly, a four-level blockchain structure has been built, including cloud level blockchain, Internet level blockchain, contract level blockchain and application level blockchain in the FinTech ecological environment to ensure the security, reliability and trustworthiness of financial services. Secondly, according to the trust structure of blockchain on FinTech payment behavior, the index system and evaluation mechanism of direct trust, indirect trust, recommendation trust and feedback trust of FinTech based on blockchain are designed. Finally, the trust simulation experiment of FinTech mechanism is carried out from three aspects: data sending, data transmission, data reception and delivery success rate. Simulation results show that the proposed MDTEM trust mechanism can better improve the safe and reliable application of FinTech trust mechanism.

How to balance the artistry and comfort of the light environment in an architecturalized immersive new media public art installation (AINMPAI) to ensure the safety of the audiences’ visual safety has become a new issue. The lack of corresponding lighting design standards makes this issue more challenging. This paper explores the appropriate luminance range of the irregularly curved LED screens of the AINMPAI with high-luminance natural light as the background. The influence of the audience behavior mode on the brightness threshold of the LED screens in the AINMPAI under the background of Internet communication is discussed. Through software simulation and field measurement, the effectiveness of the design measures based on the local characteristics of the work is verified. The overall average luminance, the regional luminance, the partial luminance, and the corresponding luminance contrast of the inner screen surface were measured at every 10° change in the solar altitude angle during daytime. The nighttime light environment parameters and the temperature of the device throughout the day were also measured. A total of 487 visitors were interviewed for subjective evaluation of the comfort of the light and thermal environments. The results show that: (1) the overall average luminance cannot wholly describe the actual luminance of the critical parts of the special-shaped curved screen in the device and that two indicators, the regional luminance and the partial average luminance, need to be added; (2) the maximum brightness limit of LED screens in the daytime can be 1000 cd/m2 but at night it should be controlled within 200 cd/m2; (3) natural light is the main factor that causes the high average brightness and low contrast of the daytime device screen; (4) the recommended indicators for such artistic installations should balance the absolute values of average brightness, artistic effect, and transmission priority. This study can provide foundational data and a methodological reference for establishing AINMPAI light environment design guidelines or recommended standards based on audiences’ visual safety.

In order to meet the latest requirements for sensor quality test in the industry, the sample sensor needs to be placed in the medium for the cold and hot shock test. However, the existing environmental test chamber cannot effectively control the temperature of the sample in the medium. This paper designs a control method based on the support vector machine (SVM) classification algorithm and K-means clustering combined with neural network correction. When testing sensors in a medium, the clustering SVM classification algorithm is used to distribute the control voltage corresponding to temperature conditions. At the same time, the neural network is used to constantly correct the temperature to reduce overshoot during the temperature-holding phase. Eventually, overheating or overcooling of the basket space indirectly controls the rapid rise or decrease in the temperature of the sensor in the medium. The test results show that this method can effectively control the temperature of the sensor in the medium to reach the target temperature within 15 min and stabilize when the target temperature is between 145 °C and −40 °C. The steady-state error is less than 0.31 °C in the high-temperature area and less than 0.39 °C in the low-temperature area, which well solves the dilemma of the current cold and hot shock test.

Trichoderma spp., a genus of fast-growing and highly adaptable fungi that form symbiotic relationships with plant roots, rendering them ideal for practical use in controlled environment agriculture. Herein, this paper aims to understand how the Nicotiana benthamiana with inoculation of Trichoderma harzianum strain TRA1-16 responds to light intensity variation. Pot experiments were conducted under low and high light intensities (50 and 150 μmol·m-2·s-1, respectively) and microbial treatments. Plant growth, physio-biochemical attributes, activities of antioxidant enzymes, and phytohormones regulation were investigated. The results showed that for non-inoculated plants, the reduction in light intensity inhibited plant growth, nitrogen (N) and phosphorus (P) uptake, chlorophyll a/b, and carotenoid content. Trichoderma inoculation resulted in 1.17 to 1.51 times higher concentrations of available N and P in the soil than the non-inoculated group, with higher concentrations at high light intensity. Plant height, dry weight, nutrient uptake, and antioxidant activity were significantly increased after inoculation (p

Activation of the cGAS-STING pathway by cytoplasmic DNA induces the production of Type-1 interferons. Recent advances in research suggest that the cGAS-STING pathway is involved in different parts of the cancer-immunity cycle (CIC) to promote or suppress antitumor immune responses. Combination therapy of STING agonists has made certain progress in preclinical as well as clinical trials, but the selection of combination therapy regimens remains a challenge. In this review, we summarize the role of the cGAS-STING in all aspects of CIC, and focus on the combination immunotherapy strategies of STING agonists and current unsolved challenges.

Abstract Background Due to the multifactorial aetiology and unpredictable long-term stability, skeletal anterior open bite (SAOB) is one of the most intractable conditions for orthodontists. The abnormal orofacial myofunctional status (OMS) may be a major risk factor contributing to the development and relapse of SAOB. This study is aimed at evaluating the OMS and the efficacy of orofacial myofunctional therapy (OMT) alone for SAOB subjects. Methods Eighteen adolescents with SAOB (4 males, 14 females; age: 12–18 years) and eighteen adolescents with normal occlusion (2 males, 16 females; age: 12–18 years) were selected. The electromyographic activity (EMGA) associated with mastication and closed mouth state was measured. Lateral cephalography was used to evaluate craniofacial morphology. Wilcoxon signed rank tests and t-tests were performed to evaluate myofunctional and morphological differences. Pearson or Spearman correlation analysis was used to investigate the correlations between EMGA and morphological characteristics. SAOB subjects were given OMT for 3 months, and the EMGA was compared between before and after OMT. Results During rest, anterior temporalis activity (TAA) and mentalis muscle activity (MEA) increased in SAOB subjects, but TAA and masseter muscle activity (MMA) decreased in the intercuspal position (ICP); and upper orbicularis activity (UOA) and MEA significantly increased during lip sealing and swallowing (P

ABSTRACT Acute pancreatitis (AP) is usually accompanied by intestinal failure, but its mechanism is still unclear. In AP patients, the functions of Paneth cells (lysozyme, HD5, Reg3γ, and Wnt3a) decreased. Compared with AP mice, injuries and inflammation of the pancreas and ileum were aggravated in AP mice treated with dithizone (Dith) (Dith+AP mice). Intestinal permeability and bacterial translocation were also increased. 16S rRNA sequencing showed that the gut microbiota of Dith mice and Dith+AP mice exhibited a marked increase in the pathogenic bacterium Helicobacter and a significant decrease in the probiotic bacterium Blautia. Lysozyme gavage in Dith+AP mice effectively alleviated injuries of the pancreas and small intestine. The beneficial effect of lysozyme was associated with a significant increase in the probiotic bacterium Blautia and a virtual absence of the pathogenic bacterium Helicobacter. The severity of AP in antibiotic-treated mice (ABX mice) was significantly aggravated when receiving feces from Dith mice and was markedly alleviated when receiving feces from lysozyme-gavaged mice. In vitro, lysozyme increased the proliferation of enteroids by promoting the activation of the Wnt pathway and Lgr5 expression in intestinal stem cells. IMPORTANCE We demonstrate that AP patients and experimental AP mice exhibited a dysfunction of Paneth cells. Our in vivo research showed that the severity of AP was exacerbated by the long-term dysfunction of Paneth cells, which was associated with gut microbiota disorder. Restoring part of Paneth cell functions through lysozyme supplementation alleviated the severity of AP and gut microbiota dysbiosis. This study provides novel insight into the link of pancreas-gut interactions in the pathogenesis of AP, providing a new direction for the clinical treatment of intestinal complications during AP.

N-methyl-D-aspartate receptors (NMDARs) are Ca2+-permeable ionotropic glutamate receptors (iGluRs) in the central nervous system and play important roles in neuronal development and synaptic plasticity. Conventional NMDARs, which typically comprise GluN1 and GluN2 subunits, have different biophysical properties than GluN3-containing NMDARs: GluN3-containing NMDARs have smaller unitary conductance, less Ca2+-permeability and lower Mg2+-sensitivity than those of conventional NMDARs. However, there are very few specific modulators for GluN3-containing NMDARs. Here, we developed a cell-based high-throughput calcium assay and identified 3-fluoro-1,2-phenylene bis (3-hydroxybenzoate) (WZB117) as a relatively selective inhibitor of GluN1/GluN3 receptors. The IC50 value of WZB117 on GluN1/GluN3A receptors expressed in HEK-293 cells was 1.15 ± 0.34 μM. Consistently, WZB117 exhibited strong inhibitory activity against glycine-induced currents in the presence of CGP-78608 but only slightly affected the NMDA-, KA- and AMPA-induced currents in the acutely isolated rat hippocampal neurons. Among the four types of endogenous currents, only the first one is primarily mediated by GluN1/GluN3 receptors. Mechanistic studies showed that WZB117 inhibited the GluN1/GluN3A receptors in a glycine-, voltage- and pH-independent manner, suggesting it is an allosteric modulator. Site-directed mutagenesis and chimera construction further revealed that WZB117 may act on the GluN3A pre-M1 region with key determinants different from those of previously identified modulators. Together, our study developed an efficient method to discover modulators of GluN3-containing NMDARs and characterized WZB117 as a novel allosteric inhibitor of GluN1/GluN3 receptors.

BackgroundImmune dysfunction is the main characteristic of severe acute pancreatitis (SAP), and the timing of immune regulation has become a major challenge for SAP treatment. Previous reports about the time point at which the immune status of SAP changed from excessive inflammatory response to immunosuppression (hypo-inflammatory response) are conflicting.PurposesThe aims of this study are to explore the immunological dynamic changes in SAP rats from the perspective of intestinal mucosal immune function, and to determine the immunoswitching point from excessive inflammatory response to immunosuppression.MethodsRetrograde injection of sodium taurocholate into the pancreaticobiliary duct was applied to establish a SAP model in rats. The survival rate and the activities of serum amylase and pancreatic lipase in SAP rats were measured at different time points after model construction. The pathological changes in the pancreas and small intestines were analyzed, and the levels of intestinal pro- and anti-inflammatory cytokines and the numbers of intestinal macrophages, dendritic cells, Th1, Th2, and T regulatory cells were assessed. Meanwhile, the SAP rats were challenged with Pseudomonas aeruginosa (PA) strains to simulate a second hit, and the levels of intestinal inflammatory cytokines and the numbers of immune cells were analyzed to confirm the immunoswitching point.ResultsThe time periods of 12–24 h and 48–72 h were the two death peaks in SAP rats. The pancreas of SAP rats showed self-limiting pathological changes, and the switching period of intestinal cytokines, and innate and adaptive immunity indexes occurred at 24–48 h. It was further confirmed that 48 h after SAP model construction was the immunoswitching point from excessive inflammatory response to immunosuppression.ConclusionThe SAP rats showed characteristics of intestinal mucosal immune dysfunction after model construction, and the 48th h was identified as the immunoswitching point from excessive inflammatory response to immunosuppression. The results are of great significance for optimizing the timing of SAP immune regulation.

Retinal inflammation underlies multiple prevalent retinal diseases. While microglia are one of the most studied cell types regarding retinal inflammation, growing evidence shows that Müller glia play critical roles in the regulation of retinal inflammation. Müller glia express various receptors for cytokines and release cytokines to regulate inflammation. Müller glia are part of the blood-retinal barrier and interact with microglia in the inflammatory responses. The unique metabolic features of Müller glia in the retina makes them vital for retinal homeostasis maintenance, regulating retinal inflammation by lipid metabolism, purine metabolism, iron metabolism, trophic factors, and antioxidants. miRNAs in Müller glia regulate inflammatory responses via different mechanisms and potentially regulate retinal regeneration. Novel therapies are explored targeting Müller glia for inflammatory retinal diseases treatment. Here we review new findings regarding the roles of Müller glia in retinal inflammation and discuss the related novel therapies for retinal diseases.