Search

To retrieve, analyze, and extract evidence related to subcutaneous emphysema in patients undergoing laparoscopic surgery systematically, and provide evidence-based recommendations for reducing its incidence. By browsing the websites of the National Institute for Health and Clinical Excellence, the International Guideline Collaboration Network, the National Guideline Library of the United States, the Registered Nurses Association of Ontario, the Scottish Intercollegiate Guideline Network, the Clinical Practice Guidelines website of the Canadian Medical Association, UpToDate, Web of Science, PubMed, OVID, Cochrane Library, Embase, Chinese Biomedical Database, CNKI, VIP, and Wanfang Database, relevant literatures, guidelines, systematic reviews, evidence summaries, expert consensus, randomized controlled trials, etc. about subcutaneous emphysema in patients undergoing laparoscopic surgery were retrieved. All searches were limited to articles published between 1st January 2010 to 1st August 2023. 2245 articles were identified in total, 10 articles were included after exclude literature that does not meet the standards, including 3 clinical decision-making articles, 2 review papers, and 5 randomized controlled trials. Evidence summarization was conducted from 5 aspects: influencing factors, prevention, establishment and management of pneumoperitoneum, intraoperative monitoring, and intervention methods, 15 pieces of best evidences were summarized. Clinical staffs should transform and apply the evidence-based practices to decrease the incidence of subcutaneous emphysema and enhance the quality of life for patients.

Abstract Background Infection of mice with mouse-adapted strains of influenza virus has been widely used to establish mouse pneumonia models. Intranasal inoculation is the traditional route for constructing an influenza virus-induced pneumonia mouse model, while intratracheal inoculation has been gradually applied in recent years. In this article, the pathogenicity of influenza virus-induced pneumonia mouse models following intranasal and aerosolized intratracheal inoculation were compared. Methods By comparing the two ways of influenza inoculation, intranasal and intratracheal, a variety of indices such as survival rate, body weight change, viral titer and load, pathological change, lung wet/dry ratio, and inflammatory factors were investigated. Meanwhile, the transcriptome was applied for the initial exploration of the mechanism underlying the variations in the results between the two inoculation methods. Results The findings suggest that aerosolized intratracheal infection leads to more severe lung injury and higher viral loads in the lungs compared to intranasal infection, which may be influenced by the initial site of infection, sialic acid receptor distribution, and host innate immunity. Conclusion Intratracheal inoculation is a better method for modelling severe pneumonia in mice than intranasal infection.

Cell senescence deters the activation of various oncogenes. Induction of senescence is, therefore, a potentially effective strategy to interfere with vital processes in tumor cells. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in various cancer types, including ovarian cancer. The mechanism by which S1PR1 regulates ovarian cancer cell senescence is currently elusive. In this study, we demonstrate that S1PR1 was highly expressed in human ovarian cancer tissues and cell lines. S1PR1 deletion inhibited the proliferation and migration of ovarian cancer cells. S1PR1 deletion promoted ovarian cancer cell senescence and sensitized ovarian cancer cells to cisplatin chemotherapy. Exposure of ovarian cancer cells to sphingosine-1-phosphate (S1P) increased the expression of 3-phosphatidylinositol-dependent protein kinase 1 (PDK1), decreased the expression of large tumor suppressor 1/2 (LATS1/2), and induced phosphorylation of Yes-associated protein (p-YAP). Opposite results were obtained in S1PR1 knockout cells following pharmacological inhibition. After silencing LATS1/2 in S1PR1-deficient ovarian cancer cells, senescence was suppressed and S1PR1 expression was increased concomitantly with YAP expression. Transcriptional regulation of S1PR1 by YAP was confirmed by chromatin immunoprecipitation. Accordingly, the S1PR1-PDK1-LATS1/2-YAP pathway regulates ovarian cancer cell senescence and does so through a YAP-mediated feedback loop. S1PR1 constitutes a druggable target for the induction of senescence in ovarian cancer cells. Pharmacological intervention in the S1PR1-PDK1-LATS1/2-YAP signaling axis may augment the efficacy of standard chemotherapy.

BackgroundAs a key to economic and social development, occupational groups with low levels of occupational health literacy (OHL) are considered vulnerable groups with high risks of work-related diseases and injuries. Therefore, improving the OHL of these groups is of great significance in reducing the burden on public health. ObjectiveTo master the four dimensional OHL levels and influencing factors of the key groups in Fuling District, Chongqing, and provide a basis for formulating health education programs for occupational groups in the future. MethodsThe Occupational Health Literacy Questionnaire of Key Populations was distributed online to investigate the key occupational groups in Fuling District through stratified cluster sampling. The survey collected data on basic demographic information, legal knowledge of occupational health, basic knowledge of occupational health protection, basic skills of occupational health protection, and healthy working style and behavior. Univariate analysis, logistic regression, and nomogram were used to analyze the above data. ResultsThis survey distributed 4824 questionnaires, of which 4677 were valid, with a recovery rate of 97.0%. The dimensional OHL levels of key occupational groups in Fuling District from high to low were: healthy working style and behavior (79.1%), basic knowledge of occupational health protection (78.4%), legal knowledge of occupational health protection (43.3%), and basic skills of occupational health protection (37.6%). The results of logistic regression showed that the occupational health legal knowledge levels in the groups of high school/vocational high school/technical secondary school and above (reference: primary school and below) (OR=1.47, 95%CI: 1.05, 2.05), ≥3000 yuan of monthly income (reference:

Abstract Patchouli alcohol (PA) is a widely used pharmaceutical ingredient in various Chinese traditional herbal medicine (THM) formulations, known for its modulatory effects on the gut microbiota. The present study investigated PA's anti-inflammatory and regulatory effects on gut microbiota and its mode of action (MOA). Based on the assessments of ulcerative colitis (UC) symptoms, PA exhibited promising preventions against inflammatory response. In accordance, the expressions of pro-inflammatory factors, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and chemokine ligand 5 were significantly attenuated under PA treatment. Furthermore, PA enhanced the intestinal barrier damage caused by dextran sodium sulfate (DSS). Interestingly, PA exhibited negligible inventions on DSS-induced gut microbiota dysbiosis. PA did not affect the diversity of the DSS gut microbiota, it did alter the composition, as evidenced by a significant increase in the Firmicutes-Bacteroidetes (F/B) ratio. Finally, the MOA of PA against inflammation in DSS-treated mice was addressed by suppressing the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS). In conclusion, PA prevented inflammatory response in the DSS-induced UC mice model via directly suppressing HO-1 and iNOS-associated antioxidant signal pathways, independent of its effects on gut microbiota composition.

Introduction Acute hypoxic respiratory failure (AHRF) is one of the most common causes of admission to paediatric intensive care units (PICUs) around the world, posing a serious health concern for the global community. Non-invasive respiratory support (NRS) is considered effective in reducing mortality and intubation rates in adults. However, it is not yet clear whether NRS is beneficial for children and which NRS modalities are most effective. This network meta-analysis aims to summarise existing evidence and compare the efficacy and safety of different NRS modalities in paediatric patients with acute hypoxaemic respiratory failure.Methods and analysis To identify randomised controlled trials, we will perform a systematic search of key databases (Embase, PubMed, CENTRAL, CINAHL Complete and Web of Science) and registered clinical trials (ClinicalTrials.gov, WHO ICTRP and ISRCTN). To ensure the inclusion of the latest literature, an initial pilot search was conducted on 8 July 2024, and an updated search will be conducted after the main research work of this study. AHRF in children treated with NRS will be included. Hospital mortality, intubation rate, treatment failure rate and serious adverse events are critical outcomes closely related to patient-centredness and importance. Two authors will independently select the studies and extract the data. The risk of bias will be assessed using the Cochrane risk of bias tool V.2.0. In order to compare the effects of different NRS modalities, pairwise meta-analysis and network meta-analysis will be conducted using R software. Several subgroup analyses will be conducted, including analyses of different causes of AHRF. We will conduct sensitivity analyses by excluding studies with a high risk of bias and those involving neonates. Using the Grading of Recommendations Assessment, Development and Evaluation methodology, we will assess the certainty of the evidence for the effect estimates of all the outcomes.Ethics and dissemination Since this research is a network meta-analysis based on published literature, no formal ethics approval is required. The results will be disseminated through a peer-reviewed journal for publication.PROSPERO registration number CRD42024529804.

IntroductionScoliosis is a pathological spine structure deformation, predominantly classified as “idiopathic” due to its unknown etiology. However, it has been suggested that scoliosis may be linked to polygenic backgrounds. It is crucial to identify potential Adolescent Idiopathic Scoliosis (AIS)-related genetic backgrounds before scoliosis onset.MethodsThe present study was designed to intelligently parse, decompose and predict AIS-related variants in ClinVar database. Possible AIS-related variant records downloaded from ClinVar were parsed for various labels, decomposed for Dinucleotide Compositional Representation (DCR) and other traits, screened for high-risk genes with statistical analysis, and then learned intelligently with deep learning to predict high-risk AIS genotypes.ResultsResults demonstrated that the present framework is composed of all technical sections of data parsing, scoliosis genotyping, genome encoding, machine learning (ML)/deep learning (DL) and scoliosis genotype predicting. 58,000 scoliosis-related records were automatically parsed and statistically analyzed for high-risk genes and genotypes, such as FBN1, LAMA2 and SPG11. All variant genes were decomposed for DCR and other traits. Unsupervised ML indicated marked inter-group separation and intra-group clustering of the DCR of FBN1, LAMA2 or SPG11 for the five types of variants (Pathogenic, Pathogeniclikely, Benign, Benignlikely and Uncertain). A FBN1 DCR-based Convolutional Neural Network (CNN) was trained for Pathogenic and Benign/ Benignlikely variants performed accurately on validation data and predicted 179 high-risk scoliosis variants. The trained predictor was interpretable for the similar distribution of variant types and variant locations within 2D structure units in the predicted 3D structure of FBN1.DiscussionIn summary, scoliosis risk is predictable by deep learning based on genomic decomposed features of DCR. DCR-based classifier has predicted more scoliosis risk FBN1 variants in ClinVar database. DCR-based models would be promising for genotype-to-phenotype prediction for more disease types.

BackgroundStudies revealed that exosomes from IFN-α-treated liver non-parenchymal cells (IFN-exo) mediate antiviral activity. MiR-106b-3p has been shown to play a paradoxical role in disease progressing from different studies. However, its specific role in HBV-related hepatocellular carcinoma (HBV-HCC) and the underlying mechanism remains unclear.MethodHuh7 cells transient transfected with plasmids of HBV-C2 and B3 were co-cultured with IFN-exo. Cell supernatants were collected to detect miR-106b-3p, HBsAg, HBeAg and HBV DNA levels. Cell proliferation, apoptosis, migration and invasion were analyzed. The putative targets of miR-106b-3p were identified by a dual-luciferase reporter system. The expression of PCGF3, migratory proteins(MMP2/9), and the PI3K/AKT signaling pathway-related proteins were assessed by western blot. The expression of PCGF3 mRNA was quantitative analyzed by using 52 pairs of paraffin-embedded tissues from HCC patients. siRNAs-PCGF3 were used to knocked-down PCGF3 expression.ResultsThe expression of miR-106b-3p was significantly higher in THP-1 cells and supernatants treated with IFN-exo than those untreated. Significantly increased expression of miR-106b-3p and decreased expression of HBsAg and HBV DNA were observed in Huh7-C2/B3 cells treated with IFN-exo. In addition, miR-106b-3p was directly target to PCGF3. Scratch healing assay and transwell assay showed that either IFN-exo or miRNA-106-3p over-expression, or siRNAs-PCGF3 inhibited migration and invasion of Huh7-C2/B3 cells, and subsequently resulted in suppression of p-AKT/AKT and p-PI3K/PI3K. Notably, the expression level of PCGF3 was significantly lower in HBeAg (+)-HCC tumor tissues than HBeAg (-)-HCC tumor.ConclusionIFN-α-induced macrophage-derived miR-106b-3p inhibits HBV replication, HBV- Huh7 cells migration and invasion via regulating PCGF3/PI3K/AKT signaling axis. miR-106b-3p and PCGF3 were potential biomarkers in the prevention and treatment of HBV-HCC.

Abstract Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING‑deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Abstract The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

Summary: Cartilage maintains the structure and function of joints, with disturbances leading to potential osteoarthritis. N6-methyladenosine (m6A), the most widespread post-transcriptional modification in eukaryotes, plays a crucial role in regulating biological processes. While current research has indicated that m6A affects the progression of osteoarthritis, its function in the development and homeostasis of articular cartilage remains unclear. Here we report that Mettl3 deficiency in chondrocytes leads to mandibular condylar cartilage morphological alterations, early temporomandibular joint osteoarthritis, and diminished adaptive response to abnormal mechanical stimuli. Mechanistically, METTL3 modulates Lats1 mRNA methylation and facilitates its degradation in an m6A-YTHDF2-dependent manner, which subsequently influences the degradation and nuclear translocation of YAP1. Intervention with the Hippo pathway inhibitor XMU-MP-1 alleviates condylar abnormality caused by Mettl3 knockout. Our findings demonstrate the role of METTL3 in cartilage development and homeostasis, offering insights into potential treatment strategies for osteoarthritis.

Abstract The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram‐negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram‐negative and Gram‐positive bacteria through a unique dual‐targeting mechanism without detectable resistance. Meanwhile, an SR25‐functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25‐incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin‐resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.

Abstract Green manuring is the process by which vegetative crops are incorporated into the soil, and it plays a good substitutable role in reducing chemical fertilizer applications while enhancing soil fertility. Field experiments were conducted at Lingao City of Hainan Province in 2020 and 2021, to evaluate the effects of in situ incorporation of different green manures (fallow (as control), rice, sesbania, and stylosanthes) on soil physical and chemical properties, nitrogen (N) uptake, grain yield, and the grain anthocyanin content in colored rice. Treatments included colored rice cultivated with previous fallow (T0), with previous rice straw manure (T1), with previous sesbania manure (T2), and with previous stylosanthes manure (T3). The seedlings of the colored rice variety Suixiangheinuo were transplanted 23 days after the incorporation of green manure. Our results indicated that both the grain yield and grain anthocyanin content of colored rice were significantly increased when green manure was incorporated into the soil compared to that of the control. Therein, grain yields of T1, T2, and T3 were increased by an average of 12.7%, 29.0%, and 24.5%, respectively, across 2 years in comparison with those of T0. And grain anthocyanin content in colored rice under T1, T2, and T3 was increased by 7.2%–7.5%, 13.9%–24.2%, and 9.8%–20.6%, respectively. In addition, in situ incorporation of leguminous green manure in the soil significantly increased soil fertility and partial factor productivity for N fertilizer. The above results suggested that colored rice crops should be followed in rotation with leguminous green manure, which was beneficial to increasing both grain yield and grain anthocyanin content of colored rice. This research elucidated that the incorporation of leguminous green manure sustained the production of colored rice in tropical regions, which was beneficial to reconcile the relationship between rice production and environmental protection.

Colored rice is a type of high-quality, high-added-value rice that has attracted increasing attention in recent years. The use of large amounts of inorganic nitrogen fertilizer in rice fields results in low fertilizer use efficiency and high environmental pollution. Organic fertilizer is a promising way to improve soil quality and sustain high yields. However, most studies focus on the effect of animal-based organic fertilizers. The effects of different ratios of plant-based organic fertilizer and inorganic fertilizer on the grain yield and quality of colored rice have rarely been reported. Therefore, a two-year field experiment was conducted in 2020 and 2021 to study the effects of replacing inorganic N fertilizers with plant-based organic fertilizers on the yield, nitrogen use efficiency (NUE), and anthocyanin content of two colored rice varieties in a tropical region in China. The experimental treatments included no nitrogen fertilization (T1), 100% inorganic nitrogen fertilizer (T2), 30% inorganic nitrogen fertilizer substitution with plant-based organic fertilizer (T3), 60% inorganic nitrogen fertilizer substitution with plant-based organic fertilizer (T4), and 100% plant-based organic fertilizer (T5). The total nitrogen provided to all the treatments except T1 was the same at 120 kg ha–1. Our results showed that the T3 treatment enhanced the grain yield and anthocyanin content of colored rice by increasing nitrogen use efficiency compared with T2. On average, grain yields were increased by 9 and 8%, while the anthocyanin content increased by 16 and 10% in the two colored rice varieties under T3 across the two years, respectively, as compared with T2. Further study of the residual effect of partial substitution of inorganic fertilizers showed that the substitution of inorganic fertilizer with plant-based organic fertilizer improved the soil physio-chemical properties, and thus increased the rice grain yield, in the subsequent seasons. The highest grain yield of the subsequent rice crop was observed under the T5 treatment. Our results suggested that the application of plant-based organic fertilizers can sustain the production of colored rice with high anthocyanin content in tropical regions, which is beneficial in reconciling the relationship between rice production and environmental protection.

Abstract Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10−7 mol·s−1·m−2·Pa−1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.

Abstract Background Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct and validate a m6A-related lncRNAs signature and assess immunotherapeutic drug sensitivity in PDAC. Methods RNA-seq data for 178 cases of PDAC patients and 167 cases of normal pancreatic tissue were obtained from TCGA and GTEx databases, respectively. A set of 21 m6A-related genes were downloaded based on the previous report. Co-expression network was conducted to identify m6A-related lncRNAs in PDAC. Cox analyses and least absolute shrinkage and selection operator (Lasso) regression model were used to construct a risk prognosis model. The relationship between signature genes and immune function was explored by single-sample GSEA (ssGSEA). The tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB) were utilized to evaluate the response to immunotherapy. Furthermore, the expression levels of 4 m6A-related lncRNAs on PDAC cell lines were measured by the quantitative real-time PCR (qPCR). The drug sensitivity between the high- and low-risk groups was validated using PDAC cell lines by Cell-Counting Kit 8 (CCK8). Results The risk prognosis model was successfully constructed based on 4 m6A-related lncRNAs, and PDAC patients were divided into the high- and low-risk groups. The overall survival (OS) of the high-risk groups was more unfavorable compared with the low-risk groups. Receiver operating characteristic (ROC) curves demonstrated that the risk prognosis model reasonably predicted the 2-, 3- and 5-year OS of PDAC patients. qPCR analysis confirmed the decreased expression levels of 4 m6A-related lncRNAs in PDAC cells compared to the normal pancreatic cells. Furthermore, CCK8 assay revealed that Phenformin exhibited higher sensitivity in the high-risk groups, while Pyrimethamine exhibited higher sensitivity in the low-risk groups. Conclusion The prognosis of patients with PDAC were well predicted in the risk prognosis model based on m6A-related lncRNAs, and selected immunotherapy drugs have potential values for the treatment of pancreatic cancer.

Abstract Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

In the present study, an investigation is conducted into the effect of different aging treatments on the hardening properties of the 6151 aluminum alloy sheet. According to the research results, the artificial aging hardening response of the pre-aging sheet is significantly stronger compared to natural aging after the solution treatment. In the stage of artificial aging, 120 oC pre-aging treatment produces a more significant strengthening effect than 80 oC and 100 oC pre-aging treatment. The longer the artificial time, the higher the hardness value. When the artificial aging temperature reaches 200 oC, the time taken to achieve peak aging is the shortest, and the occurrence of softening is evident in the over-aged state. When the artificial aging temperature is 200 oC, the softening effect becomes more significant. Natural aging can inhibit the strengthening effect of artificial aging. With the extension of natural aging, the hardening effect of artificial aging diminishes gradually.

The aboveground biomass (AGB) of summer maize is an important indicator for assessing crop growth status and predicting yield, playing a significant role in agricultural management and decision-making. Traditional on-site measurements of AGB are limited, due to low efficiency and a lack of spatial information. The development of unmanned aerial vehicle (UAV) technology in agriculture offers a rapid and cost-effective method for obtaining crop growth information, but currently, the prediction accuracy of summer maize AGB based on UAVs is limited. This study focuses on the entire growth period of summer maize. Multispectral images of six key growth stages of maize were captured using a DJI Phantom 4 Pro, and color indices and elevation data (DEM) were extracted from these growth stage images. Combining measured data such as summer maize AGB and plant height, which were collected on the ground, and based on the three machine learning algorithms of partial least squares regression (PLSR), random forest (RF), and long short-term memory (LSTM), an input feature analysis of PH was carried out, and a prediction model of summer maize AGB was constructed. The results show that: (1) using unmanned aerial vehicle spectral data (CIS) alone to predict the biomass of summer maize has relatively poor prediction accuracy. Among the three models, the LSTM (CIS) model has the best simulation effect, with a coefficient of determination (R2) ranging from 0.516 to 0.649. The R2 of the RF (CIS) model is 0.446–0.537. The R2 of the PLSR (CIS) model is 0.323–0.401. (2) After adding plant height (PH) data, the accuracy and stability of model prediction significantly improved. R2 increased by about 25%, and both RMSE and NRSME decreased by about 20%. Among the three prediction models, the LSTM (PH + CIS) model had the best performance, with R2 = 0.744, root mean square error (RSME) = 4.833 g, and normalized root mean square error (NRSME) = 0.107. Compared to using only color indices (CIS) as the model input, adding plant height (PH) significantly enhances the prediction effect of AGB (aboveground biomass) prediction in key growth periods of summer maize. This method can serve as a reference for the precise monitoring of crop biomass status through remote sensing with unmanned aerial vehicles.

Abstract Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

Colletotrichum species are plant pathogens, saprobes and endophytes on various plant hosts. It is regarded as one of the 10 most important genera of plant pathogens in the world. Walnut anthracnose is one of the most severe diseases affecting walnut productivity and quality in China. In this study, 162 isolates were obtained from 30 fruits and 65 leaf samples of walnut collected in Beijing, China. Based on morphological characteristics and DNA sequence analyses of the concatenated loci, namely internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), chitin synthase 1 (CHS-1) and beta-tubulin (TUB2), these isolates were identified as two novel species of Colletotrichum, i.e. C. juglandicola and C. peakense. Koch’s postulates indicated that both C. juglandicola and C. peakense could cause anthracnose in walnut.

Background: Acinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development.Methods: We developed a novel morphology-based screen using organoids from wildtype and p48Cre/+ (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA).Results: Of the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis. The class I HDAC inhibitors apicidin and FK228, and the histone methyltransferase inhibitor chaetocin demonstrated pronounced ADM inhibition and reversal without inducing significant cytotoxicity at 1 µM. Thioester prodrug class I HDAC inhibitor largazole attenuated ADM while its disulfide homodimer was effective in both ADM inhibition and reversal. Prioritized compounds were validated for ADM reversal in p48Cre/+; LSL-KrasG12D/+ (KC) mouse organoids using both morphological and molecular endpoints. Molecular index analysis of ADM reversal in KC mouse organoids demonstrated improved activity compared to TSA. Improved prodrug stability translated into a stronger phenotypic and molecular response. RNA-sequencing indicated that angiotensinogen was the top inhibited pathway during ADM reversal.Conclusion: Our findings demonstrate a unique epigenetic mechanism and suggest that the phenotypic screen developed here may be applied to discover potential treatments for PDAC.

Abstract Janus Kinases (JAKs) play a crucial role as therapeutic targets for various cancers. However, the current JAK inhibitors (JAKi) available have limited therapeutic benefits due to their lack of selectivity. This review focuses on the structural analysis to elucidate the molecular determinants of JAKs specificity and the discovery and design of selective JAKi. It includes descriptions and comparison of different JAK structures and their binding sites, a comparative analysis of JAKi and their binding modes, detailed interaction fingerprints (IFPs), and an extensive structure‐selectivity relationship (SSRs). Moreover, the review also explores the challenges and possibilities of using computational structure‐based methods for discovering and designing selective JAKi. Other structure‐based approaches, such as targeting the pseudokinase domain, as well as covalent and allosteric designs, are also covered. Based on this analysis, key determinants corresponding to JAK specificity and rational medicinal chemistry strategies are proposed to facilitate the development of highly selective JAKi. Overall, we aim to enhance the understanding of JAK specificity and explore strategies that can lead to the discovery of effective and selective JAKi in cancer therapy, thus improving the prognosis for cancer patients.

Abstract The Mulibrey (Muscle–liver–brain–eye) nanism caused by loss-of-function variants in TRIM37 gene is an autosomal recessive disorder characterized by severe growth failure and constrictive pericarditis. These patients also suffer from severe respiratory infections, co-incident with an increased mortality rate. Here, we revealed that TRIM37 variants were associated with recurrent infection. Trim37 FIN major (a representative variant of Mulibrey nanism patients) and Trim37 knockout mice were susceptible to influenza virus infection. These mice showed defects in follicular helper T (TFH) cell development and antibody production. The effects of Trim37 on TFH cell differentiation relied on its E3 ligase activity catalyzing the K27/29-linked polyubiquitination of Bcl6 and its MATH domain-mediated interactions with Bcl6, thereby protecting Bcl6 from proteasome-mediated degradation. Collectively, these findings highlight the importance of the Trim37-Bcl6 axis in controlling the development of TFH cells and the production of high-affinity antibodies, and further unveil the immunologic mechanism underlying recurrent respiratory infection in Mulibrey nanism.

Abstract Colorectal cancer (CRC) therapy efficiency can be influenced by the microbiota in the gastrointestinal tract. Compared with traditional intervention, prebiotics delivery into the gut is a more controllable method for gut microbiota modulatory therapy. Capecitabine (Cap), the first-line chemotherapeutic agent for CRC, lacks a carrier that can prolong its half-life. Here, we construct a Cap-loaded nanoparticle using the prebiotic xylan-stearic acid conjugate (SCXN). The oral administration of SCXN delays the drug clearance in the blood and increases the intra-tumoral Cap concentration in the CRC mouse model. SCXN also facilitates the probiotic proliferation and short chain fatty acid production. Compared with free Cap, SCXN enhances the anti-tumor immunity and increases the tumor inhibition rate from 5.29 to 71.78%. SCXN exhibits good biocompatibility and prolongs the median survival time of CRC mice from 14 to 33.5 d. This prebiotics-based nanoparticle provides a promising CRC treatment by combining gut microbiota modulation and chemotherapy.

Immunotherapy combats tumors by enhancing the body’s immune surveillance and clearance of tumor cells. Various nucleic acid drugs can be used in immunotherapy, such as DNA expressing cytokines, mRNA tumor vaccines, small interfering RNAs (siRNA) knocking down immunosuppressive molecules, and oligonucleotides that can be used as immune adjuvants. Nucleic acid drugs, which are prone to nuclease degradation in the circulation and find it difficult to enter the target cells, typically necessitate developing appropriate vectors for effective in vivo delivery. Biomimetic drug delivery systems, derived from viruses, bacteria, and cells, can protect the cargos from degradation and clearance, and deliver them to the target cells to ensure safety. Moreover, they can activate the immune system through their endogenous activities and active components, thereby improving the efficacy of antitumor immunotherapeutic nucleic acid drugs. In this review, biomimetic nucleic acid delivery systems for relieving a tumor immunosuppressive microenvironment are introduced. Their immune activation mechanisms, including upregulating the proinflammatory cytokines, serving as tumor vaccines, inhibiting immune checkpoints, and modulating intratumoral immune cells, are elaborated. The advantages and disadvantages, as well as possible directions for their clinical translation, are summarized at last.

Culters are a popular and economically important carnivorous freshwater fish, widely distributed in rivers, lakes, and reservoirs in China. An investigation of Myxozoa was conducted to enhance the understanding of Myxozoan diversity in Culters in China, as only 15 Myxosporean species have been previously reported in 6 Culters species. A new species with typical Myxobolus characteristics was discovered exclusively in the gills of Chanodichthys dabryi, Bleeker, 1871, and no other species were found in other Culters fish or organs. The new species elicited whitish plasmodia in the serosa layer of the gill arch, with no distinct inflammatory reaction observed. This species is morphologically different from all reported Myxobolus spp. from Culters, differing in plasmodium and spore size, as well as the coils of polar filaments. Molecular analysis further supports that it does not match any sequences available in GenBank. Therefore, we identified it as a new species and named it Myxobolus dabryi n. sp.

Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7 days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.

In this paper, after using the TF-IDF algorithm to calculate the weights of intellectual property keywords of digital content, the weights of fused word multi-features are improved to obtain the proportion of intellectual property keywords. Based on intellectual property keywords, combining adversarial fingerprint generation and intellectual property authentication, an intellectual property protection model based on RCNN is constructed. From the perspective of strong nation-building, the research on intellectual property affecting the artificial intelligence industry is designed, and multivariate statistical analysis of scientific governance of intellectual property in the context of strong nation-building is carried out. The results show that the SSIM values obtained by the method of this paper are much better than those obtained by the comparison method in terms of model analysis. Except for the anti-quantization attack, the rest of the indicators are all greater than 0.9. It confirms that the method presented in this paper has excellent robustness in protecting intellectual property. In the empirical analysis of the impact of intellectual property rights on the artificial intelligence industry, except for RDF, which is significant at the 5% level, the regression coefficients of the other explanatory variables are all significant at the 1% level, 2 R amounting to 0.860771 and with a DW value of 1.667387 in the range of 1.5-2.5, that is, it indicates that the level of China’s intellectual property rights protection and the competitiveness of the AI industry are positively correlated. It is positively correlated. This study promotes the improvement of China’s innovation ability and the formation of innovation mechanisms from the aspect of intellectual property protection so as to realize the comprehensive catching up of technology and economy of late-developed countries.

Background Intralesional corticosteroid administration (ICA) is a first-line therapy in keloid treatment. However, its clinical results are still highly variable and often suboptimal. Treatment results may strongly be influenced by various ways of ICA. Objective To explore the prevailing practice of ICA in keloid treatment among dermatologists and plastic surgeons in the Netherlands. Methods The survey was constructed based on a scoping review on ICA in keloid treatment. Members of the Dutch Society for Plastic surgery and the Dutch Society for Dermatology and Venereology were asked to participate. Results One hundred and thirty-six responses were obtained. One hundred and thirty (95.6%) participants used triamcinolone acetonide. The majority (54.7%) did not use local anesthesia for pain reduction. Reported corticosteroid dosing that one would inject in one specific keloid differed by a factor of 40. Treatment intervals varied from 1 week to more than 8 weeks. The keloid center was most often injected (46.9%), followed by subepidermal (18.0%). Conclusions A wide variety in ICA for keloids is noted among dermatologists and plastic surgeons, even in a limited geographic region and when evidence points toward an optimal way of treatment. Future studies and better implementation of existing evidence may reduce variation in ICA and optimize its treatment results.

Platinum-based chemotherapy is one of the predominant strategies for treating ovarian cancer (OC), however, platinum resistance greatly influences the therapeutic effect. Circular RNAs (circRNAs) have been found to participate in the pathogenesis of platinum resistance. Our aim was to explore the involvement of circ_0078607 in OC cell cisplatin (DDP) resistance and its potential mechanisms. Circ_0078607, miR-196b-5p, and growth arrest-specific 7 (GAS7) levels were assessed by qPCR. Circ_0078607 stability was assessed by ribonuclease R digestion and actinomycin D treatment. Cell viability of various conic of DDP treatment was measured by CCK-8. The cell proliferation was determined by CCK-8 and colony formation assay. Western blotting was performed for determining GAS7, ABCB1, CyclinD1 and Bcl-2 protein levels. The direct binding between miR-196b-5p and circ_0078607 or GAS7 was validated by dual-luciferase reporter and RIP assay. DDP resistance in vivo was evaluated in nude mice. Immunohistochemistry staining for detecting Ki67 expression in xenograft tumours. Circ_0078607 and GAS7 was down-regulated, but miR-196b-5p was up-regulated in OC samples and DDP-resistant cells. Overexpression of circ_0078607 inhibited DDP resistance, cell growth and induced apoptosis in DDP-resistant OC cells. Mechanistically, circ_0078607 sequestered miR-196b-5p to up-regulate GAS7. MiR-196b-5p mimics reversed circ_0078607 or GAS7 overexpression-mediated enhanced sensitivity. Finally, circ_0078607 improved the sensitivity of DDP in vivo. Circ_0078607 attenuates DDP resistance via miR-196b-5p/GAS7 axis, which highlights the therapeutic potential of circ_0078607 to counter DDP resistance in OC.

Diarrhea in piglets is one of the most important diseases and a significant cause of death in piglets. Preliminary studies have confirmed that taurine reduces the rate and index of diarrhea in piglets induced by LPS. However, there is still a lack of relevant information on the specific target and mechanism of action of taurine. Therefore, we investigated the effects of taurine on the growth and barrier functions of the intestine, microbiota composition, and metabolite composition of piglets induced by LPS. Eighteen male weaned piglets were randomly divided into the CON group (basal diet + standard saline injection), LPS group (basal diet + LPS-intraperitoneal injection), and TAU + LPS group (basal diet + 0.3% taurine + LPS-intraperitoneal injection). The results show that taurine significantly increased the ADG and decreased the F/G (p

Objective: To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms. Methods: Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis. Differentially expressed miRNAs were identified using RNA sequencing. Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs. The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101. DGL5 expression was detected using qRT-PCR and Western blot analyses. Results: The migration of breast cancer cells was significantly inhibited after addition of exosomes. RNA sequencing results showed that miR-101-3p expression was significantly upregulated. Targetscan analysis predicted that miR-101-3p could target DLG5, and this prediction was verified using the luciferase assay. The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p, and the mRNA and protein levels of DLG5 were suppressed. In contrast, inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5. Furthermore, the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells. Conclusions: Macrophage exosomes can inhibit the migration of breast cancer cells, and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process, which needs further investigation.

The sustainable development process faces two major challenges: income inequality and carbon emissions. However, there is no definitive conclusion regarding the relationship between income inequality and carbon emissions. In addition, for developed and developing countries, the impact might vary. From an international perspective, the present study examines the correlation between income inequality and carbon emissions utilizing panel data from 65 countries (32 developed and 33 developing countries) spanning from 1990 to 2019. The simultaneous quantile regression (SQR) results show that the impact of income inequality on carbon emissions varies slightly between countries with various income levels. The positive impact of income inequality on carbon emissions is significant for both developed and developing countries, indicating that an uneven income distribution can worsen environmental quality, but the impact is more significant for developed countries. Therefore, it is integral for the global world to take measures to alleviate the income gap to achieve Sustainable Development Goals (SDGs). In addition to income growth, developed countries also need to focus on income equity to reach green development.