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Abstract The Internet of Things technology allows you to transfer data to any asset through communication networks such as the Internet or intranet. One of the most important problems is security, which includes confidentiality, authenticity validation, and completeness. Among security problems, the most important ones are ensuring authenticity and protecting privacy. The elliptic curve encryption algorithm is famous protocols for maintaining privacy and verifying authenticity. Despite the capabilities they have and provide good security against network attacks, they face challenges such as response time, delay in the authentication and authentication process, as well as the amount of memory consumed. Two-factor authentication (2FA) is a security process where users provide two different authentication factors to authenticate themselves. It also provides a higher level of security than authentication methods that rely on single-factor authentication (SFA). This article presents two novel methods for 2FA that use encryption techniques, scramble architecture, and chord architecture. These methods allow for the authentication process to be initiated by both parties involved in the communication. Three scenarios and three metrics of reaction time, memory usage, and connection latency were used to assess the efficacy of the suggested approach. The average reaction time is improved and is 0.012 s when the lengths of the finger table in the chord structure are increased to 10, 15, and 20. The findings show that the suggested approach reduces computing complexity, reaction time, and communication latency. It has an average reaction time of 0.016 s, an average memory use of 30,360 kb, and an average connection latency of 0.042 s.

AlCoCrFeMo0.05Ni2 high-entropy alloy (HEA) has great potential for high-temperature applications. However, its FCC matrix will decompose during annealing, which seriously limits its high-temperature applications. Here, the lattice distortion, Gibbs free energy change, phonon spectra, density of states, and bond length distribution of the FCC matrix were calculated by first-principles calculations. The findings indicate that the primary barrier to the formation of a single homogeneous solid solution in the alloy is more closely associated with Gibbs free energy rather than the degree of lattice distortion. The vibration frequency of Al is not in sync with the overall structure, making it prone to desolvation at elevated temperatures. Furthermore, an analysis of bond lengths reveals that the Al–Ni bond length is significantly shorter than the theoretical value, facilitating the formation of a (Ni, Al)-rich phase. In contrast, the longer bond lengths of Al–Cr and Al–Mo facilitate the detachment of Cr and Mo from the (Ni, Al)-rich phase, resulting in the formation of (Cr, Mo)-rich phase. This in-depth investigation sheds light on the phase decomposition mechanism of high-entropy alloys, offering valuable insights for future research in this field.

The deposition area of the hot filament chemical vapor deposition (HFCVD) method can reach 12 inches, which has the potential to produce larger-sized single crystal diamonds. In this study, single crystal diamond with a size of 3 mm × 3 mm × 1 mm and (100) orientation was used as the substrate. Homoepitaxial growth was carried out using the HFCVD method with methane and hydrogen as precursors, and a small amount of nitrogen gas. The results show that under the conditions of a filament temperature of 2200 °C, a carbon source concentration of 4%, and a chamber pressure of 4 kPa, single crystal diamond grows at a rate of 3.41 μm/h. The surface of the diamond exhibits no defects such as polycrystals, cracks, or holes. The full width half maximum (FWHM) of the epitaxial layer’s X-ray diffraction spectrum at the (400) peak is 0.11°, which is lower than that of the substrate at 0.16°, indicating that the crystal quality of the epitaxial layer is higher than that of the substrate. The introduction of nitrogen can increase the growth rate of single crystal diamond, although it reduces the crystal quality of the epitaxial layer. A higher nitrogen concentration can also shift the growth mode of single crystal diamond change to island growth.

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, cell type specific dysregulation of transposable elements was observed in Severe COVID-19 patients. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.

BackgroundIntramuscular hemangioma is a vascular malformation occurring in muscle tissues. It is most common in skeletal muscles of limbs, especially lower limbs in childhood. The intercostal intramuscular hemangioma with sternal invasion is very rare.Case presentationThe 47-year-old female patient was hospitalized due to “suddenly chest pain for 4 days”. Chest contrast-enhanced CT indicated bony changes in the sternum, accompanied by soft tissue shadows in the posterior sternum and diaphragmatic angle. After admission, physical examination showed: peristernal tenderness, percussion pain, other no obvious positive signs. PET-CT examination indicated that there was a high possibility of benign sternal changes. No cancer cells were found by sternal puncture. Surgical biopsy was performed and pathological findings were consistent with intramuscular hemangioma.ConclusionIntramuscular hemangioma with bone invasion is very rare, imaging examination is difficult to indicate obvious evidence, preoperative diagnosis is difficult, complete surgical resection is very important, more personalized treatment should be provided according to the overall situation of the patient.

Glioma is the most common malignant tumor of the central nervous system. Drug-assisted chemotherapy is an important adjuvant treatment post-surgery, but currently, effective chemotherapy drugs for glioma are lacking. Expediting new and effective chemotherapy drugs is a persistent problem that needs to be solved. In this study, a tetramic acid derivative, trichobotrysin B, was extracted from the ascidian-derived fungus Trichobotrys effusa 4729 (denoted ADFTe4729). There is significant cytotoxicity of trichobotrysin B against glioma proliferation, which triggers apoptosis and cell cycle arrest. Furthermore, studies have found that trichobotrysin B inhibits glioma proliferation in a manner closely related to IL-6-mediated STAT3 phosphorylation and JAK2 activation. In conclusion, this study demonstrates that the small-molecule compound trichobotrysin B inhibits glioma proliferation and induces apoptosis through the IL-6-mediated STAT3/JAK2 signaling pathway, suggesting that trichobotrysin B has potential antiglioma efficiency and provides a new way to explore new small-molecule drugs with anticancer effects.

BackgroundThrough preoperative localization, surgeons can easily locate ground glass nodules (GGNs) and effectively control the extent of resection. Therefore, it is necessary to choose an appropriate puncture positioning method. The purpose of this study was to evaluate the effectiveness and safety of medical glue and positioning hooks in the preoperative positioning of GGNs and to provide a reference for clinical selection.MethodsFrom March 30, 2020 to June 13, 2022, a total of 859 patients with a CT diagnosis of GGNs requiring surgical resection were included in our study at the hospital. Among them, 21 patients who either opted out or could not undergo preoperative localization for various reasons were excluded. Additionally, 475 patients who underwent preoperative localization using medical glue and 363 patients who underwent preoperative localization through positioning hooks were also excluded. We conducted statistical analyses on the baseline data, success rates, complications, and pathological results of the remaining patients. The success rates, complication rates, and pathological results were compared between the two groups—those who received medical glue localization and those who received positioning hook localization.ResultsThere was no statistically significant difference between the two groups of patients in terms of age, body mass index, smoking history, location of the nodule, distance of the nodule from the pleura, or postoperative pathological results (P > 0.05). The success rate of medical glue and positioning hooks was 100%. The complication rates of medical glue and positioning hooks during single nodule positioning were 39.18% and 23.18%, respectively, which were significantly different (p < 0.001); the complication rates during multiple nodule positioning were 49.15% and 49.18%, respectively, with no statistically significant differences (p > 0.05). In addition, the method of positioning and the clinical characteristics of the patients were not found to be independent risk factors for the occurrence of complications. The detection rate of pulmonary nodules also showed some positive correlation with the spread of COVID-19 during the 2020–2022 period when COVID-19 was prevalent.ConclusionWhen positioning a single node, the safety of positioning hooks is greater than when positioning multiple nodes, the safety of medical glue and positioning hooks is comparable, and the appropriate positioning method should be chosen according to the individual situation of the patient.

As the nonlinear and coupling characteristics of autonomous underwater vehicles (AUVs) are the challenges for motion modeling, the nonparametric identification method is proposed based on dung beetle optimization (DBO) and deep temporal convolutional networks (DTCNs). First, the improved wavelet threshold is utilized to select the optimal threshold and wavelet basis functions, and the raw model test data are denoising. Second, the bidirectional temporal convolutional networks, the bidirectional gated recurrent unit, and the attention mechanism are used to achieve the nonlinear nonparametric model of the AUV motion. And the hyperparameters are optimized by the DBO. Finally, the lazy-search-based path planning and the line-of-sight-based path following control are used for the proposed AUV model. The simulation shows that the prediction accuracy of the DBO-DTCN is better than other artificial intelligence methods and mechanical models, and the path following of AUV is feasible. The methods proposed in this paper can provide an effective strategy for AUV modeling, searching, and rescue cruising.

Abstract EZH2 is the catalytic subunit of the histone methyltransferase Polycomb Repressive Complex 2 (PRC2), and its somatic activating mutations drive lymphoma, particularly the germinal center B‐cell type. Although PRC2 inhibitors, such as tazemetostat, have demonstrated anti‐lymphoma activity in patients, the clinical efficacy is not limited to EZH2‐mutant lymphoma. In this study, Activin A Receptor Type 1 (ACVR1), a type I Bone Morphogenetic Protein (BMP) receptor, is identified as critical for the anti‐lymphoma efficacy of PRC2 inhibitors through a whole‐genome CRISPR screen. BMP6, BMP7, and ACVR1 are repressed by PRC2‐mediated H3K27me3, and PRC2 inhibition upregulates their expression and signaling in cell and patient‐derived xenograft models. Through BMP‐ACVR1 signaling, PRC2 inhibitors robustly induced cell cycle arrest and B cell lineage differentiation in vivo. Remarkably, blocking ACVR1 signaling using an inhibitor or genetic depletion significantly compromised the in vitro and in vivo efficacy of PRC2 inhibitors. Furthermore, high levels of BMP6 and BMP7, along with ACVR1, are associated with longer survival in lymphoma patients, underscoring the clinical relevance of this study. Altogether, BMP‐ACVR1 exhibits anti‐lymphoma function and represents a critical PRC2‐repressed pathway contributing to the efficacy of PRC2 inhibitors.

Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

Although the human body needs nickel as a trace element, too much nickel exposure can be hazardous. The effects of nickel on cells include inducing oxidative stress, interfering with DNA damage repair, and altering epigenetic modifications. Glucose metabolism and lipid metabolism are closely related to oxidative stress; however, their role in nickel-induced damage needs further study. In Institute of Cancer Research (ICR) mice, our findings indicated that nickel stress increased the levels of blood lipid indicators (triglycerides, high-density lipoprotein, and cholesterol) by about 50%, blood glucose by more than two-fold, and glycated serum protein by nearly 20%. At the same time, nickel stress increased oxidative stress (malondialdehyde) and inflammation (Interleukin 6) by about 30% in the kidney. Based on next-generation sequencing technology, we detected and analyzed differentially expressed genes in the kidney caused by nickel stress. Bioinformatics analysis and experimental verification showed that nickel inhibited the expression of genes related to lipid metabolism and the AMPK and PPAR signaling pathways. The finding that nickel induces kidney injury and inhibits key genes involved in lipid metabolism and the AMPK and PPAR signaling pathways provides a theoretical basis for a deeper understanding of the mechanism of nickel-induced kidney injury.

For the application of Delta robots with a 3-R(RPaR) configuration in machining tasks, this paper constructed a 54-parameter kinematic error model and a simplified dynamic model incorporating an integrated joint’s position error and friction, respectively. Utilizing Singular Value Decomposition (SVD) of the Linear Model Coefficient Matrix (LMCM) and the coefficient chart, a criterion for identifiability of error components is established. For good identification results, the optimal measurement surface with Fourier series form is obtained using a combination of the Hook–Jeeves Direct Search Algorithm (DSA) and Inner Point Method (IPM). The friction coefficients and other dynamic parameters are obtained through fitting the integrated joint torque-angle pairs measured along specific trajectories using nonlinear least squares regression. The validation of the calibration process is conducted through simulations and experiments. The calibration results provide a foundation for the precise control of integrated joints and the high-precision motion of robots.

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine–choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase–mammalian target of rapamycin (AMPK–mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPKα/AMPKα, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.

Background Gastric cancer (GC) is one of the most common malignant tumours in the digestive system. Serine hydroxymethyltransferase 2 (SHMT2) is one of the key enzymes associated with serine metabolism. However, the prognostic role of SHMT2 in GC carcinogenesis has yet to be studied. Methods The expression of SHMT2 in human tumors and normal tissues was detected by the Assistant for Clinical Bioinformatics and Immunohistochemistry (IHC). The relationship of the expression of SHMT2 with clinical characteristics and survival data was analysed by the chi-square test, survival analysis and online databases. Finally, the correlation between SHMT2 expression and associated signalling channels, and molecules was analysed by online databases. Results SHMT2 was strongly expressed in numerous human cancers. The expression rate of SHMT2 was 56.44% in GC (P = 0.018). The survival analysis indicated that patients with high expression of SHMT2 had the worse overall survival (OS; log-rank P = 0.007). The expression of SHMT2 was correlated with tumour size (P = 0.034) and, TNM stage (P = 0.042). In particular, SHMT2, vessel invasion and M stage were independent factors for OS in GC (P = 0.044, P < 0.001, P < 0.001). The SHMT2 gene was substantially correlated with cell signalling pathways. Conclusions SHMT2 is highly expressed in GC and is associated with a poor prognosis. The exploration of its mechanism may be related to tumour proliferation, DNA repair and replication. SHMT2 is an independent prognostic risk factor and a potential biomarker for the diagnosis and treatment of GC.

A severe torrential rain attacked Henan province from July 19 to 21, 2021, resulting in extensive social and economic damages. The models’ sub-seasonal prediction skill for this extreme event remains to be evaluated. Based on the real-time data of 5 models (CMA, ECMWF, NCEP, KMA, and UKMO) from the sub-seasonal to seasonal (S2S) prediction project, our study compared the models’ predictability and explored the possible reasons. Results indicate that most models can predict the spatial distribution of accumulated precipitation for this event 1 week in advance. Two models (NCEP and CMA) still have specific reference values in predicting precipitation intensity 2–3 weeks ahead. However, the predicted maximum rainfall is only about 20% of the observation, and all models cannot catch the extremes of this event. While large-scale atmospheric circulation can be predicted with some accuracy, there are still significant deviations in predicting the location and intensity of the western North Pacific subtropical high (WNPSH) and Typhoon In-Fa. The models predict weaker intensity of the southeast airflow transporting water vapor into the rainstorm area, resulting in significantly weaker precipitation. This is mainly attributed to unsatisfactory predicted typhoon circulation in most models. The model ECMWF and KMA predict a better moisture flux at 925hPa, about 60% of the observations. The characteristics of local high SST centers in the Sea of Japan cannot be caught, resulting in the position of the predicted WNPSH eastward and weak. Therefore, to improve the prediction skill for extreme precipitation events, it is imperative to enhance the interaction mechanisms among atmospheric circulation systems within the model.

Abstract Glioma is the most prevalent type of primary brain tumor, and glioblastoma multiforme (GBM) is the highest and most deadly type of primary central nervous system (CNS) tumor, affecting a significant number of patients each year, with a median overall survival of approximately 14.6 months after diagnosis. Despite intensive treatment, nearly all GBM patients experience recurrence, with a 5-year survival rate of about 5%. The protective BBB and high tumor heterogeneity prevent the effective delivery of drugs, resulting in the treatment failure of various drugs. The emergence of nanometer-scale diagnosis and treatment methods has provided new promising approaches to overcome these difficulties. Thus, our review focuses on the development of BBB-crossing nanomedicine-enhanced chemotherapy and combined therapy applications for glioma. Meanwhile, we also reviewed the strategies to overcome the blood–brain barrier. Additionally, we discuss recent achievements in the area of brain tumor treatment with nanomedicine and the rational design approach, which will offer recommendations for anti-GBM nanomedicine development.

The extensometer of Xuzhou seismic station is mainly disturbed by rainfall and atmospheric pressure. The influence of rainfall and atmospheric pressure on extensometer is quantitatively analyzed. The results show that the response of EW component rainfall is more sensitive. The main reason for the rapid acceleration of observation data in a short time is that the sensor core is not centered in the differential voltage transformer sensor. The induced area of the biased sensor core in the differential voltage transformer sensor increases greatly, leading to an increase of the induced voltage in the observation.

Abstract Background Chronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration. Methods To compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol. Results A total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P

Objectives: To evaluate the relation between metagenomic next-generation sequencing (mNGS) and the prognosis of patients with infectious diseases undergoing mechanical ventilation in the intensive care unit (ICU). Methods: This is a single-center observational study, comparing nonrandomly assigned diagnostic approaches. We analyzed the medical records of 228 patients with suspected infectious diseases undergoing mechanical ventilation in the ICU from March 2018 to May 2020. The concordance of pathogen results was also assessed for the results of mNGS, culture, and polymerase chain reaction assays. Results: The 28-day mortality of the patients in the mNGS group was lower after the baseline difference correction (19.23% (20/104) vs 29.03% (36/124) , P = 0.039). Subgroup analysis showed that mNGS assay was associated with improved 28-day mortality of patients who are not immunosuppressed (14.06% vs 29.82%, P = 0.018). Not performing mNGS assay, higher acute physiology and chronic health evaluation II score, and hypertension are independent risk factors for 28-day mortality. The mNGS assay presented an advantage in pathogen positivity (69.8% double-positive and 25.0% mNGS-positive only), and the concordance between these two assays was 79.0%. Conclusion: mNGS survey may be associated with a better prognosis by reducing 28-day mortality of patients with infectious diseases on mechanical ventilation in the ICU. This technique presented an advantage in pathogen positivity over traditional methods.

BackgroundPrevious studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC).MethodsBased on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments.ResultsThis study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration.ConclusionPANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.

Lung cancer originating from the bronchial epithelium is the most common lung malignancy. It has been reported that programmed cell death 1 ligand 1 (PD-L1) and tumor-associated macrophages are closely related to the development of lung cancer. However, whether tumor-derived exosomal PD-L1 could mediate the regulation of macrophage polarization in lung cancer remains unclear. For this research, the level of PD-L1 in normal tissues and lung cancer tissues was evaluated using RT-qPCR. Next, the apoptosis of lung cancer cells was evaluated using flow cytometry assay. Then, the structure and morphology of vesicles were observed using transmission electron microscopy and nanoparticle tracking analysis. Later on, the internalization of exosomes by macrophage was observed using fluorescence microscopy. Our results showed that the level of PD-L1 was upregulated in tumor tissues and lung cancer cells. Knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. In addition, lung cancer cells-derived exosomal PD-L1 could be absorbed by macrophages. Meanwhile, exosomal PD-L1 was able to promote macrophages M2 polarization. Moreover, macrophages M2 polarization induced by exosomal PD-L1 further remarkably promoted the viability, migration, invasion, and epithelial-mesenchymal transition process of lung cancer cells. Collectively, knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. Tumor cell-derived exosomal PD-L1 could promote the growth of lung cancer cells by mediating macrophages M2 polarization. Thus, inhibiting macrophages M2 polarization might be a promoting therapy for the treatment of lung cancer.

It has been widely accepted that mass-accreting white dwarfs (WDs) are the progenitors of Type Ia supernovae (SNe) or electron-capture supernovae. Previous work has shown that the accretion rate could affect the elemental abundance on the outer layers of CO WDs, and therefore affect the observational characteristics after they exploded as SNe Ia. However, it has not been well studied how elemental abundance changes on the outer layers of He-accreting ONe WDs as they approach the Chandrasekhar mass limit. In this paper, we investigated the evolution of He-accreting ONe WDs with MESA. We found that a CO-rich mantle will accumulate beneath the He layers resulting from the He burning, after which the ignition of the CO-rich mantle could transform carbon into silicon (Si). The amount of Si produced by carbon burning is strongly anticorrelated with the accretion rate. As the ONe WD nearly approaches the Chandrasekhar mass limit ( M _ch ) through accretion, it is likely to undergo accretion-induced collapse, resulting in the formation of a neutron star.

Abstract Invasive fungal infections are a growing public health threat. As fungi become increasingly resistant to existing drugs, new antifungals are urgently needed. Here, it is reported that 405‐nm‐visible‐light‐activated synthetic molecular machines (MMs) eliminate planktonic and biofilm fungal populations more effectively than conventional antifungals without resistance development. Mechanism‐of‐action studies show that MMs bind to fungal mitochondrial phospholipids. Upon visible light activation, rapid unidirectional drilling of MMs at ≈3 million cycles per second (MHz) results in mitochondrial dysfunction, calcium overload, and ultimately necrosis. Besides their direct antifungal effect, MMs synergize with conventional antifungals by impairing the activity of energy‐dependent efflux pumps. Finally, MMs potentiate standard antifungals both in vivo and in an ex vivo porcine model of onychomycosis, reducing the fungal burden associated with infection.

The imbalance of gut microbiota has been confirmed to have a close pathological and physiological correlation with obesity and metabolic syndrome. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) derived from twigs of mulberry was approved by the National Medical Products Administration of China in 2020 for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic effect, previous studies have confirmed that SZ-A also alleviates high-fat diet-induced obesity and non-alcoholic fatty liver disease and ameliorates obesity-linked adipose tissue metabolism and inflammation, indicating the potential of SZ-A to regulate obesity and metabolic syndrome. However, whether SZ-A can improve obesity and metabolic syndrome by regulating gut microbiota and its metabolism profiles remains unclear. The purpose of this study was to assess the effect of SZ-A on gut microbiota in obese mice and to explore the association among changes in gut microbiota, obesity, and lipid metabolism. The results showed that oral administration of SZ-A could significantly reduce body weight, fat mass, and the level of total cholesterol and low-density lipoprotein in serum in obese mice induced by a high-fat diet. Interestingly, SZ-A also regulated gut microbiota and changed the fecal metabolite composition of obese mice. Compared with the high-fat diet group, the ratio of Firmicutes to Bacteroides changed at the phylum level and the abundance of Bifidobacterium and Akkermansia muciniphila significantly increased at the genus level in the SZ-A group. The gut microbiota of the SZ-A group was reshaped and the relative abundance of microbial genes in bile acid metabolism and fatty acid metabolism were altered, which was consistent with the metabolomics results. Additionally, SZ-A greatly enriched the number of goblet cells and reduced inflammatory colon injury and pro-inflammatory macrophage infiltration induced by a high-fat diet in obese mice. In conclusion, SZ-A can alleviate obesity and metabolic syndrome by improving the gut microbiota and its metabolism profiles of obese mice induced by a high-fat diet.

Frequent monitoring of crop moisture levels can significantly improve crop production efficiency and optimise water resource utilisation. The aim of the present study was to generate moisture status maps using thermal infrared imagery, centring on the development of a predictive model for the cotton leaf water potential. The model was constructed using particle swarm optimisation (PSO) in conjunction with the least squares support vector machine (LS-SVM). Traditional SVM models suffer from high computational complexity, long training times, and inequality constraints in predicting leaf water potential. To address such issues, the PSO algorithm was introduced to improve the performance of the LS-SVM model. The PSO-optimised LS-SVM model exhibited notable improvements in performance when evaluated on two distinct test datasets (Alaer and Tumushuke). The research results indicate that the predictive accuracy of the PSO-LS-SVM model significantly improved, as evidenced by an increase of 0.05 and 0.04 in the R2 values, both of which reached 0.95. This improvement is reflected in the corresponding RMSE values, which were reduced to 0.100 and 0.103. Furthermore, a model was established based on data from three cotton growth stages, achieving high predictive accuracy even with fewer training samples. By using the PSO-LS-SVM model to predict leaf water potential information, the predicted data were mapped onto drone images, enabling the transformation of the leaf water potential from a point to an area. The present findings contribute to a more comprehensive understanding of the cotton leaf water potential by visually representing the spatial distribution of crop water status on a large scale. The results hold substantial significance for the improvement of crop irrigation management.

The valley pseudospin properties of electrons in two-dimensional hexagonal materials result in many fascinating physical phenomena, which opens up the new field of valleytronics. The valley-contrasting physics aims at distinguishing the valley degree of freedom based on valley-dependent effects. Here, we theoretically demonstrate that both of the valley-selective high harmonic generation and valley-selective electronic excitation can be achieved by using an orthogonal two-color (OTC) laser field in gapped graphene. It is shown that the asymmetry degrees of harmonic yields in the plateaus, cutoff energies of generated harmonics and electron populations from two different valleys can be precisely controlled by the relative phase of the OTC laser field. Thus, the selectivity of the dominant valley for the harmonic radiation and electronic polarization can be switched by adjusting the relative phase of the OTC laser field. Our work offers an all-optical route to produce the valley-resolved high harmonic emissions and manipulate the ultrafast valley polarization on a femtosecond timescale in condensed matter.

Background: The development of distant metastasis (DM) results in poor prognosis of breast cancer (BC) patients, however, it is difficult to predict the risk of distant metastasis.Methods: Differentially expressed genes (DEGs) were screened out using GSE184717 and GSE183947. GSE20685 were randomly assigned to the training and the internal validation cohort. A signature was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Gene set enrichment analysis (GSEA) was used for functional analysis. Finally, a nomogram was constructed and calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. The clinical benefit of this nomogram was revealed by decision curve analysis (DCA). Finally, we explored the relationships between candidate genes and immune cell infiltration, and the possible mechanism.Results: A signature containing CD74 and TSPAN7 was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Mechanistically, the signature reflect the overall level of immune infiltration in tissues, especially myeloid immune cells. The expression of CD74 and TSPAN7 is heterogeneous, and the overexpression is positively correlated with the infiltration of myeloid immune cells. CD74 is mainly derived from myeloid immune cells and do not affect the proportion of CD8+T cells. Low expression levels of TSPAN7 is mainly caused by methylation modification in BC cells. This signature could act as an independent predictive factor in patients with BC (p = 0.01, HR = 0.63), and it has been validated in internal (p = 0.023, HR = 0.58) and external (p = 0.0065, HR = 0.67) cohort. Finally, we constructed an individualized prediction nomogram based on our signature. The model showed good discrimination in training, internal and external cohort, with a C-index of 0.742, 0.801, 0.695 respectively, and good calibration. DCA demonstrated that the prediction nomogram was clinically useful.Conclusion: A new immune infiltration related signature developed for predicting metastatic risk will improve the treatment and management of BC patients.

Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from twigs of mulberry (Morus alba L., genus Morus in the Moraceae family) was approved by the National Medical Products Administration in 2020 for the treatment of type 2 diabetes mellitus. In addition to excellent hypoglycemic effect, increasing evidence has confirmed that SZ-A exerts multiple pharmacological effects, such as protecting pancreatic ß-cell function, stimulating adiponectin expression, and alleviating hepatic steatosis. Importantly, a specific distribution of SZ-A in target tissues following oral absorption into the blood is essential for the induction of multiple pharmacological effects. However, there is a lack of studies thoroughly exploring the pharmacokinetic profiles and tissue distribution of SZ-A following oral absorption into the blood, particularly dose-linear pharmacokinetics and target tissue distribution associated with glycolipid metabolic diseases. In the present study, we systematically investigated the pharmacokinetics and tissue distribution of SZ-A and its metabolites in human and rat liver microsomes, and rat plasma, as well as its effects on the activity of hepatic cytochrome P450 enzymes (CYP450s). The results revealed that SZ-A was rapidly absorbed into the blood, exhibited linear pharmacokinetic characteristics in the dose range of 25–200 mg/kg, and was broadly distributed in glycolipid metabolism-related tissues. The highest SZ-A concentrations were observed in the kidney, liver, and aortic vessels, followed by the brown and subcutaneous adipose tissues, and the heart, spleen, lung, muscle, pancreas, and brain. Except for the trace oxidation products produced by fagomine, other phase I or phase II metabolites were not detected. SZ-A had no inhibitory or activating effects on major CYP450s. Conclusively, SZ-A is rapidly and widely distributed in target tissues, with good metabolic stability and a low risk of triggering drug-drug interactions. This study provides a framework for deciphering the material basis of the multiple pharmacological functions of SZ-A, its rational clinical use, and the expansion of its indications.

IntroductionReal-time evaluations of the severity of depressive symptoms are of great significance for the diagnosis and treatment of patients with major depressive disorder (MDD). In clinical practice, the evaluation approaches are mainly based on psychological scales and doctor-patient interviews, which are time-consuming and labor-intensive. Also, the accuracy of results mainly depends on the subjective judgment of the clinician. With the development of artificial intelligence (AI) technology, more and more machine learning methods are used to diagnose depression by appearance characteristics. Most of the previous research focused on the study of single-modal data; however, in recent years, many studies have shown that multi-modal data has better prediction performance than single-modal data. This study aimed to develop a measurement of depression severity from expression and action features and to assess its validity among the patients with MDD.MethodsWe proposed a multi-modal deep convolutional neural network (CNN) to evaluate the severity of depressive symptoms in real-time, which was based on the detection of patients’ facial expression and body movement from videos captured by ordinary cameras. We established behavioral depression degree (BDD) metrics, which combines expression entropy and action entropy to measure the depression severity of MDD patients.ResultsWe found that the information extracted from different modes, when integrated in appropriate proportions, can significantly improve the accuracy of the evaluation, which has not been reported in previous studies. This method presented an over 74% Pearson similarity between BDD and self-rating depression scale (SDS), self-rating anxiety scale (SAS), and Hamilton depression scale (HAMD). In addition, we tracked and evaluated the changes of BDD in patients at different stages of a course of treatment and the results obtained were in agreement with the evaluation from the scales.DiscussionThe BDD can effectively measure the current state of patients’ depression and its changing trend according to the patient’s expression and action features. Our model may provide an automatic auxiliary tool for the diagnosis and treatment of MDD.

CsCu2I3 crystal is a promising Cu-based halide material for scintillation detection. In this paper, Na+ ion-doped CsCu2I3 crystals with a size of ϕ12 mm × 50 mm were grown successfully using the vertical Bridgman method, and the properties were systematically investigated. CsCu2I3:Na crystals exhibit yellow light emission peaking at 575 nm and a large Stokes shift of 1.55 eV. Based on the results of the XRD and XPS, the Na+ was introduced successfully. The optical absorption spectra show that the band gap of CsCu2I3 crystals was narrowed when the Na+ was doped. The photoluminescence quantum efficiency (PLQY) is improved from 16.4% to 19.6%. Finally, the X-ray-induced afterglow, and scintillation (energy resolution, light yield and decay time) under a 137Cs source were measured and discussed. These results illustrate that CsCu2I3:Na crystals have potential applications in the radiation detection field.

A microstructure determines macro functionality. A controlled periodic structure gives the surface specific functions such as controlled structural color, wettability, anti-icing/frosting, friction reduction, and hardness enhancement. Currently, there are a variety of controllable periodic structures that can be produced. Laser interference lithography (LIL) is a technique that allows for the simple, flexible, and rapid fabrication of high-resolution periodic structures over large areas without the use of masks. Different interference conditions can produce a wide range of light fields. When an LIL system is used to expose the substrate, a variety of periodic textured structures, such as periodic nanoparticles, dot arrays, hole arrays, and stripes, can be produced. The LIL technique can be used not only on flat substrates, but also on curved or partially curved substrates, taking advantage of the large depth of focus. This paper reviews the principles of LIL and discusses how the parameters, such as spatial angle, angle of incidence, wavelength, and polarization state, affect the interference light field. Applications of LIL for functional surface fabrication, such as anti-reflection, controlled structural color, surface-enhanced Raman scattering (SERS), friction reduction, superhydrophobicity, and biocellular modulation, are also presented. Finally, we present some of the challenges and problems in LIL and its applications.

Background: We hypothesized that the fine needle aspiration (FNA) supernatant from tumor might contain tumor-derived exosomes. The objective of this pilot study was to test if tumor-derived exosomal RNA could be found in FNA supernatants for molecular diagnosis of cancer.Methods: 10 FNA samples from pancreatic tumor were included. After the routine recuperation of cellular material by centrifugation, the cell-free Cytolyt liquid was collected instead of being discarded. 10 ml Cytolyt was used to isolate the exosomes. Transmission electronic microscopy (TEM) was used to examine the presence of exosomes. The exosomal marker CD63 was analyzed by flow cytometry. The exosomal RNA was extracted. RT-qPCR was performed to detect the GAPDH and the tumor marker of glypican 1 gene expression.Results: TEM confirmed the presence of exosomes from FNA supernatants. Flow cytometry showed a strong positive expression of exosome marker CD63. The concentration of exosomal RNA ranged from 18.81 to 354.75 ng/μl with an average of 81.76 ng/μl. The average exosomal RNA quantity was 1390.01 ng (range from 319.77 to 6030.75 ng) with an average 260/280 ratio of 2.12. GAPDH was detectable in all samples. Exosomal glypican 1 was detected in all samples of pancreatic ductal adenorcarcinomas (3/3) and absent from benign cystic samples (3/3). Furthermore, exosomal glypican 1 was positive in one sample with a non-contributive cytology and in one sample in which no malignant cell was found.Conclusion: This is the first report that the supernatants from FNA biopsy may contain tumor-derived exosomal RNA. These tumor-derived exosomes from FNA may provide a new liquid biopsy for the molecular diagnosis of cancer.

BackgroundVarious studies show that sleep quality, life skills, and cortisol are associated with depressive symptoms, separately. However, the relationships between sleep quality, life skills, cortisol, and depressive symptoms remain unclear. Thus, this study aims to examine the mediating or moderating roles of life skills and cortisol in the relationship between sleep quality and depressive symptoms.MethodsA retrospective cross-sectional study was performed among 212 adolescents with childhood household dysfunction (CHD) from August to October 2020 in China. We used the Pittsburgh Sleep Quality Index, the Secondary School Student Life Skills Rating Scale, and the Center for Epidemiologic Studies Depression Scale to measure sleep quality, life skills, and depressive symptoms, respectively. Additionally, 65 participants provided blood samples to assess their blood cortisol levels. Analyses included correlations, regressions, and structural equation models. Bootstrapping was performed to examine the mediation effect. Multiple regression analysis was performed to examine the moderation effect.ResultsThe results showed that sleep quality and life skills were significantly associated with depressive symptoms (p < 0.01). Life skills mediated the relationship between sleep quality and depressive symptoms. Cortisol moderated the relationship between sleep quality and depressive symptoms.ConclusionOur findings support potential mediating and moderating roles of life skills and cortisol in the relationship between sleep quality and depressive symptoms, which suggests improving sleep quality, life skills are of great significance in the prevention and intervention of depression in adolescents with CHD, and disseminating knowledge about the high risk of developing increased depressive symptoms among adolescents with CHD with higher cortisol levels is indicated.

Abstract Disease progression prediction and therapeutic drug target discovery for Coronavirus disease 2019 (COVID-19) are particularly important, as there is still no effective strategy for severe COVID-19 patient treatment. Herein, we performed multi-platform omics analysis of serial plasma and urine samples collected from patients during the course of COVID-19. Integrative analyses of these omics data revealed several potential therapeutic targets, such as ANXA1 and CLEC3B. Molecular changes in plasma indicated dysregulation of macrophage and suppression of T cell functions in severe patients compared to those in non-severe patients. Further, we chose 25 important molecular signatures as potential biomarkers for the prediction of disease severity. The prediction power was validated using corresponding urine samples and plasma samples from new COVID-19 patient cohort, with AUC reached to 0.904 and 0.988, respectively. In conclusion, our omics data proposed not only potential therapeutic targets, but also biomarkers for understanding the pathogenesis of severe COVID-19.

Taking the tight oil of the Zhongnan sag in the Ordos Basin, Jimusar sag in the Junggar Basin and Qingxi sag in the Jiuquan Basin as study objects, based on field survey, dissection of tight oil reservoirs, sample test, modeling experiment and comprehensive analysis, this study reveals that the tight oil accumulates at start-up pressure, advances under differential pressure, diffuses at alternating fast and low speeds, charges in stepped large area and migrates rapidly through fractures, and enriches in dominant fractures and pores. The root cause of ladder-like charge is the multiple scales of pores. The widespread source rock with high hydrocarbon generation intensity is the material basis for tight oil enrichment; the dominant source reservoir assemblage is the basic unit for tight oil enrichment; fractures and beddings are conducive to local rapid migration of tight oil; fractures and pores work together to control the enrichment of tight oil. Two typical accumulation models of tight oil are established, namely “source reservoir in coexistence, four optimal factors controlling enrichment around central area, and large-scale continuous distribution” for a large freshwater lake clastic rock basin and “source reservoir integration, four optimal factors controlling enrichment, central area distribution, small in size but high in enrichment degree “ for a small saline lake diamictite depression.

Concerns regarding the ecological and health risks posed by synthetic insecticides have instigated the exploration of alternative methods for controlling insects, such as entomopathogenic fungi (EPF) as biocontrol agents. Therefore, this review discusses their use as a potential alternative to chemical insecticides and especially focuses on the two major ones, Beauveria bassiana and Metarhizium anisopliae, as examples. First, this review exemplifies how B. bassiana- and M. anisopliae-based biopesticides are used in the world. Then, we discuss the mechanism of action by which EPF interacts with insects, focusing on the penetration of the cuticle and the subsequent death of the host. The interactions between EPF and the insect microbiome, as well as the enhancement of the insect immune response, are also summarized. Finally, this review presents recent research that N-glycans may play a role in eliciting an immune response in insects, resulting in the increased expression of immune-related genes and smaller peritrophic matrix pores, reducing insect midgut permeability. Overall, this paper provides an overview of the EPF in insect control and highlights the latest developments relating to the interaction between fungi and insect immunity.

Abstract Background Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary. Methods We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate. Results A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51–2·23; P = 0.87; I 2 = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias. Conclusions The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.

Abstract Background Sika deer is one of the most popular and valued animals in China. However, few studies have been conducted on the microsatellite of Sika deer, which has hampered the progress of genetic selection breeding. To develop and characterize a set of microsatellites for Sika deer which provide helpful information for protection of Sika deer natural resources and effectively increase the yield and quantity of velvet antler. Results We conducted a transcriptome survey of Sika deer using next-generation sequencing technology. One hundred eighty-two thousand two hundred ninety-five microsatellite markers were identified in the transcriptome, 170 of 200 loci were successfully amplified across panels of 140 individuals from Shuangyang Sika deer population. And 29 loci were found to be obvious polymorphic. Number of alleles is from 3 to 14. The expected heterozygosity ranged from 0.3087 to 0.7644. The observed heterozygosity ranged from 0 to 0.7698. The polymorphism information content values of those microsatellites varied ranged from 0.2602 to 0.7507. The marker-trait association was tested for 6 important and kernel characteristics of two-branched velvet antler in Shuangyang Sika deer through one-way analysis of variance. The results showed that marker-trait associations were identified with 8 different markers, especially M009 and M027. Conclusions This study not only provided a large scale of microsatellites which were valuable for future genetic mapping and trait association in Sika deer, but also offers available information for molecular breeding in Sika deer.

Abstract Background Intraoperative Extracorporeal membrane oxygenation (ECMO) is increasingly being applied as life-support for lung transplantation patients. However, factors associated with this procedure in lung transplantation patients have not yet been characterized. The aim of this study was to identify preoperative factors of intraoperative ECMO support during lung transplantation and to evaluated the outcome of lung transplantation patients supported with ECMO. Methods Patients underwent lung transplantation treated with and without ECMO in Guangzhou Institute of Respiratory Diseases between January 2015 to August 2018 were retrospectively reviewed. Patient demographics and clinical variables were collected and analyzed. Multivariate logistic regression was performed to identify factors independently associated with intraoperative extracorporeal membrane oxygenation support during lung transplantation. Results During the study period, 138 patients underwent lung transplantation at our institution, the mean LAS was (56.63 ± 18.39) (range, 32.79 to 88.70). Fourty four patients were treated with veno-venous/veno-arterial ECMO. Among the patients, 32 patients wean successfully ECMO after operation, 12 patients remain ECMO after operation, and 32 patients (62.74%) survived to hospital discharge. In multiple analysis, the following factors were associated with intraoperative ECMO support: advanced age, high PAP before operation, duration of mechanical ventilation before operation, a higher APACHE II and primary diagnosis for transplantation. The overall survival rates at 1, 3, and 12 months were 90.91, 72.73, and 56.81% in the ECMO group, and 95.40, 82.76, and 73.56% in the non-ECMO group, respectively (log-rank P = 0.081). Patients who underwent single lung transplant had a lower survival rates in ECMO group as compared with non-ECMO group at 1, 3, and 12 months (90.47% vs 98.25, 71.43% vs 84.21, and 52.38% vs 75.44%) (log-rank P = 0.048). Conclusions The preoperative factors of intraoperative ECMO support during lung transplantation included age, high PAP before operation, preoperative mechanical ventilation, a higher APACHE II and primary diagnosis for transplantation based on multivariate analysis.

Ningbo Zhoushan port handled 1.08 billion tons cargoes in 2018 which is considered as the one of biggest ports in the world. There are more than 1 000 ships enter or depart the port per day. Therefore, it is of importance to assess the collision risk for ships passing through the harbor area. In this article, a novel approach is initially proposed to assess ship collision risk in the harbor area based on collision detection technology of ship domain using automatic identified system (AIS) data. This study aims to build a unified framework of collision risk assessment which does not need to build different models in accordance with the ship domain we selected. To clean the historical motion data of ships, a method for anomaly detection of ship static information based on autoencoder (AE) is proposed. Based on the above proposed method, the ship collision frequency can be estimated, besides, the risk area can also be determined. The results obtained from the method could provide a reference on furthering enhance the navigational safety for the Maritime and Port Authority.

Mastitis is a common inflammatory disease caused by bacterial infection to the mammary gland that impacts human and animal health and causes economic losses. Houttuynia essential oil (HEO), extracted from Houttuynia cordata Thunb, exhibits excellent antibacterial and anti-inflammatory properties. The aim of the study was to investigate the effects of HEO and a self-microemulsion preparation of HEO (SME-HEO) on inflammation and the blood–milk barrier (BMB) in lipopolysaccharide-induced murine mastitis. HEO and SME-HEO significantly downregulated pro-inflammatory factors TNF-α and IL-1β, upregulated anti-inflammatory factor IL-10, inhibited MPO expression, and alleviated histopathological injury in murine mammary gland tissues. Additionally, HEO and SME-HEO protected the integrity of the BMB by upregulating the expression of junction proteins ZO-1, claudin-1, claudin-3, and occludin. The anti-inflammatory effect of HEO against murine mastitis was mediated by blocking the MAPK signaling pathway and expression of iNOS. By inhibiting the release of inflammatory factors and protecting the integrity of the BMB, HEO may provide a novel treatment for mastitis.

To improve the oil recovery of a block in the Wutonggou Formation of the Changji Oilfield, viscosity reducing and foaming agent was optimized to improve the development effect of the water flooding reservoir. The core flooding experiment and microscopic visual experiment were conducted to investigate the production characteristics and EOR mechanism of nitrogen foam flooding. The results show that the 0.5 wt% viscosity reducing and foaming agent DXY-03 was optimized. In the process of microscopic oil displacement by nitrogen foam, nitrogen foam continuously expands and spreads, improves oil displacement efficiency, and greatly improves oil recovery through emulsification and viscosity reduction, squeezing action, dragging action, and Jamin effect. The core flooding experiment shows that on the basis of the water flooding recovery rate of 20.3%, the nitrogen foam huff and puff is increased by 9.2%. The viscosity reducing and foaming agent flooding is increased by 7.8%, and the nitrogen foam flooding is increased by 12.9%. The main EOR mechanism of the viscosity reducing and foaming agent is that it can reduce the interfacial tension between oil and water and can promote heavy oil emulsification and dispersion, thereby forming an oil/water- (O/W-) type emulsion. The reduction in the viscosity of heavy oil makes crude oil easier to extract, realizing the synergistic viscosity reducing and efficiency enhancing effect of nitrogen and viscosity reducing and foaming agents. This study is helpful to provide reference for the development of low-permeability and high-viscosity medium-deep heavy oil reservoirs by chemical agents combined with cold production.

The prevention of the COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent, and re-detectable positive cases. We identified a set of V–J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V–J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.

BackgroundViral causes of acute respiratory distress syndrome (ARDS) are mostly limited to influenza. However, adenovirus has been emerging as a cause of ARDS with a high mortality rate and described in adults are rare.MethodsWe conducted a prospective, single-center observational study of viral pneumonia with ARDS and confirmed adenovirus-associated ARDS in adults at our quaternary referral institution between March 2019 and June 2020. We prospectively analyzed clinical characteristics, laboratory test results, radiological characteristics, viral load from nasopharyngeal swabs and endotracheal aspirates, treatments, and outcomes for the study participants.ResultsThe study enrolled 143 ARDS patients, including 47 patients with viral pneumonia-related ARDS, among which there were 14 adenovirus-associated ARDS patients, which accounted for 29.79% of the viral pneumonia-related ARDS cases. Among the adenovirus-associated ARDS patients, 78.57% were men with a mean age of 54.93 ± 19.04 years, younger than that of the non-adenovirus associated ARDS patients. Adenovirus-associated ARDS patients had no specific clinical characteristics, but they presented with decrease in the number of CD3+CD4+ T cells and higher serum creatinine during the early stage. The viral load and the positivity rate in the lower respiratory tract were higher than that of the upper respiratory tract in the patients with adenovirus-associated ARDS. All patients required invasive mechanical ventilation treatment. The average time from shortness of breath to the application of invasive ventilation was 24 h. Ten patients (71.43%) complicated by acute kidney injury, while 13 patients (71.43%) in the non-adenovirus associated ARDS group (P = 0.045). Additionally, 85.71% of the 14 adenovirus-associated ARDS patients survived. No significant differences were detected between the two groups regarding duration of ventilation, length of ICU stay and mortality.ConclusionAdenovirus infection is an important cause of virus-related ARDS. The positivity rate of adenovirus infection in lower respiratory tract secretions was higher than that in upper respiratory tract secretions in these patients. Age, lower CD3+CD4+ T cells, and high serum creatinine may be were associated with adenovirus induce ARDS in adults required mechanical ventilation. Early identification and intervention to prevent disease progression are essential for reducing the mortality rate in these patients.

To solve the edge crack problem of AZ31B magnesium alloy cold rolling, a strong pulsed electric current was introduced to the cold rolling process. The influence of intensity, frequency, width of pulsed electric current and other parameters on edge cracking of AZ31B magnesium alloy plate cold rolling was analyzed based on the principle of a single variable. According to the experimental results, the assistance of pulsed electric current cut down edge cracking and the inhibition effect increased obviously with larger current parameters. When the parameters of pulsed electric current reached 4800 A, 500 Hz, 50 μs, zero edge cracking was achieved. Statistics of edge cracks, rolling load change, and microstructure analysis showed that the current thermal effect was not obvious and non-thermal effect played a more important role in the rolling process under pulse electric current. Edge cracks initiate at the shear bands. The addition of pulse current increases the number of shear bands and presents a blanket structure. Therefore, the amount of strain experienced by a single shear band decrease, which has a positive effect on inhibiting the formation of edge cracks. Furthermore, electroplastic rolling refines the grains and weakens the basal plane. As the current parameter increases, the hardness of the magnesium strip decreases and the yield and tensile strengths increase.