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Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4–11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. Results In this study, we first utilized next-generation sequencing technique and existing microarray datasets to identify significant differentially expressed genes between PDAC and non-tumor adjacent tissue. By comparing top significant survival genes in PDAC Gene Expression Profiling Interactive Analysis database and PDAC transcriptome data from patients, our integrated analysis discovered five potential central genes (i.e., MYEOV, KCNN4, FAM83A, S100A16, and DDX60L). Subsequently, we analyzed the cellular functions of the potential novel oncogenes MYEOV and DDX60L, which are highly expressed in PDAC cells. Notably, the knockdown of MYEOV and DDX60L significantly inhibited the metastasis of cancer cells and induced apoptosis. Further RNA sequencing analyses showed that massive signaling pathways, particularly the TNF signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway, were affected in siRNA-treated cancer cells. The siDDX60L and siMYEOV significantly inhibited the expression of chemokine CXCL2, which may potentially affect the tumor microenvironment in PDAC tissues. Conclusions The present findings identified the novel oncogene DDX60L, which was highly expressed in PDAC. Transcriptome profiling through siRNA knockdown of DDX60L uncovered its functional roles in the PDAC in humans.

Background: Employing network pharmacology in neurodegenerative diseases (NDs) has been extensively studied recently. However, no comprehensive study has conducted on this subject employing bibliometrics so far. The purpose of this study was to find out the developmental trends and hotspots, and to predict potential research directions in this filed.Methods: Relevant research were collected from the Web of Science Core Collection Bibliometrics and visual analysis were executed using CiteSpace, VOSviewer, Histcite and R-bibliometrix.Results: A total of 420 English articles on network pharmacology in NDs published in 2008–2022 were obtained from the WOSCC database. From 2008 to 2022, annual publications showed a steady growing trend, especially in 2014–2022. China, Beijing Univ Chinese Med, Frontiers in Pharmacology, and Geerts H are the most prolific country, institution, journal, and author, respectively. China, Nucleic Acids Research, and Hopkins AL are the most highly cited country, journal, and author, respectively. Moreover, network pharmacology and Alzheimer’s disease are the focal areas of current researches according to analysis of co-cited references and keywords. Finally, in the detection of burst keywords, systems pharmacology and database are new approaches to disease and drug research, while traditional Chinese medicine (TCM) and Alzheimer’s disease are hot research directions. The above keywords are speculated to be the research frontiers.Conclusion: Network pharmacology and Alzheimers’ disease are the main topics of researches on network pharmacology in NDs. Network pharmacology and the TCM treatment of Alzheimer’s disease have been the recent research hotspots. To sum up, the potential for exploring TCM treatment of AD with network pharmacology is huge.

BackgroundTraumatic spinal cord injury (TSCI) is a type of highly disabling central nervous system trauma. In this study, we investigated the epidemiological characteristics of 1,806 TSCI patients and compared the characteristics of patients with traumatic cervical spinal cord injury (TCSCI) caused by cervical fracture/dislocation and disc herniation/bulging.MethodsWe retrospectively reviewed the hospital records of 1,806 TSCI patients. The detailed information included gender, marital status, occupation, age, neurological level of injury, etiology, American Spinal Injury Association (ASIA) grade, combined injuries, complications, treatment, the interval between admission and surgery, intubation/tracheostomy requirement, and the length of hospital stay.ResultsCervical spinal cord injury (CSCI) was the most common injury. Compared to non-CSCI cases, patients with TCSCI were older, and more likely to suffer from tetraplegia and require intubation/tracheostomy, but had fewer other injuries or complications and a shorter length of hospital stay. Compared to patients with cervical fracture/dislocation, those with TCSCI caused by disc herniation/bulging were older and more likely to suffer from paraplegia, but required intubation/tracheostomy less frequently, exhibited fewer other injuries and complications, and required shorter hospitalization.ConclusionsMen, married individuals, manual laborers, and individuals aged 31–75 years had the highest risk of TSCI. Patients with TCSCI tended to have a shorter length of hospital stay than patients with non-CSCI. More attention should be paid to the other injuries and complications of non-CSCI patients, which may increase the length of hospital stay and delay rehabilitation. Compared to patients with cervical disc herniation, the patients with fracture/dislocation tended to be younger, but prognosis was severely compromised by tetraplegia, a greater need for intubation/tracheostomy, additional injuries, and complications.

Compressed white tea (CWT) is a reprocessed tea of white tea. Long-term storage has greatly changed its aroma characteristics, but the material basis and transformation mechanism of its unique aroma are still unclear. In this study, flavor wheel, headspace gas chromatography ion mobility spectroscopy, chemometrics, and microbiomics were applied to study the flavor evolution and important aroma components during long-term storage of CWT, and core functional bacteria were screened. During long-term storage, the aroma of CWT gradually changed from sweet, fruity and floral to stale flavor, woody and herbal. A total of 56 volatile organic compounds (VOCs) were identified, 54 of which were significantly differences during storage. The alcohols content was the highest during 1–5 years of storage, the esters content was the highest during 7–13 years of storage, and the aldehydes content was the highest during 16 years of storage. Twenty-nine VOCs were identified as important aroma components, which were significantly correlated with 6 aroma sub-attributes (P < 0.05). The functional prediction of bacterial community reminded that bacterial community could participate in the transformation of VOCs during storage of CWT. Twenty-four core functional bacteria were screened, which were significantly associated with 29 VOCs. Finally, 23 characteristic differential VOCs were excavated, which could be used to identify CWT in different storage years. Taken together, these findings provided new insights into the changes in aroma characteristics during storage of CWT and increased the understanding of the mechanism of characteristic aroma formation during storage.

Spatial distribution information offers a valuable resource for the growing research on evaluating and managing aquaculture and the mechanism of its interaction with the environment, especially concerning landside clustering aquaculture ponds (LCAP). However, studies aimed at obtaining data on global LCAP distribution remains limited. This study combined edge detection and the morphology implemented on Google Earth Engine (GEE) platform to produce the first global spatial distribution data of LCAP using 4,015,054 tiles of the 10-m Sentinel-2 time-series images collected throughout 2020. The study findings showed a total area of global LCAP of 55,337.03 km2. Asia, led by China, had the highest distribution area of LCAP, accounting for 89.12 % of global LCAP. The main LCAP distribution area was the landside 30-km buffer region of coastline, accounting for 75.57 % of global LCAP. Meanwhile, the greatest proportion of LCAP (69.63 %) was located in China. Accuracy verification revealed that the precision and recall error of the results were 83.91 % and 92.49 % respectively, and F1 score was 0.88. A comparison of China, Vietnam, and India, based on data drawn from most of the existing local studies that used remote sensing methods, showed that these countries’ aquaculture area differs by less than 10 %. Despite some variation from FAO statistics or official national statistics, the results of our remote sensing-based method show promise in such aspects as global coverage and temporal coherency when compared with the classical statistical method.

Three systemic biological systems, i.e., the nervous, the immune, and the cardiovascular systems, form a mutually responsive and forward-acting tissue network to regulate acute and chronic cardiovascular function in health and disease. Two sub-circuits within the cardiovascular system have been described, the artery brain circuit (ABC) and the heart brain circuit (HBC), forming a large cardiovascular brain circuit (CBC). Likewise, the nervous system consists of the peripheral nervous system and the central nervous system with their functional distinct sensory and effector arms. Moreover, the immune system with its constituents, i.e., the innate and the adaptive immune systems, interact with the CBC and the nervous system at multiple levels. As understanding the structure and inner workings of the CBC gains momentum, it becomes evident that further research into the CBC may lead to unprecedented classes of therapies to treat cardiovascular diseases as multiple new biologically active molecules are being discovered that likely affect cardiovascular disease progression. Here, we weigh the merits of integrating these recent observations in cardiovascular neurobiology into previous views of cardiovascular disease pathogeneses. These considerations lead us to propose the Neuroimmune Cardiovascular Circuit Hypothesis.

China is one of the countries that suffers severe damage from storm surges. Assessing the vulnerability to storm surges holds great significance for promoting sustainable development and minimizing disaster losses in coastal areas. This study first developed a vulnerability index by integrating 15 indicators from three components (exposure, sensitivity, and adaptability) that provide a comprehensive portrayal of the multidimensional structure of vulnerability. Subsequently, the vulnerability of Chinese coastal areas was comprehensively evaluated from the perspective of prefecture-level cities using a weight combination strategy. Furthermore, spatial statistical techniques were utilized to analyze the spatial heterogeneity of vulnerability. The results show that 64% of coastal cities are classified as being in the very high and high vulnerability categories, with Zhanjiang, Lingao, Dalian, Yancheng, and Shanwei exhibiting the highest vulnerability levels. Among the provinces, Guangxi and Hainan Provinces demonstrate the highest vulnerability, with more than 90% of their coastal cities facing high vulnerability. Additionally, the vulnerability of Chinese coastal cities exhibits significant spatial heterogeneity. Specifically, coastal cities located in the Yangtze River Delta and the Pearl River Delta regions are identified as low–low (LL) vulnerability clusters, whereas high–high (HH) vulnerability clusters are observed in coastal cities within the Beibu Gulf region. These results provide valuable insights for the formulation of disaster reduction policies at the provincial level and the focus for action at the local level.

Currently, many globally accessible forest mapping products can be utilized to monitor and assess the status of and changes in forests. However, substantial disparities exist among these products due to variations in forest definitions, classification methods, and remote sensing data sources. This becomes particularly conspicuous in regions characterized by significant deforestation, like Southeast Asia, where forest mapping uncertainty is more pronounced, presenting users with challenges in selecting appropriate datasets across diverse regions. Moreover, this situation impedes the further enhancement of accuracy for forest mapping products. The aim of this research is to assess the consistency and accuracy of six recently produced forest mapping products in Southeast Asia. These products include three 10 m land cover products (Finer Resolution Observation and Monitoring Global LC (FROM-GLC10), ESA WorldCover 10 m 2020 (ESA2020), and ESRI 2020 Land Cover (ESRI2020)) and three forest thematic mapping products (Global PALSAR-2 Forest/Non-Forest map (JAXA FNF2020), global 30 m spatial distribution of forest cover in 2020 (GFC30_2020), and Generated_Hansen2020, which was synthesized based on Hansen TreeCover2010 (Hansen2010) and Hansen Global Forest Change (Hansen GFC) for the year 2020). Firstly, the research compared the area and spatial consistency. Next, accuracy was assessed using field validation points and manual densification points. Finally, the research analyzed the geographical environmental and biophysical factors influencing consistency. The results show that ESRI2020 had the highest overall accuracy for forest, followed by ESA2020, FROM-GLC10, and Generated_Hansen2020. Regions with elevations ranging from 200 to 3000 m and slopes below 15° or above 25° showed high spatial consistency, whereas other regions showed low consistency. Inconsistent regions showed complex landscapes heavily influenced by human activities; these regions are prone to being confused with shrubs and cropland and are also impacted by rubber and oil palm plantations, significantly affecting the accuracy of forest mapping. Based on the research findings, ESRI2020 is recommended for mountainous areas and abundant forest regions. However, in areas significantly affected by human activities, such as forest and non-forest edges and mixed areas of plantations and natural forests, caution should be taken with product selection. The research has identified areas of forest inconsistency that require attention in future forest mapping. To enhance our understanding of forest mapping and generate high-precision forest cover maps, it is recommended to incorporate multi-source data, subdivide forest types, and increase the number of sample points.

In order to build an efficient and energy-saving CO2 heat pump system and to improve the heat transfer efficiency of the gas cooler, a novel honeycomb gas cooler with a compact structure, high heat transfer efficiency, and high pressure-bearing capacity was proposed in our previous work. To clarify the components in the system that need further optimization and to improve its performance, an exergy analysis of a transcritical CO2 air-source heat pump system with the novel honeycomb gas cooler is studied in this paper. Based on the second law of thermodynamics, the exergy model of each component in the heat pump system is established, and the irreversible loss of each component is analyzed. In addition, the degree of energy loss of the honeycomb gas cooler is clarified, and the possibility and direction of system optimization are pointed out. The results show that the exergy efficiency of the system is 35.33% under nominal operating conditions, and there is a lot of room for improvement in its energy utilization. The three components with the largest exergy destruction percentage are the compressor, throttle valve, and evaporator in the order of 36.13%, 22.90%, and 19.51%, respectively. These components with high exergy destruction percentages are the main reasons for the large irreversible losses of the system.

The aim of this study is to enhance the efficiency and lower the expense of detecting cracks in large-scale concrete structures. A rapid crack detection method based on deep learning is proposed. A large number of artificial samples from existing concrete crack images were generated by a deep convolutional generative adversarial network (DCGAN), and the artificial samples were balanced and feature-rich. Then, the dataset was established by mixing the artificial samples with the original samples. You Only Look Once v5 (YOLOv5) was trained on this dataset to implement rapid detection of concrete bridge cracks, and the detection accuracy was compared with the results using only the original samples. The experiments show that DCGAN can mine the potential distribution of image data and extract crack features through the deep transposed convolution layer and down sampling operation. Moreover, the light-weight YOLOv5 increases channel capacity and reduces the dimensions of the input image without losing pixel information. This method maintains the generalization performance of the neural network and provides an alternative solution with a low cost of data acquisition while accomplishing the rapid detection of bridge cracks with high precision.

Abstract Background The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable mortality. The risk factors, clinical treatments, especially comprehensive risk models for COVID-19 death are urgently warranted. Methods In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex, and comorbidities were enrolled from January 13, 2020 to March 31, 2020. Results Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cell subsets, and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, which was significant for early clinical management for COVID-19. Conclusions The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.

Abstract Constitutive activation of JAK2/STAT3 is a major oncogenic signaling event involved in the development of Burkitt lymphoma (BL). In the present study, we investigated the antilymphoma activity of TG101209, a specific JAK2 inhibitor, on EBV-positive and EBV-negative Burkitt lymphoma cell lines and primary BL cells. The results showed that TG101209 had a significant antilymphoma effect by inhibiting BL cell growth and inducing apoptosis along with cell differentiation toward mature B cells in vitro. We also found that TG101209 displayed significant synergistic action and a sensitizing effect on the anti-Burkitt lymphoma activity of doxorubicin. In vivo experiments indicated that TG101209 could suppress tumor growth and prolong the overall survival of BL cell-bearing mice. The mechanistic study indicated that TG101209, by suppressing the JAK2/STAT3/c-MYB signaling axis and crosstalk between the downstream signaling pathways, plays an antilymphoma role. These data suggested that TG101209 may be a promising agent or alternative choice for the treatment of BL.

Although long non-coding RNA LINC00963 has been reported to play a crucial regulatory role in osteoporosis (OP), its specific mechanism has not been well studied. Cell viability of human bone marrow mesenchymal stem cells (hBMSCs) transfected with short hairpin RNA targeting LINC00963 (sh-LINC00963) and negative control (sh-NC) was analysed by cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity in hBMSCs transfected with sh-LINC00963 and sh-NC after induction by osteogenic medium (OM) on day 7 was detected. The protein expression levels of osteocalcin (OCN) and osteopontin (OPN) in hBMSCs transfected with sh-LINC00963 and sh-NC during OM induction on day 3 were detected by western blot. The relationship among LINC00963, miR-760, and E26 transformation specific-1 (ETS1) was determined by bioinformatics analysis, luciferase reporter assay, and RNA-binding protein immunoprecipitation (RIP) assay. A rat model with OP was established to confirm the role of LINC00963 in vivo. The expression level of LINC00963 was much lower in hBMSCs isolated from the discarded femoral head tissues of OP patients compared with that in health patients. Meanwhile, the expression level of LINC00963 was significantly increased and the expression level of miR-760 was decreased in hBMSCs during osteogenic induction. LINC00963 could bind to the 3′-untranslated region (3′-UTR) of miR-760 and negatively regulate the expression of miR-760, then promote the osteogenic differentiation in hBMSCs. ETS1 was identified as a target of miR-760. Moreover, overexpression of LINC00963 obviously reduced bone mineral density (BMD) of the left femur in OP rats and alleviated OP progression in vivo. Our results demonstrated that LINC00963 positively regulated the expression of ETS1 by directly targeting miR-760, and then promoted osteogenic differentiation of hBMSCs in vitro, and also attenuated OP progression in vivo, suggesting that LINC00963 might be a potential therapeutic target for OP.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38–0.63 for T allele; P = 1.38 × 10−8; and index rs10831496: OR = 1.66; 95% CI, 1.38–1.98 for A allele; P = 4.04 × 10−8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.

BackgroundIntracranial aneurysm (IA) causes more than 80% of nontraumatic subarachnoid hemorrhages (SAHs). The mechanism of ferroptosis involved in IA formation remains unclear. The roles played by competitive endogenous RNA (ceRNA) regulation networks in many diseases are becoming clearer. The goal of this study was to understand more fully the ferroptosis-related ceRNA regulation network in IA.Materials and methodsTo identify differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially expressed lncRNAs (DELs) across IA and control samples, the GEO datasets GSE122897 and GSE66239 were downloaded and analyzed with the aid of R. Ferroptosis DEGs were discovered by exploring the DEGs of ferroptosis-related genes of the ferroptosis database. Potentially interacting miRNAs and lncRNAs were predicted using miRWalk and StarBase. Enrichment analysis was also performed. We utilized the STRING database and Cytoscape software to identify protein-protein interactions and networks. DAB-enhanced Prussian blue staining was used to detect iron in IA tissues.ResultsIron deposition was evident in IA tissue. In all, 30 ferroptosis DEGs, 5 key DEMs, and 17 key DELs were screened out for constructing a triple regulatory network. According to expression regulation of DELs, DEMs, and DEGs, a hub triple regulatory network was built. As the functions of lncRNAs are determined by their cellular location, PVT1-hsa-miR-4644-SLC39A14 ceRNA and DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA networks were constructed.ConclusionCeRNA (PVT1-hsa-miR-4644-SLC39A14 and DUXAP8-hsa-miR-378e/378f-SLC2A3) overexpression networks associated with ferroptosis in IA were established.

We recently identified a high-affinity C1q-ApoE complex in human artery atherosclerotic intima lesions and in human amyloid plaques of Alzheimer’s Disease brains defining a common pathogenetic pathway of two diverse diseases, i.e. atherosclerosis and dementia. C1q is the initiating and controlling protein of the classical complement cascade (CCC), which occupies a key role in multiple acute and chronic inflammatory tissue responses. C1q is largely produced by myeloid cells including Kupffer cells (KCs) and subsequently secreted into the circulation as an inactive preprotein. Its binding partner, Apolipoprotein E (ApoE), is produced by KCs and hepatocytes and it is also secreted into the circulation, where it regulates essential steps of lipid transport. In addition to its major source, ApoE can be produced by non-liver cells including immune cells and multiple other cells depending on local tissue contexts. To initiate the CCC cascade, C1q must be activated by molecules as varied as oxidized lipids, amyloid fibrils, and immune complexes. However, ApoE is mute towards inactive C1q but binds at high-affinity to its activated form. Specifically, our studies revealed that ApoE is a CCC-specific checkpoint inhibitor via the formation of the C1q-ApoE complex. We proposed that it may arise in multiple if not all CCC-associated diseases and that its presence indicates ongoing CCC activity. Here, we turned to the liver to examine C1q-ApoE complexes in human B- and C-viral hepatitis and nonalcoholic fatty liver disease (NAFLD). In addition, we used multidrug-resistance-2 gene-knockout (Mdr2-KO) mice as a model for inflammatory liver disease and hepatocellular carcinoma (HCC) pathogenesis. In normal murine and human livers, KCs were the major C1q-producing cell type while hepatocytes were the primary ApoE-forming cell type though the C1q-ApoE complex was rare or nonexistent. However, significant numbers of C1q-ApoE complexes formed in both Mdr2-KO, human viral hepatitis, and NAFLD around portal triads where immune cells had infiltrated the liver. Additionally, high numbers of C1q-ApoE complexes emerged in human livers in areas of extracellular lipid droplets across the entire liver parenchyma in NAFLD-affected patients. Thus, the C1q-ApoE complex is a new pathological hallmark of viral hepatitis B and C and NAFLD.

Environmental regulation and economic development are consistent in the long run, but there are certain contradictions in the short term. Examining the characteristics of available environmental regulation tools and using them in a way that will align the interests of local governments and enterprises can improve environmental regulation and enhance green transformation and development. This study considers two general types of environmental regulation tools: negative punishment types and positive incentive types. Applying an intermediary effect model and the two-stage least squares method, a sample of Chinese A-share listed companies from 2007 to 2019 is used to test the impact of these different types of environmental regulation tools on the financial investment levels of entity enterprises. The mechanism through which these macro-environmental regulation tools function and the micro-enterprise heterogeneity factors that influence their impact are systematically studied. The results show that negative punishment type environmental regulation tools have a positive impact on the financial investment levels of entity enterprises, while positive incentive type environmental regulation tools inhibit financial investment levels. This impact is formed through managerial incentive mechanisms referred to as “whipping the fast ox” and “heavy rewards and light punishments.” Factors such as financing constraints, relocation costs, pollution levels, and enterprise scale have heterogeneous effects on these paths. Policy suggestions are offered based on the findings. This study makes a significant contribution to the literature by clarifying the channel through which environmental regulation influences micro-enterprise decision-making. It provides a theoretical basis and policy reference for local government officials as they address the conflict between economic growth and environmental protection in the short term. Moreover, the results offer long-term development decision-making ideas for shareholders and managers in the process of green transformation and upgrading of enterprises.

Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3]) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequent mutations in sporadic SPTCL, suggesting the individuals harboring HAVCR2(TIM-3) germline mutations are highly susceptible to familial or sporadic SPTCL. Here, we identify a novel germline compound heterozygous mutation of TIM-3 gene,c.245A>G (p.Tyr82Cys) and c.265C>T(p.Arg89Cys) variations in a single familial case with EBV-positive peripheral T-cell lymphoma(NOS),accompanied HLH;we also detected Tyr82Cys germline mutation in TIM-3 gene in one sporadic patient with cutaneous T cell lymphoma. We screened the distributive frequencies for TIM-3 mutations in healthy controls(n=87), B-(n=79) or T-cell lymphoma(n=25) not SPTCL, and the results showed that the mutation was found in two out of 25 patients with T-cell lymphoma but was not detected in 79 patients with B-cell lymphoma nor in a group of 87 controls. The mRNA expression of TIM-3 on primary cells and transfected HEK293 cells reduced significantly, indicating Tyr82Cys and Arg89Cys mutations is a loss-of function mutations on TIM-3,resulting in a weakened TIM-3 signaling. Our results suggest Tyr82Cys TIM-3 germline mutations are not only limited in SPTCL, and also occurred in other types of T-cell lymphoma, especially complicated HLH. TIM-3 mutations may be an predisposing factor for T-cell lymphoma and molecular marker for auxiliary diagnosis in T cell lymphoma,especially complicated with HLH.

Behçet’s syndrome (BS) is a chronic form of relapsing multisystem vasculitis, characterized by recurrent oral and genital ulcers. Intestinal BS is a special type of BS. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BS, and punched-out ulcers can be observed in the intestine or esophagus. At present, there is no recognized radical treatment for intestinal BS. Glucocorticoids and immunosuppressants are currently the main drugs used to improve the condition. Although it has been reported that monoclonal anti-TNF antibodies may be effective for some refractory intestinal BS, further randomized, prospective trials are necessary to confirm these findings. Some patients are restricted from using biological agents because of serious allergic reactions of drugs, inconvenient drug injections or the impact of the novel coronavirus epidemic. If endoscopic remission (endoscopic healing) is not achieved for a prolonged period of time, serious complications, such as perforation, fistula formation, and gastrointestinal bleeding can be induced. Therefore, it is necessary to develop new treatment methods for controlling disease progression. We reviewed the relevant literature, combined with the analysis of the correlation between the pathogenesis of BS and the mechanism of Janus kinase (JAK) inhibition, and considered that tofacitinib (TOF) may be effective for managing refractory intestinal BS. We report for the first time that four patients with severe refractory intestinal BS were successfully treated with TOF. We hope to provide valuable information on JAK inhibitors as potential therapeutic targets for the treatment of severe refractory intestinal BS.

Objective: Owing to the intensification of the aging process worldwide, the prevalence of adult degenerative scoliosis (ADS) is increasing at an alarming rate. However, genomic research related to the etiology of ADS is rarely reported worldwide. Since long noncoding RNAs (lncRNAs) play a pivotal role in the progression of human diseases, this study aimed to investigate ADS-associated messenger RNAs (mRNAs) and lncRNAs by RNA sequencing (RNA-seq), as well as performed comprehensive bioinformatics analysis based on the lncRNA–mRNA coexpression network and protein–protein interaction (PPI) network.Methods: Initially, six whole blood (WB) samples were obtained from three ADS and three nondegenerative lumbar trauma patients who underwent surgical operation for RNA-seq exploration to construct differential mRNA and lncRNA expression profiles. Subsequently, quantitative RT-PCR (qRT-PCR) was performed to validate three randomly selected differentially expressed mRNAs and lncRNAs derived from the nucleus pulposus (NP) tissue of 14 other subjects (seven ADS patients and seven nondegenerative lumbar trauma patients), respectively.Results: A total of 1,651 upregulated and 1,524 downregulated mRNAs and 147 upregulated and 83 downregulated lncRNAs were screened out from the RNA-Seq data, which constructed coexpression networks to investigate their regulatory interactions further. GO gene function prediction revealed that lncRNA-targeted genes might play a vital role in ADS via participation in multiple biological processes such as the AMPK signaling pathway, lysosomes, and ubiquitin-mediated proteolysis, as well as cellular metabolic processes. Moreover, the expression levels of three selected lncRNAs and mRNAs were validated by qRT-PCR, respectively, demonstrating that the relative expression levels were consistent with the RNA-seq data. Notably, the dysregulated RNAs, AKT1, UBA52, PTPN12, and CLEC16A, were significantly differentially expressed in ADS WB samples and might serve as potentially regulated genes for research in the future.Conclusions: This study provides the first insight into the altered transcriptome profile of long-stranded noncoding RNAs associated with ADS, which paves the way for further exploration of the clinical biomarkers and molecular regulatory mechanisms for this poorly understood degenerative disease. However, the detailed biological mechanisms underlying these candidate lncRNAs in ADS necessitate further elucidation in future studies.

Abstract Background Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration. Methods We performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence. Results We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3–3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients. Conclusions Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.

Abstract Background Acid-tolerant enteric pathogens can evade small intestinal acid barriers, colonize and infect the intestinal tract. However, broad-spectrum antibiotics are not the best therapeutic strategy because of the disruption of intestinal flora caused by its indiscriminate antimicrobial activity against beneficial and harmful bacteria. So that is what inspired us to combine pH regulation with nanotechnology to develop a pH-triggered site-targeted antimicrobial peptide with entrapping function. Results A pH-triggered dual biological functional self-assembled peptide (SAP) was designed according to the features of amino-acid building blocks and the diagonal cation–π interaction principle. The results of characterization experiments showed that changes in pH conditions could trigger microstructural transformation of the nanopeptide from nanospheres to nanofibers. The subsequent antibacterial and toxicity experiments determined that SAP had great antimicrobial activity against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Bacillus cereus above 15.6 μg/mL under acidic conditions by disrupting bacterial membrane integrity, excellent biocompatibility in vitro even at 250 μg/mL and high tolerance in physical environment. Moreover, at peptide concentrations greater than 62.5 μg/mL, SAP showed the entrapment property, which played an important role in phagocytic clearance in infection forces. Meanwhile, the in vivo results revealed that SAP possessed excellent therapeutic effect and good biosafety. Conclusions Our study revealed the antibacterial activity of a short β-hairpin forming self-assembled peptide, and established an innovative design strategy for peptide-based nanomaterials and a new treatment strategy for gastrointestinal bacterial infections. Graphic Abstract

In this paper, three different shapes of indenters were used to perform quasi-static out-of-plane uniaxial compression and indentation tests on three commercial hexagonal aluminum honeycombs with different densities. In order to distinguish the different tearing conditions of the single-layer and double-layer aluminum honeycomb walls during indentation, a new indentation experiment was designed. By controlling the shape of pattern and the location of indentation, different tearing conditions in indentation experiment were measured separately. The deformation mode of the aluminum honeycomb when pressed was analyzed. It is found that as the size of the pattern increases, the peak stress of the indentation experiment decreases significantly. As the size of the indenter increases, the platform stress of aluminum honeycomb shows a downward trend and tends to approach the compression platform stress, while the tear strength remains basically stable within a certain scale. As the size of the indenter continues to increase, the proportion of tearing force to the total indenting force gradually decreases, and the tearing strength loses its stability. At this time, the tear strength can no longer be used as a stable mechanical parameter to measure the tearing condition during indentation.

Abstract Background Tai Chi exercise has been reported to enhance physical and mental health in the older adults; however, the mechanism remains elusive. Trial design We recruited 289 older adults practicing Tai Chi for over 3 years, together with 277 age-matched older and 102 young adults as controls. 168 Tai Chi practitioners were successfully matched to 168 older controls aged 60–69 based on a propensity score for statistics. Methods Cerebrovascular function was evaluated by measuring the hemodynamics of the carotid artery. Spearman correlation was performed to validate the age-associated physiological parameters. Results Cerebrovascular function in older adults significantly degenerated compared with the young, and was substantially correlated with age. Compared with the older control group, Tai Chi practitioners showed significant improvements in CVHI (cerebral vascular hemodynamics indices) Score (P = 0.002), mean blood flow velocity (P = 0.014), maximal blood flow velocity (P = 0.04) and minimum blood flow velocity (P

In 2020, energy-related CO2 emissions reached 31.5 Gt, leading to an unprecedented atmospheric CO2 level of 412.5 ppm. Hydrogen blending in natural gas (NG) is a solution for maximizing clean energy utilization and enabling long-distance H2 transport through pipelines. However, insufficient comprehension concerning the combustion characteristics of NG, specifically when blended with a high proportion of hydrogen up to 80%, particularly with minority species, persists. Utilizing the heat flux method at room temperature and 1 atm, this experiment investigated the laminar burning velocities of CH4/NG/H2/air/He flames incorporating minority species, specifically C2H6 and C3H8, within NG. The results point out the regularity of SL enhancement, reaching its maximum at an equivalence ratio of 1.4. Furthermore, the propensity for the enhancement of laminar burning velocity aligned with the observed thermoacoustic oscillation instability during fuel-rich regimes. The experimental findings were contrasted with kinetic simulations, utilizing the GRI 3.0 and San Diego mechanisms to facilitate analysis. The inclusion of H2 augments the chemical reactions within the preheating zone, while the thermal effect from temperature is negligible. Both experimental and simulated results revealed that CH4 and NG with a large proportion of H2 had no difference, no matter whether from a laminar burning velocity or a kinetic analysis aspect.

High-intensity human activities have caused dramatic transformations of land function in China’s coastal zone, putting enormous pressure on the region’s ecological environment. It is urgent to fully understand the spatiotemporal evolution of the land-use function in the coastal zone to promote sustainable development. Therefore, based on CNLUCC data for 2000, 2010, and 2020, this study quantitatively explored the spatiotemporal evolution of production–living–ecological land (PLEL) and its eco-environmental response in China’s coastal zone by using multiple land-use analysis methods, gradient analysis, and the eco-environmental quality index. The results showed that over the past 20 years, the production land (PL) continued to decrease, whereas the living land (LL) and blue ecological land (BEL) increased. In the vertical direction, PL and the ecological land (EL) dominated in the northern and the southern coastal zone, respectively. In the horizontal direction, with increasing distance from the coastline, the green ecological land (GEL) increased, whereas it was the opposite for BEL. The transformations of PLEL were high and low frequency in the north and south, respectively. From 2000 to 2020, the eco-environmental quality of China’s coastal zone slightly degraded, with conditions that were “excellent in the south and poor in the north”. The eco-environmental qualities of each sub-coastal zone gradually improved with increasing distance from the coastline. The main transformation types that led to eco-environmental improvement and degradation were from other production lands (OPL) to blue ecological land (BEL) and BEL to OPL, respectively. The findings will guide PLEL planning, eco-environmental protection, and science-based land usage.

The harlequin ladybird, Harmonia axyridis, is a valuable asset in integrated pest management (IPM); however, issues related to low-temperature storage and transportation have resulted in low hatching rate, while the use of pesticides may lead to non-target effects against this natural enemy during field application. Fluctuating thermal regimes (FTR) have been shown to be beneficial during the low-temperature storage, and the type and concentration of insecticides used are crucial for field application of H. axyridis. Despite this, little research has been conducted on the effects of FTR on the hatching rate of ladybird eggs, and the impact of pesticides on their egg viability remains unclear. To address these gaps, we investigated the effects of different thermal temperatures, recovery frequencies (the number of changes in temperature conditions per unit time), and recovery durations (the duration of the treated temperature condition) on egg hatching under constant low-temperature conditions. We also examined the toxicity and safety of seven commonly used insecticides on egg hatching. Our results indicate that the temperature during FTR application did not significantly affect egg hatching, but the interaction between temperature and recovery frequency can significantly affect egg hatching. Moreover, the recovery frequency and recovery duration had a significant impact on hatching. Under specific conditions, the hatching rate of eggs subjected to FTR was similar to that of eggs stored at 25 °C. Furthermore, we found that matrine (a kind of alkaloid pesticide isolated from Sophora flavescens) had low toxicity to ladybird eggs and is a safe pesticide for use in conjunction with this natural enemy. The study provides valuable information on effectively managing H. axyridis by taking into account both storage temperature and pesticide exposure.