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Pneumonia is the fourth leading cause of death globally, and the reason for the high mortality rate of patients with severe community-acquired pneumonia (SCAP) remains elusive. Corticosteroid treatment reduces mortality in adults with SCAP but can cause numerous adverse events. Therefore, novel therapeutic targets need to be explored and new adjunctive immune drugs are urgently required. We analyzed the transcriptome data of peripheral blood leukocytes from patients with SCAP and healthy controls from three perspectives: differentially expressed genes, predicted functions of differentially expressed long non-coding RNAs, and transcriptional read-through. We discovered that the NETosis pathway was top-ranked in patients with SCAP caused by diverse kinds of pathogens. This provides a potential therapeutic strategy for treating patients. Furthermore, we calculated the correlation between the expression of genes involved in NETosis and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified four novel potential therapeutic targets for NETosis in patients with SCAP, including H4C15, H3-5, DNASE1, and PRKCB. In addition, a higher occurrence of transcriptional read-through is associated with a worse outcome in patients with SCAP, which probably can explain the high mortality rate of patients with SCAP.

BackgroundAcute pulmonary embolism (APE) is associated with peak incidence and mortality rate in winter. The present study sought to characterize the clinical and hemodynamic features of cold weather on APE patients.MethodsAll enrolled 224 APE patients underwent clinical and hemodynamic evaluation and baseline parameters were collected. Recruited patients were grouped by weather pattern on admission into cold and warm weather group. The correlation and prognostic values among cold weather and other variables were analyzed.ResultsCompared to warm weather group, patients in cold weather group present with more severe cardiac function, with adverse WHO-functional class (P = 0.032) and higher NT-proBNP concentration [1,853.0 (398.0, 5,237.0) pg/ml vs. 847.5 (56.8, 3,090.5) pg/ml, P = 0.001]. The cold weather group also displayed much critical hemodynamic status and heavier thrombosis load, with higher mPAP (29.1 ± 11.2mmHg vs. 25.6 ± 14.2mmHg, P = 0.045), higher PVR [3.3 (1.7, 6.0) wood units vs. 1.8 (0.9, 3.8) wood units, P < 0.001], higher Miller index (21.4 ± 5.9 vs. 19.1 ± 8.0, P = 0.024), and higher D-dimer levels [2,172.0 (854.5, 3,072.5) mg/L vs. 1,094.5 (210.5, 2,914.5) mg/L, P = 0.008]. Besides, cold weather showed well correlation with the above variables. Survival analysis showed APE patients in cold weather had significantly higher clinical worsening event rate (P = 0.010) and could be an independent predictor of adverse clinical outcome in the multivariate analysis (HR 2.629; 95% CI 1.127, 6.135; P = 0.025).ConclusionAPE patients in cold weather were associated with thrombus overload, cardiac dysfunction, hemodynamic collapse and higher clinical worsening event rate. Cold weather proves to be an independent predictor of adverse clinical outcome.

ObjectivesTo investigate the relationship between multimorbidity and health-related quality of life (HRQoL), and explore the effects of functional status and cognitive function on Chinses elderly behind this relationship.MethodsThe Multivariate logistic regression and Tobit regression models were used to determine the influence of multimorbidity on HRQoL. Bootstrap analysis was used to probe the mediating effects of functional status and the moderating role of cognition on multimorbidity and HRQoL.ResultsResults of the 2,887 participants age ≥ 60 years included in the analysis, 51.69% had chronic diseases. Stroke (β = −0.190; 95% confidence interval [CI], −0.232, −0.149; p

Background and aimsThis study aimed to examine whether the combination of elevated-C-reactive protein (CRP) levels and hypertension increased the risk of stroke among middle-aged and elderly Chinese.MethodsThis analysis included 9,821 Chinese participants aged ≥45 years in the China Health and Retirement Longitudinal Study (CHARLS). Data based on three waves of CHARLS were used (2011, 2013, and 2015). Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with a 95% confidence interval (95%CI) of new-onset stroke risk according to elevated-CRP level and hypertension. Moreover, the area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the incremental predictive value.ResultsA total of 184 stroke events occurred during follow-up. The median follow-up time was 4 years. Compared with those with normal CRP levels (CRP ≤ 3 mg /L) and blood pressure, the adjusted HRs and 95%CI were 1.86 (0.90–3.85) for individuals with elevated-CRP levels alone, 2.70 (1.71–4.28) for those with hypertension alone, and 4.80 (2.83–8.12) for those with comorbid elevated-CRP levels and hypertension. People with the coexistence of elevated-CRP levels and hypertension had the highest risk of new-onset stroke among all subgroup analyses. Finally, adding the combination of elevated-CRP levels and hypertension to conventional factors significantly improved the risk prediction for new-onset stroke.ConclusionOur findings indicate that the combined effect of elevated-CRP levels and hypertension increase the risk of new-onset stroke among the middle-aged and geriatric Chinese population.

Breast cancer is the most common malignancy in women, and there is evidence for the dual role of cell pyroptosis in tumor development. However, little is known about the relationship between cell pyroptosis and breast cancer and its prognostic value. We aimed to construct a prognostic model using cell-pyroptosis-related genes to provide innovative insights into the prognosis and treatment of breast cancer. We screened candidate genes for pyroptosis using public databases and identified 10 cell pyroptosis signature genes with the random forest method. Finally, a nomogram for predicting 1-, 3-, and 5-year survival probabilities was constructed. The differences in immune cell distributions between survival periods were similar across the breast cancer datasets. The 10 identified key pyroptosis factors showed a significant correlation with Her2, tumor–node–metastasis (TNM) stage, and survival of breast cancer. The risk scores correlated positively with the infiltration features of naive B cells, CD8+ T cells, atpdelnd mast cells, while they correlated negatively with those of M0 macrophages and dendritic cells. In conclusion, our findings confirm that cell pyroptosis is closely associated with breast cancer. Importantly, the prognostic complex values generated from the 10 cell-pyroptosis-related genes based on various clinical features may provide an important basis for future studies on the prognosis of breast cancer.

The detoxification of crops grown in Cadmium (Cd)-contaminated acid soil has been widely studied, but for contaminated alkaline soil, there is still inadequate research or information. In order to investigate the effects of calcium and sulfur fertilizers, accompanied by different side elements, on the growth and Cd uptake of Spinacia oleracea grown in Cd-contaminated alkaline soil, the plants were subjected to five treatments, including calcium silicate (Ca-Si), calcium biphosphate (Ca-P), magnesium sulfate (S-Mg), ferric sulfate (S-Fe), and zinc sulfate (S-Zn), and a control group. The results showed that the S-Fe achieved the highest shoot fresh mass and dry mass and the highest shoot Cd concentration and accumulation, which were 30%, 68%, 4.6%, and 73% higher than the control group, respectively. The Ca-Si, Ca-P, S-Mg, and S-Zn reduced the root Cd concentration by 18%, 42%, 7%, and 49%, respectively, and reduced the shoot Cd concentration by 25%, 36%, 15%, and 27%, respectively, as compared to the control. S-Fe increases plant N uptake and photosynthesis, which is beneficial to biomass accumulation. Ca-P improves soil and plant P nutrition status, as well as plant K and Ca status, and helps alleviate plant Cd stress. Overall, calcium fertilizers accompanied by phosphorus have the potential to reduce plant Cd contamination risk, while sulfur fertilizers accompanied by iron show potential for enhancing Cd extraction.

Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

MicroRNAs (miRNAs) have been regarded as modulators in vascular pathologies, including hypertension. Dysregulated proliferation and migration of VSMCs (vascular smooth muscle cells) contributes to vascular remodeling during hypertension. miR-634 was reported to be dysregulated in hypertensive patients. The involvement of miR-634 in hypertension and the role of miR-634 on VSMCs proliferation and migration were then evaluated. Firstly, HASMCs (human aortic smooth muscle cells) were incubated with 2 μM angiotensin (Ang) II for 12 hours to establish the cell model of Ang II-induced hypertension. Results showed that Ang II treatment promoted proliferation and migration of HASMCs. Secondly, miR-634 was down-regulated in the hypertensive patients, and reduced in Ang II-induced HASMCs in a time dependent manner. Functional assays revealed that Ang II promoted proliferation and migration of HASMCs were suppressed by miR-634 mimic. Lastly, miR-634 targeted 3′ untranslated region (UTR) of Wnt4, and reduced Wnt4 expression in HASMCs. miR-634 inhibited β-catenin nuclear translocation. Over-expression of Wnt4 counteracted the suppressive effects of miR-634 on Ang II-induced proliferation and migration of HASMCs. In conclusion, miR-634 inhibited HASMCs proliferation and migration through inactivation of Wnt4/β-catenin pathway.

Abstract Glioblastoma (GBM), the most malignant tumor of the central nervous system, is marked by its dynamic response to microenvironmental niches. In particular, this cellular plasticity contributes to the development of an immediate resistance during tumor treatment. Novel insights into the developmental trajectory exhibited by GBM show a strong capability to respond to its microenvironment by clonal selection of specific phenotypes. Using the same mechanisms, malignant GBM do develop intrinsic mechanisms to resist chemotherapeutic treatments. This resistance was reported to be sustained by the paracrine and autocrine glutamate signaling via ionotropic and metabotropic receptors. However, the extent to which glutamatergic signaling modulates the chemoresistance and transcriptional profile of the GBM remains unexplored. In this study we aimed to map the manifold effects of glutamate signaling in GBM as the basis to further discover the regulatory role and interactions of specific receptors, within the GBM microenvironment. Our work provides insights into glutamate release dynamics, representing its importance for GBM growth, viability, and migration. Based on newly published multi-omic datasets, we explored the and characterized the functions of different ionotropic and metabotropic glutamate receptors, of which the metabotropic receptor 3 (GRM3) is highlighted through its modulatory role in maintaining the ability of GBM cells to evade standard alkylating chemotherapeutics. We addressed the clinical relevance of GRM3 receptor expression in GBM and provide a proof of concept where we manipulate intrinsic mechanisms of chemoresistance, driving GBM towards chemo-sensitization through GRM3 receptor inhibition. Finally, we validated our findings in our novel human organotypic section-based tumor model, where GBM growth and proliferation was significantly reduced when GRM3 inhibition was combined with temozolomide application. Our findings present a new picture of how glutamate signaling via mGluR3 interacts with the phenotypical GBM transcriptional programs in light of recently published GBM cell-state discoveries.

Abstract Porcine reproductive and respiratory syndrome (PRRS) induces respiratory disease and reproductive failure accompanied by gastroenteritis-like symptoms. The mechanism of intestinal barrier injury caused by PRRSV infection in piglets has yet to be investigated. An in vivo PRRSV-induced model was established in 30-day-old piglets by the intramuscular injection of 2 mL of 104 TCID50/mL PRRSV for 15 days. Observations of PRRSV replication and histology were conducted in the lungs and intestine, and goblet cell counts, relative MUC2 mRNA expression, and tight junction protein, proinflammatory cytokine, TLR4, MyD88, IκB and p-IκB expression were measured. PRRSV replicated in the lungs and small intestine, as demonstrated by absolute RT-qPCR quantification, and the PRRSV N protein was detected in the lung interstitium and jejunal mucosa. PRRSV infection induced both lung and gut injury, markedly decreased villus height and the villus to crypt ratio in the small intestine, and obviously increased the number of goblet cells and the relative expression of MUC2 mRNA in the jejunum. PRRSV infection aggravated the morphological depletion of tight junction proteins and increased IL-1β, IL-6, IL-8 and TNF-α expression by activating the NF-κB signalling pathway in the jejunum. PRRSV infection impaired intestinal integrity by damaging physical and immune barriers in the intestine by inducing inflammation, which may be related to the regulation of the gut-lung axis. This study also provides a new hypothesis regarding the pathogenesis of PRRSV-induced diarrhoea.

Memory accuracy involves two major processes: pattern separation and pattern completion. Pattern separation refers to the ability to reduce overlap among similar inputs to avoid interference, and pattern completion refers to the ability to retrieve the whole information from partial or degraded cues. Impairments in pattern separation/pattern completion contribute to cognitive deficits in several diseases of the nervous system. Therefore, it is better to evaluate both pattern separation and pattern completion in one apparatus. However, few tools are available to assess pattern separation and pattern completion within the same apparatus for rodents. In this study, we designed a series of images with varying degrees of similarity to the correct image to evaluate pattern separation and pattern completion. First, mice were trained to discriminate between two totally different images, and once the correct percentage reached above 77% for two consecutive days, the images with different degrees of similarity were used to measure pattern separation and pattern completion. The results showed the mice performed progressively worse from S0 to S4 (increasing similarity) when discriminating similar images in pattern separation, and the mice performed progressively worse from C0 to C4 (decreasing cues information) when recalling the correct image according to partial cues in pattern completion, implying a good image similarity-dependent manner for memory accuracy evaluation. In sum, we designed a convenient, effective paradigm to evaluate pattern separation and pattern completion based on a touchscreen pairwise discrimination task, which may provide a new method for the studies of the effects and mechanisms of memory accuracy enhancing drugs.

BackgroundThe reported rate of cardiovascular adverse events (CAE) caused by immune checkpoint inhibitors (ICI) is low but potentially fatal. Assess the risk of CAE in cancer patients and compare the incidence of CAE between Chinese developed ICIs and imported ICIs.MethodsA retrospective analysis was performed on cancer patients treated with ICI for at least four cycles in the Second Affiliated Hospital of Dalian Medical University from January 2018 to March 2022. Baseline characteristics, physiological and biochemical values, electrocardiographic and echocardiographic findings were compared between patients with and without CAE.ResultsAmong 495 patients treated with ICIs, CAEs occurred in 64 patients (12.93%). The median time to the event was 105 days (61–202). The patients with low neutrophil-to-lymphocyte ratio (L-NLR) were significantly associated with the risk of developing CAE (hazard ratio HR 3.64, 95% confidence ratio CI 1.86–7.15, P = 0.000). Patients with higher comorbidity burden significantly increased the risk of developing CAE (HR 1.30, 95% CI 1.05–1.61, P = 0.014). Those who received a combination of ICI and vascular endothelial growth factor receptor (VEGFR) inhibitors (HR 2.57, 95% CI 1.37–4.84, P = 0.003) or thoracic radiation therapy (HR 32.93, 95% CI 8.81–123.14, P = 0.000) were at a significantly increased risk of developing CAE. Compared to baseline values, creatine kinase is -oenzymes (CK-MB) (95% CI -9.73 to -2.20, P = 0.003) and cardiac troponin I (cTnI) (95% CI -1.06 to -0.06, P = 0.028) were elevated, and the QTc interval prolonged (95% CI -27.07 to -6.49, P = 0.002). Using nivolumab as a control, there was no difference in CAE risk among the eight ICIs investigated. However, the results of the propensity matching showed that programmed death-ligand 1 (PD-L1) inhibitors had lower CAE occurrence compared with programmed cell death protein 1 (PD-1) inhibitors (adjusted HR = 0.38, P = 0.045).ConclusionPatients who received concurrent VEGFR inhibitors and ICIs had a history of thoracic radiation therapy, L-NLR, and higher comorbidity burden had an increased risk of CAEs. Elevated cTnI, CK-MB, and QTc, can be used to monitor CAEs. There was no significant difference in CAE risks between Chinese domestic and imported ICIs. PD-L1 inhibitors had lower CAE occurrence than PD-1 inhibitors.

Purpose The Liyang cohort study on chronic diseases and risk factors monitoring in China (Liyang Study) is a prospective population-based study which aims to investigate and identify the determinants of the most prevalent chronic non-communicable diseases (NCDs) and to evaluate the impact of demographic characteristics, lifestyle, dietary habits, cognition, disability and NCDs on the health-related quality of life.Participants Between March 2019 and June 2020, 10 056 individuals aged ≥18 years were administered a baseline survey through a multistage cluster random sampling in Liyang City, southern Jiangsu Province, China.Findings to date The Liyang Study included detailed sociodemographic, anthropometric and health-related behaviour, common NCDs and blood sample information. Moreover, the study gathered a series of data on specific scales including the activities of daily living, instrumental activities of daily living, abbreviated mental test, Food Frequency Questionnaire and EuroQol 5-Dimensions 5-Levels Scale. Of the 10 056 participants, 52.92% (n=5322) were female and 92.26% (n=9278) came from rural areas. The mean age was 49.9±16.2 years. Men were more likely to have a higher level of education, annual income and a paid job than women (p

BackgroundVogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease.MethodsHigh throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves.ResultsA total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease.ConclusionSix immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.

BNIP3 is a BH3-only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here, we undertook a quantitative analysis of BNIP3 expression and functions in single-cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer 3D organoid cultures compared with 2D culture. Taken together, the combination of in silico perturbations using public single-cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.

AimTo investigate the status of positive mental characters and humanistic care ability among Chinese nursing students, and confirm the association between positive mental characters and humanistic care ability.MethodsA cross-sectional survey was conducted. Nine hundred eighty-one Chinese nursing students were recruited from hospitals and community healthcare services in Changsha, Hunan, China. Three different self-reported questionnaires were applied: The Demographic Characteristics Questionnaire, Humanistic care ability of Nursing Undergraduates Assessment Scale and Positive Mental Characters Scale for Chinese College Students. Pearson correlation analysis and multiple liner regression analysis were performed to analyze the association between positive mental character and humanistic care ability for Chinese nursing students.ResultsThe mean scores of nursing students' humanistic care ability and positive mental character were 125.94 ± 21.19, 233.18 ± 38.59, respectively. The Pearson correlation results showed that positive mental character (r = 0.655, P < 0.001) was significantly associated with humanistic care ability. Multiple liner regression analysis indicated that positive mental characters, four dimensions of courage, humanity, justice and transcendence in positive mental character, care from classmates were found to be independent predictors of humanistic care ability.ConclusionPositive mental characters are important considerations in the development, implementation and evaluation of humanistic care ability interventions.

Objectives: The purpose of this study was to examine correlates of taking a COVID-19 test among late middle-aged and older adults using nationally representative data. Methods: Data were obtained from the 2020 Health and Retirement Study midway release COVID-19 module. Our sample was representative of community residing adults aged 51 and over in the United States (n = 2,870). Measurements: We regressed taking a COVID-19 test on demographic characteristics, medical comorbidities, and measures related to the health belief model (i.e., perceived severity, perceived susceptibility, cues to action, and perceived barriers) using logistic regression, stratifying the model by 10-year age categories. Results: Concern about the pandemic was associated with an increase in the likelihood of taking a test among late middle-aged adults. Knowing someone who was diagnosed with COVID-19 was associated with taking a test in most age categories. Financial barriers and knowing someone who died of COVID-19 were not associated with taking a test. Conclusions: How late middle-aged and older adults perceive the COVID-19 pandemic may significantly influence their likelihood of taking a COVID-19 test.

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/d-phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

B cell progenitors differentiate into multiple subsets with distinct functions. Here the authors analyze the epigenetic landscapes of sorted B cell subsets using multiple platforms and show that the epigenetic regulator, DNMT3A, is essential for modulating the activity of enhancers critical for B1 and B2 lineage-determining genes.

AIM: To understand the epidemic situation of retinopathy of prematurity in Sanya region and its related factors analysis so as to provide a reference for the prevention of the disease in this region.METHODS: A total of 243 premature infants(486 eyes)with gestational age of less than 36 weeks and 35 cases of full moon(70 eyes)who were delivered in Sanya Maternal and Child Health Care Hospital from January to December 2019 were selected as the research objects. Fundus screening was performed. And the incidence of retinopathy of prematurity was calculated according to the diagnostic criteria, and univariate and multivariate Logistic regression analysis was performed on the related data of the mothers before and during pregnancy.RESULTS: There was no retinopathy in the whole moon, but 36 cases of premature infants with retinopathy of prematurity. And the incidence of the disease was 14.8%(36/243). Among them, about half(58.3%)of the children with stage Ⅰ disease. Followed by stage Ⅱ disease(30.6%), stage Ⅲ disease(8.3%)and stage Ⅳ disease(2.8%), no stage Ⅴ disease were found. Meanwhile, 2 children with threshold lesions(5.6%). Except for the gestational age, there were no significant differences in the related factors of menstruation, gestational age, gestational births and pregnancy complications between full-term and normal preterm mothers(P>0.05), but compared with the mothers of premature infants, the differences were statistically significant(P

A two-layer optimization strategy for the battery energy storage system is proposed to realize primary frequency regulation of the grid in order to address the frequency fluctuation problem caused by the power dynamic imbalance between the power system and load when a large number of new energy sources are connected to the grid. An integrated control mode combining virtual sag control and virtual inertia control is proposed in the adaptive regulation layer to provide fast frequency support for the grid while effectively reducing steady-state frequency difference fluctuation. The equal consumption micro-increment criterion is used in the equalization control layer to distribute the energy output of each group while maintaining a good battery charge level. The results of the final simulation in Matlab/Simulink show that the proposed control strategy can effectively improve the system’s primary frequency regulation performance.

Background: Definite noninvasive characterisation of renal tumours positive on 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) examination including renal oncocytomas (ROs), hybrid oncocytic chromophobe tumours (HOCTs), and chromophobe renal cell carcinoma (chRCC) is currently not feasible. Objective: To investigate whether combined 99mTc-sestamibi SPECT/CT and in situ metabolomic profiling can accurately characterise renal tumours exhibiting 99mTc-sestamibi uptake. Design, setting, and participants: A tissue microarray analysis of 33 tumour samples from 28 patients was used to investigate whether their in situ metabolomic status correlates with their features on 99mTc-sestamibi SPECT/CT examination. In order to validate emerging data, an independent cohort comprising 117 tumours was subjected to matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). Outcome measurements and statistical analysis: MALDI MSI data analysis and image generation were facilitated by FlexImaging v. 4.2, while k-means analysis by SCiLS Lab software followed by R-package CARRoT analysis was used for assessing the highest predictive power in the differential of RO versus chRCC. Heatmap-based clustering, sparse partial least-squares discriminant analysis, and volcano plots were created with MetaboAnalyst 3.0. Results and limitations: We identified a discriminatory metabolomic signature for 99mTc-sestamibi SPECT/CT–positive Birt-Hogg-Dubè–associated HOCTs versus other renal oncocytic tumours. Metabolomic differences were also evident between 99mTc-sestamibi–positive and 99mTc-sestamibi–negative chRCCs, prompting additional expert review; two of three 99mTc-sestamibi–positive chRCCs were reclassified as low-grade oncocytic tumours (LOTs). Differences were identified between distal-derived tumours from those of proximal tubule origin, including differences between ROs and chRCCs. Conclusions: The current study expands the spectrum of 99mTc-sestamibi SPECT/CT–positive renal tumours, encompassing ROs, HOCTs, LOTs, and chRCCs, and supports the feasibility of in situ metabolomic profiling in the diagnostics and classification of renal tumours. Patient summary: For preoperative evaluation of solid renal tumours, 99mTc-sestamibi single photon emission computed tomography/computed tomography (SPECT/CT) is a novel examination method. To increase diagnostic accuracy, we propose that 99mTc-sestamibi–positive renal tumours should be biopsied and followed by a combined histometabolomic analysis.

Abstract Well‐preserved molecular cargo in circulating extracellular vesicles (EVs) offers an ideal material for detecting oncogenic gene alterations in cancer patients, providing a noninvasive diagnostic solution for detection of disease status and monitoring treatment response. Therefore, technologies that conveniently isolate EVs with sufficient efficiency are desperately needed. Here, a lipid labeling and click chemistry‐based EV capture platform (“Click Beads”), which is ideal for EV message ribonucleic acid (mRNA) assays due to its efficient, convenient, and rapid purification of EVs, enabling downstream molecular quantification using reverse transcription digital polymerase chain reaction (RT‐dPCR) is described and demonstrated. Ewing sarcoma protein (EWS) gene rearrangements and kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation status are detected and quantified using EVs isolated by Click Beads and matched with those identified in biopsy specimens from Ewing sarcoma or pancreatic cancer patients. Moreover, the quantification of gene alterations can be used for monitoring treatment responses and disease progression.

The outstanding role of hydrogels in promoting wound repair has been studied extensively, but the development of hydrogels with multiple functions to deal with the complex wound environments remains as a challenge and a research focus. Thus, inspired by mussel chemistry, the dopamine grafted gelatin (GelDA) and polydopamine coated graphene oxide (pGO) were prepared firstly. Then, the GelDA/pGO hydrogels with multifunction of adhesion, conductivity, antioxidant, and antibacterial activity were designed through an oxidative coupling reaction between catechol groups. The rheology, mechanical properties, and conductivity of hydrogels could be adjusted appropriately by changing the concentration of pGO. Furthermore, the catechol groups made the hydrogel possessed an adequate adhesive hemostasis in the rat liver hemorrhage model. While the introducion of pGO enabled the hydrogels to get the satisfactory photothermal antibacterial properties, which were verified by both gram-positive and gram-negative bacteria tests. Finally, in vivo wound healing experiment demonstrated the beneficial effect of hydrogel on promoting burn wound healing. The prepared GelDA/pGO hydrogels could be considered as promising multifunctional wound dressings for accelerating wound healing.

Canine distemper (CD) caused by canine distemper virus (CDV) is one of the major infectious diseases in minks, bringing serious economic losses to the mink breeding industry. By an integrated analysis of microRNA (miRNA)-messenger RNA (mRNA), the present study analyzed the changes in the mink transcriptome upon CDV infection in mink lung epithelial cells (Mv. l. Lu cells) for the first time. A total of 4,734 differentially expressed mRNAs (2,691 upregulated and 2,043 downregulated) with |log2(FoldChange) |>1 and P-adj2 and P-adj

Nuclear signals are sensitive to noise which may affect final monitoring results significantly. In order to suppress the nuclear signal noise, a sparse representation method, which is based on the sparse representation of signals and a matching pursuit algorithm, has been proposed for denoising. Time–frequency matching “atoms” have been selected for building an over-complete library by training atoms matching with the characteristics of nuclear signals regardless of the noise. The best time–frequency matching atoms have been extracted by sparsely representing the noisy signals with an Orthogonal Matching Pursuit (OMP) algorithm and the library. The residual ratio threshold has been chosen as a stopping criterion in the OMP algorithm for avoiding the influence of improper selection of iterations on denoising results. At the end, the pulse matching the atom extracted by each iteration has been optimized by performing effective sparse representation on the original noiseless nuclear signal component in noisy nuclear signals. The proposed method has been used to denoise the simulated and measured signals and has been compared with the nuclear denoising result using traditional wavelet theory. The results show that the proposed method can accurately suppress the noise interference of nuclear signals, and the denoising effect is better than that of the traditional wavelet method.

Stress can induce learning and memory impairment; corticosterone is often used to study the effects and mechanisms of stress in animal models. Long-term potentiation (LTP) has been widely used for tackling the mechanisms of memory. Liuwei Dihuang decoction-active fraction combination (LW-AFC) can improve stress-induced LTP and cognition impairment; stachyose is an oligosaccharide in LW-AFC. The effects and mechanisms of stachyose on stress are unknown. In this study, stachyose showed protective effects against LTP impairment by corticosterone in vivo only via intragastric administration for 7 consecutive days, but there was little effect even after direct intracerebroventricular injection; the protective effect of stachyose could be canceled by non-absorbable antibiotics (ATB) which disturbed gut flora. 16S rRNA sequencing, alpha diversity, and principal coordinate analysis (PCoA) revealed that the gut flora in corticosterone-treated mice was disturbed and stachyose could improve corticosterone-induced gut flora disturbance. Bacteroidetes were decreased and Deferribacteres were increased significantly in corticosterone-treated mice, and stachyose restored Bacteroidetes and Deferribacteres to the normal level. D-serine, a coactivator of NMDA receptors, plays an important role in synaptic plasticity and cognition. Here, corticosterone had little effect on the content of D-serine and L-serine (the precursor of D-serine), but it reduced the D-serine release-related proteins, Na+-independent alanine–serine–cysteine transporter-1 (ASC-1), and vesicle-associated membrane protein 2 (VAMP2) significantly in hippocampus; stachyose significantly increased ASC-1 and VAMP2 in corticosterone-treated mice, and ATB blocked stachyose’s effects on ASC-1 and VAMP2. NMDA receptors co-agonists L-serine, D-serine, and glycine significantly improved LTP impairment by corticosterone. These results indicated that stachyose might indirectly increase D-serine release through the gut–brain axis to improve LTP impairment by corticosterone in the hippocampus in vivo.

Abstract Background Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. At present, there is few literature reports on the effective prevention and treatment of PCV2 infection by a combination of two or more compounds. Previously, we have demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further evaluated. Literatures have proven that Osthole has a variety of pharmacological activities, and we tested the ability of Osthole to inhibit PCV2 replication in cell culture. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and their synergistic anti-apoptotic mechanism. Results Osthole alone had an anti-PCV2 effect, and then its synergistic anti-PCV2 effect of Osthole and Matrine was better than that of Matrine or Osthole alone as demonstrated by qRT-PCR, IFA and Western blotting results. The anti-apoptotic mechanism of these two compounds by inducing the PERK pathway by PCV2 was elucidated through Annexin V-FITC/PI, JC-1 and Western blotting. Matrine and Osthole combination could inhibit the expression of Cap in Cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. Ribavirin was used as a positive control. Conclusions The combination of Osthole and Matrine had the synergistic effect of anti-PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The combination of these two compounds also inhibited PERK apoptosis induced by PCV2 Cap protein, possibly by regulating the level of GRP78. The results formed a base for further studies on the mechanism of anti-PCV2 in vivo using Matrine and Osthole combination and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets.

Extracellular vesicles (EVs) are present in circulation at relatively early stages of disease, providing potential opportunities for early cancer diagnosis. Here, the authors report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific EV purification system for early detection of HCC by performing digital scoring on the purified EVs.

Abstract Background Porcine circovirus type 2 (PCV2) is an immunosuppressive pathogen with high prevalence rate in pig farms. It has caused serious economic losses to the global pig industry. Due to the rapid mutation of PCV2 strain and co-infection of different genotypes, vaccination could not eradicate the infection of PCV2. It is necessary to screen and develop effective new compounds and explore their anti-apoptotic mechanism. The 13 natural compounds were purchased, with a clear plant origin, chemical structure and content and specific biological activities. Results The maximum no-cytotoxic concentration (MNTC) and 50% cytotoxic concentration (CC50) of 13 tested compounds were obtained by the cytopathologic effect (CPE) assay and (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in PK-15 cells. The results of qPCR and Western blot showed that, compared with the PCV2 infected group, the expression of Cap in Paeonol (0.4 mg/mL and 0.2 mg/mL), Cepharanthine (0.003 mg/mL, 0.0015 mg/mL and 0.00075 mg/mL) and Curcumin (0.02 mg/mL, 0.001 mg/mL and 0.005 mg/mL) treated groups were significantly lowered in a dose-dependent manner. The results of Annexin V-FITC/PI, JC-1, Western blot and ROS analysis showed that the expression of cleaved caspase-3 and Bax were up-regulated Bcl-2 was down-regulated in Cepharanthine or Curcumin treated groups, while ROS and MMP value were decreased at different degrees and the apoptosis rate was reduced. In this study, Ribavirin was used as a positive control. Conclusions Paeonol, Cepharanthine and Curcumin have significant antiviral effect. And the PCV2-induced Mitochondrial apoptosis was mainly remitted by Cepharanthine and Curcumin.

Abstract Background Aleutian mink disease parvovirus (AMDV) causes Aleutian mink disease (AMD), which is a serious infectious disease of mink. The aim of this study was to get a better understanding of the molecular epidemiology of AMDV in northeast China to control and prevent AMD from further spreading. This study for the first time isolated AMDV from fecal swab samples of mink in China. Results A total of 157/291 (54.0%) of the fecal swab samples were positive for AMDV. Of these, 23 AMDV positive samples were randomly selected for sequence alignment and phylogenetic analysis based on the acquired partial fragments of VP2 gene with the hypervariable region. Comparative DNA sequence analysis of 23 AMDV isolates with a reference nonpathogenic (AMDV-G) strain revealed 8.3% difference in partial VP2 nucleotide sequences. Amino acid alignment indicated the presence of several genetic variants, as well as one single amino acid residue deletion. The most concentrated area of variation was located in the hypervariable region of VP2 protein. According to phylogenetic analysis, the Chinese AMDV strains and the other reference AMDV strains from different countries clustered into three groups (clades A, B and C). Most of the newly sequenced strains were found to form a Chinese-specific group, which solely consisted of Chinese AMDV strains. Conclusion These findings indicated that a high genetic diversity was found in Chinese AMDV strains and the virus distribution were not dependent on geographical origin. Both local and imported AMDV positive species were prevalent in the Chinese mink farming population. The genetic evidence of AMDV variety and epidemic isolates have importance in mink farming practice.

Recent studies indicate that MEG3, a long non-coding RNA (lncRNA) and microRNA-184 (miR-184) are abnormally expressed in osteosarcoma (OS). To this end, we show here that MEG3 negatively regulates the expression of miR-184 and down-stream effectors of WNT/β-catenin pathway including β-catenin, T-cell factor 4 (TCF4) and c-MYC. MEG3 overexpression by adenoviral vectors down-regulate proliferation, migration and apoptosis of OS in vitro and restrict the tumor growth in vivo. We also show that the effects of MEG3 can be effectively reversed by miR-184 mimic. Together these studies show that both MEG3 and miR-184 cooperatively regulate the proliferation, migration and apoptosis of OS.

Wind speed and streamflow series always are nonlinear and unstable because the effects of chaotic weather systems. These inherent features make them difficult to forecast, especially in a changing environment. To improve forecasting accuracy, an innovation uncertainty forecasting architecture is developed by coupling data decomposition method, feature selection, multiple artificial intelligence (AI) techniques and composite strategy to do unstable time series forecasting. In the designed architecture, the AVMD (adaptive variational mode decomposition) is first applied to excavate implicit information from the original time series. Then, the random forest is utilized to select the suitable inputs for each mode. After that, the GPR (Gaussian Process Regression), a very famous probabilistic AI technique, is driven by various neural networks (ELM (Extreme Learning Machine), BP (Back Propagation Neural Networks), GRNN(Generalized Regression Neural Networks) and RBF (Radial Basis Function Neural Networks)) to produce both deterministic and probabilistic forecasting results in a nonlinear manner to play strengths of each other. The effectiveness and applicability of the proposed approach is verified by unstable wind speed data and streamflow data, and also compared with eleven related models. Results indicate that the proposed model not only improves the forecasting accuracy for deterministic predictions, but also provides more probabilistic information for decision making. The proposed method achieves significantly better performance than the traditional forecasting models both on wind speed forecasting and streamflow forecasting with at least 50% average performance promotion over all the eleven competitors. Comprehensive comparisons demonstrate the superior performance of the proposed method than the involved models as a powerful tool for unstable series forecasting.

Retinal progenitor cells (RPCs) transplantation has become a promising therapy for retinal degeneration, which is a major kind of ocular diseases causing blindness. Since RPCs have limited proliferation and differentiation abilities toward retinal neurons, it is urgent to resolve these problems. MicroRNAs have been reported to have vital effects on stem cell fate. In our study, the data showed that overexpression of miR-381-3p repressed Hes1 expression, which promoted RPCs differentiation, especially toward neuronal cells, and inhibited RPCs proliferation. Knockdown of endogenous miR-381-3p increased Hes1 expression to inhibit RPCs differentiation and promote proliferation. In addition, a luciferase assay demonstrated that miR-381-3p directly targeted the Hes1 3’ untranslated region (UTR). Taken together, our study demonstrated that miR-381-3p regulated RPCs proliferation and differentiation by targeting Hes1, which provides an experimental basis of RPCs transplantation therapy for retinal degeneration.

Objective Gastric cancer (GC) is one of the most common tumour diseases worldwide and has poor survival, especially in the Asian population. Exploration based on biomarkers would be efficient for better diagnosis, prediction, and targeted therapy. Methods Expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Survival-related genes were identified by gene set enrichment analysis (GSEA) and univariate Cox. Then, we applied a Bayesian hierarchical lasso Cox model for prognostic signature screening. Protein-protein interaction and Spearman analysis were performed. Kaplan–Meier and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prediction performance. Multivariate Cox regression was used to identify prognostic factors, and a prognostic nomogram was constructed for clinical application. Results With the Bayesian lasso Cox model, a 9-gene signature included TNFRSF11A, NMNAT1, EIF5A, NOTCH3, TOR2A, E2F8, PSMA5, TPMT, and KIF11 was established to predict overall survival in GC. Protein-protein interaction analysis indicated that E2F8 was likely related to KIF11. Kaplan-Meier analysis showed a significant difference between the high-risk and low-risk groups (PConclusion Our findings suggested that a novel prognostic model based on a 9-gene signature was developed to predict GC patients in high-risk and improve prediction performance. We hope our model could provide a reference for risk classification and clinical decision-making.

The aim of the study was to investigate the factors influencing contrast-induced acute kidney injury (CI-AKI) after percutaneous intervention (PCI) in patients with acute coronary syndrome (ACS) with diabetes mellitus (DM). A total of 1073 patients with ACS combined with DM who underwent PCI at the Affiliated Hospital of Xuzhou Medical University were included in this study. We divided the patients into the CI-AKI and non-CI-AKI groups according to whether CI-AKI occurred or not. The patients were then randomly assigned to the training and validation sets at a proportion of 7 : 3. Based on the results of the LASSO regression and multivariate analyses, we determined that the subtypes of ACS, age, multivessel coronary artery disease, hyperuricemia, low-density lipoprotein cholesterol, triglyceride-glucose index, and estimated glomerular filtration rate were independent predictors on CI-AKI after PCI in patients with ACS combined with DM. Using the above indicators to develop the nomogram, the AUC-ROC of the training and validation sets were calculated to be 0.811 (95% confidence interval (CI): 0.766-0.844) and 0.773 (95% CI: 0.712-0.829), respectively, indicating high prediction efficiency. After verification by the Bootstrap internal verification, we found that the calibration curves showed good agreement between the nomogram predicted and observed values. And the DCA results showed that the nomogram had a high clinical application. In conclusion, we constructed and validated the nomogram to predict CI-AKI risk after PCI in patients with ACS and DM. The model can provide a scientific reference for predicting the occurrence of CI-AKI and improving the prognosis of patients.

Drying is one of the most common methods for processing and preserving sea cucumber. Based on the research of pretreatment and drying process, this paper develops a dried sea cucumber product that can be quickly rehydrated in only 8 hours. By setting the pretreatment at heated water temperature of 80°C and the drying temperature from 30°C to 60°C, the fitting model is found by comparing empirical formulas and artificial neural networks. The ANN-based model was demonstrated to fit the experimental data for the adequate drying of sea cucumber. Following the increased drying temperature, the drying time was decreased and the rehydration ratio was increased. The sensory evaluation and texture properties dried at 40°C and 50°C were much better than those dried at 30°C and 60°C. Microstructure of rehydrated dried sample showed that increasing the temperature leads to the increase of fiber pore space, and the rehydration rate increases. The results of drying time and the rehydration properties of sea cucumber showed that 50°C is the best drying condition for hot-air drying of sea cucumber. The developed rapid rehydration dried sea cucumber can effectively simplify the rehydration time and steps of the dried sea cucumber and improve the quality of the sea cucumber, and it is considered to be a good technology for drying the sea cucumber and making a fast rehydration dried sea cucumber that can be further used for value-added product.

Ulcerative colitis (UC) is a complex inflammatory bowel disease (IBD) associated with mitochondrial function. Atractylenolide III (AT III) is a natural product with anti-inflammatory effects. The aim of this work is to investigate the protective effect of AT III on UC and its underlying mechanisms. Herein, dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated intestinal epithelial cells (IEC-6) were employed to mimic UC pathologies in vivo and in vitro. The results showed that in DSS-induced mice, AT III significantly reversed the body weight loss, colon length reduction, disease activity index (DAI) increase, and histological damage. The production of proinflammatory factors and reduction of antioxidants in colitis were suppressed by AT III. In addition, we demonstrated that AT III attenuated the intestinal epithelial barrier destruction and mitochondrial dysfunction induced by DSS, which was similar to the in vitro results in LPS-treated IEC-6 cells. The protein levels of p-AMPK, SIRT1, and PGC-1α along with acetylated PGC-1α were also upregulated by AT III in vivo and in vitro. In conclusion, these findings support that AT III may protect against mitochondrial dysfunction by the activation of the AMPK/SIRT1/PGC-1α signaling pathway during UC development.

The molecular basis of porcine red blood cell immune adhesion function stems from the complement receptor type 1-like (CR1-like) on its cell membrane. The ligand for CR1-like is C3b, which is produced by the cleavage of complement C3; however, the molecular mechanism of the immune adhesion of porcine erythrocytes is still unclear. Here, homology modeling was used to construct three-dimensional models of C3b and two fragments of CR1-like. An interaction model of C3b–CR1-like was constructed by molecular docking, and molecular structure optimization was achieved using molecular dynamics simulation. A simulated alanine mutation scan revealed that the amino acids Tyr761, Arg763, Phe765, Thr789, and Val873 of CR1-like SCR 12–14 and the amino acid residues Tyr1210, Asn1244, Val1249, Thr1253, Tyr1267, Val1322, and Val1339 of CR1-like SCR 19–21 are key residues involved in the interaction of porcine C3b with CR1-like. This study investigated the interaction between porcine CR1-like and C3b using molecular simulation to clarify the molecular mechanism of the immune adhesion of porcine erythrocytes.

At present, in the situation that wind power penetration is increasing year by year, the use of a hybrid energy storage system (HESS) to smooth out wind power fluctuations becomes an effective method. However, the existing control strategy has the problem of inadequate utilization of fluctuating power. In this paper, we propose a control strategy for smoothing wind power fluctuations based on double Kalman filters with adaptive adjustment of the state of charge (SOC). Firstly, considering the wind power’s active power grid constraint, the parameters of the dual Kalman filter are adaptively adjusted according to the original output power to obtain the target grid power synchronously, and the total smoothing command of the energy storage system is determined with the goal of improving the SOC of the lithium battery. On this basis, the SOC of the supercapacitor is considered to be improved, and the adaptive low-pass filter is used for the secondary distribution of the energy storage power command to achieve fine-grained management of the output power of HESS. The final simulation results show that the obtained smoothed wind power satisfies the 1 min and 10 min fluctuation criteria, and the minimum capacity required for lithium batteries is reduced by 0.07 MW·h under the same initial conditions as in the proposed method in this paper; it can use the fluctuating power when the SOC crosses the limit, and has a regulating effect on the SOC of HESS to improve the wind power smoothing ability and realize the stable grid-connection requirement of wind power.

Extracellular vesicles (EVs) have been regarded as one of the most potential diagnostic biomarkers for different cancers, due to their unique physiological and pathological functions. However, it is still challenging to precisely analyze the contents and sources of EVs, due to their heterogeneity. Herein, we summarize the advances in technologies for a single EV analysis, which may provide new strategies to study the heterogeneity of EVs, as well as their cargo, more specifically. Furthermore, the applications of a single EV analysis on cancer early diagnosis are also discussed.

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.

Bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) are members of the genus Pestivirus that cause disease in wild and domestic animals and are responsible for extensive economic losses of livestock and biological industry. BVDV is also a significant laboratory contaminant. Currently, no effective antiviral therapeutics are available to control their infection. Ginsenosides, as major pharmacological ingredients in the plants of ginseng, have various biological activities. In the present work, the antiviral activity of 9 ginsenosides and 3 other saponins from Araliaceae plants was investigated against Pestivirus. Ginsenoside Rb2 and Rb3 showed low cytotoxicity and obvious antiviral effect. They were able to inhibit the replication and proliferation of BVDV and CSFV. In addition, our results suggest that the possible antiviral mechanism of Rb2 might be related to its ability to affect the translation of these viruses. Obtained results suggest that ginsenoside Rb2 and Rb3 have a potential for effective treatment against Pestivirus infection.

The development of high nature value farmland (HNVf) can effectively improve the problems of biodiversity reduction, non-point source pollution and carbon loss in intensive farmland. To this end, we developed a set of general indicators based on Landsat 8 OLI imagery, including land cover (LC), normalized difference vegetation index (NDVI), Shannon diversity (SH) and Simpson’s index (SI). Combined with a Kohonen neural network (KNN), we assigned weights and developed the first potential HNVf map of the Yellow River Delta in China. The results showed that the four indicators were very effective for the expression of HNVf characteristics in the study area, and that SH and SI, in particular, could reflect the potential characteristics of HNVf at the edge of intensive farmland. LC, NDVI, SH and SI were weighted as 0.45, 0.25, 0.15 and 0.15, respectively. It was found that the potential HNVf type 2 (i.e., low-intensity agriculture, and natural and structural elements such as shrubs, woodlands and small rivers) in the study area was concentrated at the edges of intensive farmland, the transition zones from farmland to rivers and the estuary wetland areas of northern and eastern rivers. LC played a leading role in identifying HNVf. Based on six randomly selected real-world verification data from Map World, it was found that the accuracy of the validation set for HNVf type 2 was 83.33%, which exhibited the good development potential of HNVf in the study area. This is the first potential HNVf type 2 map of the Yellow River Delta in China and could provide a great deal of potential guidance for the development and protection of farmland biodiversity and regional carbon sequestration.

Introduction: Online sales of antibiotics have increased public access to these medicines. This study aimed to analyze the online antibiotic purchase behavior of the Chinese residents and identify its associated factors.Methods: We conducted a nationwide cross-sectional online survey among Chinese community residents from January 20 to February 28, 2019. A structured questionnaire was used to collect data on their sociodemographic characteristics, health-related variables, and the online antibiotic purchase behavior in the past 3 months. Descriptive statistics and logistic regression analyses were used. The statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.).Results: A total of 101,120 respondents were included in the analysis. The weighted prevalence of antibiotic purchase online was 3.71% (95% CI, 3.53–3.88%). Residents who purchased antibiotics online were more likely to be older (age≥65 years), be a male, live in rural areas, have a higher education level, report an excellent economic status, suffer from chronic diseases, and search for health information on the internet.Conclusion: Numerous residents had purchased antibiotics online in the past 3 months throughout China. We should pay more attention to this behavior. There is a need to strengthen regulation of antibiotic sales online and improve public education on antibiotic purchase online. More comprehensive information on antibiotic purchase online as well as the advantages and disadvantages of online sales of antibiotics should be investigated in the future studies.

Opioids are the last option for the pharmacological treatment of neuropathic pain, but their antinociceptive effects are limited. Decreased mu opioid receptor (MOR) expression in the peripheral nervous system may contribute to this. Here, we showed that nerve injury induced hypermethylation of the Oprm1 gene promoter and an increased expression of methyl-CpG binding protein 2 (MeCP2) in injured dorsal root ganglion (DRG). The downregulation of MOR in the DRG is closely related to the augmentation of MeCP2, an epigenetic repressor, which could recruit HDAC1 and bind to the methylated regions of the Oprm1 gene promoter. MeCP2 knockdown restored the expression of MOR in injured DRG and enhanced the analgesic effect of morphine, while the mimicking of this increase via the intrathecal infusion of viral vector-mediated MeCP2 was sufficient to reduce MOR in the DRG. Moreover, HDAC1 inhibition with suberoylanilide hydroxamic acid, an HDAC inhibitor, also prevented MOR reduction in the DRG of neuropathic pain mice, contributing to the augmentation of morphine analgesia effects. Mechanistically, upregulated MeCP2 promotes the binding of a high level of HDCA1 to hypermethylated regions of the Oprm1 gene promoter, reduces the acetylation of histone H3 (acH3) levels of the Oprm1 gene promoter, and attenuates Oprm1 transcription in injured DRG. Thus, upregulated MeCP2 and HDAC1 in Oprm1 gene promoter sites, negatively regulates MOR expression in injured DRG, mitigating the analgesic effect of the opioids. Targeting MeCP2/HDAC1 may thus provide a new solution for improving the therapeutic effect of opioids in a clinical setting.

BackgroundApigenin (APG), a natural flavonoid, can affect the development of a variety of tumors, but its role in ovarian cancer remains unclear. There has been an increasing amount of evidence supporting the vital role played by mast cells and the bioactive mediators they release, as components of the tumor microenvironment, in the progression of ovarian cancer (OC); however, the mechanism warrants further exploration.Methods and ResultsIn this study, a combination of transcriptomics analysis and application of TCGA database was performed, and we found that the expression of genes related to mast cell degranulation in ovarian cancer tissues changed remarkably. We then explored whether histamine, a major constituent of mast cell degranulation, could affect the development of ovarian cancer through immunohistochemistry analysis and cell proliferation assays. The results showed that a certain concentration of histamine promoted the proliferation of ovarian cancer cells by upregulating the expression of estrogen receptor α (ERα)/estrogen receptor β (ERβ). Additionally, we found that the inhibition of ERα or the activation of ERβ could inhibit the proliferation of ovarian cancer cells induced by histamine through real-time PCR and western blot assays. Finally, we demonstrated the attenuation effect imparted by apigenin in histamine-mediated ovarian cancer via the PI3K/AKT/mTOR signaling pathway.ConclusionOur research revealed that apigenin decelerated ovarian cancer development by downregulating ER-mediated PI3K/AKT/mTOR expression, thus providing evidence of its applicability as a potentially effective therapeutic agent for ovarian cancer treatment.

The improvement in the quality of life is accompanied by an accelerated pace of living and increased work-related pressures. Recent decades has seen an increase in the proportion of obese patients, as well as an increase in the prevalence of breast cancer. More and more evidences prove that obesity may be one of a prognostic impact factor in patients with breast cancer. Obesity presents unique diagnostic and therapeutic challenges in the population of breast cancer patients. Therefore, it is essential to have a better understanding of the relationship between obesity and breast cancer. This study aims to construct a prognostic risk prediction model combining obesity and breast cancer. In this study, we obtained a breast cancer sample dataset from the GEO database containing obesity data [determined by the body mass index (BMI)]. A total of 1174 genes that were differentially expressed between breast cancer samples of patients with and without obesity were screened by the rank-sum test. After weighted gene co-expression network analysis (WGCNA), 791 related genes were further screened. Relying on single-factor COX regression analysis to screen the candidate genes to 30, these 30 genes and another set of TCGA data were intersected to obtain 24 common genes. Finally, lasso regression analysis was performed on 24 genes, and a breast cancer prognostic risk prediction model containing 6 related genes was obtained. The model was also found to be related to the infiltration of immune cells. This study provides a new and accurate prognostic model for predicting the survival of breast cancer patients with obesity.

Soil restoration is a crucial approach to improving plant productivity in orchards with soil degradation, yield reduction, and fruit quality declination in China. A self-invented root-zone ecological restoration practice (RERP) with soil conditioner, or organic fertilizer, was employed in a degraded peach orchard in Beijing in 2020 to investigate the consequent impacts on soil bacterial composition and functionality at soil depths of 0–20 cm and 20–40 cm. Bacterial diversity was sensitive to RERP, especially in subsurface soil. RERP with soil conditioner significantly increased bacterial diversity, and affected abundances of certain genera, such as a significantly increased amount of Bacillus in surface soil and Blastococcus, Microvirga, Nocardioides, and Sphingomonas in subsurface soil. It also significantly affected abundances of bacterial functions related to metabolism in subsurface soil, particularly those with low abundance such as decreased transcription abundance and increased amino acid metabolism abundance. Soil bacterial functions were observably affected by bacterial diversity and composition, particularly in the deep soil layer. RERP affected bacterial functionality via responses of soil bacteria and bacteria-mediated alterations to the changed soil property. Correlation analysis between soil properties, bacterial taxonomy, and bacterial functions revealed that RERP affected bacterial functionality by altering the soil microenvironment with ample nutrients and water supply in root zone. Consequently, shifted bacterial functionality could have a potential in orchard ecosystem services in view of fruit yield and quality. Taken together, RERP had notably positive impacts on soil bacterial diversity and functions, and a prospect of increased plant productivity in the degrade orchard ecosystem.