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As an essential micronutrient element in organisms, copper controls a host of fundamental cellular functions. Recently, copper-dependent cell growth and proliferation have been defined as "cuproplasia". Conversely, "cuproptosis" represents copper-dependent cell death, in a nonapoptotic manner. So far, a series of copper ionophores have been developed to kill cancer cells. However, the biological response mechanism of copper uptake has not been systematically analyzed. Based on quantitative proteomics, we revealed the crosstalk between copper stress and cuproptosis in cancer cells, and also explored the feasibility of curcumin as anticancer copper ionophore. Copper stress not only couples with cuproptosis, but also leads to reactive oxygen species (ROS) stress, oxidative damage and cell cycle arrest. In cancer cells, a feedback cytoprotection mechanism involving cuproptosis mediators was discovered. During copper treatment, the activation of glutamine transporters and the loss of Fe-S cluster proteins are the facilitators and results of cuproptosis, respectively. Through copper depletion, glutathione (GSH) blocks the cuproptosis process, rescues the activation of glutamine transporters, and prevents the loss of Fe-S cluster proteins, except for protecting cancer cells from apoptosis, protein degradation and oxidative damage. In addition, the copper ionophore curcumin can control the metabolisms of lipids, RNA, NADH and NADPH in colorectal cancer cells, and also up-regulates positive cuproptosis mediators. This work not only established the crosstalk between copper stress and cuproptosis, but also discolored the suppression and acceleration of cuproptosis by GSH and curcumin, respectively. Our results are significant for understanding cuproptosis process and developing novel anticancer reagents based on cuproptosis.

PurposeExisting empirical studies emphasize the role of customer preference measurement accuracy (CPMA) on customized product quality while neglecting the role of manufacturing flexibility. However, the rise of web-based technology has highlighted consumer-manufacturer interaction in mass customization (MC). This paper explores the relationships between CPMA, manufacturing flexibility, customer participation and customized product quality, inspired by module decomposition and integration theory.Design/methodology/approachThe study carried out a questionnaire survey of 241 directors who are specifically responsible for MC in the apparel industry in China and tested hypotheses with structural equation modeling (SEM).FindingsCPMA has a direct positive influence on customized product quality and an indirect positive effect through manufacturing flexibility. Also, customer participation after placing an order (CPAPO) has a negative moderating effect on the linkage between CPMA and manufacturing flexibility.Research limitations/implicationsA more dynamic relationship between CPMA and MF can be explored in the future, and the findings can be tested in other industries with more abundant data.Practical implicationsManufacturing flexibility should be improved along with CPMA in MC. Also, disruptions caused by customer participation in the post-design stage should be noticed. In this context, better consumer service in the early design stage may be one possible solution.Originality/valueFirst, the essential but unexplored mediating role of manufacturing flexibility is identified, adding knowledge to the consumer–manufacturer interaction literature in MC production. Second, module decomposition and integration are applied to unify consumers and manufacturers into one empirical model, enriched theoretical research on modular theory. Third, this study opens new discussions on the moderating role of customer participation.

Introduction: Contamination of large grit sandblasting and acid-etching (SLA) with hydrocarbons make the surface hydrophobic and influence its bioactivity. Preservation in dH2O (modified SLA, modSLA) and ultraviolet (UV) irradiation were proven to be effective in decreasing hydrocarbon contamination and keeping the SLA surface hydrophilic. Aims: The aim of this study was to detect the in vitro bioactivity of SLA, modSLA and UV-SLA surfaces. Design: The SBF model was used to compare the bone-like apatite forming ability. Setting: The experiment was conducted at Southern Medical University. Materials and methods: The quantity of apatite was assessed by SEM and weighed on an electronic balance. The elemental composition and crystal phase were assessed by EDS and XRD analysis, respectively. Results: The sediments that completely covered the modSLA and UV-SLA surfaces after 4 weeks of soaking reached 3.23 ± 0.35 mg and 2.13 ± 0.95 mg, respectively. They were eight- and five-fold than that on the SLA surface (0.43 ± 0.15 mg) with statistical significance ( p Discussion: Hydrophilicity and abundant hydroxyl groups drive modSLA and UV-SLA surfaces to absorb more Ca2+ to accelerate the formation of apatite. Conclusion: SLA preservation in dH2O and UV irradiation were recognized as trustworthy methods to acquire greater bioactivity of the SLA surface.

The characteristics and related mechanisms of the interannual variability of late summer (August) extreme precipitation in West China (WC) were investigated from 1961 to 2021. Precipitation and extreme precipitation (defined as the 99th percentile) generally decreased in the southeast-northwest direction, with a maximum in the Sichuan Basin. The non-linear trends in extreme precipitation have increased since the 1980s. Therefore, we further found that the interannual increase in extreme precipitation in the WC was significantly related to the eastward-strengthened South Asian high, western-stretched Western Pacific Subtropical high, enhanced westerly jet, anomalous cyclone in Mongolia, and anomalous anticyclone in the western Pacific. The anti-cyclonic anomaly is a Gill-type response to increase the sea surface temperature in the western Pacific. A mid-high latitude barotropic Rossby-wave train can be induced and has essential effects on the above key circulation patterns, further cooperating with the strong updrafts rather than strengthening and maintaining extreme precipitation in the WC.

Figure S6 shows the correlation of CD8-IHC and tumoruptake as determined by gamma-counting or PET.

CD8-expressing T cells are the main effector cells in cancer immunotherapy. Treatment-induced changes in intratumoral CD8+ T cells may represent a biomarker to identify patients responding to cancer immunotherapy. Here, we have used a 89Zr-radiolabeled human CD8-specific minibody (89Zr-Df-IAB22M2C) to monitor CD8+ T-cell tumor infiltrates by PET. The ability of this tracer to quantify CD8+ T-cell tumor infiltrates was evaluated in preclinical studies following single-agent treatment with FOLR1-T-cell bispecific (TCB) antibody and combination therapy of CEA-TCB (RG7802) and CEA-targeted 4-1BB agonist CEA-4-1BBL. In vitro cytotoxicity assays with peripheral blood mononuclear cells and CEA-expressing MKN-45 gastric or FOLR1-expressing HeLa cervical cancer cells confirmed noninterference of the anti-CD8-PET-tracer with the mode of action of CEA-TCB/CEA-4-1BBL and FOLR1-TCB at relevant doses. In vivo, the extent of tumor regression induced by combination treatment with CEA-TCB/CEA-4-1BBL in MKN-45 tumor–bearing humanized mice correlated with intratumoral CD8+ T-cell infiltration. This was detectable by 89Zr-IAB22M2C-PET and γ-counting. Similarly, single-agent treatment with FOLR1-TCB induced strong CD8+ T-cell infiltration in HeLa tumors, where 89Zr-Df-IAB22M2C again was able to detect CD8 tumor infiltrates. CD8-IHC confirmed the PET imaging results. Taken together, the anti-CD8-minibody 89Zr-Df-IAB22M2C revealed a high sensitivity for the detection of intratumoral CD8+ T-cell infiltrates upon either single or combination treatment with TCB antibody–based fusion proteins. These results provide further evidence that the anti-CD8 tracer, which is currently in clinical phase II, is a promising monitoring tool for intratumoral CD8+ T cells in patients treated with cancer immunotherapy.Significance:Monitoring the pharmacodynamic activity of cancer immunotherapy with novel molecular imaging tools such as 89Zr-Df-IAB22M2C for PET imaging is of prime importance to identify patients responding early to cancer immunotherapy.

Figure S2 shows the PET scans of each experimental mouse of the CEA-4-1BBL/CEA-TCB study.

Figure S1 shows the in vitro tumor cell lysis mediated by CEA-TCB and CEA-4-1BBL) or FOLR1-TCB ni presence of the CD8 Mb IAB22M2C.

Figure S4 shows the IHC analysis for tumor density, necrosis and blood vessels.

Supplementary Material and Methods

Figure S5 shows PET scans of each experimental animal of the FOLR1-TCB study.

Figure S3 shows autoradiography slides after CEA-4-1BBL/CEA-TCB single or combo treatment.

Background The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. Methods Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. Results The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p F = 3.82, p = 0.05). Serum IL-8 levels were positively correlated with sub-scores of delayed memory (r = 0.37, p = 0.04) and visuospatial/constructional (r = 0.43, p = 0.02) in MDD patients with SSRIs but not in in healthy controls (delayed memory score: r = -0.12, p = 0.24; visuospatial/constructional score: r = 0.02, p = 0.81). Conclusions Our findings suggested that increased serum IL-8 level might not only be involved in the MDD psychopathology or the use of SSRIs but also correspond to improving MDD delayed memory and visuospatial/constructional function.

Background The circular RNA (circRNA) plays a vital role in the pathogenesis of tumors as a competitive endogenous RNA (ceRNA). Given the high aggressiveness and fatality rate of glioblastoma (GBM) as well as poor prognosis, it is necessary to construct a circRNA-related ceRNA network for further studies on the mechanism of GBM and identify possible biomarkers as well as therapeutic drugs. Methods Three datasets from the gene expression omnibus (GEO) database were downloaded to distinguish differential circRNAs, microRNAs, and messenger RNAs respectively in GBM. With the help of GEPIA2, circBank, CSCD, TargetScan, miRDB, and miRTarBase databases, we established a circRNAs-related ceRNA network in GBM. Functional enrichments were employed to profile the most relevant mRNAs to indirectly clarify the mechanisms of the ceRNA network. Based on the expression profile data and survival information of GBM patients from the GEO and the cancer genome atlas (TCGA) databases, we performed survival analysis to select prognostic mRNAs and constructed a novel circRNA-miRNA-mRNA central regulatory subnetwork. The DGIdb database was used to find potential drug–gene interactions. Results The datasets obtained from the GEO and TCGA databases were analyzed, and 504 differentially expressed mRNAs (DEmRNAs), 71 differentially expressed microRNAs (DEmiRNAs), and 270 differentially expressed circRNAs (DEcircRNAs) were screened out. The novel ceRNA regulatory network included 22 circRNAs, 11 miRNAs, and 15 mRNAs. FZD1 and KLF10 were significantly correlated with the overall survival rate of patients with GBM (P Conclusions Results of this study demonstrate that FZD1 and KLF10 may exert regulatory functions in GBM, and the ceRNA-mediated network could be a therapeutic strategy for GBM.

The main problems lying in the learning process of learners in different majors are that they study blindly and do not have a complex knowledge structure, which are seriously affecting their learning effects. But if a knowledge graph can be modeled for the major-specific curriculum system using the quantitative method from the perspective of knowledge network, it may be able to improve the existing teaching problems and optimize the teaching quality. The existing major-specific knowledge graphs were all constructed in an abstract form, ignoring the inherent prior learning relationship between teaching units and curriculum knowledge. To this end, taking English major as an example, this paper studied the construction and application of a major-specific knowledge graph based on the big data in education. Firstly, the English major-specific knowledge graph was modeled, the calculation process of node importance was shown, and a localized graph of the knowledge network of English major courses was given. Then, a multi-node feature selection framework for the English major-specific knowledge graph was constructed based on the context of nodes, and the importance of the top k nodes in the constructed knowledge graph was extracted using the multi-node feature extraction technology. After that, the experimental results verified the stability and connectivity of the nodes in the constructed knowledge graph.

ObjectiveInvasive pituitary adenomas (IPAs) are common tumors of the nervous system tumors for which invasive growth can lead to difficult total resection and a high recurrence rate. The basement membrane (BM) is a special type of extracellular matrix and plays an important role in the invasion of pituitary adenomas (PAs). The aim of this study was to develop a risk model for predicting the invasiveness of PAs by analyzing the correlation between the expression of BM genes and immune infiltration.MethodsFour datasets, featuring samples IPAs and non-invasive pituitary adenomas (NIPAs), were obtained from the Gene Expression Omnibus database (GEO). R software was then used to identify differentially expressed genes (DEGs) and analyze their functional enrichment. Protein-protein interaction (PPI) network was used to screen BM genes, which were analyzed for immune infiltration; this led to the generation of a risk model based on the correlation between the expression of BM genes and immunity. A calibration curve and receiver operating characteristic (ROC) curve were used to evaluate and validate the model. Subsequently, the differential expression levels of BM genes between IPA and NIPA samples collected in surgery were verified by Quantitative Polymerase Chain Reaction (qPCR) and the prediction model was further evaluated. Finally, based on our analysis, we recommend potential drug targets for the treatment of IPAs.ResultsThe merged dataset identified 248 DEGs that were mainly enriching in signal transduction, the extracellular matrix and channel activity. The PPI network identified 11 BM genes from the DEGs: SPARCL1, GPC3, LAMA1, SDC4, GPC4, ADAMTS8, LAMA2, LAMC3, SMOC1, LUM and THBS2. Based on the complex correlation between these 11 genes and immune infiltration, a risk model was established to predict PAs invasiveness. Calibration curve and ROC curve analysis (area under the curve [AUC]: 0.7886194) confirmed the good predictive ability of the model. The consistency between the qPCR results and the bioinformatics results confirmed the reliability of data mining.ConclusionUsing a variety of bioinformatics methods, we developed a novel risk model to predict the probability of PAs invasion based on the correlation between 11 BM genes and immune infiltration. These findings may facilitate closer surveillance and early diagnosis to prevent or treat IPAs in patients and improve the clinical awareness of patients at high risk of IPAs.

Additional file 1: Supplementary Table 1. Characteristics of patients who underwent abdominal surgery before and after propensity score-matching. Presented as n (%) or mean (SD). Supplementary Table 2. Univariate relationship between patient characteristics and outcome, based on the propensity score-matched cohort.

Data supplementation and interpretation

It is a common phenomenon for corporate insiders to pledge their stock as collateral for personal loans in China. Using Chinese data, this paper examines the effects of CEOs’ share pledge on the firms’ future innovation output. Evidence suggests that the existence of CEOs with share pledge has a significantly negative effect on firms’ innovation output. The baseline results are consistent with a variety of robust tests. Furthermore, we propose the effect of CEOs’ share pledge works on the corporate innovation through the market value management channel. Finally, we find that the good corporate governance is a possible channel to relieve the agency cost on CEOs.

Background Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD). Methods The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020. Results In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients. Conclusions Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline.

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1β, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.

Schizophrenia (SCZ) and obsessive-compulsive disorder (OCD) are complex polygenic disorders with brain morphology abnormalities. The etiologies and relationship of both disorders remain elusive, and should be further investigated. Thus, induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) from an OCD patient, his mother with SCZ and his healthy father with reprograming method. All iPSCs were characterized to have normal karyotype and expression of pluripotency makers. These iPSCs will be a valuable model to elucidate the pathophysiological mechanisms and association of both diseases.

Haematological diseases with pancreatic masses as the first symptom are clinically rare but should not be ignored. This case report describes a 60-year-old female patient with acute leukaemia that had a pancreatic mass as her first symptom. The patient was admitted and elastography combined with endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (EUS-FNA) was used for diagnosis, treatment planning and determination of prognosis. The site selected for the EUS-FNA puncture was the caudal section of the pancreatic body and the posterior wall of the gastric body was used as the puncture point. The elastography view of the head of the pancreas was blue/green with predominant blue colour. A 19 G puncture needle with a slow-draw core and two stitches of micro-negative pressure were used. Cytology detected heterotypic cells, pancreatic puncture histopathology, the presence of pancreatic alveolar structures and heterotypic tumour cells in the interstitium. Immunohistochemistry of the pancreatic puncture tissue showed B-cell lymphoblast-derived tumours and bone marrow puncture indicated acute lymphoblastic leukaemia. The patient was diagnosed with acute lymphoblastic leukaemia invading the pancreas and was treated with chemotherapy. After treatment, her condition was stable. Follow-up is ongoing and there have been no signs of tumour recurrence or metastasis.

This study aims to investigate mechanism ofquot;Ephedrae Herba-Descurainiae Semen Lepidii Semenquot; combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and thequot;Chinese medicine-active component-target-pathway-diseasequot; network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-β1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and β-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and β-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and β-sitosterol are the candidate active components.

Diminazene aceturate (DA) has been used in the treatment of infections of trypanosomes in animals. Interestingly, its anti-inflammatory effect has recently gained increased interests. However, DA has been reported to have toxic side effects that limit its application. Therefore, we synthesized and screened a novel low-toxic DA derivative, namely the DA derivative 3 (DAD3). In the present study, anti-inflammatory effect of DAD3 was evaluated bovine mammary epithelial cells (BMECs) in vitro model. The results demonstrated that DAD3 had less cytotoxicity, and had a stronger effect in inhibiting secretion of inflammatory factors in BMECs, compared to DA. Mechanistically, DAD3 was able to inhibit the production of pro-inflammatory factors in part by suppressing the generation of mitochondrial reactive oxygen species (ROS) in BMECs upon LPS stimulation. Molecular analysis further indicated that DAD3 was capable of resolving inflammation in BMECs through a mechanism by preventing nuclear translocation of NF-p65, subsequently inhibiting transcription of inflammatory factors. In this context, DAD3 inhibited the phosphorylation of IκB, ERK, JNK and P-38 proteins of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. These results suggested the DAD3 was a novel DA derivative with low toxicity and strong anti-inflammatory effects in BMECs exposed to LPS, through a mechanism by blocking the NF-κB and MAPK signaling pathways. This study also provides an evidence that the DAD3 may be a novel anti-inflammatory agents warranted for further investigation in treatment of mastitis in cows.

This study investigated the air quality improvement in terms of bacterial and fungal contamination in an exercise room of a fitness center under normal operating conditions. Environmental conditions including air conditioning, ventilation, moisture, CO2, particulate matters, and total number of users were also recorded. In addition, fungal and bacterial load were assessed and disinfection on sports equipment surface was also examined. Background bacteria and fungi densities in bioaerosols were in the range of 249 ± 65 to 812 ± 111 CFU/m3 and 226 ± 39 to 837 ± 838 CFU/m3 in the exercise room of the fitness center and 370 ± 86 to 953 ± 136 CFU/m3 and 465 ± 108 to 1734 ± 580 CFU/m3 in the outdoor air, respectively. Chlorine dioxide and weak acid hypochlorous water aerosols could remove both bacteria and fungi much better than water scrubbing. Contact time of 15 min was sufficient to control both bacteria and fungi to comply with the official air quality standards. User density and carbon dioxide deteriorated both bacteria and fungi disinfection performance whereas temperature was only statistically significant on fungi disinfection. Other factors including relative humidity, airflow velocity, and particulate matters did not have any statistically significant effect on microbial inactivation. Apart from bioaerosol disinfection, inactivation of microorganisms on surfaces of sports equipment was also conducted using chlorine dioxide, zinc oxide, weak acid hypochlorous water, and commercial disinfectant. The surfaces of bicycle handle, dumbbell, and sit-up bench were found to be contaminated with bacteria. Overall bacterial load was 390 to 3720 CFU/cm2 with Escherichia coli specifically 550 to 1080 CFU/cm2. Chlorine dioxide and zinc oxide were noticeably better than weak acid hypochlorous water and commercial disinfectant in terms of bacteria inactivation whereas all tested disinfectants had comparable effectiveness on E. coli disinfection. Targeted microorganisms on the sports equipment surface were sufficiently inactivated within 2 min after the application of disinfectant.

BackgroundEsophagogastric junction adenocarcinoma (EGJA) is a special malignant tumor with unknown biological behavior. PD-1 checkpoint inhibitors have been recommended as first-line treatment for advanced EGJA patients. However, the biomarkers for predicting immunotherapy response remain controversial.MethodsWe identified stromal immune-related genes (SIRGs) by ESTIMATE from the TCGA-EGJA dataset and constructed a signature score. In addition, survival analysis was performed in both the TCGA cohort and GEO cohort. Subsequently, we explored the differences in tumor-infiltrating immune cells, immune subtypes, immune-related functions, tumor mutation burden (TMB), immune checkpoint gene expression, immunophenoscore (IPS) between the high SIRGs score and low SIRGs score groups. Finally, two validation cohorts of patients who had accepted immunotherapy was used to verify the value of SIRGs score in predicting immunotherapy response.ResultsEight of the SIRGs were selected by LASSO regression to construct a signature score (SIRGs score). Univariate and multivariate analyses in the TCGA and GEO cohort suggested that SIRGs score was an independent risk factor for the overall survival (OS) and it could increase the accuracy of clinical prediction models for survival. However, in the high SIRGs score group, patients had more immune cell infiltration, more active immune-related functions, higher immune checkpoint gene expression and higher IPS-PD1 and IPS-PD1-CTLA4 scores, which indicate a better response to immunotherapy. The external validation illustrated that high SIRGs score was significantly associated with immunotherapy response and immune checkpoint inhibitors (ICIs) can improve OS in patients with high SIRGs score.ConclusionThe SIRGs score may be a predictor of the prognosis and immune-therapy response for esophagogastric junction adenocarcinoma.

Background: A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. Methods: We performed public database bioinformatics analysis, surgical specimen histological validation, RNA sequencing, and exATP/extracellular adenosine (exADO) assays to reveal the role of PANX1 in regulating the immune microenvironment of basal-like breast cancer. Results: Our results revealed that PANX1 acted as a poor prognostic factor for breast cancer and had high expression in basal-like breast cancer. PANX1 expression was positively correlated with exATP and exADO levels in basal-like breast cancer TME. PANX1 expression was also positively correlated with tumor-associated neutrophil (TAN) infiltration in breast cancer TME and TANs highly expressed ENTPD1 (CD39)/NT5E (CD73). Conclusions: This study suggests that high PANX1 expression is associated with high TAN infiltration and adenosine production to induce local immunosuppression in basal-like breast cancer TME.

Two new cyclotrypyamine alkaloids equisetinines A and B, as well as three known alkaloids (

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a proprotein convertase that increases plasma low-density lipoprotein cholesterol (LDL-C) levels by triggering the degradation of LDL receptors (LDLRs). Beyond the regulation of circulating LDL-C, PCSK9 also has direct atherosclerotic effects on the vascular wall and is associated with coronary plaque inflammation. Interestingly, emerging data show that women have higher circulating PCSK9 concentrations than men, suggesting that the potential roles of PCSK9 may have different impacts according to sex. In this review, we summarize the studies concerning sex difference in circulating levels of PCSK9. In addition, we report on the sex differences in the relations of elevated circulating PCSK9 levels to the severity and prognosis of coronary artery disease, the incidence of type 2 diabetes mellitus, and neurological damage after cardiac arrest and liver injury, as well as inflammatory biomarkers and high-density lipoprotein cholesterol (HDL-C). Moreover, sex difference in the clinical efficacy of PCSK9 inhibitors application are reviewed. Finally, the underlying mechanisms of sex difference in circulating PCSK9 concentrations and the clinical implications are also discussed.

Background Improvements in the early osseointegration of titanium implants require investigations on the bone-implant interface, which is a critical and complex challenge. The surface cleanliness of titanium implants plays an important role at this interface. However, the implant surface would inevitably absorb contamination such as organic hydrocarbons, which is not conductive to the establishment of early osseointegration. Herein, an optimized approach for removing contamination from titanium surfaces was studied. Methods The TiO2-B＠anatase NWs (nanowires) were prepared on titanium substrates through a hydrothermal process. A methylene blue degradation experiment was performed to assess the photodegradation activity. The cleaning effect of the photocatalysis of TiO2-B＠anatase NWs on a titanium surface and the cellular early response was determined by analyzing cell morphology, attachment, proliferation and differentiation. Results The results indicated that the photocatalysis of TiO2-B＠anatase NWs could effectively remove hydrocarbons on titanium surfaces without sacrificing the favourable titanium surface morphology. The methylene blue degradation experiment revealed that the photocatalysis of TiO2-B＠anatase NWs had powerful degradation activity, which is attributed to the presence of strong oxidants such as ·OH. In addition, compared to the merely ultraviolet-treated titanium surfaces, the titanium surfaces treated after the NWs photocatalytic cleaning process markedly enhanced cellular early response. Conclusion The photocatalysis of TiO2-B＠anatase NWs for the removal of contamination from titanium surfaces has the potential to enable the rapid and complete establishment of early osseointegration.

Aegilops tauschii Coss, a notorious wheat field weed, poses a serious threat to wheat in China. Tillers are an important agronomic tool for yield. In this study, a total of 12 Ae. tauschii populations were collected from China to investigate the effect of plant density on tiller occurrence and its phytohormonal regulation. We assayed the growth parameters of Ae. tauschii and the levels of endogenous hormones at different plant densities. The results showed that plant density had a significant effect on the quantity and quality of Ae. tauschii seeds produced per plant. In particular, the tiller and spike numbers per plant were negatively affected by plant density (P 0.0001). The contents of 13 endogenous hormones in the tiller nodes changed in response to plant density. Among them, indole-3-acetic acid (IAA) and gibberellin (GA) positively responded to plant density. However, the reverse result was found for cytokinin (CTK). Interestingly, phylogenetic tree analysis of auxin (AeYUCCA), CK (AeIPT) and GA (AeCPS) biosynthesis related genes found that phylogenies in the Gramineae for the three different genes were various, hinting at horizontal gene transfer. Moreover, the dynamics of the expression of AeYUCCA, AeIPT and AeCPS were roughly consistent with their phytohormone contents during tillering stage. When externally sprayed on plants of Ae. tauschii, 2,4-D isooctyl ester and GA

Digital storytelling is a short form of multimedia production that can foster digital literacy and facilitate subject matter learning. This study describes how middle school students learned about mental health by composing digital stories, showing how this also influenced their attitudes toward mental health in their own lives. Using a qualitative multiple-case method, we explored three immigrant students’ digital storytelling in a psychology class. We use a visual grammar derived from systemic functional linguistics to analyze their digital stories, examining representational, relational, configurational, and social functions. Our analysis shows how students chose design elements to reflect their learning about and reactions to mental illness. We analyze how students projected relationships with the audience and how these projected relationships both reflected and influenced their learning and personal development. We conclude that digital storytelling can be an excellent pedagogical tool that allows students to engage both in subject matter learning and self-reflection.

In recent years, there have been several outbreaks of infectious diseases around the world, including severe acute respiratory syndrome, Ebola virus disease, Middle East respiratory syndrome, and corona virus disease 2019 Experience suggests that the detection and research of emergent infectious diseases play a crucial role in the process of responding to the epidemic, which also brings great challenges to biosafety laboratories In the face of unknown biological risk factors, the non-standard biosafety protection measures have a serious impact on the life safety of laboratory staff and the research of infectious diseases, which stresses the necessity of safety protection in biosafety laboratories This article will briefly review the current status and future prospect of management of biosafety laboratories both in China and other countries in terms of safety protection measures during new sudden infectious disease incidents © The Author(s) 2020

ObjectiveThe interleukin-8 (IL-8) has been reported to play an important role in depression, which might be modulated by the selective serotonin reuptake inhibitors (SSRIs). Thus, the aim of this study was to investigate serum IL-8 levels, depressive symptom, and their associations in drug-free MDD patients, MDD patients with SSRIs, and healthy controls (HCs).MethodsFifty-seven drug-free MDD patients (male/female = 35/22, mean age: 39.24 years), 30 MDD patients with SSRIs (male/female = 11/19, mean age: 39.73 years), and 101 HCs (male/female = 52/49, mean age: 37.38 years) were recruited in this cross-sectional study. Serum IL-8 levels and depressive symptom were assessed using the Flow Cytometer and Hamilton Depression Scale (HAMD). The analysis of variance was used for the comparison between groups. The relationship between serum log10IL-8 levels and HAMD score was analyzed by Pearson correlation.ResultsSerum log10IL-8 levels were lower in all patients than HCs after controlling for covariates (F= 4.86,p= 0.03). There was significant difference in serum Log10IL-8 levels among three groups after controlling for covariates (F= 14.63,p< 0.001). Serum Log10IL-8 levels in drug-free patients were lower compared to HCs (F= 19.38,p< 0.001) or patients with SSRIs (F= 21.89,p< 0.001) after controlling for covariates. However, there was not difference in serum log10IL-8 levels between patients with SSRIs and HCs after controlling for covariates. Moreover, serum Log10IL-8 levels were negatively correlated with HAMD score in all patients (r= −0.37,p= 0.02). Also, serum Log10IL-8 levels were negatively correlated with HAMD score in drug-free patients (r= −0.74,p= 0.01), but not in patients with SSRIs.ConclusionOur data supported that the decline in serum IL-8 levels was association with depression. Moreover, the SSRIs might modulate increased serum IL-8 levels of depression.

Purpose: To investigate the changes in choroidal vascular structures after exercise in patients with glaucoma using an image binarisation algorithm with enhanced-depth imaging optical coherence tomography.Methods: Thirty-four eyes of 19 patients with primary open-angle glaucoma and 40 eyes of 20 normal subjects were included in the glaucoma and control groups, respectively. All subjects were evaluated before, immediately after, and 30 min after 20-min running at moderate speed. The subfoveal choroidal area was segmented into the luminal area (LA) and stromal area (SA), and the choroidal vascularity index (CVI) was measured by calculating the ratio of LA to the total choroidal area (TCA). The mean intraocular pressure (IOP), subfoveal choroidal thickness, CVI, SA, CA, and TCA were compared within and between both groups. The correlation between CVI, IOP, and other vascular indexes was investigated.Results: In the glaucoma group, a significantly lower CVI was found immediately after exercise and recovered 30 min after exercise. Higher TCA and LA levels were demonstrated 30 min after exercise compared to immediately after exercise. In both groups, IOP decreased immediately after exercise but was restored after a 30-min rest. In the glaucoma group, there was a higher correlation between CVI and other choroidal vascular parameters than in the control group. There was no difference in IOP or choroidal parameters between the groups at different time points.Conclusion: In patients with glaucoma, CVI decreased significantly immediately after exercise, indicating that the choroidal layer is affected by exercise and an unhealthy vascular regulatory mechanism.