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Cancer metastasis is responsible for the vast majority of cancer‐related deaths worldwide. In contrast to numerous discoveries that reveal the detailed mechanisms leading to the formation of the primary tumor, the biological underpinnings of the metastatic disease remain poorly understood. Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle, and grow at other parts of the body. Epithelial‐mesenchymal transition and anoikis resistance of tumor cells are the main forces to promote metastasis, and multiple components in the tumor microenvironment and their complicated crosstalk with cancer cells are closely involved in distant metastasis. In addition to the three cornerstones of tumor treatment, surgery, chemotherapy, and radiotherapy, novel treatment approaches including targeted therapy and immunotherapy have been established in patients with metastatic cancer. Although the cancer survival rate has been greatly improved over the years, it is still far from satisfactory. In this review, we provided an overview of the metastasis process, summarized the cellular and molecular mechanisms involved in the dissemination and distant metastasis of cancer cells, and reviewed the important advances in interventions for cancer metastasis., Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle and grow at other parts of the body. A variety of stromal cells, immune cells and other molecular components surrounding the tumor provide signals that enhance the metastatic potential of cancer cells. With the deepening understanding of mechanisms of tumorigenesis and metastasis in recent years, a plethora of treatment approaches have been established in patients with metastatic cancer.

GATA binding protein 3 (GATA3), a member of the zinc finger-binding transcription factor GATA gene family, plays an important role in regulating the development and differentiation of various tissues and organs. Previous studies have manifested that GATA3 is implicated in inhibiting the development of breast cancer, including suppressing the growth, metastasis, and invasion of cancer cells. However, the exact role of GATA3 in breast cancer remains to be fully elucidated. Interestingly, recent studies have further shown that GATA3 can regulate a variety of new target genes, including ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3), semaphorin 3B (SEMA3B), and microRNAs (miRNAs) to promote tumorigenesis, epithelial-mesenchymal transformation (EMT), and metastasis of breast cancer. Meanwhile, GATA3 mutations can affect the role of GATA3 in inhibiting the growth and metastasis of breast cancer cells, which indicates that GATA3 might be a promising target for breast cancer treatment. Undoubtedly, these new evidence further uncover the complexity of the GATA3/targets network in breast cancer development. In this article, we review related research progress and put forward some questions about the development of GATA3 in the future in order to be helpful for the understanding on the exact role of GATA3 in the progress of breast cancer and the development of related new clinical treatment strategies that will ultimately benefit the clinical outcome of breast cancer patients.

BACKGROUND Septic shock leads to multiple organ failure, and bacterial endotoxins and endogenous cytokines play essential roles in the pathogenesis. The oXiris® hemofilter can efficiently adsorb endotoxins and cytokines. CASE SUMMARY We admitted a critically ill 59 year-old male patient with gastrointestinal septic shock due to infection by a Gram-negative bacterium and septic acute kidney injury (AKI). Prior to intensive care unit admission, the patient reported intermittent diarrhea and decreased urine output. His blood pressure was 70/40 mmHg, necessitating fluid resuscitation and large doses of noradrenaline. Based on the results of a blood culture and the presence of hypotension, oliguria, and hypoxemia, we diagnosed septic shock, AKI, and multiple organ dysfunction. We administered continuous renal replacement therapy (CRRT) with an oXiris® hemofilter for 72 h with intermittent continuous veno-venous hemodiafiltration (CVVHDF), and changed the filter every 12 h. After his hemodynamic parameters were stable, we used a traditional filter (AN69 hemofilter) with intermittent CVVHDF. The 72 h CRRT with the oXiris® hemofilter led to stabilization of his vital signs, marked reductions in disease severity scores, and decreased levels of procalcitonin, endotoxin, and inflammatory factors. After 8 d of CRRT, his kidney function had completely recovered. CONCLUSION We conclude that the oXiris® hemofilter combined with appropriate antibacterial therapy was an effective treatment for this patient with gastrointestinal septic shock.

Chemokines play a significant role in cancer. CXC-motif chemokine ligands (CXCLs) are associated with the tumorigenesis and progression of head and neck squamous cell carcinoma (HNSC); however, their specific functions in the tumor microenvironment remain unclear. Here, we analyzed the molecular networks and transcriptional data of HNSC patients from the Oncomine, GEPIA, String, cBioPortal, Metascape, TISCH, and TIMER databases. To verify immune functions of CXCLs, their expression was analyzed in different immune cell types. To our knowledge, this is the first report on the correlation between CXCL9-12 and 14 expression and advanced tumor stage. CXCL2, 3, 8, 10, 13, and 16 were remarkably related to tumor immunity. Kaplan-Meier and TIMER survival analyses revealed that high expression of CXCL1, 2, 4, and 6-8 is correlated with low survival in HNSC patients, whereas high expression of CXCL9, 10, 13, 14, and 17 predicts high survival. Only CXCL13 and 14 were associated with overall survival in human papilloma virus (HPV)-negative patients. Single-cell datasets confirmed that CXCLs are associated with HNSC-related immune cells. Thus, CXCL1-6, 8-10, 12-14, and 17 could be prognostic targets for HNSC, and CXCL13 and 14 could be novel biomarkers of HPV-negative HNSC.

Prosthetic infection is one of the severe postoperative complications of arthroplasty. Mixed bacterial-fungal prosthetic infection is rare but can be disastrous. This case was a 76-year-old female suffered from prosthetic infection following total hip replacement due to femoral neck fracture and underwent multiple debridements. The culture of periprosthetic tissue was bacteriologically sterile following the first debridement, while the Staphylococcus hominis was identified in the second debridement in the previous hospitalization where fungal infection had not been considered. Thus the pathogen spectrum of anti-infection therapy failed to contain fungus. Ultimately, the culture result of our sampled periprosthetic tissue during the third debridement was Candida albicans without bacterium in our hospital. The fungal prosthetic infection was successfully treated by a two-stage revision with antifungal drugs. Accurate diagnosis and standardized treatment is the key to the therapy of infection after hip arthroplasty, especially for mixed bacterial-fungal prosthetic infection.

Objectives The aim of this study was to investigate the electrocardiographic characteristics of ventricular arrhythmias (VAs) originating near the His bundle (HB) and use the R/S ratio in lead III (RIII/SIII ratio) to predict successful ablation of para-Hisian VAs. Background Catheter ablation for idiopathic VAs near the HB is often challenging, and data are limited. Methods The present study included 134 consecutive patients undergoing catheter ablation of para-Hisian VAs. The electrocardiographic characteristics in these patients were retrospectively evaluated with successful ablation and failed ablation. Results Successful ablation was achieved in 115 (85.8%) of the 134 patients. There was no significant difference in QRS duration between the successful and the failed ablation groups. The ablation success rate was significantly lower for para-Hisian VAs with a predominantly positive R wave in lead III than those with a predominantly negative S wave in lead III. The significant factor associated with successful ablation was the RIII/SIII ratio. The RIII/SIII ratio ≤1.1 predicted the successful ablation of para-Hisian VAs with high sensitivity (80.9%) and specificity (94.7%). The RIII/SIII ratio of >1.2 had high sensitivity (100.0%) and specificity (82.8%) to predict the distance Conclusions The RIII/SIII ratio was a helpful predictor of the successful ablation of VAs originating in the vicinity of the HB. This may be useful for planning ablation of para-Hisian VAs and minimizing the risk of inadvertent atrioventricular block.

Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo. CD68 and CD163, the specific markers of M2 type macrophages, were upregulated in TAMs presented in intra-cancer tissues. M2 macrophages and M2 macrophage-derived exosomes (M2 exos) both can promote OSCC growth and tumorigenicity. An exosomal RNA-seq analysis was conducted to predict regulatory exosomal miRNAs related to OSCC growth, which determined miR-31-5p and LATS2 for subsequent experiments. Mechanistically, miR-31-5p was delivered to recipient OSCC cells through M2 exos and complementary pairing with the large tumor suppressor 2 (LATS2) coding sequence, thus suppressing the expression of LATS2 and inactivation the Hippo signaling pathway to support OSCC growth. Collectively, our findings demonstrate that M2 macrophage-derived exosomal miR- 31-5p can make tumor suppressor LATS2 gene inhibited and facilitate the progression of OSCC via inhibiting the Hippo signaling pathway, which possibly provides new targets for the molecular therapy of OSCC.

ObjectivesThe WHO Access, Watch and Reserve (AWaRe) classification has been developed to support countries and hospitals in promoting rational use of antibiotics while improving access to these essential medicines. We aimed to describe patterns of worldwide antibiotic use according to the AWaRe classification in the adult inpatient population.MethodsThe Global Point Prevalence Survey on Antimicrobial Consumption and Resistance (Global-PPS) collects hospital antibiotic use data using a standardized PPS methodology. Global-PPS 2015, 2017 and 2018 data, collected by 664 hospitals in 69 countries, were categorized into AWaRe groups to calculate proportional AWaRe use, Access-to-Watch ratios and the most common indications for treatment with selected Watch antibiotics. Only prescriptions for systemic antibiotics on adult inpatient wards were analysed.ResultsRegional Access use ranged from 28.4% in West and Central Asia to 57.7% in Oceania, whereas Watch use was lowest in Oceania (41.3%) and highest in West and Central Asia (66.1%). Reserve use ranged from 0.03% in sub-Saharan Africa to 4.7% in Latin America. There were large differences in AWaRe prescribing at country level. Watch antibiotics were prescribed for a range of very different indications worldwide, both for therapeutic and prophylactic use.ConclusionsWe observed considerable variations in AWaRe prescribing and high use of Watch antibiotics, particularly in lower- and upper-middle-income countries, followed by high-income countries. The WHO AWaRe classification has an instrumental role to play in local and national stewardship activities to assess prescribing patterns and to inform and evaluate stewardship activities.

To explore whether anxiety and depression are prognostic indexes for overall survival in patients with nasopharyngeal carcinoma (NPC) who underwent intensity-modulated radiotherapy (IMRT). Clinical data were collected for NPC patients who underwent IMRT. Anxiety and depression were investigated before radiotherapy by using the Hospital Anxiety and Depression Scale (HADS). The survival rate was calculated by the Kaplan-Meier method, and survival curves were compared among patients with different levels of anxiety and depression. The Cox risk regression model was used to screen the factors affecting survival. A total of 390 initially treated NPC patients were included in the study. Among them, 166 patients suffered from anxiety, and 95 patients suffered from depression before radiotherapy. The 5-year overall survival rates for patients with and without anxiety before radiotherapy were 71.6% and 81.8% (χ2 = 5.31, P = 0.021), respectively. The 5-year overall survival rates for patients with and without depression before radiotherapy were 74.3% and 78.1% (χ2 = 0.05, P = 0.82), respectively. Cox regression analysis indicated clinical stages (HR = 3.982, 95% CI: 2.365~6.705), anxiety (HR = 1.832, 95% CI: 1.140~2.944), and gender (HR = 0.555, 95% CI: 0.313~0.984) as independent prognostic factors. Anxiety before radiotherapy is associated with poor prognosis in NPC patients.

Menstrual-related migraine (MRM) results in moderate to severe intensity headaches accompanied by physical and emotional disability over time in women. Neuroimaging methodologies have advanced our understanding of migraine; however, the neural mechanisms of MRM are not clearly understood. In this study, fourteen MRM patients in the interictal phase and fifteen age- and education-matched healthy control females were recruited. Resting-state functional magnetic resonance imaging (fMRI) and pulsed arterial spin labeling (PASL) MRI were collected for both the subject groups outside of their menstrual periods. Eigenvector centrality mapping (ECM) was performed on resting-state fMRI, and the relative cerebral blood flow (relCBF) was assessed using PASL-MRI. MRM patients showed a significantly increased eigenvector centrality in the right medial frontal gyrus compared to healthy controls. Seed-based ECM analysis revealed that increased centrality was associated with the right medial frontal gyrus’s hyperconnectivity with the left insula and the right supplementary motor area. The perfusion MRI revealed significantly increased relCBF in the hyperconnected regions. Furthermore, the hyperconnection positively correlated with the attack frequency, while the hyperperfusion showed a positive correlation with the disease duration. The results suggest that menstrual-related migraine is associated with cerebral hyperconnection and hyperperfusion in critical pain-processing brain regions. Furthermore, this elevated cerebral activity is correlated with different aspects of functional impairment in MRM patients suggesting that perfusion analysis, along with whole-brain connectivity analysis, can provide a comprehensive understanding of neural mechanisms of MRM.

Duck blood is rich in protein. It is one of the main by-products in the slaughter industry. The objective of this research was to optimize and establish a method for producing duck plasma antioxidant peptides. The composition of duck plasma powder was analyzed. Protease selection experiment (Alcalase, Protamex, and Flavourzyme) and single-factor experiment were performed, and response surface methodology was used to determine the optimal hydrolysis conditions for duck plasma. Among the proteases, Alcalase hydrolysate exhibited the strongest 1,1-diphenyl-2-picrylhydrazyl scavenging rate. The optimum enzymatic hydrolysis conditions were hydrolysis time of 6 h, temperature of 65.5°C, pH 10.0, and enzyme-to-substrate ratio of 0.3%. The 1,1-diphenyl-2-picrylhydrazyl scavenging rate reached 64.84%, and the ratio of essential amino acids was 38.76%. Briefly, the duck plasma hydrolysate exhibited strong antioxidant properties and reasonable composition of amino acids. Thus, it may be used as a nutritional or functional ingredient in foods or medicines. This research provides a theoretical basis for comprehensive processing and high value utilization of duck plasma.

To understand and improve the stability of the insecticidal activity of tobacco extract, the 3rd instar larvae of Malacosoma neustria testacea was determined by the leaf film method. Spectrophotometry identified extract effects on activities of several enzymes. In addition, to improve the stability of the extract, microcapsules were prepared by complex coacervation and phase separation with the extract as core material, and gelatin and gum arabic as wall material. With the embedding rate as the evaluation index, the response surface method was used to optimize the preparation process of the microcapsules. The results show that the extract had a strong insecticidal activity on the larvae, with inhibitory effects on several enzymes examined of carboxylesterase, acetylcholinesterase, glutathione-S transferase, catalase, and superoxide dismutase. The inhibition rate increased with time. The best preparation process of tobacco extract microcapsules was 25% mass fraction of emulsifier, 2.05% mass fraction of gelatin, 3% mass fraction of gum arabic, 1.34 wall core ratio, 36 min of complex coacervation time. The embedding rate was 58.4% which is approximately the theoretical embedding rate (58.9%). The microcapsules prepared by this method have a smooth surface, good combining form and particle size distribution, and a median diameter of 8.6 μm. Infrared characteristic peaks of the extracts were preserved at 877.55 cm‒1 and 2922.13 cm‒1. Microencapsulation can improve the thermal stability of the tobacco extract. Indoor toxicity tests showed that LC50 of extract microcapsules was 20.2 mg·mL‒1, equivalent to the toxicity level of the tobacco extract itself, indicating that microencapsulation did not reduce extract insecticidal effects. This research may provide a reference for the optimization of the tobacco extract microcapsule preparation process.

O-Acetylation of polysaccharides predominantly modifies plant cell walls by changing the physicochemical properties and, consequently, the structure and function of the cell wall. Expression regulation and specific function of cell wall-acetylating enzymes remain to be fully understood. In this report, we cloned a previously identified stunted growth mutant named sucrose uncoupled1 (sun1) in Arabidopsis (Arabidopsis thaliana). SUN1 encodes a member of the TRICHOME BIREFRINGEN-LIKE family, AtTBL37. AtTBL37 is highly expressed in fast-growing plant tissues and encodes a Golgi apparatus-localized protein that regulates secondary cell wall thickening and acetylation. In sun1, jasmonate signaling and expression of downstream chemical defense genes, including VEGETATIVE STORAGE PROTEIN1 and BRANCHED-CHAIN AMINOTRANSFERASE4, are increased but, unexpectedly, sun1 is more susceptible to insect feeding. The central transcription factor in jasmonate signaling, MYC2, binds to and induces AtTBL37 expression. MYC2 also promotes the expression of many other TBLs. Moreover, MYC activity enhances cell wall acetylation. Overexpression of AtTBL37 in the myc2-2 background reduces herbivore feeding. Our study highlights the role of O-acetylation in controlling plant cell wall properties, plant development, and herbivore defense.

Intimal injury is an early stage of several cardiovascular diseases. Endothelial progenitor cells (EPCs) play a significant role in endothelial repair following vascular injury. Once the intima is damaged, EPCs are mobilized from the bone marrow to the injury site. Meanwhile, the injury to the intimal surface triggers platelet degranulation, aggregation, and adhesion to the damaged endothelium, and exposed collagen stimulates platelet to secrete platelet-derived microvesicles (PMVs). However, the role of PMVs in EPC function during this process remains unknown. In an in vivo study, EPCs and platelets were found to adhere to the injury site in Sprague-Dawley (SD) rat vascular injury model. In vitro, collagen stimulation induced the release of PMVs, and collagen-activated PMVs (ac.PMVs) significantly promoted EPC proliferation. Transforming growth factor-β1 (TGF-β1) content was increased in ac.PMVs. Activated PMVs significantly upregulated Smad3 phosphorylation in EPCs and increased Smad3 nuclear translocation from the cytoplasm. TGF-β1 knockdown ac.PMVs downregulated EPC proliferation. Recombinant TGF-β1 enhanced EPC proliferation. The TGF-β1 inhibitor SB431542 significantly repressed the intracellular signal triggered by ac.PMVs. Furthermore, the Smad3-specific phosphorylation inhibitor SIS3 effectively reversed the cell proliferation induced by ac.PMVs. Smad3 translocated to the nucleus and enhanced EPC proliferation via its downstream genes tenascin C (TNC), CDKN1A, and CDKN2A. r-TGF-β1 promoted reendothelialization and EPC proliferation in vivo. Our data demonstrate that activated PMVs deliver TGF-β1 from collagen-activated platelets to EPCs, which in turn activates Smad3 phosphorylation and regulates TNC, CDKN1A, and CDKN2A expression to promote EPC proliferation, suggesting that PMVs act as a key transporter and a potential therapeutic target for vascular injury.

Background Serum lipid abnormalities are generally considered as a major risk factor for type 2 diabetes mellitus (T2DM). However, evidence for the effect of long-term serum lipid fluctuations on future T2DM probability remains limited. Methods A total of 4475 nondiabetic participants who underwent annual health examinations between 2010 and 2013 were followed for the subsequent 5-year risk of T2DM. The Cox proportional hazards model was performed to evaluate the associations of visit-to-visit variabilities and trajectories of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) with T2DM probability. Results During the five-year follow-up, 223 newly developed T2DM cases were identified. Compared with the “Low” TG trajectory, “Moderate” and “Moderate-High” TG trajectories were significantly associated with T2DM incidence, with adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of 1.51 (1.12-2.03) and 2.55 (1.62-4.03), respectively. Additionally, participants in the third and fourth quartiles of TG/standard deviation (SD) were associated with increased T2DM probability when compared with those in the lowest quartile. After excluding individuals with prediabetes, participants with “Moderate-High” TG trajectory still had a 2.43-fold greater risk of T2DM compared with those with “Low” TG trajectory (95 % CI: 1.28-4.63). In addition, compared with participants in “Low” HDL-c trajectory, the future T2DM probability was significantly reduced in those with “Moderate” and “High” HDL-c trajectories, with HR (95 % CI) of 0.52 (0.37-0.72) and 0.38 (0.18-0.80), respectively. After excluding individuals with prediabetes, the “Moderate” HDL-c trajectory remained associated with decreased T2DM probability when compared with “Low” HDL-c trajectory (HR: 0.55, 95 % CI: 0.35-0.88). However, the incidence of T2DM was not associated with the long-term fluctuations of TC and LDL-c. Conclusions Long-term visit-to-visit variability of TG, and the change trajectories of TG and HDL-c were significantly associated with future T2DM probability. Moreover, these associations were not affected after excluding individuals with prediabetes.

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609–0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780–0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.

Detection of lumen and media-adventitia (MA) borders in intravascular ultrasound (IVUS) image has long been investigated by medical imaging researchers. Recent progress in convolutional neural network (CNN) shows marked improvement of image segmentation performance comparing with traditional methods, and has been successfully applied to IVUS. Deep learning based image segmentation requires significant amount of annotated data. However, image annotation for semantic segmentation is tedious and time-consuming. In this study, we proposed a coarse-to-fine strategy to facilitate image annotation and employed BASNet architecture for IVUS lumen and MA border detection. Results on 34 patient data show high annotation efficiency with mean intersection over union (IoU) of 0.927.

Objective To investigate the changes in serum growth hormone (GH), testosterone, and insulin-like growth factor 1 (IGF-1) during low-intensity resistance exercise under different cuff pressures. Methods We performed a single-blind, cross-over design study. Twenty-five healthy young men performed three exercise protocols as follows: 1) no blood flow restriction exercise (control group), 2) resistance exercise at 40% of arterial occlusion pressure (AOP) (low group), and 3) resistance exercise at 70% of AOP (high group). Blood lactate, GH, testosterone, and IGF-1 levels were measured at four time points. Results There were no differences in the indices before exercise. The blood flow restriction exercise under different pressures had different effects on each index and there was an interactive effect. GH levels were significantly higher in the high group than in the other groups after exercise. Immediately after exercise, IGF-1 and testosterone levels were significantly higher in the high group than in the other groups. At 15 minutes after exercise, testosterone levels were significantly higher in the high group than in the other groups. Conclusions Low-intensity resistance exercise combined with blood flow restriction effectively increases GH, IGF-1, and testosterone levels in young men. Increasing the cuff pressure results in greater levels of hormone secretion.

Phenotypic switch of vascular smooth muscle cells (VSMCs) is important in vascular remodeling which causes hyperplasia and restenosis after intimal injury. Platelets are activated at injured intima and secrete platelet-derived microvesicles (PMVs). Herein, we demonstrated the role of PMVs in VSMC phenotypic switch and the potential underlying mechanisms. In vivo, platelets were locally adhered and activated at intimal injury site, while Lamtor1 was promoted and VSMCs were dedifferentiated. PMVs, collected from collagen-activated platelets in vitro which mimicked collagen exposure during intimal injury, promoted VSMC dedifferentiation, induced Lamtor1 expression, and activated mTORC1 signaling, reflected by the phosphorylation of two downstream targets, i.e., S6K and 4E-BP1. Knockdown of Lamtor1 with small interfering RNA attenuated these processes induced by PMVs. Based on the previously published proteomic data, Ingenuity Pathway Analysis revealed that Src may participate in regulating effects of PMVs. Src inhibitor significantly reversed the effects of PMVs on VSMC dedifferentiation, Lamtor1 expression and mTORC1 activation. Furthermore, in SMC-specific Lamtor1 knockout mice, intimal hyperplasia was markedly attenuated after intimal injury compared with the wild type. Our data suggested that PMVs secreted by activated platelets promoted VSMC dedifferentiation via Src/Lamtor1/mTORC1 signaling pathway. Lamtor1 may be a potential therapeutic target for intimal hyperplasia after injury.

Background: Limited details are available regarding the vertical transmission potential of COVID-19 infection in pregnant women. The authors' current study aimed to report the vertical transmission potential of COVID-19 infection in a woman pregnant with twins. Case description: The authors report the case of a 27-year-old woman infected with SARS-CoV-2. The patient was pregnant with dichorionic diamniotic fraternal twins and admitted to Renmin Hospital of Wuhan University, Wuhan, China. After undergoing a cesarean section, the patient gave birth to premature twins, who tested positive for COVID-19 infection. Interpretation: Findings from this case suggest a possibility of intrauterine infection caused by vertical transmission in a woman infected with COVID-19.

Residues, potential sources and ecotoxicological effects of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were analyzed in typical urban river networks of Shanghai. In total, 47 surface sediments were collected in each of the sampling seasons (summer and winter). Laboratory analysis by GC-ECD showed that OCPs and PCBs concentrations were in medium levels compared to other national and international areas. As for OCP compounds, HCHs and DDTs were two dominant pollutants, with ∑HCHs concentrations ranging from 1.74 to 28.78 ng/g and ∑DDTs concentrations ranging from 0.88 to 25.45 ng/g. For individual HCHs, β-HCH was the most dominant HCH compound, with a mean value of 5.06 ng/g, followed by α-HCH (3.50 ng/g) in winter. A similar case of HCHs was also found in the summer season. Concentrations of ∑18PCBs varied from 6.67 to 37.10 ng/g in winter and from 10.63 to 45.55 ng/g in summer. Individual PCB 28, 101, 118 and 123 were dominant among all congeners, with averages of 3.16, 1.55, 2.47 and 2.37 ng/g in winter, 3.11, 2.34, 4.92 and 4.41 ng/g in summer, respectively. ∑20OCPs (the sum of twenty OCPs) concentrations in cultivated land areas were more abundant than that in artificial surface areas, indicating an abundance of pesticides and fertilizers in cultivated lands. Analysis of possible sources indicated that both industrial and agricultural residues contributed to higher HCHs and DDTs concentrations, which mainly originated from weathered pesticides with aerobic transformation processes. For PCB compounds, a significant seasonal variation, atmospheric precipitation, and surface runoff were the major factors for fluctuated PCBs concentrations. Ecotoxicological assessment based on established sediment quality guidelines (SQGs) showed that DDT compounds have a potential threat to the aquatic environment of our study area.

Background: Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC. Methods: RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development. Results: RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC. Conclusion: RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis. Key words: Hepatocellular carcinoma; Transcription factor; Apoptosis; P53

Background Varicella-zoster virus (VZV) infection in children is an important public health problem in China. We performed the current study to explore the seroprevalence of VZV infection in Chinese children in order to provide more information for improvement of varicella vaccination in China. Methods 3014 serum samples were collected from Chinese kindergarten students aged from four to six years. Anti-VZV IgG and IgM were assayed using enzyme-linked immunosorbent assay. Both ORF22 and ORF62 of VZV were amplified, sequenced, and analyzed by nested PCR. Results Totally, 43.9% of boys and 46.3% of girls were vaccinated with varicella vaccine, respectively. The seroprevalence of anti-VZV IgG was 54.4% in the children with varicella vaccination, which was significantly higher than those in unvaccinated children (49.2%) (χ2=8.206, P=0.004). Among of the vaccinated children, the detection rates of VZV IgG antibody increased with age, with 49.4%, 50.9% and 58.9% in 4, 5 and 6-year groups, respectively (Trend χ2=17.202, P=0.002). However, there was no difference in anti-VZV IgG detection rates among those unvaccinated children in different age groups (Trend χ2=8.681, P=0.070). In addition, thirteen boys and 13 girls were positive for anti-VZV IgM, respectively. Among of them, eight children (0.6%) have received varicella vaccination, which was similar to those in unvaccinated children (1.1%). However, only one ORF22 sequence was isolated from an unvaccinated 5-year boy. Compared to the reference VZV sequences, the nucleotide homology was estimated to be 99.7% with genotype J. Conclusions Our study indicated that about half of Chinese children aged four to six years have a high risk of VZV infection. It should be helpful for the evaluation on the necessity of varicella immunization in China.

Viruses constitute a major constraint to soybean production worldwide and are responsible for significant yield losses every year. Although varying degrees of resistance to specific viral strains has been identified in some soybean genetic sources, the high rate of mutation in viral genomes and mixed infections of different viruses or strains under field conditions usually hinder the effective control of viral diseases. In the present study, we generated transgenic soybean lines constitutively expressing the double-strand RNA specific ribonuclease gene PAC1 from Schizosaccharomyces pombe to evaluate their resistance responses to multiple soybean-infecting virus strains and isolates. Resistance evaluation over three consecutive years showed that the transgenic lines displayed significantly lower levels of disease severity in field conditions when challenged with soybean mosaic virus (SMV) SC3, a prevalent SMV strain in soybean-growing regions of China, compared to the non-transformed (NT) plants. After inoculation with four additional SMV strains (SC7, SC15, SC18, and SMV-R), and three isolates of bean common mosaic virus (BCMV), watermelon mosaic virus (WMV), and bean pod mottle virus (BPMV), the transgenic plants exhibited less severe symptoms and enhanced resistance to virus infections relative to NT plants. Consistent with these results, the accumulation of each virus isolate was significantly inhibited in transgenic plants as confirmed by quantitative real-time PCR and double antibody sandwich enzyme-linked immunosorbent assays. Collectively, our results showed that overexpression of PAC1 can increase multiple virus resistance in transgenic soybean, and thus provide an efficient control strategy against RNA viruses such as SMV, BCMV, WMV, and BPMV.

IntroductionThere are more than 900,000 new cases of head and neck tumors in the world every year, which is the sixth most common tumor in the world. During the treatment of head and neck cancer, patients often face various symptoms and psychological problems. In this qualitative study, patients with head and neck cancer were invited to share their psychological journey during diagnosis, treatment, and recovery to (1) understand their psychological status and feelings during different treatment stages, (2) their needs and concerns during different treatment stages, and (3) difficulties and problems in self-management.Methods and analysisWe adopt qualitative study to understand these patient’ psychological journey with head and neck cancer, especially when they are at different times in the diagnosis, treatment and completion of head and neck tumors. Thematic analysis will be carried out following the six-phase iterative process suggested by Braun and Clarke: (1) familiarising oneself with data, (2) generating initial codes, (3) searching for themes, (4) reviewing themes,(5) defining and naming themes and (6) providing the report, which will be used to analyse the qualitative data.Ethics and disseminationThis study has ethical approval from the Sichuan Cancer Hospital Ethics Committee. We will disseminate the findings through national and international conferences and international peer-reviewed journals.Strengths and limitationsIn this study, qualitative research was used to better understand the psychological process and feelings of patients with head and neck tumor at different stages of treatment.The subjects were interviewed in the same tumor hospital. Patients in different grade hospitals in different regions may have different psychological processes and experiences.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, yet the molecular mechanisms underlying its onset and development have not yet been fully elucidated. Indeed, an in-depth understanding of the potential molecular mechanisms underlying HNSCC oncogenesis may aid the development of better treatment strategies. Recent epigenetic studies have revealed that the m6A RNA modification plays important roles in HNSCC. In this review, we summarize the role of m6A modification in various types of HNSCC, including thyroid, nasopharyngeal, hypopharyngeal squamous cell, and oral carcinoma. In addition, we discuss the regulatory roles of m6A in immune cells within the tumor microenvironment, as well as the potential molecular mechanisms. Finally, we review the development of potential targets for treating cancer based on the regulatory functions of m6A, with an aim to improving targeted therapies for HNSCC. Together, this review highlights the important roles that m6A modification plays in RNA synthesis, transport, and translation, and demonstrates that the regulation of m6A-related proteins can indirectly affect mRNA and ncRNA function, thus providing a novel strategy for reengineering intrinsic cell activity and developing simpler interventions to treat HNSCC.

Haze pollution is a major environmental problem in the development of new urbanization in China. Haze is the product of the interaction between human activities and a specific climate. Haze can not only induce cardiovascular, respiratory, and other diseases, seriously damage human health, but also cause extremely low visibility on the road, leading to serious traffic accidents, casualties, and economic losses. This paper analyzes the causes and losses of haze pollution in the process of new urbanization development in Shenyang through big data, and puts forward effective measures to solve the problem of economic losses in haze control in Shenyang, and speed up the process of new urbanization development in Shenyang.

The arterial mechanical microenvironment, including stiffness, is a crucial pathophysiological feature of vascular remodeling, such as neointimal hyperplasia after carotid endarterectomy and balloon dilatation surgeries. In this study, we examined changes in neointimal stiffness in a Sprague-Dawley rat carotid artery intimal injury model and revealed that extracellular matrix (ECM) secretion and vascular stiffness were increased. Once the endothelial layer is damaged in vivo, activated platelets adhere to the intima and may secrete platelet-derived extracellular vesicles (pEVs) and communicate with vascular smooth muscle cells (VSMCs). In vitro, pEVs stimulated VSMCs to promote collagen secretion and cell adhesion. MRNA sequencing analysis of a carotid artery intimal injury model showed that ECM factors, including col8a1, col8a2, col12a1, and elastin, were upregulated. Subsequently, ingenuity pathway analysis (IPA) was used to examine the possible signaling pathways involved in the formation of ECM, of which the Akt pathway played a central role. In vitro, pEVs activated Akt signaling through the PIP3 pathway and induced the production of Col8a1. MicroRNA (miR) sequencing of pEVs released from activated platelets revealed that 14 of the top 30 miRs in pEVs targeted PTEN, which could promote the activation of the Akt pathway. Further research showed that the most abundant miR targeting PTEN was miR-92a-3p, which promoted Col8a1 expression. Interestingly, knockdown of Col8a1 expression in vivo abrogated the increase in carotid artery stiffness and simultaneously increased the degree of neointimal hyperplasia. Our results revealed that pEVs may deliver miR-92a-3p to VSMCs to induce the production and secretion of Col8a1 via the PTEN/PIP3/Akt pathway, subsequently increasing vascular stiffness. Therefore, pEVs and key molecules may be potential therapeutic targets for treating neointimal hyperplasia.

Background Although previous studies have reported the gut microbiome is closely related to hypertension development, whether the change in blood microbiome is associated with the risk of hypertension remains unclear. Methods One hundred and fifty incident hypertension cases and 150 age (± 2 years) and gender (1:1) matched nonhypertension controls included in this nested case–control study were recruited from a prospective cohort study of “135.” The composition of the blood microbiome was characterized using bacterial 16S ribosomal RNA gene sequencing. The relative abundance of detected bacteria was converted to a negative logarithm of 10 for the statistical analysis. Results Totally, 10,689,961 high-quality sequences were acquired. The Chao1 index of the blood microbiome in nonhypertension controls was significantly higher than in hypertensive group (2,302.08 ± 752.78 vs. 1,598.21 ± 500.88, P < 0.001). Compared with the nonhypertension controls, the relative abundance of Proteobacteria phylum was significantly increased (P < 0.001), whereas the relative abundance of phyla Firmicutes and Bacteroidetes were significantly reduced in the hypertensive cases (P < 0.001 and P = 0.039, respectively). At genus level, the risk of hypertension was directly associated with the relative abundance of Acinetobacter (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.01–2.03), Sphingomonas (OR: 1.84, 95% CI: 1.32–2.56), and Staphylococcus (OR: 0.51, 95% CI: 0.36–0.73), respectively. In addition, the relative abundance of Pseudomonas was minor positively correlated with the total cholesterol level. However, the relative Staphylococcus level was minor positively correlated with high-density lipoprotein cholesterol level. Conclusions The composition of the blood microbiome is significantly associated with the development of hypertension.