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Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. Method An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. Results It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. Conclusion It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.

ABSTRACT: Objectives: Cystic fibrosis (CF) is a hereditary recessive disease that affects the mucous clearance of the lungs and allows bacteria such as Staphylococcus aureus to settle in the lung and cause infection. This study examined the prevalence of antibiotic resistance of S. aureus in cystic fibrosis infection using a systematic review and meta-analysis. Methods: A comprehensive and systematic search of related articles was conducted through the PubMed, Scopus, and Web of Science databases until March 2022. The weighted pooled resistance rate of antibiotics was analysed with Freeman-Tukey double arcsine transformation in the Stata software version 17.1 using the Metaprop command. Results: In this meta-analysis, 25 studies were used based on criteria to evaluate the pattern of S. aureus resistance in CF. Vancomycin and teicoplanin were the most effective options for treatment of CF patients; the highest level of antibiotic resistance observed was to erythromycin and clindamycin. Conclusion: High levels of resistance to most of the antibiotics studied was observed. The high levels of antibiotic resistance observed are worrisome and indicate the need to monitor antibiotic use.

Objective To investigate the effectiveness of SMI in evaluating hepatic IRI and detecting its therapy response. Methods Thirty rats were randomly divided into sham (n = 12), IRI (n = 12), and andrographolide pretreatment (n = 6) groups. SMI, pathological, and biochemical examinations were conducted for the sham and IRI groups at 4 (n = 6) and 24 h (n = 6) after reperfusion, respectively. Two ultrasonologists measured the vascular index (VI). The interobserver agreement was evaluated using the intraclass correlation coefficient (ICC). The rat liver parameters, including Suzuki's score, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were obtained at different time steps in each group. For the andrographolide pretreatment group, data were obtained at 24 h after reperfusion to further verify the advantage of VI. Parameters were analyzed for correlations and compared between each group at 4 and 24 h. Results The ICC between two ultrasonologists who measured the VI was 0.912 (95%CI: 0.889-0.940). Suzuki's score and VI were negatively correlated (r = -0.504, P = 0.012). Compared with the sham group, the IRI group showed a significant decrease in the VI at 4 and 24 h after reperfusion [(24.78 ± 3.23) versus (20.22 ± 2.55); (22.67 ± 1.36) versus (19.27 ± 2.23), P < 0.05)]. The VI in the andrographolide pretreatment group was higher than that in the IRI group [(21.90 ± 1.47) versus (19.27 ± 2.23), P

BackgroundThe prevalence of pulmonary tuberculosis (PTB) as an infectious disease continues to contribute significantly to global mortality. According to recent studies, the gut microbiota of PTB patients and healthy controls (HCs) show significant disparities. However, the causal relationship between them has yet to be elucidated.MethodsWe conducted a study using Mendelian Randomization (MR) to explore the potential causal link between gut microbiota and pulmonary tuberculosis (PTB). The summary statistics of the gut microbiota were acquired from the MiBioGen consortium, while data on PTB were sourced from pheweb.jp. A range of statistical methodologies were employed to evaluate causality, encompassing inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted model, and simple model. We utilized instrumental variables (IVs) that have a direct causal relationship with PTB to annotate SNPs, aiming to discover the genes harboring these genetic variants and uncover potential associations between host genes and the microbiome in patients with PTB.ResultsAmong the 196 bacterial traits in the gut microbiome, we have identified a total of three microbiomes that exhibit a significant association with PTB. The occurrence of Dorea (P = 0.0458, FDR-adjusted P = 0.0458) and Parasutterella (P = 0.0056, FDR-adjusted P = 0.0168) was linked to an elevated risk of PTB, while the presence of Lachnoclostridium (P = 0.0347, FDR-adjusted P = 0.0520) demonstrated a protective effect against PTB. Our reverse Two-Sample Mendelian Randomization (TSMR) analysis did not yield any evidence supporting the hypothesis of reverse causality from PTB to alterations in the intestinal flora.ConclusionWe have established a connection between the gut microbiota and PTB through gene prediction analysis, supporting the use of gut microecological therapy in managing PTB and paving the way for further understanding of how gut microbiota contributes to PTB’s development.

ObjectiveTo investigate the clinical manifestations, imaging and pathological features, treatment methods and prognosis of primary leiomyosarcoma of kidney, and the choice of treatment with tumor thrombus.MethodsThe clinical data of a patient with primary renal leiomyosarcoma complicated with inferior vena cava and right atrial tumor thrombus were retrospectively analyzed. Radical resection of right kidney without cardiopulmonary bypass and removal of inferior vena cava and right atrial tumor thrombus were performed. Adjuvant intravenous chemotherapy was given according to the results, and follow-up observation was made.ResultsPostoperative pathological findings were: leiomyosarcoma (right renal tumor), the size of the mass was about 12.1 cm, and no cancer was found at the incision end of the right ureter.ConclusionPrimary leiomyosarcoma of kidney is rare in clinical practice, and complication of right atrial tumor embolus is even rarer. The disease has high malignant degree and poor prognosis. The clinical manifestations and imaging examinations were non-specific, and pathological diagnosis was the gold standard. Radical surgical resection is the main treatment method at present, and it provides experience for the treatment of grade IV tumor thrombus without cardiopulmonary bypass.

Abstract Background The cancer-immunity cycle (CI cycle) provides a theoretical framework to illustrate the process of the anticancer immune response. Recently, the update of the CI cycle theory emphasizes the importance of tumor’s immunological phenotype. However, there is lack of immunological phenotype of pan-cancer based on CI cycle theory. Methods Here, we applied a visualizing method termed ‘cancer immunogram’ to visualize the state of CI cycle of 8460 solid tumors from TCGA cohort. Unsupervised clustering of the cancer immunogram was performed using the nonnegative matrix factorization (NMF) analysis. We applied an evolutionary genomics approach (dN/dS ratio) to evaluate the clonal selection patterns of tumors with distinct immunogram subtypes. Results We defined four major CI cycle patterns across 32 cancer types using a cancer immunogram approach. Immunogram-I was characterized by ‘hot’ and ‘exhausted’ features, indicating a favorable prognosis. Strikingly, immunogram-II, immunogram-III, and immunogram-IV represented distinct immunosuppressive patterns of ‘cold’ tumor. Immunogram-II was characterized by ‘cold’ and ‘radical’ features, which represented increased expression of immune inhibitor molecules and high levels of positive selection, indicating the worst prognosis. Immunogram-III was characterized by ‘cold’ and ‘recognizable’ features and upregulated expression of MHC I molecules. Immunogram-IV was characterized by ‘cold’ and ‘inert’ features, which represented overall immunosuppression, lower levels of immunoediting and positive selection, and accumulation of more tumor neoantigens. In particular, favorable overall survival was observed in metastatic urothelial cancer patients with immunogram-I and immunogram-IV after immune checkpoint inhibitor (ICI) therapy. Meanwhile, a higher response rate to ICI therapy was observed in metastatic gastric cancer patients with immunogram-I phenotype. Conclusions Our findings provide new insight into the interaction between immunity and cancer evolution, which may contribute to optimizing immunotherapy strategies.

Abstract The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.

With the high flexibility and low cost of the deployment of UAVs, the application of UAV-assisted data collection has become widespread in the Internet of Things (IoT) systems. Meanwhile, the age of information (AoI) has been adopted as a key metric to evaluate the quality of the collected data. Most of the literature generally focuses on minimizing the age of all information. However, minimizing the overall AoI may lead to high costs and massive energy consumption. In addition, not all types of data need to be updated highly frequently. In this paper, we consider both the diversity of different tasks in terms of the data update period and the AoI of the collected sensing information. An efficient data collection method is proposed to maximize the system utility while ensuring the freshness of the collected information relative to their respective update periods. This problem is NP-hard. With the decomposition, we optimize the upload strategy of sensor nodes at each time slot, as well as the hovering positions and flight speeds of UAVs. Simulation results show that our method ensures the relative freshness of all information and reduces the time-averaged AoI by 96.5%, 44%, 90.4%, and 26% when the number of UAVs is 1 compared to the corresponding EMA, AOA, DROA, and DRL-eFresh, respectively.

β-glucan from Candida albicans promotes high-fat diet induced insulin resistance and related metabolic disorders in mice and C. albicans is enriched in type 2 diabetes (T2D) patients, supporting a role of gut mycobiota in the progress of T2D.

The ascomycete Cordyceps genus has been used as valued traditional Chinese medicine and functional food. Solid-state fermentation (SSF) of soybean, chickpea, black bean, and mung bean with Cordyceps militaris was performed for 35 days at 22°C, and then the biomass, total phenolic content (TPC), and total flavonoid content (TFC) increased significantly with the extension of fermentation time. The cordycepin content in four SSF-beans was as high as 8.33, 11.12, 10.43, and 6.64 mg/g, respectively. Moreover, the fermentation improved the 1,1′-diphenyl-2- picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTs) radical scavenging capacity, ferric reducing antioxidant power (FRAP) and ACE inhibition ability. Overall, the findings of the study stated clearly that SSF of beans with C. militaris was a potentially promising way to enhance the nutritional, physico-chemical, and biological properties of the substrate. Cordyceps-fermented products may serve as a novel valuable nutritional and functional food in health industry.

Abstract Background Germline mutations represent a high risk of hereditary cancers in population. The landscape and characteristics of germline mutations in genitourinary cancer are largely unknown, and their correlation with patient prognosis has not been defined. Methods Variant data and relevant clinical data of 10,389 cancer patients in The Cancer Genome Atlas (TCGA) database was downloaded. The subset of data of 206 genitourinary cancer patients containing bladder urothelial carcinoma (BLCA), kidney chromophobe carcinoma (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP) and prostate adenocarcinoma (PRAD) cancer with germline mutation information was filtered for further analysis. Variants were classified into pathogenic, likely pathogenic and non-pathogenic categories based on American College of Medical Genetics and Genomics (ACMG) guidelines. Genome Aggregation Database (gnomAD) database was used to assist risk analysis. Results There were 48, 7, 44, 45 and 62 patients with germline mutations identified in BLCA, KICH, KIRC, KIRP and PRAD, respectively. Pathogenic germline mutations from 26 genes and likely pathogenic mutations from 33 genes were revealed. GJB2, MET, MUTYH and VHL mutations ranked top in kidney cancers, and ATM and CHEK2 mutations ranked top for bladder cancer, while ATM and BRCA1 mutations ranked top for prostate cancer. Frameshift, stop gained and missense mutations were the predominant mutation types. BLCA exhibited the highest ratio of stop gained mutations (22/48 = 45.8%). No difference in patient age was found among pathogenic, likely pathogenic and non-pathogenic groups for all cancer types. The number of male patients far overweight female patients whether PRAD was included (P = 0) or excluded (P

The accumulation of myeloid derived suppressor cells (MDSC) has been associated with prostate cancer progression and castration resistance. Here the authors show that loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, results in polymorphonuclear-MDSC infiltration and cooperates with Pten loss to accelerate prostate tumorigenesis.

Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.

Objective: Variants of the polycystic kidney and hepatic disease 1 (PKHD1) gene are associated with autosomal recessive polycystic kidney disease (ARPKD). This study aimed to identify the genetic causes in a Chinese pedigree with ARPKD and design a minigene construct of the PKHD1 gene to investigate the impact of its variants on splicing.Methods: Umbilical cord samples from the proband and peripheral blood samples from his parents were collected, and genomic DNA was extracted for whole-exome sequencing (WES). Bioinformatic analysis was used to identify potential genetic causes, and Sanger sequencing confirmed the existence of variants within the pedigree. A minigene assay was performed to validate the effects of an intronic variant on mRNA splicing.Results: Two variants, c.9455del (p.N3152Tfs*10) and c.2408-13C>G, were identified in the PKHD1 gene (NM_138694.4) by WES; the latter has not been previously reported. In silico analysis predicted that this intronic variant is potentially pathogenic. Bioinformatic splice prediction tools revealed that the variant is likely to strongly impact splice site function. An in vitro minigene assay revealed that c.2408-13C>G can cause aberrant splicing, resulting in the retention of 12 bp of intron 23.Conclusion: A novel pathogenic variant of PKHD1, c.2408-13C>G, was found in a fetus with ARPKD, which enriches the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and the diagnosis of ARPKD. Minigenes are optimal to determine whether intron variants can cause aberrant splicing.

Given their relevance in various physiological and pathophysiological mechanisms, gaseous signaling molecules (GSMs), such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), are promising therapeutics for derailing various diseases at precisely controlled concentrations. However, the delivery and release of GSMs have been challenged by the heterogeneity of biological systems. Carefully constructed hybrid materials have exhibited enhanced functional ability owing to the adjusted individual characteristics. In this minireview, we surveyed the mechanisms of gas therapy, recent exceptional studies on the controlled release of GSMs from hybrid nanoplatforms, and their applications in the treatment of various diseases. Single gas therapies and their combined modalities with conventional treatments such as chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy have been summarized, with critical analysis of the contribution of the metallic elements in the various nanoplatforms. Moreover, the challenges and prospects of hybrid GSM releasers as promising healings have been discussed.

Abstract Purpose The angiogenesis is among the primary factors that affect tumor recurrence and distant organ metastasis in colorectal cancer (CRC). N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic mRNA, especially at the post-transcriptional level. Methyltransferase-like 3 (METTL3) promoting angiogenesis in a variety of tumors has been reported. However, the mechanism of how METTL3 dual-regulates the stability of long non-coding RNAs (lncRNAs) and vascular-related factor RNAs to affect angiogenesis in CRC is unclear. Methods 64 paired CRC and adjacent normal tissues were collected. In vitro, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), actinomycin assay, methylated RNA immunoprecipitation (MeRIP) experiment,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assay were performed. The functions were also studied in zebrafish model animals in vivo. Results We found that the vascular endothelial growth factor A(VEGFA), METTL3 and LINC00662 RNAs were highly expressed in CRC, and that METTL3 was significantly positively correlated with LINC00662 and VEGFA. The protein expression levels of CD31, CD34, VEGFA, m6A and METTL3 were all significantly increased in the CRC tissues. The angiogenesis experiments both in vivo and in vitro found that METTL3 and LINC00662 promoted angiogenesis in CRC. The actinomycin assay indicated that METTL3 maintained the stability of LINC00662 and VEGFA RNAs. In addition, the MeRIP experiment confirmed that the LINC00662 and VEGFA RNAs had METTL3-enriched sites. Conclusion These findings suggest that METTL3 and LINC00662 may both serve as diagnostic and prognostic predictive biomarkers for CRC and potential targets for anti-vascular therapy.

Introduction:Cordyceps militaris, which has many potential medicinal properties, has rarely been reported to alleviate type 2 diabetes mellitus (T2DM).Methods: The effects of C. militaris extracts (CE) and cordycepin (CCS) on high-fat diet and streptozotocin (STZ) induced T2DM mice were analysed by gut microbiome and metabolomics methods in this study.Results: The results demonstrated that glucose and lipid metabolism parameters, oxidative stress biomarkers and inflammation cytokines were down-regulated in the CCS and CE groups. A comparative analysis of the fecal samples from mice in the model and experimental groups showed that experimental groups resulted in a higher abundance of Firmicutes/Bacteroidetes.Conclusion: This study provides evidence that C. militaris can be used as a food supplement to relieve T2DM, which provides a promising prospect for new functional food in it.

Permselectivity of cellular membranes is crucial to normal cellular function but this has been hard to replicate in artificial cells. Here, the authors use pH-responsive polymersomes containing Schiff base moieties which can be used to control mesh size allowing for selective permeability control creating responsive systems.

Solid-state fermentation (SSF) of Chinese jujube with Cordyceps militaris was performed in the present study. The results revealed that the contents of total phenolic and flavonoid in rice medium with 50% jujube content increased to 1.59 mg GAE/g d.w. and 0.46 mg RE/g, respectively. The changes of phenolic acid composition showed a similar tendency, and three forms of individual phenolic compounds, namely free phenol, free/conjugated phenol, and bound phenol increased with the extension of the fermentation time. The determination of DPPH, ABTS, FRAP, and the ferrous ion chelating capacity showed that the fermentation significantly enhanced the antioxidant activity in vitro, and the protective functions against ethanol-induced oxidative stress in zebrafish were also then investigated. SSF co-treatment with EtOH reduced MDA elevation and enhanced the activities of SOD and GSH-Px, along with the T-AOC levels in a dose-dependent manner in adult and larval zebrafish. Moreover, the qRT-PCR findings demonstrated that SSF-jujube was capable of upregulating the mRNA expressions of Nrf2 and HO-1 and downregulated the levels of NF-κB in zebrafish larvae. In conclusion, solid-state fermented Chinese jujube with C. militaris was an effective process, exhibited a good antioxidant activity, and demonstrated a better protective effect against ethanol-induced oxidative stress.

Background: Inflammation is currently recognized as one of the major causes of premature delivery. As a member of the interleukin-1β (IL-1β) family, interleukin-33 (IL-33) has been shown to be involved in normal pregnancy as well as a variety of pregnancy-related disorder. This study aims to investigate the potential function of IL-33 in uterine smooth muscle cells during labor. Methods: Myometrium samples from term pregnant (≥37 weeks gestation) women were either frozen or cells were isolated and cultured. Immunohistochemistry and western blotting were used to assess the distribution of IL-33. Cultured cells were incubated with lipopolysaccharide (LPS) to mimic inflammation as well as in the presence of 4μ8C (IRE1 inhibitor III) to block endoplasmic reticulum (ER) stress and BAPTA-AM, a calcium chelator. Results: LPS reduced the expression of nuclear IL-33 in a time-limited manner and induced ER stress. However, knockdown of IL-33 increased LPS-induced calcium concentration, ER stress and phosphorylation of nuclear factor kappa-B (NF-κB), and P38 mitogen-activated protein kinase (P38 MAPK). In addition, siRNA IL-33 further stimulates LPS enhanced cyclooxygenase-2 (COX-2) expression via NF-κB and p38 pathways. IL-33 expression was decreased in the nucleus with the onset of labor. LPS-induced ER stress and increased expression of the labor-associated gene, COX-2, as well as IL-6 and IL-8 in cultured myometrial cells. IL-33 also increased COX-2 expression, but after it was knocked down, the stimulating effect of LPS on calcium was enhanced. 4μ8C also inhibited the expression of COX-2 markedly. The expression of calcium channels on the membrane and intracellular free calcium ion were both increased which was accompanied by phosphorylated NF-κB and p38. Conclusions: These data suggest that IL-33 may be involved in the initiation of labor by leading to stress of the ER via an influx of calcium ions in human uterine smooth muscle cells. Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81300507).

Abstract Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

ObjectivesThis study aimed to investigate the predictive utility of respiratory variations of inferior vena cava diameters on fluid responsiveness in children with septic shock.DesignA prospective observational single-center study.SettingA pediatric intensive care unit in a tertiary hospital in China.ParticipantsPatients with sepsis shock who require invasive mechanical ventilation were recruited between 1 December 2017 and 1 November 2021.Interventions and MeasurementsVolume expansion (VE) was induced by a 30-min infusion of 20 ml/kg of normal saline. Hemodynamics indexes were obtained through bedside transthoracic echocardiography (TTE) measurement and calculation.ResultsA total of 86 patients were enrolled in this study, among them, 45 patients (52.3%) were considered to be non-responders (NR), with an increase in stroke volume variation (SVV)

BackgroundAge-induced sarcopenia negatively affects walking stability and increases the risk of falls, which is the leading cause of accidental death in the elderly.ObjectiveThis study aimed to analyze and contrast body composition and gait characteristics in those with sarcopenia in relation to healthy controls to shed some light on the prevention of falls in elderly patients with sarcopenia.Materials and MethodsIn this study, 68 community dwellers were scanned by the Hologic QDR-4500A Dual-energy X-ray absorptiometry (DXA). The appendicular lean mass index (ALMI) results were used to distinguish the normal participants from those with sarcopenia: 24 in the sarcopenia group, and 44 into the normal group. The participants were asked to undergo gait analysis on a plantar pressure measurement system. Statistical analysis was conducted to contrast both groups' gait and butterfly parameters from their gait test, and then a gait forward dynamics method was performed to quantify the analysis for both groups.ResultsThe ALMI of the female was not related to their age (r = 0.06) while that of the male was weakly related (r = 0.17). Body mass index (BMI) from both groups was normal, although with a statistically greater BMI from the normal group compared with sarcopenia (p < 0.001). Greater values and significant differences were found in step length and stride length from the normal elderly group (p < 0.01), and so was the length of the gait line and single support line (p < 0.05). Gait forward dynamics analysis results showed no motor neural or musculoskeletal disorders in their gait performance from the sarcopenia group.ConclusionFor the elderly, age did not largely affect the ALMI, BMI, or T-score, but BMI and ALMI were strongly correlated. In this study, significant differences were found in certain gait parameters between the elderly with sarcopenia and the normal elderly, which were related to absolute muscle strength, suggesting that sarcopenia was a disease mainly caused by decreased muscle mass. In addition, when abnormities were identified in step length, stride length, length of gait line, or length of single support line, it is proposed to take a DXA scan to confirm whether the elderly suffer from sarcopenia.

Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2 in addition to its activity against lung cancer. TBrC showed extracellular inhibition of SARS-CoV-2 Mpro/3CL and the host cell receptor ACE2 while interacting with the viral spike glycoproteins (wild-type, Delta, and Omicron mutants). Moreover, TBrC and L-theanine significantly suppressed growth and TNFα-induced nuclear transcriptional activation of NF-κB in human lung cancer cells without affecting the viability of normal lung cells, suggesting a potential protection of TBrC and L-theanine from pulmonary damages in SARS-CoV-2 infected patients, especially for lung cancer patients with SARS-CoV-2 infection.

ObjectivesAdequate maternal thyroid hormone availability is crucial for fetal neurodevelopment, but the role of maternal mild hypothyroidism is not clear. We aim to investigate the association of maternal mild hypothyroidism with neurodevelopment in infants at 1 year of age among TPOAb-negative women.MethodsThe present study was conducted within the Jiangsu Birth Cohort. A total of 793 mother–infant pairs were eligible for the present study. Maternal thyroid function was assessed by measuring serum thyroid-stimulating hormone, free thyroxine, and thyroid peroxidase antibodies. Neurodevelopment of infants was assessed by using the Bayley Scales of Infant and Toddler Development third edition screening test (Bayley-III screening test).ResultsIn the multivariate adjusted linear regression analyses, infants of women with subclinical hypothyroidism and isolated hypothyroxinemia were associated with decreased receptive communication scores (β = −0.68, p = 0.034) and decreased gross motor scores (β = −0.83, p = 0.008), respectively. Moreover, infants of women with high-normal TSH concentrations (3.0–4.0 mIU/L) and low FT4 concentrations were significantly associated with lower gross motor scores (β = −1.19, p = 0.032), while no differences were observed in infants when the mothers had a high-normal TSH concentration and normal FT4 levels.ConclusionsMaternal subclinical hypothyroidism is associated with decreased receptive communication scores in infants at 1 year of age. In addition, maternal TSH concentration greater than 4.0 mIU/L and maternal isolated hypothyroxinemia are associated with impaired gross motor ability of infants, especially in infants of women with high-normal TSH concentrations (3.0–4.0 mIU/L).

Abstract Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.

IFN-γ–stimulated MHC class I (MHC-I) antigen presentation underlies the core of antitumor immunity. However, sustained IFN-γ signaling also enhances the programmed death ligand 1 (PD-L1) checkpoint pathway to dampen antitumor immunity. It remains unclear how these opposing effects of IFN-γ are regulated. Here, we report that loss of the histone dimethyltransferase WHSC1 impaired the antitumor effect of IFN-γ signaling by transcriptional downregulation of the MHC-I machinery without affecting PD-L1 expression in colorectal cancer (CRC) cells. Whsc1 loss promoted tumorigenesis via a non-cell-autonomous mechanism in an Apcmin/+ mouse model, CRC organoids, and xenografts. Mechanistically, we found that the IFN-γ/STAT1 signaling axis stimulated WHSC1 expression and, in turn, that WHSC1 directly interacted with NLRC5 to promote MHC-I gene expression, but not that of PD-L1. Concordantly, silencing Whsc1 diminished MHC-I levels, impaired antitumor immunity, and blunted the effect of immune checkpoint blockade. Patient cohort analysis revealed that WHSC1 expression positively correlated with enhanced MHC-I expression, tumor-infiltrating T cells, and favorable disease outcomes. Together, our findings establish a tumor-suppressive function of WHSC1 that relays IFN-γ signaling to promote antigen presentation on CRC cells and provide a rationale for boosting WHSC1 activity in immunotherapy.

BackgroundGlucose variability (GV) is a common complication of dysglycemia in critically ill patients. However, there are few studies on the role of GV in the prognosis of pediatric patients, and there is no consensus on the appropriate method for GV measurement. The objective of this study was to determine the “optimal” index of GV in non-diabetic critically ill children in a prospective multicenter cohort observational study. Also, we aimed to confirm the potential association between GV and unfavorable outcomes and whether this association persists after controlling for hypoglycemia or hyperglycemia.Materials and MethodsBlood glucose values were recorded for the first 72 h and were used to calculate the GV for each participant. Four different metrics [SD, glycemic lability index (GLI), mean absolute glucose (MAG), and absolute change of percentage (ACACP)] were considered and compared to identify the “best” GV index associated with poor prognosis in non-diabetic critically ill children. Among the four metrics, the SD was most commonly used in previous studies, while GLI- and MAG-integrated temporal information, that is the rate and magnitude of change and the time interval between glucose measurements. The fourth metric, the average consecutive ACACP, was introduced in our study, which can be used in real-time clinical decisions. The primary outcome of this study was the 28-day mortality. The receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive power of different metrics of GV for the primary outcome. The GV index with the largest area under ROC curve (AUC) was chosen for subsequent multivariate analyses. Multivariate Cox regression analysis was performed to identify the potential predictors of the outcome. To compare the contribution in 28-day mortality prognosis between glycemic variability and hyper- or hypoglycemia, performance metrics were calculated, which included AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).ResultsAmong 780 participants, 12.4% (n = 97) died within 28 days after admission to the pediatric intensive care unit (PICU). Statistically significant differences were found between survivors and non-survivors in terms of four GV metrics (SD, GLI, MAG, and ACACP), in which MAG (AUC: 0.762, 95% CI: 0.705–0.819, p < 0.001) achieved the largest AUC and showed a strong independent association with ICU mortality. Subsequent addition of MAG to the multivariate Cox model for hyperglycemia resulted in further quantitative evolution of the model statistics (AUC = 0.651–0.681, p = 0.001; IDI: 0.017, p = 0.044; NRI: 0.224, p = 0.186). The impact of hyperglycemia (adjusted hazard ratio [aHR]: 1.419, 95% CI: 0.815–2.471, p = 0.216) on outcome was attenuated and no longer statistically relevant after adjustment for MAG (aHR: 2.455, 95% CI: 1.411–4.270, p = 0.001).ConclusionsGV is strongly associated with poor prognosis independent of mean glucose level, demonstrating more predictive power compared with hypoglycemia and hyperglycemia after adjusting for confounding factors. GV metrics that contain information, such as time and rate of change, are the focus of future research; thus, the MAG may be a good choice. The findings of this study emphasize the crucial role of GVs in children in the PICU. Clinicians should pay more attention to GV for clinical glucose management.

Objectives The purpose of this paper is to describe the prevalence of depressive symptoms in the Chinese labor force; to explore the relationship between depressive symptoms and socioeconomic status among the Chinese labor force, including both the structural determinants and the intermediary determinants of health inequities; and to identify vulnerable populations who would benefit from intervention measures. Methods Data were from the China Labor-Force Dynamics Survey (CLDS) 2016. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms. The World Health Organization’s theoretical framework of the social determinants of health was adopted to analyze the relationship between social determinants and depressive symptoms. Results Of the participants in the research from the Chinese labor force, 17.34% were identified as having depressive symptoms. Depression was significantly related to socioeconomic factors such as hukou status (p < 0.05 in the age < 45 model), education (p < 0.01 in all five models), employment (p < 0.05 in the male model), income (p < 0.05 in all five models), and self-assessed social class position (p < 0.01 in all five models). Intermediary factors were also related to depressive symptoms, such as gender (p < 0.001 in the overall model), age (p < 0.05 in the overall model), marriage (p < 0.05 in the female model), occupational exposure (p < 0.01 in the overall model), exercise (p < 0.05 in all five models), and health insurance (p < 0.05 in the overall model). The results showed that low socioeconomic status was associated with an increased risk of depression and there were some gradient changes in the distribution of depressive symptoms in socioeconomic status. Conclusions The findings showed that depression symptoms are significantly related to structural determinants and intermediary determinants in China’s labor force. There are some gradient changes in the distribution of depressive symptoms among people of different socioeconomic status. Low socioeconomic status is associated with increased risk of depression. Women, older people, and single and divorced people are the relative vulnerable groups in China’s labor force.

Polyion complex vesicles have advantageous applications but have poorly tuneable permeability and nanostructure stability. Here, the authors develop polyion complex vesicles created using a stimuli-triggered transition from polymersomes and show high stability and switchable bilayer permaselectivity.

Abstract Background Chronic nonhealing wounds represent one of the most common complications of diabetes and require advanced treatment strategies. Increasing evidence supports the important role of mesenchymal stem cells in diabetic wound healing; however, the underlying mechanism remains unclear. Here, we explored the effects of umbilical cord-matrix stem cells (UCMSCs) on diabetic wound healing and the underlying mechanism. Methods UCMSCs or conditioned medium (UCMSC-CM) were injected into the cutaneous wounds of streptozotocin-induced diabetic mice. The effects of this treatment on macrophages and diabetic vascular endothelial cells were investigated in vivo and in vitro. Results Our results reveal that UCMSCs or UCMSC-CM accelerated wound healing by enhancing angiogenesis. The number of host macrophages recruited to the wound tissue by local infusion of UCMSCs was greater than that recruited by fibroblast transplantation or control. The frequency of M2 macrophages was increased by UCMSC transplantation or UCMSC-CM injection, which promoted the expression of cytokines derived from M2 macrophages. Furthermore, when cocultured with UCMSCs or UCMSC-CM, lipopolysaccharide-induced macrophages acquired an anti-inflammatory M2 phenotype characterized by the increased secretion of the cytokines interleukin (IL)-10 and vascular endothelial growth factor and the suppressed production of tumor necrosis factor-α and IL-6. UCMSC-CM-activated macrophages significantly enhanced diabetic vascular endothelial cell functions, including angiogenesis, migration, and chemotaxis. Moreover, the action of UCMSC-CM on macrophages or vascular endothelial cells was abrogated by the administration of neutralizing antibodies against prostaglandin E2 (PGE2) or by the inhibition of PGE2 secretion from UCMSCs. Conclusions Our findings demonstrate that UCMSCs can induce the functional restoration of vascular endothelial cells via the remodeling of macrophage phenotypes, which might contribute to the marked acceleration of wound healing in diabetic mice. Graphical Abstract

Anticancer peptide (ACP) is a class of anti-cancer peptide which can inhibit and kill tumor cells. Identification of ACPs is of great significance for the development of new anti-cancer drugs. However, most of computational methods make predictions based on machine learning using hand-crafted features. In this article, we propose a new graph learning based computational model, named ACP-GCN, to automatically and accurately predict ACPs based on graph convolution networks. In this model, we for the first time take the ACP prediction as a graph classification task, where each peptide sample is represented as a graph. The experimental results show that the proposed model outperforms most of state-of-the-art methods, demonstrating that the proposed method can effectively distinguish ACPs from non-ACPs. The excellent predictive ability will rapidly push forward their applications in cancer therapy.

The seismic Gutenberg discontinuity has long been associated with the lithosphere-asthenosphere boundary, yet the physical explanation of what is causing the discontinuity remains debated. Here, the authors report geochemical evidence, including Mg isotopes, and suggest that melting of recycled crust is responsible for the Gutenberg discontinuity.

BackgroundBladder cancer (BC) is a molecular heterogeneous malignant tumor; the treatment strategies for advanced-stage patients were limited. Therefore, it is vital for improving the clinical outcome of BC patients to identify key biomarkers affecting prognosis. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. Ferroptosis-related genes (FRGs) can be promising candidate biomarkers in BC. The objective of our study was to construct a prognostic model to improve the prognosis prediction of BC.MethodsThe mRNA expression profiles and corresponding clinical data of bladder urothelial carcinoma (BLCA) patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. FRGs were identified by downloading data from FerrDb. Differential analysis was performed to identify differentially expressed genes (DEGs) related to ferroptosis. Univariate and multivariate Cox regression analyses were conducted to establish a prognostic model in the TCGA cohort. BLCA patients from the GEO cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were used to explore underlying mechanisms.ResultsNine genes (ALB, BID, FADS2, FANCD2, IFNG, MIOX, PLIN4, SCD, and SLC2A3) were identified to construct a prognostic model. Patients were classified into high-risk and low-risk groups according to the signature-based risk score. Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) survival analysis confirmed the superior predictive performance of the novel survival model based on the nine-FRG signature. Multivariate Cox regression analyses showed that risk score was an independent risk factor associated with overall survival (OS). GO and KEGG enrichment analysis indicated that apart from ferroptosis-related pathways, immune-related pathways were significantly enriched. ssGSEA analysis indicated that the immune status was different between the two risk groups.ConclusionThe results of our study indicated that a novel prognostic model based on the nine-FRG signature can be used for prognostic prediction in BC patients. FRGs are potential prognostic biomarkers and therapeutic targets.

Metabolomics is an essential method to study the dynamic changes of metabolic networks and products using modern analytical techniques, as well as reveal the life phenomena and their inherent laws. Currently, more and more attention has been paid to the development of metabolic histochemistry in the fungus field. This paper reviews the application of metabolomics in fungal research from five aspects: identification, response to stress, metabolite discovery, metabolism engineering, and fungal interactions with plants.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12885-019-5750-x

Pandemics from various viruses make natural organisms face challenges over and over again. Therefore, new antiviral drugs urgently need to be found to solve this problem. However, drug research and development is a very difficult task, and finding new antiviral compounds is desirable. A range of medicinal fungi such as Ganoderma lucidum and Cordyceps sinensis are widely used all over the world, and they can enhance human immunity and direct anti-virus activities and other aspects to play an antiviral role. Medicinal fungi are used as foods or as food supplements. In this review, the species of medicinal fungi with antiviral activity in recent decades and the mechanism of antiviral components were reviewed from the perspectives of human, animal, and plant viruses to provide a comprehensive theory based on better clinical utilization of medicinal fungi as antiviral agents.

Histones are cationic nuclear proteins that are essential for the structure and functions of eukaryotic chromatin. However, extracellular histones trigger inflammatory responses and contribute to death in sepsis by unknown mechanisms. We recently reported that inflammasome activation and pyroptosis trigger coagulation activation through a tissue-factor (TF)-dependent mechanism. We used a combination of various deficient mice to elucidate the molecular mechanism of histone-induced coagulation. We showed that histones trigger coagulation activation in vivo, as evidenced by coagulation parameters and fibrin deposition in tissues. However, histone-induced coagulopathy was neither dependent on intracellular inflammasome pathways involving caspase 1/11 and gasdermin D (GSDMD), nor on cell surface receptor TLR2- and TLR4-mediated host immune response, as the deficiency of these genes in mice did not protect against histone-induced coagulopathy. The incubation of histones with macrophages induced lytic cell death and phosphatidylserine (PS) exposure, which is required for TF activity, a key initiator of coagulation. The neutralization of TF diminished the histone-induced coagulation. Our findings revealed lytic cell death as a novel mechanism of histone-induced coagulation activation and thrombosis.

Abstract Background Histone H2AX phosphorylation at the site of Tyr-142 can participates in multiple biological progressions, which is including DNA repair. Ras pathway is closely involved in human cancers. Our study investigated the effects of Ras pathway via regulating H2AX.Y142ph. Methods Gastric cancer cell line SNU-16 and MKN1 cells were transfected with Ras for G12D and T35S site mutation. The phosphorylation of H2A.XY142 and ERK1/2, WSTF and MDM2 was detected by western blot. Cell viability, cell colonies and migration was analyzed by MTT assay, soft-agar colony formation assay, and Transwell assay, respectively. The expression of Ras pathway related downstream factors, EYA3 and WSTF was detected by qRT-PCR. The relationship between Ras and downstream factors were detected by ChIP. The cell cycle progression was measured by flow cytometry. Results RasG12D/T35V transection decreased the phosphorylation of H2A.XY142 and activated phosphorylation of ERK-1/2. H2A.XY142 inhibited cell viability, colonies and migration. H2A.XY142ph altered the expression of Ras downstream factors. CHIP assay revealed that RasG12D/T35V could bind to the promoters of these Ras pathway downstream factors. Silence of EYA3 increased H2A.XY142ph and inhibited cell viability, migration and percent cells in S stage. Furthermore, silence of EYA3 also changed the downstream factors expression. WSTF and H2A.XY142ph revealed the similar trend and MDM2 on the opposite. Conclusion Ras/ERK signal pathway decreased H2A.XY142ph and promoted cell growth and metastasis. This Ras regulation process was down-regulated by the cascade of MDM2-WSTF-EYA3 to decrease H2A.XY142ph in SNU-16 cells.

The study was aimed to investigate the effect of baicalein, a flavonoid molecule isolated from the plant Oroxylum indicum on bladder cancer cell viability. The results revealed that baicalein treatment of T24 and 253J bladder cancer cells targeted the expression of mRNA and proteins corresponding to the anti-apoptotic genes. RT-PCR assay showed that anti-apoptotic genes were markedly over-expressed in the bladder cancer cells. Exposure of the bladder cancer cells to baicalein at 5 mg/mL doses for 72 h led to reduction in the expression of mRNA levels of antiapoptotic genes. In T24 cells, the levels of BCL2, Bcl-xL, XIAP and surviving was reduced by 65, 69, 58 and 72%, respectively. In T24 and 253J cells exposure to baicalein for 72 h resulted respectively in 39 and 46% reduction in cell viability. Baicalein treatment also induced apoptosis in the bladder cancer cells. In T24 and 253J cells baicalein treatment at 5 mg/mL for 72 h induced apoptosis in 79 and 86% cells respectively. Thus, baicalein mediated reduction in antiapoptotic gene expression inhibits viability and induces apoptosis in bladder cancer cells. Therefore, baicalein is of therapeutic importance for the development of bladder cancer treatment strategy. Keywords: Survivin, Bladder cancer, Apoptosis, Viability, Reduction

Gradation has an important influence on the mechanical properties of earth and stone materials after compaction, and a reasonable gradation is the key to ensure compaction quality. In this paper, a set of earth and stone materials gradation detection system based on digital image processing was proposed, which was suitable for detection in the construction sites. The system obtained images which were taken from multiple directions of materials transport vehicle, used the thresholding method to segment the images, detected particle contours through edge detection algorithm of Canny to realize the image recognition of particle size, and drew the gradation curve of earth and rock materials finally. It was verified by selecting limestone aggregates of different gradations, and the results showed high accuracy. The system can realize on-site detection of the earthwork gradation rapidly and accurately at a dam construction site.

Background. Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide and in China. Early CRC screening is the best approach to reduce its incidence and mortality rates. The ColoDefense test, a multiplex qPCR assay simultaneously detecting both methylated SEPT9 and SDC2 genes, has demonstrated improved clinical performance on either methylation biomarker alone for CRC screening with both blood and stool samples. Method. Leftover blood chemistry test samples from 125 CRC, 35 advanced adenoma, and 35 small polyp patients and 92 healthy control subjects were examined by the ColoDefense test. Among these samples, the levels of three circulating tumor markers, CEA, AFP, and CA19-9, were also measured for 106 CRC, 28 advanced adenoma, and 20 small polyp patients and all control subjects. Results. Due to the smaller volume and extended storage in nonfrozen state, the ColoDefense test with these samples exhibited reduced performance for all stages of CRC and advanced adenomas. The performance of CEA, AFP, and CA19-9 and their various combinations was also evaluated for CRC screening to identify the tumor marker combinations with the best performance. When combined with the ColoDefense test, the identified combinations did improve the clinical performance. Conclusion. These results suggested a rational path towards developing a CRC screening method that takes advantage of leftover blood chemistry test samples. The successful development of such a method will undoubtedly help promote early CRC screening by increasing its accessibility for the general public.

Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC. Methods. A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis. Results. After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793–0.994) and 0.812 (95% CI, 0.675–0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC (AUC=0.953). Conclusion. The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.

Abstract Purpose: To develop a simpler animal model for benign tracheal stenosis and introduce a low-cost household endoscope for postmodeling endotracheal evaluation. Methods: Twenty rabbits were randomly divided into a model group (15 rabbits, subjected to transoral nylon brush scraping of the trachea) and a mock group (5 rabbits, merely exempted from scraping), a household endoscope was then introduced for weekly endoscopic examination. Meanwhile, other 15 rabbits (modeling like the model group) underwent batch tracheal resection at different postintervention times for pathological analysis. Results: The model group presented a low mortality and few complications. The endoscope could obtain adequate images for stenosis assessment, which showed that the models presented homogeneous injury after scraping and developed a mature scar stricture at 28 days postoperatively with a mean stenosis degree of 65.9%, and 71.4% (10/14) above Myer–Cotton’s grade II. The pathological findings were consistent with the clinicopathological process of human. No stenosis was found in mock group. Conclusion: The modified model is simpler, minimally invasive and reliable, while the household endoscope is competent for model’s follow-up, providing easily accessible and useful tools for facilitating more extensive studies of benign tracheal stenosis.

Affected by the uneven concentration of coal dust and low illumination, most of the images captured in the top-coal caving face have low definition, high haze and serious noise. In order to improve the visual effect of underground images captured in the top-coal caving face, a novel single-channel Retinex dedusting algorithm with frequency domain prior information is proposed to solve the problem that Retinex defogging algorithm cannot effectively defog and denoise, simultaneously, while preserving image details. Our work is inspired by the simple and intuitive observation that the low frequency component of dust-free image will be amplified in the symmetrical spectrum after adding dusts. A single-channel multiscale Retinex algorithm with color restoration (MSRCR) in YIQ space is proposed to restore the foggy approximate component in wavelet domain. After that the multiscale convolution enhancement and fast non-local means (FNLM) filter are used to minimize noise of detail components while retaining sufficient details. Finally, a dust-free image is reconstructed to the spatial domain and the color is restored by white balance. By comparing with the state-of-the-art image dedusting and defogging algorithms, the experimental results have shown that the proposed algorithm has higher contrast and visibility in both subjective and objective analysis while retaining sufficient details.

Rubus phoenicolasius Maxim. is a traditional Tibetan medicine and widely used in the clinical pharmacology. In current study, the complete chloroplast genome of R. phoenicolasius was reported. The total length of the genome was 155,144 bp with the GC content of 37.9%. We predicted 130 genes in the genome including 84 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene. 17 genes were duplicated in the IR regions including 7 tRNA, 4 rRNA and 6 protein-coding genes. Phylogenomic analysis revealed that R. phoenicolasius forms a strong supported branch with R. amabilis and R. coreanus under the Rosaceae clade.

Fatsia Japonica seed, which is mainly composed of glucose, has potential as a porous carbon matrix precursor for supercapacitors that can achieve high-value utilization. Cost-effective hierarchical porous carbon materials (HPC) were prepared from Fatsia Japonica by annealing at high temperature. The pore size and distribution of the HPC can be precisely controlled and adjusted by altering the activation temperature. The HPC obtained at 600°C showed favorable features for electrochemical energy storage, with a surface area of 870.3 m2/g. The HPC for supercapacitors (a three-electrode system) exhibited good specific capacitance of 140 F/g at a current density of 1 A/g and a long cycling life stability (87.5% remained after 10,000 cycles). In addition, the HPC electrode showed an excellent energy density of 23 Wh/Kg. Such hierarchical porous biomass-derived carbon would be a good candidate for application in the electrodes of supercapacitors due to its simple preparation process and the outstanding electrochemical performance.

Abstract CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in regulating platelet activation. Thrombin- or collagen-induced platelet aggregation and secretion are increased in TRAF3 knockout mice. The expression levels of collagen receptor GPVI and integrin αIIbβ3 in platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in the TRAF3 knockout mice was not due to increased expression platelet receptors. Time to formation of thrombi in a FeCl3-induced thrombosis model was significantly shortened in the TRAF3 knockout mice. However, mouse tail-bleeding times were not affected by deletion of TRAF3. Thus, TRAF3 plays a negative role in platelet activation and in thrombus formation in vivo.

Rhodiola kirilowii is a widely used Tibetan medicine. Here, we report the complete sequence of the chloroplast genome of R. kirilowii. The genome was 150,896 bp in length with 131 genes comprising 85 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene, with 20 of them occurring in double copies. Phylogenomic analysis suggested that R. kirilowii forms a clade with R. rosea, R. yunnanensis, R. fastigiata and R. crenulata in Rhodiola genus.