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Abstract Background Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. Methods RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. Results We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5′-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. Conclusions These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.

An ectopic origin of the right coronary artery from the pulmonary artery is an extremely rare congenital malformation. This case report aimed to review our experience in the diagnosis and treatment of coronary artery anomalies. We report a case of ectopic origin of the right coronary artery from the pulmonary artery. We analyzed the taxonomy and clinical implications of the ectopic origin of the coronary artery. The findings of this case may increase patients’ and clinicians’ awareness of this anomaly.

AbstractSarcophaga (Liosarcophaga) angarosinica (Rohdendorf, 1937) (Diptera: Sarcophagidae) is a species of both medical and ecological significance. In this study, the complete mitochondrial genome (mitogenome) of S. angarosinica was sequenced and characterized. The mitogenome has a total length of 15,215 bp, including 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and an adenine and thymine-rich region. This mitogenome comprises 39.5% adenine, 9.4% guanine, 14.4% cytosine, and 36.8% thymine. Phylogenetic analysis revealed that S. angarosinica is closely related to Sarcophaga similis. This study enriches the genetic data on S. angarosinica and will contribute to establishing the phylogenetic relationships among flesh flies.

Summary: Background: The prevalence, epidemiological and clinical heterogeneities, and impact profiles of individuals with preserved ratio impaired spirometry (PRISm), pre-COPD, young COPD, and mild COPD in general Chinese population were not known yet. Methods: Data were obtained from the China Pulmonary Health study (2012–2015), a nationally representative cross-sectional survey that recruited 50,991 adults aged 20 years or older. Definitions of the four early disease status were consistent with the latest publications and the Global Initiative for Chronic Obstructive Lung Disease criteria. Findings: The age-standardised prevalences of PRISm, pre-COPD, young COPD, and mild COPD were 5.5% (95% confidence interval, 4.3–6.9), 7.2% (5.9–8.8), 1.1% (0.7–1.8), and 3.1% (2.5–3.8), respectively. In summary, mild COPD was under more direct or established impact factor exposures, such as older age, male gender, lower education level, lower family income, biomass use, air pollution, and more accumulative cigarette exposures; young COPD and pre-COPD experienced more personal and parents’ events in earlier lives, such as history of bronchitis or pneumonia in childhood, frequent chronic cough in childhood, parental history of respiratory diseases, passive smoke exposure in childhood, and mother exposed to passive smoke while pregnant; pre-COPD coexisted with heavier symptoms and comorbidities burdens; young COPD exhibited worse airway obstruction; and most of the four early disease status harbored small airway dysfunction. Overall, older age, male gender, lower education level, living in the urban area, occupational exposure, frequent chronic cough in childhood, more accumulated cigarette exposure, comorbid with cardiovascular disease and gastroesophageal reflux disease were all associated with increased presence of the four early COPD status; different impact profiles were additionally observed with distinct entities. Over the four categories, less than 10% had ever taken pulmonary function test; less than 1% reported a previously diagnosed COPD; and no more than 13% had received pharmaceutical treatment. Interpretation: Significant heterogeneities in prevalence, epidemiological and clinical features, and impact profiles were noted under varied defining criteria of early COPD; a unified and validated definition for an early disease stage is warranted. Closer attention, better management, and further research need to be administrated to these population. Funding: Chinese Academy of Medical Sciences Institute of Respiratory Medicine Grant for Young Scholars (No. 2023-ZF-9); China International Medical Foundation (No. Z-2017-24-2301); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-049); National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01); Major Program of National Natural Science Foundation of China (No. 82090011).

Abstract Background Heat tolerance is a distinct abiotic factor affecting the distribution and abundance of insects. Gut microbiota can contribute to host fitness, thereby increasing resistance to abiotic stress conditions. In this study, Sarcophaga peregrina is closely associated with human life in ecological habits and shows remarkable adaptability to daily and seasonal temperature fluctuations. To date, the role of gut microbiota in S. peregrina response to heat stress and its influence on the host phenotypic variability remain poorly studied. Methods We exposed S. peregrina to heat stress at 40 °C for 3 h every day throughout the developmental stages from newly hatched larva to adult, after which gut DNA was extracted from third-instar larvae, early pupal stage, late pupal stage, and newly emerged adults, respectively. Then, 16S rRNA microbial community analyses were performed. Results Firstly, we analyzed whether heat stress could have an impact on the life history traits of S. peregrina and showed that the growth rate of larvae was higher and the developmental time was significantly shorter after heat stress. We then proposed the role of the gut microbiota in the heat tolerance of S. peregrina, which indicated that the bacterial abundance and community structure changed significantly after heat tolerance. In particular, the relative abundance of Wohlfahrtiimonas and Ignatzschineria was higher in the third-instar larval larvae; the former increased and the latter decreased significantly after heat stress. To further explore the effect of disturbing the microbial community on thermotolerant phenotype, newly hatched larvae were fed with amikacin under heat stress, which indicated that the larval length and the whole developmental cycle was significantly shorter. Conclusion This study indicated that Wohlfahrtiimonas and Ignatzschineria should play an important role in the post-feeding stage under heat stress, but further study is still needed. In general, heat tolerance can affect the gut microbial community structure, which in turn affects the fitness of the host. Graphical Abstract

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was

Liver fibrosis is a severe global health problem. However, no effective antifibrotic drugs have been approved. Surf4 is primarily located in the endoplasmic reticulum (ER) and mediates the transport of secreted proteins from the ER to the Golgi apparatus. Knockout of hepatic Surf4 (Surf4LKO) in mice impairs very-low-density lipoprotein secretion without causing overt liver damage. Here, we found that collagen levels are significantly reduced in the liver of Surf4LKO mice compared with control Surf4flox mice, as demonstrated by proteomics, Western blot, and quantitative reverse transcription polymerase chain reaction. Therefore, this study aims to investigate whether and how hepatic Surf4 affects liver fibrosis. We observed that CCl4-induced liver fibrosis is significantly lower in Surf4LKO mice than in Surf4flox mice. Mechanistically, hepatic Surf4 deficiency reduces serum amyloid A1 (SAA1) secretion and hepatic stellate cell (HSC) activation. Surf4 coimmunoprecipitates and colocalizes with SAA1. Lack of hepatic Surf4 significantly reduces SAA1 secretion from hepatocytes, and SAA1 activates cultured human HSCs (LX-2 cells). Conditioned medium (CM) from Surf4-deficient primary hepatocytes activates LX-2 cells to a much lesser extent than CM from Surf4flox primary hepatocytes, and this reduced effect is restored by the addition of recombinant SAA1 to CM from Surf4-deficient hepatocytes. Knockdown of SAA1 in primary hepatocytes or TLR2 in LX-2 cells significantly reduces LX-2 activation induced by CM from Surf4flox hepatocytes but not from Surf4LKO hepatocytes. Furthermore, knockdown of SAA1 significantly ameliorates liver fibrosis in Surf4flox mice but does not further reduce liver fibrosis in Surf4LKO mice. We also observe substantial expression of Surf4 and SAA1 in human fibrotic livers. Therefore, hepatic Surf4 facilitates SAA1 secretion, activates HSCs, and aggravates liver fibrosis, suggesting that hepatic Surf4 and SAA1 may serve as treatment targets for liver fibrosis.

Abstract Background A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. Methods We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. Results After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10−14), ABO rs582094 (p-value = 1.16 × 10−10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10−17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. Conclusions We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

Abstract Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC.

Introduction: As psychoneuroimmunology flourishes, there is compelling evidence that depression suppresses the anti-tumor immune response, promotes the progression of cancer, and inhibits the effectiveness of cancer immunotherapy. Recent studies have reported that antidepressants can not only alleviate the depressant condition of cancer patients, but also strengthen the anti-tumor immunity, thus suppressing tumors. Tumor necrosis factor receptor 2 (TNFR2) antagonistic antibodies (Anti-TNFR2) targeting tumor-infiltrating regulatory T cells (Tregs) has achieved great results in preclinical studies, and with a favorable toxicity profile than existing immunotherapies, and is expected to become a new generation of more effective treatment strategies. Understanding the effects of combination therapy with antidepressants and Anti-TNFR2 may help design new strategies for cancer immunotherapy.Methods: We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0–50 µM), ansofaxine hydrochloride (0–50 µM) and amitifadine hydrochloride (0–150 µM) to examine their effects on cell proliferation and apoptosis. We explored the antitumor effects of ansofaxine hydrochloride in combination with or without Anti-TNFR in subcutaneously transplanted CT26 cells in tumor-bearing mouse model. Antitumor effects were evaluated by tumor volume. NK cell, M1 macrophage cell, CD4+ T cell, CD8+ T cell, exhausted CD8+ T and regulatory T cell (Tregs) subtypes were measured by flow cytometry. 5-hydroxytryptamine, dopamine and norepinephrine levels were measured by ELISA.Results: Oral antidepression, ansofaxine hydrochloride, enhanced peripheral dopamine levels, promoted CD8+T cell proliferation, promoted intratumoral infiltration of M1 and NK cells, decreased the proportion of tumor-infiltrating exhausted CD8+T cells, and strengthened anti-tumor immunity, thereby inhibiting colon cancer growth. In combination therapy, oral administration of ansofaxine hydrochloride enhanced the efficacy of Anti-TNFR2, and produced long-term tumor control in with syngeneic colorectal tumor-bearing mice, which was attributable to the reduction in tumor-infiltrating Treg quantity and the recovery of CD8+ T cells function.Discussion: In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8+T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2.

Summary: ALDH1A1 is one of the classical stem cell markers for bladder cancer. Lysine 2-hydroxyisobutyrylation (Khib) is a newfound modification to modulate the protein expression, and the underlying mechanisms of how ALDH1A1 was regulated by Khib modification in bladder cancer remains unknown. Here, ALDH1A1 showed a decreased K260hib modification, as identified by protein modification omics in bladder cancer. Decreasing ALDH1A1 expression significantly suppressed the proliferation, migration and invasion of bladder cancer cells. Moreover, K260hib modification is responsible for the activity of ALDH1A1 in bladder cancer, which is regulated by HDAC2/3. Higher K260hib modification on ALDH1A1 promotes protein degradation through chaperone-mediated autophagy (CMA), and ALDH1A1 K260hib could sensitize bladder cancer cells to chemotherapeutic drugs. Higher ALDH1A1 expression with a lower K260hib modification indicates a poor prognosis in patients with bladder cancer. Overall, we demonstrated that K260hib of ALDH1A1 can be used as a potential therapeutic target for bladder cancer treatment.

Background: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an underestimated sleep disorder that leads to multiple organ damages, including lung injury (LI). This paper sought to analyze the molecular mechanism of extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) in OSAHS-induced lung injury (LI) via the miR-22–3p/histone lysine demethylase 6 B (KDM6B)/high mobility group AT-hook 2 (HMGA2) axis. Methods: ADSCs and ADSCs-EVs were separated and characterized. Chronic intermittent hypoxia (CIH) was used to mimic OSAHS-LI, followed by ADSCs-EVs treatment and hematoxylin and eosin staining, TUNEL, ELISA, and assays of inflammation and oxidative stress (MPO/ROS/MDA/SOD). The CIH cell model was established and treated with ADSCs-EVs. Cell injury was assessed by the assays of MTT, TUNEL, ELISA, and others. Levels of miR-22–3p, KDM6B, histone H3 trimethylation at lysine 27 (H3K27me3), and HMGA2 were determine by RT-qPCR or Western blot analysis. The transfer of miR-22–3p by ADSCs-EVs was observed by fluorescence microscopy. Gene interactions were analyzed by dual-luciferase assay or chromatin immunoprecipitation. Results: ADSCs-EVs effectively alleviated OSAHS-LI by reducing lung tissue injury, apoptosis, oxidative stress, and inflammation. In vitro, ADSCs-EVs increased cell viability and reduced apoptosis, inflammation and oxidative stress. ADSCs-EVs delivered enveloped miR-22–3p into pneumonocytes to upregulate miR-22–3p expression, inhibit KDM6B expression, increase H3K27me3 levels on the HMGA2 promoter, and decrease HMGA2 mRNA levels. Overexpression of KDM6B or HMGA2 attenuated the protective role of ADSCs-EVs in OSAHS-LI. Conclusion: ADSCs-EVs transferred miR-22–3p to pneumonocytes and reduced apoptosis, inflammation, and oxidative stress through KDM6B/HMGA2, mitigating OSAHS-LI progression.

Estimating the age of pupa during the development time of the blow fly Chrysomya megacephala (Diptera: Calliphoridae) is of forensic significance as it assists in determining the time of colonization (TOC), which could help to determine the postmortem interval (PMI). However, establishing an objective, accurate, and efficient method for pupa age inference is still a leading matter of concern among forensic entomologists. In this study, we utilized hyperspectral imaging (HSI) technology to analyze the reflectance changes of pupa development under different temperatures (15 °C, 20 °C, 25 °C, and 30 °C). The spectrograms showed a downtrend under all temperatures. We used PCA to reduce the dimensionality of the spectral data, and then machine learning models (RF, SVR-RBF, SVR-POLY, XGBR, and Lasso) were built. RF, SVR with RBF kernel, and XGBR could show promise in accurate developmental time estimation using accumulated degree days. Among these, the XGBR model consistently exhibited the most minor errors, ranging between 3.9156 and 7.3951 (MAE). This study has identified the value of further refinement of HSI in forensic applications involving entomological specimens, and identified the considerable potential of HSI in forensic practice.

Objective We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. Methods Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. Results After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 − 0.71); specificity 0.72 (0.71 − 0.73), PPV 0.25 (0.24 − 0.26) and NPV 0.94 (0.94 − 0.95). Conclusion We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

Primary malignant melanoma of the lung (PMML) is an extremely rare and refractory tumor, and its diagnosis is a significant challenge. The current study presents the case of a 62-year-old man who presented to the Department of Cardiothoracic Surgery (Lishui Municipal Central Hospital, Lishui, China) with chest tightness and fatigue for 3 months. Chest computed tomography (CT) revealed a 1.5- × 1.9-cm mass with irregular borders and heterogenous density located in the right lower lung lobe. Contrast-enhanced CT revealed slight enhancement of the mass, but there was no clear evidence of malignancy. Positron emission tomography (PET)/CT revealed a defined-margin mass, with slightly high uptake (standardized uptake value [SUV]: 3.6). The patient underwent video-assisted thoracoscopic surgery (VATS), and the final diagnosis was PMML on the basis of the results of the pathological examination. The patient received four courses of immunotherapy after the operation, and eventually declined further immunotherapy owing to the high cost. The patient was followed-up for 1 year without metastasis or recurrence.

The intestinal bacteria of insects are crucial to the growth and development of the host. It has been found that various physiological processes of insects, such as immune response, metabolism, reproductive ability, and growth and development, involve the gastrointestinal flora. However, many external factors affect the composition of insects’ intestinal microorganisms, such as the type of dietary substrate. Sarcophaga peregrina (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae) is of great significance in medicine and forensic science. In this study, we investigated the effects of ciprofloxacin on the growth and gut microbiota of S. peregrina. The results demonstrated that the maximum body length of larvae was not affected by ciprofloxacin, while the growth rate of body length quickened as the concentration of the drug increased. The weight of the pupa and adult was reduced significantly due to the effect of ciprofloxacin. After analyzing the gut microbiota composition of S. peregrina in different drug groups, it was indicated that Ignatzschineria, Providencia, Wohlfahrtiimonas, Proteus, Myroides, and Bacteroides play important roles in the growth of S. peregrina. However, they still need to be further studied. In general, ciprofloxacin can affect the gut microbial community structure, which in turn affects the fitness of the host.

Microbial communities can undergo significant successional changes during decay and decomposition, potentially providing valuable insights for determining the postmortem interval (PMI). The microbiota produce various gases that cause cadaver bloating, and rupture releases nutrient-rich bodily fluids into the environment, altering the soil microbiota around the carcasses. In this study, we aimed to investigate the underlying principles governing the succession of microbial communities during the decomposition of pig carcasses and the soil beneath the carcasses. At early decay, the phylum Firmicutes and Bacteroidota were the most abundant in both the winter and summer pig rectum. However, Proteobacteria became the most abundant in the winter pig rectum in late decay. Using genus as a biomarker to estimate the PMI could get the MAE from 1.375 days to 2.478 days based on the RF model. The abundance of bacterial communities showed a decreasing trend with prolonged decomposition time. There were statistically significant differences in microbial diversity in the two periods (pre-rupture and post-rupture) of the four groups (WPG 0–8Dvs. WPG 16–40D, p < 0.0001; WPS 0–16Dvs. WPS 24–40D, p = 0.003; SPG 0D vs. SPG 8–40D, p = 0.0005; and SPS 0D vs. SPS 8–40D, p = 0.0208). Most of the biomarkers in the pre-rupture period belong to obligate anaerobes. In contrast, the biomarkers in the post-rupture period belong to aerobic bacteria. Furthermore, the genus Vagococcus shows a similar increase trend, whether in winter or summer. Together, these results suggest that microbial succession was predictable and can be developed into a forensic tool for estimating the PMI.

In forensic medical examinations, estimating the postmortem interval (PMI) is an important factor. Methamphetamine (MA) is a synthetic stimulant that is commonly abused, and estimation of the PMI after MA abuse has become one of the main tasks in forensic investigation. Microorganisms play a vital role in carrion decomposition. Analysing the bacterial succession patterns can be used as a forensic tool to estimate the PMI. The present study aimed to analyse bacterial succession changes during the decomposition of MA to estimate the PMI. We analysed bacterial communities in rabbits treated with three different concentrations of MA (0, 22.5, and 90 mg/kg) under the natural conditions of 20 °C and 70% humidity by sequencing 16S rRNA gene amplicons using the Illumina MiSeq system. We obtained 2 774 209 high-quality sequences and 2937 operational taxonomic units (OTUs). The relative abundances of the bacterial communities varied markedly in response to different MA concentrations. Interestingly, in response to the different concentrations of MA, Bacteroidetes became disparate in the rectum in the late PMI. Increased numbers of bacterial taxa were identified in the rectum and buccal cavity samples, except at the highest concentration of MA in the rectum samples when PMI was 0–h, than were present in live rabbits. Meanwhile, the PMI correlated significantly with bacterial succession at different taxonomic levels. Our results suggested that bacterial community succession could be used as a “microbial clock” to estimate the PMI in cases of MA-related death; however, further study is required to gain a deeper understanding of this concept.KeypointsAs a forensic tool, microbiome succession patterns have great potential for PMI estimation.At different taxonomic levels, the variation in the succession of microorganisms’ under three different concentrations of MA during the processes of decomposition is significantly related to PMI for estimating MA abuse.These findings provide a new idea for the estimation of PMI of MA abused by changes in microorganisms.

Flesh flies (Diptera: Sarcophagidae) are regarded as significant in medical and veterinary entomology, and their development models can be utilized as considerable markers to ascertain the minimum postmortem interval (PMImin). In this research, we explored the growth cycle and larval body length of Sarcophaga crassipalpis Macquart 1839 (Diptera: Sarcophagidae) reared under variable temperatures ranging from 15.7 to 31.1 °C, with an average of 24.55 °C and relative humidity ranges from 31.4 to 82.8% and at six fixed temperatures of 15, 20, 25, 30, 32, and then 35 °C. Moreover, pteridine from the head was used to assess adult age grading. Our results allowed us to provide three development models: the isomorphen chart, the isomegalen chart, and the thermal summation models. The time taken for S. crassipalpis to complete its development from larviposition to adult emergence at constant temperatures of 15, 20, 25, 30, 32, and 35 °C was 1256.3 ± 124.2, 698.6 ± 15.1, 481.8 ± 35.7, 366.0 ± 13.5, and 295.8 ± 20.5 h, respectively, except 35 °C, where all pupae were unable to attain adulthood. They lasted 485.8 ± 5.4 h under variable temperatures. The minimum developmental limit (D0) temperature and the thermal summation constant (K) of S. crassipalpis were 9.31 ± 0.55 °C and 7290.0 ± 388.4 degree hours, respectively. The increase in pteridine content exhibited variations across different temperatures. There was quite a considerable distinction in the pteridine contents of male and female S. crassipalpis at 15 °C (p = 0.0075) and 25 °C (p = 0.0213). At 32 °C and variable temperatures, the pteridine content between female and male S. crassipalpis was not statistically divergent. However, temperature and gender remain the main factors influencing the pteridine content in the head of S. crassipalpis. We aim to provide detailed developmental data on S. crassipalpis that can be used as a valuable resource for future research and PMI estimation.

ATM serine/threonine kinase (ATM; previously known as ataxia‐telangiectasia mutated) plays a critical role in maintaining genomic stability and regulates multiple downstream pathways, such as DNA repair, cell cycle arrest, and apoptosis. As a serine/threonine kinase, ATM has an array of downstream phosphorylation substrates, including checkpoint effector checkpoint kinase 2 (CHK2). ATM inhibits cell cycle progression by phosphorylating and activating CHK2, which plays an important role in the formation and development of tumors and participates in DNA repair responses after double‐stranded DNA breaks. In this study, we used a recently developed mammalian functional genetic screening system to explore a series of ATM substrates and their role in DNA damage to enhance our understanding of the DNA damage response. Ubiquilin 4 (UBQLN4), which belongs to the ubiquilin family characterized by its ubiquitin‐like (UBL) and ubiquitin‐associated (UBA) domains, was identified as a new substrate for ATM. UBQLN4 is involved in various intracellular processes, such as autophagosome maturation, p21 regulation, and motor axon morphogenesis. However, the biological function of UBQLN4 remains to be elucidated. In this study, we not only identified UBQLN4 as a substrate for ATM, but also found that UBQLN4 interacts with and stabilizes the anti‐apoptotic proteins Bcl‐2‐related protein A1 (BCL2A1) and Bcl‐2‐like protein 10 (BCL2L10) and prevents mesothelioma cell apoptosis in response to DNA damage. These findings expand our understanding of the role of UBQLN4 in mesothelioma and provide new insights into potential mesothelioma treatments targeting substrates for ATM.

Abstract Background The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) is a current worldwide threat for which the immunological features after infection need to be investigated. The aim of this study was to establish a highly sensitive and quantitative detection method for SARS-CoV-2 IgG antibody and to compare the antibody reaction difference in patients with different disease severity. Results Recombinant SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to establish an indirect IgG ELISA detection system. The sensitivity of the ELISA was 100% with a specificity of 96.8% and a 98.3% concordance when compared to a colloidal gold kit, in addition, the sensitivity of the ELISA was 100% with a specificity of 98.9% and a 99.4% concordance when compared to a SARS-CoV-2 spike S1 protein IgG antibody ELISA kit. The increased sensitivity resulted in a higher rate of IgG antibody detection for COVID-19 patients. Moreover, the quantitative detection can be conducted with a much higher serum dilution (1:400 vs 1:10, 1:400 vs 1:100). The antibody titers of 88 patients with differing COVID-19 severity at their early convalescence ranged from 800 to 102,400, and the geometric mean titer for severe and critical cases, moderate cases, asymptomatic and mild cases was 51,203, 20,912, and 9590 respectively. Conclusion The development of a highly sensitive ELISA system for the detection of SARS-CoV-2 IgG antibodies is described herein. This system enabled a quantitative study of rSARS-CoV-2-N IgG antibody titers in COVID-19 patients, the occurrence of higher IgG antibody titers were found to be correlated with more severe cases.

Abstract The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods. Graphical Abstract

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed.

In non-open environments, pathogenic microorganisms are more likely to invade the human respiratory tract due to their limited diffusion in the environment, which has received little attention. In this study, we explored the distribution characteristics of particulate matter (PM) in non-open environments, and included sewage treatment plants and farms, which are occupational exposure risks, and G-series high-speed trains and waiting rooms, which are crowded. The results showed orders of magnitude differences in PM and microbial concentrations and the DNA/PM values of adsorption in the different non-open spaces. The concentration of PM with a size in the 4.7–10.0 μm range was higher than those of PM in the 1.1–4.7 μm and 0.43–1.1 μm ranges in all three types of places, accounting for 74.64%, 46.59%, and 51.49%, respectively. The DNA/PM value for the 1.1–4.7 μm range was higher than those for PM in the other two ranges in all three types of places at 0.175, 3.78 × 10−3, and 9.98 ng/μg, respectively. Although the relative abundances of Class II potentially pathogenic bacteria with sizes ranging from 1.1 to 4.7 μm were higher in all three types of places, the total abundance and the relative abundance of identified pathogenic microorganisms with sizes ranging from 4.7 to 10.0 μm were higher in all three types of places. Here, in non-open spaces, the pathogen exposure risk associated with PM10, particularly the coarse fraction of PM10, deserves special attention. Infectious diseases caused by aerosol transmission of pathogens in non-open environments should receive more attention and require further investigation in the future.

Growth traits, such as fresh weight, diameter, and leaf area, are pivotal indicators of growth status and the basis for the quality evaluation of lettuce. The time-consuming, laborious and inefficient method of manually measuring the traits of lettuce is still the mainstream. In this study, a three-stage multi-branch self-correcting trait estimation network (TMSCNet) for RGB and depth images of lettuce was proposed. The TMSCNet consisted of five models, of which two master models were used to preliminarily estimate the fresh weight (FW), dry weight (DW), height (H), diameter (D), and leaf area (LA) of lettuce, and three auxiliary models realized the automatic correction of the preliminary estimation results. To compare the performance, typical convolutional neural networks (CNNs) widely adopted in botany research were used. The results showed that the estimated values of the TMSCNet fitted the measurements well, with coefficient of determination (R2) values of 0.9514, 0.9696, 0.9129, 0.8481, and 0.9495, normalized root mean square error (NRMSE) values of 15.63, 11.80, 11.40, 10.18, and 14.65% and normalized mean squared error (NMSE) value of 0.0826, which was superior to compared methods. Compared with previous studies on the estimation of lettuce traits, the performance of the TMSCNet was still better. The proposed method not only fully considered the correlation between different traits and designed a novel self-correcting structure based on this but also studied more lettuce traits than previous studies. The results indicated that the TMSCNet is an effective method to estimate the lettuce traits and will be extended to the high-throughput situation. Code is available at https://github.com/lxsfight/TMSCNet.git.

Background Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results Chronic cough was found in 3.6% (95% CI 3.1–4.1) of Chinese adults, 2.4% (95% CI 1.9–3.1) of those aged 20–49 years and 6.0% (95% CI 5.3–6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p

Epithelial–myoepithelial carcinoma (EMC) of the esophagus is a rare biphasic tumor with low malignant potential, which has not previously been reported in the published literature. The present study describes the case of an asymptomatic, 53-year-old male who presented with EMC in the esophagus during a gastroscopic examination. Esophageal computed tomography (CT) showed thickening of the wall of the lower esophagus with a thickness of about 0.7 cm, and an enhanced scan showed uneven enhancement of the thickened esophageal wall. Thoracoscopic esophagectomy was performed because the tumor was malignant. Histopathology revealed that the tumor was characterized by a biphasic architecture consisting of cuboidal ductal cells and myoepithelial cells. The patient’s postoperative recovery was eventful, an anastomotic fistula occurred, and the patient was discharged from the hospital after 84 days. One year postsurgery, the patient remained in good health, with no evidence of metastasis and recurrence.

A mild traumatic brain injury (mTBI) can increase the risk of neurodegenerative-related disease, and serious long-term outcomes are often overlooked. In forensic science, the accurate identification of mTBIs can directly affect the application of evidence in practice cases. Recent research has revealed that the oral cavity and fecal microbiota play a fundamental role in deeply interconnecting the gut and brain injury. Therefore, we investigated the relationship between the temporal changes of the oral cavity and fecal bacterial communities with damage identification and post-injury time estimation after mTBI. In this study, we analyzed the oral cavity and fecal bacterial communities in mTBI rats under 12 different post-injury times (sham, 0 h, 2 h, 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, 7 d, 10 d, and 14 d post-injury) using 16S rRNA sequencing technology. The sequence results revealed bacteria belonging to 36 phyla, 82 classes, 211 orders, 360 families, 751 genera, and 1398 species. Compared to the sham group, the relative abundance of the bacterial communities varied markedly in the post-injury groups. Importantly, our data demonstrated that Fusobacteria, Prevotellaceae, Ruminococcaceae, and Lactobacillaceae might be the potential candidates for mTBI identification, and 2 h post-injury was a critical time point to explore the temporal changes of mTBI injury-time estimation. The results also provide new ideas for mTBI treatment in the clinic.

Sarcophaga peregrina (Robineau-Desvoidy, 1830) has the potential to estimate the minimum postmortem interval (PMImin). Development data and intra-puparial age estimation are significant for PMImin estimation. Previous research has focused on constant temperatures, although fluctuating temperatures are a more real scenario at a crime scene. The current study examined the growth patterns of S. peregrina under constant (25.75 °C) and fluctuating temperatures (18–36 °C; 22–30 °C). Furthermore, differentially expressed genes, attenuated total reflectance Fourier-transform infrared spectroscopy, and cuticular hydrocarbons of S. peregrina during the intra-puparial period were used to estimate age. The results indicated that S. peregrina at fluctuating temperatures took longer to develop and had a lower pupariation rate, eclosion rate, and pupal weight than the group at constant temperatures did. Moreover, we found that six DEG expression profiles and ATR-FTIR technology, CHCs detection methods, and chemometrics can potentially estimate the intra-puparial age of S. peregrina at both constant and fluctuating temperatures. The findings of the study support the use of S. peregrina for PMImin estimation and encourage the use of entomological evidence in forensic practice.

Sarcophaga tsinanensis (Fan, 1964) (Diptera: Sarcophagidae), a species from subgenus Heteronychia. In this study, we report the complete mitochondrial genome (mitogenome) of S. tsinanensis. The length of this mitogenome was 14,972 bp in total, containing 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a non-coding control region. The arrangement of genes was the same as that of ancestral metazoan. Sarcophaga tsinanensis has a high nucleotide bias in A/T accounting for 76.80% of total nucleotides (A 39.9%, G 9.2%, C 13.9%, and T 36.9%). The result of phylogenetic analysis revealed that S. tsinanensis cluster together with species from the same subgenus Heteronychia, showing a clear monophyletic relationship. Sarcophaga tsinanensis is closely related to its sister species Sarcophaga depressifrons, Sarcophaga plotnikovi, and Sarcophaga shnitnikovi. This study provides the mitochondrial data of S. tsinanensis for further research on evolutionary relationships and species identification of flesh flies.

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.

BackgroundPatients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.MethodsCOPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV1) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV1 >15% and >400 ml after bronchodilator.ResultsCOPD with concomitant features of asthma was found in 1.62% (95% CI 1.31–2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0–17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, P < 0.001), and with a lower post-bronchodilator FEV1%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, P < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.ConclusionsCOPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.

Sarcophaga peregrina (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae) is a forensically important flesh fly that has potential value in estimating the PMImin. The precise pupal age estimation has great implications for PMImin estimation. During larval development, the age determination is straightforward by the morphological changes and variation of length and weight, however, the pupal age estimation is more difficult due to anatomical and morphological changes not being visible. Thus, it is necessary to find new techniques and methods that can be implemented by standard experiments for accurate pupal age estimation. In this study, we first investigated the potential of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and cuticular hydrocarbons (CHCs) for the age estimations of S. peregrina pupae at different constant temperatures (20 °C, 25 °C, and 30 °C). The orthogonal projections latent structure discrimination analysis (OPLS-DA) classification model was used to distinguish the pupae samples of different developmental ages. Then, a multivariate statistical regression model, partial least squares (PLS), was established with the spectroscopic and hydrocarbon data for pupal age estimations. We identified 37 CHCs with a carbon chain length between 11 and 35 in the pupae of S. peregrina. The results of the OPLS-DA model show a significant separation between different developmental ages of pupae (R2X > 0.928, R2Y > 0.899, Q2 > 0.863). The PLS model had a satisfactory prediction with a good fit between the actual and predicted ages of the pupae (R2 > 0.927, RMSECV < 1.268). The results demonstrate that the variation tendencies of spectroscopy and hydrocarbons were time-dependent, and ATR-FTIR and CHCs may be optimal for the age estimations of pupae of forensically important flies with implications for PMImin estimation in forensic practice.

Abstract Background Previous studies have focused on the clinical characteristics of hospitalized patients with the novel 2019 coronavirus disease (COVID-19). Limited data are available for convalescent patients. This study aimed to evaluate the clinical characteristics of discharged COVID-19 patients. Methods In this retrospective study, we extracted data for 134 convalescent patients with COVID-19 in Guizhou Provincial Staff Hospital from February 15 to March 31, 2020. Cases were analyzed on the basis of demographic, clinical, and laboratory data as well as radiological features. Results Of 134 convalescent patients with COVID-19, 19 (14.2%) were severe cases, while 115 (85.8%) were non-severe cases. The median patient age was 33 years (IQR, 21.8 to 46.3), and the cohort included 69 men and 65 women. Compared with non-severe cases, severe patients were older and had more chronic comorbidities, especially hypertension, diabetes, and thyroid disease (P

Among the many treatments for Bladder cancer (BCa) patients, radiotherapy is an effective way to preserve the bladder. However, as the frequency of irradiation increases, the tumor cells appear ''acquired radio-resistance'' (ARR) and loss the sensitivity to radiotherapy. To explore the molecular mechanism of ARR, two BCa cell lines, 5637 and T24, were enrolled here and their ARR counterparts, 5637R and T24R, were obtained by exposure to γ-ray of 2 Gy for 30 times. Compared to parental cells, ARR cells have significantly enhanced stem cell-like phenotype, robust DNA damage repair capabilities and elevated expression of zeste homolog 2 (EZH2). Decreasing EZH2 expression, both parental and ARR cells exhibited reduced abilities of forming microsphere and repairing DNA damage, but enhanced cells radio-sensitivity and intracellular autophagy compared to untreated cells. Down-regulation the expression of EZH2 induced an increasing of both LC3 and P62 in parental cells, while in ARR cells, only LC3 increased upon EZH2 reduction. On the other hand, UNC1999 treatment caused the increasing of LC3B and P62 in all cells, suggested that siEZH2 and UNC1999 affect ARR cells autophagy through different mechanisms. In vivo study showed that pre-treated with UNC1999 greatly enhanced T24R cells sensitivity to IR, and knocking down the expression of EZH2 significantly suppressed the tumor growth. Combined with bioinformatics data analysis, we speculate that EZH2 is an important biomolecule linking the diagnosis, radiotherapy and prognosis of BCa. EZH2 targeted therapy may be an effective way to overcome ARR of BCa, and is worthy of in-depth study.

The Calliphoridae (blowflies) are significant for forensic science, veterinary management, medical science, and economic issues. However, the phylogenetic relationships within this family are poorly understood and controversial, and the status of the Calliphoridae has been a crucial problem for understanding the evolutionary relationships of the Oestroidea these years. In the present study, seven mitochondrial genomes (mitogenomes), including six calliphorid species and one Polleniidae species, were sequenced and annotated. Then a comparative mitochondrial genomic analysis among the Calliphoridae is presented. Additionally, the phylogenetic relationship of the Calliphoridae within the larger context of the other Oestroidea was reconstructed based on the mitogenomic datasets using maximum likelihood (ML) and Bayesian methods (BI). The results suggest that the gene arrangement, codon usage, and base composition are conserved within the calliphorid species. The phylogenetic analysis based on the mitogenomic dataset recovered the Calliphoridae as monophyletic and inferred the following topology within Oestroidea: (Oestridae (Sarcophagidae (Calliphoridae + (Polleniidae + (Mesembrinellidae + Tachinidae))))). Although the number of exemplar species is limited, further studies are required. Within the Calliphoridae, the Chrysomyinae were recovered as sister taxon to Luciliinae + Calliphorinae. Our analyses indicated that mitogenomic data have the potential for illuminating the phylogenetic relationships in the Oestroidea as well as for the classification of the Calliphoridae.

The devices used for human position detection in mechanical safety mainly include safety light curtain, safety laser scanner, safety pad, and vision system. However, these devices may be bypassed when used, and human or equipment cannot be distinguished. To solve this problem, a depth camera is proposed as a human position detection device in mechanical safety. The process of human position detection based on depth camera image information is given; it mainly includes image information acquisition, human presence detection, and distance measurement. Meanwhile, a human position detection method based on Intel RealSense depth camera and MobileNet-SSD algorithm is proposed and applied to robot safety protection. The result shows that the image information collected by the depth camera can detect the human position in real time, which can replace the existing mechanical safety human position detection device. At the same time, the depth camera can detect only human but not mobile devices and realize the separation and early warning of people and mobile devices.

Abstract Background The family cluster is one of most important modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission throughout China, and more details are needed about how family clusters cause the spread of coronavirus disease 2019 (COVID-19). Case presentation We retrospectively reviewed 7 confirmed cases from one family cluster. Both clinical features and laboratory examination results were described. Patient 1 had been in close contact with someone who was later confirmed to have COVID-19 in Wuhan City before he returned back to his hometown. He had dinner with 6 other members in his family. All the persons developed COVID-19 successively except for one older woman who neither had dinner with them nor shared a sleeping room with her husband. Six patients had mild or moderate COVID-19 but one older man with underlying diseases progressed into the severe type. After general and symptomatic treatments, all the patients recovered. Conclusions In a family cluster, having dinner together may be an important mode for the transmission of SARS-CoV-2. In this setting, most cases are mild with a favorable prognosis, while elderly patients with underlying diseases may progress into the severe type. For someone who has close contact with a confirmed case, 14-day isolation is necessary to contain virus transmission.

Abstract Background Although the fact that long non-coding RNA MCM3AP antisense RNA 1 (MCM3AP-AS1) is oncogenic in several cancers is well documented, very few researchers investigate its expression and function in prostate cancer. Methods Paired prostate cancer samples were selected, and expressions of MCM3AP-AS1, miR-876-5p and WNT5A were examined by qRT-PCR. MCM3AP-AS1 shRNA was transfected into LNCaP and PC-3 cell lines, and then the proliferative activity and apoptosis of cancer cells were detected by CCK-8 assay, EdU assay and flow cytometry analysis, respectively. qRT-PCR and Western blot were used to analyze the changes of miR-876-5p and WNT5A. Luciferase reporter gene assay was employed to determine the regulatory relationship between miR-876-5p and MCM3AP-AS1, miR-876-5p and WNT5A. Results MCM3AP-AS1 was significantly up-regulated in cancerous tissues of prostate cancer samples, positively correlated with the expression of WNT5A, while negatively related with miR-876-5p. After transfection of MCM3AP-AS1 shRNA into prostate cancer cells, the proliferative ability of cancer cells was signally inhibited, but the apoptosis of cancer cells was increased. MCM3AP-AS1 shRNA could reduce the expression of WNT5A on both mRNA and protein levels. Besides, MCM3AP-AS1 was identified as a sponge of miR-876-5p. WNT5A was validated as a target gene of miR- 876-5p. Conclusion MCM3AP-AS1 is abnormally up-regulated in prostate cancer tissues and can modulate the proliferation and apoptosis of prostate cancer cells, which has the potential to be the “ceRNA” to regulate the expression of WNT5A by targeting miR-876-5p.

Abstract Background The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria are widely used in the diagnosis of invasive pulmonary aspergillosis (IPA), but they only apply to immunocompromised patients. We here aimed to identify clinical characteristics helpful to the diagnosis of IPA in non-immunocompromised patients. Methods This is a multicenter retrospective study. Data were collected from adult patients with IPA admitted to 15 tertiary hospitals in China from 2010 to 2016. Results We included 254 patients in the study, of whom 66 (26.0%) were immunocompromised, and 188 (74.0%) were not. Airway-invasion-associated computed tomography (CT) signs including patchy exudation along the airway (67.6% vs. 45.5%, P = 0.001) and thickened airway wall (42.0% vs. 16.7%, P

Objectives: To explore the knowledge, attitude and practice of Chinese nurses regarding nursing interruptions and related factors. Methods: A total of 6,400 nurses from 31 hospitals in China were investigated by using the Knowledge, Attitude and Practice (KAP) Questionnaire of Nursing Interruptions. The questionnaire consists of three dimensions, knowledge, attitude and practice, containing 10, 9 and 7 items, with full score of 50, 45 and 28, respectively. Results: The mean overall KAP score regarding nursing interruptions of Chinese nurses was 74.05 ± 16.65 (range: 26–123), with scores for the knowledge, attitude, and practice component being 21.74 ± 9.80, 34.83 ± 6.98, and 17.49 ± 4.97, respectively. Among the nurses, 70.8% of them experienced an average level of KAP toward nursing interruptions while 15.5% were at a poor level. The knowledge, attitude, and practice of nursing interruptions were better in chief nurses, managers, nurses with a master degree or above, nurses ever received training, and nurses with a strong agreement to leadership compared to nurses in other groups (P

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

Primary pulmonary high-grade mucoepidermoid carcinoma (MEC) with a cystic airspace is uncommon, and early metastasis is extremely rare. In such cases, however, it is clinically important for clinicians to consider whether the tumor has spread to the lymph nodes through the cystic airspace. A 77-year-old man presented to our hospital with cough and hemoptysis. Chest computed tomography showed a 25-mm-diameter mass with a cystic airspace located in the upper lobe of the left lung. The possibility of malignancy was considered. Without a definitive preoperative diagnosis, left upper lobectomy and mediastinal lymphadenectomy were performed. Histopathological examination revealed the typical histological characteristics of high-grade MEC (stage IA) and no lymph node metastasis. However, lymph node metastasis was found 6 months after surgical resection, and radiochemotherapy was performed. The patient developed widespread metastatic disease 4 months following completion of radiochemotherapy and died 2 months later. Primary pulmonary MEC with a cystic airspace is a rare malignant disease with uncommon imaging findings. Complete surgical resection is the main treatment method for high-grade MEC. In this case, we hypothesize that early metastasis was caused by seeding of tumor cells through the cystic airspace.

Empty puparium are frequently collected at crime scenes and may provide valuable evidence in cases with a long postmortem interval (PMI). Here, we collected the puparium of Sarcophaga peregrina (Diptera: Sarcophagidae) (Robineau-Desvoidy, 1830) for 120 days at three temperatures (10 °C, 25 °C, and 40 °C) with the aim to estimate the weathering time of empty puparium. The CHC profiles were analyzed by gas chromatography-mass spectrometry (GC-MS). The partial least squares (PLS), support vector regression (SVR), and artificial neural network (ANN) models were used to estimate the weathering time. This identified 49 CHCs with a carbon chain length between 10 and 33 in empty puparium. The three models demonstrate that the variation tendency of hydrocarbon could be used to estimate the weathering time, while the ANN models show the best predictive ability among these three models. This work indicated that puparial hydrocarbon weathering has certain regularity with weathering time and can gain insight into estimating PMI in forensic investigations.

Sarcophaga caerulescens (Zetterstedt 1838) (Diptera: Sarcophagidae) belongs to Sarcophagidae, which is closely associated with human life in ecological habits and has a clear environmental preference. Sarcophaga caerulescens can be better correlated with migration and postmortem interval (PMI) inference in forensic practice. In this study, we reported the complete mitochondrial genome (mitogenome) of S. caerulescens. The length of this mitogenome was 15,720 bp in total (GenBank accession No. MW551788), containing 13 protein-coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and a non-coding control region. Its nucleotide composition was A (39.7%), C (14.1%), G (9.4%), and T (36.9%). The phylogenetic relationships indicated that the species of S. caerulescens was closely related to S. similis. This study provides the mitochondrial data of S. caerulescens for further study of mitochondrial genome and enriches our understanding of the phylogenetic relationship of sarcophagid flies.