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Abstract Background The objective of this study was to develop a scale to assess eating behaviors of school-aged children (6–12 years old) in China. Methods To develop the scale, a literature review and qualitative interviews were conducted. The draft scale contained 115 items and went through three evaluations among three groups of caregivers (n = 140, 400, 700) selected from suburban and urban kindergartens in Xi’an, Hanzhong, and Yanan, China, from March 2017 to October 2018. The psychometric properties of the scale were assessed using exploratory, confirmatory factor analysis, and variability analysis. Results The final scale consisted of 46 items across eight dimensions including food fussiness, satiety responsiveness, food responsiveness, bad eating habits, susceptible diet, restrained eating, enjoyment of food, and junk food addiction. The total cumulative variance contribution rate was 52.16%. The scale and dimensions' Cronbach’s α coefficients, Guttman split-half reliability, and test- retest reliability were all above 0.65. The fitting indices for the confirmatory factor analysis were all close to 1. The scores for education of caregiver, family structure, and the body mass index of children were different among dimensions and groups, thus suggesting good discriminative utility. Conclusions All of the results indicated that the scale has good reliability and construct validity for evaluating the eating behaviors of school-aged children in China.

Abstract Baicalein is a biologically important flavonoid in extracted from the Scutellaria baicalensis Georgi, which can effectively inhibit the influenza virus. This study aimed to analyze the safety and pharmacokinetic (PK) characteristics of baicalein tablets in healthy Chinese subjects and provide more information for phase II clinical trials. In this multiple‐ascending‐dose placebo‐controlled trial, 36 healthy subjects were randomized to receive 200, 400, and 600 mg of baicalein tablet or placebo once daily on day 1 and day 10, 3 times daily on days 4–9. All groups were intended to produce safety and tolerability outcomes (lowest dose first). Blood and urine samples were collected from subjects in the 600 mg group for baicalein PK analysis. Our study had shown that Baicalein tablet was generally safe and well‐tolerated. All adverse events were mild and resolved without any intervention except one case of fever reported in the 600 mg group, which was considered as moderate but not related with baicalein as judged by the investigator. Oral baicalein tablets were rapidly absorbed with peak plasma levels being reached within 2 h after multiple administration. The highest urinary excretion of baicalein and its metabolites peaked in 2 h, followed by 12 h, with a double peak trend.

Cervical cancer, as the second most common female malignancy, brings a great health burden to women worldwide. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are the most common histological subtypes of cervical cancer. CXC chemokines (CXCLs) within the tumor microenvironment can modulate carcinogenesis and progression. The present study aimed to explore the therapeutic and prognostic value of different CXCLs in CESC. ONCOMINE, GEPIA, cBioPortal, TRRUST, GeneMANIA, STRING and TIMER were utilized to explore the expression, mutation and function of CXCLs in CESC, as well as their correlation with pathological and survival features of CESC patients. We found that the mRNA expression levels of CXCL1/8/9/10/11/13/16/17 in CESC were upregulated compared with normal cervical tissues, whereas CXCL12 was downregulated. No significant correlation was found between the expression levels and pathological stage of CESC patients. CESC patients with high expression of CXCL1/2/3/4/5/8 were significantly associated with poor overall survival, additionally, low mRNA level of CXCL3 was associated with better disease-free survival. Besides, a high mutation rate (43%) of CXCLs in CESC was observed. Depicted by co-expression analysis, the expression of CXCL1/2/3/6/8 showed a modest to strong correlation, while that of CXCL9/10/11/13 showed a very strong correlation. Differentially expressed CXCLs primarily functioned in chemokine signaling pathway and inflammation response, such as cell chemotaxis, chemokine activity and chemokine receptor binding. We also found the association of CXCLs with the tumor-infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells) in CESC patients. The present study elucidated that CXCLs may have the potential to be novel therapeutic targets and prognosis predictors of CESC patients.

Abstract Severe coronavirus disease 2019 (COVID-19) is often indicated by lymphopenia and increased myelopoiesis; however, the underlying mechanism is still unclear, especially the alteration of hematopoiesis. It is important to explore to what extent and how hematopoietic stem cells contribute to the impairment of peripheral lymphoid and myeloid compartments in COVID-19 patients. In this study, we used single-cell RNA sequencing to assess bone marrow mononuclear cells from COVID-19 patients with peripheral blood mononuclear cells as control. The results showed that the hematopoietic stem cells in these patients were mainly in the G1 phase and prone to apoptosis, with immune activation and anti-viral responses. Importantly, a significant accumulation of immature myeloid progenitors and a dramatic reduction of lymphoid progenitors in severe cases were identified, along with the up-regulation of transcription factors (such as SPI1, LMO4, ETS2, FLI1, and GATA2) that are important for the hematopoietic stem cell or multipotent progenitor to differentiate into downstream progenitors. Our results indicate a dysregulated hematopoiesis in patients with severe COVID-19.

Abstract. Background:. Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service (EMS). This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China. Methods:. A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally. Four status of awareness and annual income were identified: unaware and low-income, unaware-only, low-income-only, and aware and regular income. The outcomes were whether they intended to call EMS or not. The regional distribution of each status and their associations with not calling EMS were presented. Results:. The status of unaware and low-income, unaware-only, and low-income-only accounted for 6.3% (11,806/187,673), 11.9% (22,241/187,673), and 21.5% (40,289/187,673) of the total sample, respectively. Not calling EMS was significantly associated with the status of unaware and low-income (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 3.07–3.35), unaware-only (OR: 2.38, 95% CI: 2.31–2.46), and low-income-only (OR: 1.67, 95% CI: 1.63–1.71), compared with the aware and regular income status. The Midwest regions had higher percentages of people in the unaware and low-income status; the East, South, and Central had higher percentages of unaware-only status; the North and Northeast regions had a higher percentage of low-income-only status, compared with other regions. Conclusion:. The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.

Abstract Background It remains challenging to differentiate tuberculosis (TB) from non-TB pulmonary infections in HIV-infected patients. Herein, we developed a scoring system aimed to rapidly determine the likelihood of TB or non-TB pathology in HIV-infected patients presenting with pulmonary infections. Methods We collected and collated data of hospitalized HIV-infected patients with pulmonary infections, followed by univariate and multivariate data analyses to determine risk variables that were significantly different between HIV/TB patients and HIV/non-TB patients. Subsequently, a regression coefficient was calculated for each variable, and a score was assigned to each variable in line with its regression coefficient. The sum of the scores for each variable in our scoring model was used to predict the likelihood of TB or non-TB pulmonary infection in each patient. Finally, we tested the diagnostic accuracy of the scoring system in our retrospective cohort, as well as in a prospective cohort. Results A total of 598 HIV-infected patients were enrolled in our retrospective cohort, among whom 288 had TB and 310 had non-TB pulmonary infections. Eight variables, including fever, highest body temperature, erythrocyte sedimentation rate (ESR), cervical lymphadenopathy, hilar and/or mediastinum lymphadenopathy, pulmonary cavitation, pleural effusion, and miliary nodules, were found to be mathematically significantly different via univariate analysis and multivariate logistic regression analysis. After regression coefficient calculation followed by score assignment, a receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) was calculated to be 0.902. When the total score for a patient is > 12, the sensitivity and specificity for TB prediction using our scoring system were 76.4% and 87.7% respectively in the retrospective cohort, and its diagnostic accuracy was 82.7% in the prospective cohort. Conclusions Our results demonstrate that our proposed diagnostic scoring system could be helpful in differentiating pulmonary TB from non-TB pulmonary infections in HIV-infected patients.

Abstract Novel modalities such as PROTAC and RNAi have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target binding or activity of small molecules, do not fully assess the off-target effects of PROTAC and are not applicable to RNAi. To address this gap, we developed a proteomics-based platform to comprehensively evaluate the abundance of off-target proteins. First, we selected off-target proteins using genetics and pharmacology evidence. This process yielded 2813 proteins, which we refer to as the “selected off-target proteome” (SOTP). An iterative algorithm was then used to identify four human cell lines out of 932. The 4 cell lines collectively expressed ~ 80% of the SOTP based on transcriptome data. Second, we used mass spectrometry to quantify the intracellular and extracellular proteins from the selected cell lines. Among over 10,000 quantifiable proteins identified, 1828 were part of the predefined SOTP. The SOTP was designed to be easily modified or expanded, owing to the rational selection process developed and the label free LC–MS/MS approach chosen. This versatility inherent to our platform is essential to design fit-for-purpose studies that can address the dynamic questions faced in investigative toxicology.

Abstract Background The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome. Methods Adult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment. Results The results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI. Conclusions Our findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.

Abstract Background Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis. Methods This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established. Results Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0–30, 31–60, 61–90, 91–120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups. Conclusions Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.

Abstract Objectives To comprehend the relationship between various indicators of health service equity and patients’ health expenditure poverty in different regions of China, identify areas where equity in health service is lacking and provide ideas for improving patients’ health expenditure poverty. Method Data from China Family Panel Studies (CFPS) in 2018 and the HFGT index formula were used to calculate the health expenditure poverty index of each province. Moreover, Global Moran’s I and Local Moran’s I test are applied to measure whether there is spatial aggregation of health expenditure poverty. Finally, an elastic net regression model is established to analyze the impact of health service equity on health expenditure poverty, with the breadth of health expenditure poverty as the dependent variable and health service equity as the independent variable. Results In the developed eastern provinces of China, the breadth of health expenditure poverty is relatively low. There is a significant positive spatial agglomeration. “Primary medical and health institutions per 1,000 population”, “rural doctors and health workers per 1,000 population”, “beds in primary medical institutions per 1,000 population”, “proportion of government health expenditure” and “number of times to participate in medical insurance (be aided) per 1,000 population” have a positive impact on health expenditure poverty. “Number of health examinations per capita” and “total health expenditure per capita” have a negative impact on health expenditure poverty. Both effects passed the significance test. Conclusion To enhance the fairness of health resource allocation in China and to alleviate health expenditure poverty, China should rationally plan the allocation of health resources at the grassroots level, strengthen the implementation of hierarchical diagnosis and treatment and encourage the investment in business medical insurance industry. Meanwhile, it is necessary to increase the intensity of medical assistance and enrich financing methods. All medical expenses of the poorest should be covered by the government.

Anthropogenic pressures are the main drivers of freshwater biodiversity loss. Lakes can act as sentinels of both local and regional changes and experience increased anthropogenic disturbances. Functional traits have been developed to elucidate the consequential functional progression of community changes, yet only a few studies on rotifer functional approaches exist compared with other biotic community attributes. Here, we investigate the responses of rotifer taxonomic and functional diversity metrics to an environmental gradient representing changing lake morphology, land use and physicochemical conditions in 30 lakes along the Yangtze River, China. Based on the distinct lake morphological gradient, land use patterns and environmental conditions, the 30 lakes were clustered into three groups with decreasing anthropogenic stress from Group 1 to Group 3. Our findings indicated that both species and functional richness decreased from Group 1 to Group 3 and that functional richness exhibited better correspondence with multiple stressors than did taxonomic richness. Moreover, we found that the rotifer assemblages varied significantly among the three lake groups along land use and environmental gradients, and the community-weighted means (CWM) of trait expression of the corresponding communities changed simultaneously. Types of trophi and corona were considered as the most variable traits among the three lake groups. We highlight that trait-based approaches are more sensitive, responsive and informative than taxonomic approaches in indicating human-induced environmental alterations in freshwater ecosystems.

A newly excavated ritual site, Xuechi, exposed abundant sacrificial livestock, allowing to understand the supplies and managements of livestock during the early Chinese Qin-Han Empires. Here we reported animal enamel 87Sr/86Sr values from the Xuechi site that are obviously higher than those of local snails and surface water, as well as calcites of the Chinese Loess Plateau (CLP) where the site was located, strongly suggesting that these sacrificial animals were not raised in the vicinity of the site. The regional bioavailable 87Sr/86Sr isoscape further indicates that some livestock were probably derived more than one hundred kilometers away, suggesting a complex social network for recruiting and managing the sacrificial activities. In the context of other Neolithic-Bronze Age records on the CLP, an increasing trend in variation of faunal 87Sr/86Sr values shows a robust correlation to Chinese states’ trajectory, in concordance with the territorial expansion model for state formation.

BackgroundConcomitant intrahepatic ectopic thyroid is rare in patients with hepatocellular carcinoma. Thyroid follicular structures outside the hepatocellular carcinoma lesions are regarded as satellite nodules or intrahepatic metastases of hepatocellular carcinoma, which often leads to misdiagnosis and overtreatment of hepatocellular carcinoma patients.Case presentationWe report the case of an 83-year-old man with moderately differentiated hepatocellular carcinoma (2.5 cm) whose liver contained ectopic thyroid tissue. An encapsulated, multinodular grayish-yellow mass and multiple satellite nodules were detected and removed by right hepatic lobectomy. Microscopically, the main tumor displayed a predominant trabecular, cord-like structure. Liver tissue 0.5 cm from the tumor had a benign-appearing follicular thyroid structure. The follicles contained colloid tissue and were lined with low cuboidal cells with scant cytoplasm; lymphatic tissue was also present in the area. The hepatocellular carcinoma cells were positive for hepatocyte antigen and glypican-3 and negative for cytokeratin 19. The follicular thyroid cells expressed thyroglobulin, PAX8, and thyroid transcription factor-1. A metastatic thyroid neoplasm was excluded clinically and by ultrasound and computed tomography. One month after surgery, all of the patient's serological markers were normal; no tumor recurrence or metastasis has been detected for 7 postoperative months.ConclusionsThe finding of ectopic thyroid tissue in the liver of a patient with hepatocellular carcinoma is very rare. The possibility of hepatocellular carcinoma forming satellite nodules and intrahepatic metastasis should be ruled out first and immunohistochemistry may be definitive in making the diagnosis. Further examination is needed to exclude thyroid cancer liver metastases.

Colon cancer (CC) is a multistage disease and one of the most common cancers worldwide. Establishing an effective treatment strategies of early colon cancer is of great significance for preventing its development and reducing mortality. The occurrence of colon cancer is closely related to changes in the intestinal flora structure. Therefore, remodelling the intestinal flora structure through prebiotics is a powerful approach for preventing and treating the occurrence and development of colon cancer. Isomaltooligosaccharides (IMOs) are often found in fermented foods and can directly reach the gut for use by microorganisms. In this study, a rat model of early colon cancer (DMH) was established by subcutaneous injection of 1,2-dimethylhydrazine, and the model rats were fed IMOs as a dietary intervention (DI). The untargeted faecal metabolomics, gut metabolome and intestinal function of the model rats were investigated. The results showed that DMH, DI and IMOs alone (IMOs) groups exhibited gut microbial community changes. In the DI group, there was an increased abundance of probiotics (Lactobacillus) and decreased abundance of CC marker bacteria (Fusobacterium). The key variations in the faecal metabolites of the DI group included decreased levels of glucose, bile acids (including deoxycholic acid and chenodeoxycholic acid) and amino acids (including L-glutamic acid and L-alanine). In addition, dietary intake of IMOs attenuated the intestinal inflammatory response, improved the intestinal microecological environment, and slowed the development of DMH-induced early CC in rats. This work provides a theoretical basis and technical support for the clinical prevention or treatment of CC with prebiotics.

The Burkholderia cepacia complex (BCC) is a group of opportunistic pathogens, including Burkholderia cepacia, Burkholderia multivorans, Burkholderia vietnamiensis and Burkholderia ambifaria, which can cause severe respiratory tract infections and lead to high mortality rates among humans. The early diagnosis and effective treatment of BCC infection are therefore crucial. In this study, a novel and rapid recombinase-aided amplification (RAA) assay targeting the 16S rRNA gene was developed for BCC detection. The protocol for this RAA assay could be completed in 10 min at 39°C, with a sensitivity of 10 copies per reaction and no cross-reactivity with other pathogens. To characterize the effectiveness of the RAA assay, we further collected 269 clinical samples from patients with bacterial pneumonia. The sensitivity and specificity of the RAA assay were 100% and 98.5%, respectively. Seven BCC-infected patients were detected using the RAA assay, and three BCC strains were isolated from the 269 clinical samples. Our data showed that the prevalence of BCC infection was 2.60%, which is higher than the 1.40% reported in previous studies, suggesting that high sensitivity is vital to BCC detection. We also screened a patient with B. vietnamiensis infection using the RAA assay in clinic, allowing for appropriate treatment to be initiated rapidly. Together, these data indicate that the RAA assay targeting the 16S rRNA gene can be applied for the early and rapid detection of BCC pathogens in patients with an uncharacterized infection who are immunocompromised or have underlying diseases, thereby providing guidance for effective treatment.

Abstract Background The C–C chemokine receptor 5 (CCR5) is mainly expressed in a variety of immune cells. It interacts with multiple chemokine ligands that mediate the trafficking and recruitment of effector cells toward sites of inflammation. CCR5 not only plays a critical role in cell growth, activation, differentiation, adhesion, and migration but also participates in the development of acute graft‐versus‐host disease (GVHD) after allogeneic hematopoietic cell transplantation. Methods This is a literature review article. The research design method is an evidence‐based rapid review. The present discourse aim is first to scrutinize and assess the available literature on CCR5 and acute GVHD. Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. Results CCR5 is a marker of GVHD effector cells, and CCR5 expression is elevated when acute GVHD occurs. CCR5 blockade with maraviroc in clinical trials results in a low incidence of acute GVHD. The immune mechanism includes that CCR5 blockade inhibits donor T cell migration and recruitment toward target organs, reduces the absolute numbers of donor T cells, is capable of slightly suppressing dendritic cell maturation, and reduces the percentage of Th1 and Th17 subsets. CCR5 blockade also inhibits internalization and activation of chemokines, inhibits proliferation and chemotaxis of T cells, and decreases the production of TNF‐α and IFN‐γ. In addition, there may be a form of crosstalk between CCR5 and CCR2. Inconsistently, infusion of CCR5−/− Tregs into lethally irradiated mice significantly increased the infiltration of CD4+ and CD8+ T cells into the liver, resulting in earlier and more severe GVHD. Conclusion This review indicates that CCR5 plays an important role in pathogenesis and development of acute GVHD. Elucidating its role in different immune cells will aid the development of targeted therapeutic treatments.

Objective: Immune inflammatory cells and cytokines play an important role in the occurrence and development of diabetic nephropathy (DN). Acteoside has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of acteoside on the expressions of MCP-1 and TGF-β 1 on nephropathy in diabetic mice. Methods: C57BL/6J mice in the model group were given a single intraperitoneal injection of STZ (150 mg/kg). Model mice were divided randomly into two groups: 5 without treatment, 5 treated with acteoside. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected, then, ralated biochemical parameters, pathological characteristics and MCP-1 and TGF-β1 mRNA or protein were detected. The NRK-52E cells were divided into three groups as follows: the normal control group (NC group), the high glucose group (HS group), the high glucose+acteoside group (HS+ACT group). The expressions of MCP-1 and TGF-β 1 in the mRNA and protein levels were assessed with RT-PCR, western blot and ELISA. Results: The expressions of MCP-1 and TGF-β 1 were significantly enhanced in DN group and dramatically reduced after acteoside treatment. Compared with those in NC group, the expressions of MCP-1 and TGF-β 1 in NRK-52E cell of HS group were significantly enhanced, while both were significantly decreased in HS+ACT group compared with HS group. Conclusion: Our findings indicate that Acteoside has protective effects on DN via inhibiting the expressions of MCP-1 and TGF-β 1 .

Background: Inappropriate medication use is common around the world, particularly among older patients, and, despite potentially being preventable, often leads to adverse clinical and economic outcomes. However, there is a dearth of information regarding this prominent issue in China.Objectives: To evaluate the extent to which the physician can correctly identify potentially inappropriate medication (PIM) in older patients and to understand physicians’ attitudes towards improving PIM knowledge.Methods: An online, cross-sectional survey was conducted anonymously among practicing physicians in China from November through December 2020. Knowledge of PIM was accessed using seven clinical vignettes covering a wide variety of therapeutic areas. Source of information and perceived barriers regarding PIM were also evaluated. We performed the ordinary least square regression analysis to understand the potential factors related to physicians’ knowledge of PIM.Results: A total of 597 study participants were included in the analysis. More than half of them had never heard of any screening tool for PIMs (n = 328, 54.9%) and the most frequently acknowledged tool was the China PIM Criteria (n = 259, 43.4%). For the seven clinical vignettes testing physicians’ knowledge on the medications that should be generally avoided in older patients, the mean score was 2.91 points out of 7 (SD: 1.32), with the median score of three points (IQR: 2–4). Only one-third of the respondents were feeling confident when prescribing for older patients (n = 255, 35.08%). Package inserts have been used as the major source of PIM information (always, n = 177, 29.65%; frequently, n = 286, 47.91%). Perceived barriers to appropriate prescribing include polypharmacy (n = 460, 77.05%), lack of formal education on prescribing for the older patients (n = 428, 71.69%).Conclusion: In this online survey evaluating physicians’ ability to detect PIM for older patients, approximately 40% of PIM were recognized, suggesting an insufficient level of knowledge about appropriate prescribing.

Obtaining various structures of the entire mature heart at single-cell resolution is highly desired in cardiac studies; however, effective methodologies are still lacking. Here, we propose a pipeline for labeling and imaging myocardial and vascular structures. In this pipeline, the myocardium is counterstained using fluorescent dyes and the cardiovasculature is labeled using transgenic markers. High-definition dual-color fluorescence micro-optical sectioning tomography is used to perform heart-wide tissue imaging, enabling the acquisition of whole-heart data at a voxel resolution of 0.32 × 0.32 × 1 μm3. Obtained structural data demonstrated the superiority of the pipeline. In particular, the three-dimensional morphology and spatial arrangement of reconstructed cardiomyocytes were revealed, and high-resolution vascular data helped determine differences in the features of endothelial cells and complex coiled capillaries. Our pipeline can be used in cardiac studies for examining the structures of the entire heart at the single-cell level.

Summary: Optical visualization of complex microstructures in the entire organ is essential for biomedical research. However, the existing methods fail to accurately acquire the detailed microstructures of whole organs with good morphological and biochemical preservation. This study proposes a cryo-fluorescence micro-optical sectioning tomography (cryo-fMOST) to image whole organs in three dimensions (3D) with submicron resolution. The system comprises a line-illumination microscope module, cryo-microtome, three-stage refrigeration module, and heat insulation device. To demonstrate the imaging capacity and wide applicability of the system, we imaged and reconstructed various organs of mice in 3D, including the healthy tongue, kidney, and brain, as well as the infarcted heart. More importantly, imaged brain slices were performed sugar phosphates determination and fluorescence in situ hybridization imaging to verify the compatibility of multi-omics measurements. The results demonstrated that cryo-fMOST is capable of acquiring high-resolution morphological details of various whole organs and may be potentially useful for spatial multi-omics.

Rapid development of aquaculture industry and increasing demand of various inputs (especially antibiotics), are suspected to promote the occurrence and spread of ARGs in aquaculture related environments. However, the occurrences of ARGs under different freshwater aquaculture practices are rarely known. Here, we investigated the seasonal profiles of the main ARGs, intI1 and bacteria in waters from three kinds of predominant freshwater aquaculture practices around the Honghu Lake (China), as well as their co-occurrences and interrelationships with antibiotics, heavy metals and general water quality. The results indicate that quinolone resistance genes (qnrB), tetracycline resistance genes (tetB and tetX) and sulfonamide resistance genes (sul1 and sul2) were the top five predominant ARGs with seasonal variations of abundance. Fish ponds were of the highest absolute abundances of tested ARGs than the other two modes. Crayfish ponds and their adjacent ditches shared similar ARGs profile. Different subtypes of ARGs belonging to the same class of resistance were varied in abundances. Some bacteria were predicted to carry different ARGs, which indicating multi-antibiotic resistances. Moreover, the combined environmental factors (antibiotics, heavy metals and water quality) partially shaped the profiles of ARGs and bacteria composition. Overall, this study provides new comprehensive understanding on the characterization of ARGs contamination in different freshwater aquaculture practices from the perspectives of environmental chemistry, microbiology and ecology. The results would benefit the optimization of aquaculture practices toward environmental integrity and sustainability.

The dynamic assembly of SKP1•CUL1•F-box protein (SCF) ubiquitin ligases is important for protein ubiquitination and degradation. This process is enabled by CAND1, which exchanges F-box proteins associated with the common CUL1 scaffold, and thereby, recycles the limited CUL1 core and allows diverse F-box proteins to assemble active SCFs. Previous human cell biological and computational studies have led to the adaptive exchange hypothesis, which suggests that the CAND1-mediated exchange confers plasticity on the SCF system, allowing cells to tolerate large variations in F-box protein expression. Here, we tested this hypothesis using Arabidopsis thaliana, a multicellular organism expressing hundreds of F-box protein genes at variable levels in different tissues. The cand1 null mutant in Arabidopsis is viable but produce almost no seeds. Bioinformatic, cell biological, and developmental analyses revealed that the low fertility in the cand1 mutant is associated with cell death in pollen, where the net expression of F-box protein genes is significantly higher than any other Arabidopsis tissue. In addition, we show that the transmission efficiency of the cand1 null allele was reduced through the male but not the female gametophyte. Our results suggest that CAND1 activity is essential in cells or tissues expressing high levels of F-box proteins. This finding is consistent with the proposed adaptive exchange hypothesis, demonstrating the necessity of the evolutionarily conserved CAND1-mediated exchange system in the development of a multicellular organism.

Liver transplantation is widely acknowledged as the only effective treatment for end-stage liver disease, and infection is reportedly an important cause of postoperative death. Clinical use of metagenomic next-generation sequencing (mNGS) to diagnose postoperative infection and successfully guide drug therapy remains rare. This study included patients with infectious complications after liver transplantation from July 2019 to December 2020 and was divided into three groups: pneumonia, unknown fever, and others (including hepatic failure, kidney failure, cirrhosis after LT, and other postoperative complications that predispose to infection). The mNGS sequencing was used to detect microorganisms, and the results were compared with traditional culture. We found that mNGS yielded improved sensitivity over culture (85.19 vs. 22.22%; p

Molecular assays on nasopharyngeal swabs act as a confirmatory test in coronavirus disease (COVID-19) diagnosis. However, the technical requirements of nasopharyngeal sampling and molecular assays limit the testing capabilities. Recent studies suggest the use of saliva for the COVID-19 diagnostic test. In this study, 44 patients diagnosed with COVID-19 in The Third People’s Hospital of Shenzhen were enrolled. Saliva and serum specimens were obtained at different time points and the immunoglobulins against SARS-CoV-2 were measured. The results showed that saliva IgA presented a higher COI value than IgG and IgM. In matched saliva and serum samples, all saliva samples presented lower IgG levels than serum samples, and only one saliva sample presented a higher IgM level. The conversion rates of saliva IgA and the detection of viral nucleic acids were analyzed in the first and second weeks after hospitalization. The positive rates increased when combining saliva IgA and viral nucleic acid detection. In conclusion, our results provide evidence that saliva IgA could serve as a useful index for the early diagnosis of COVID-19.

Malaria is caused by infection of the erythrocytes by the parasites Plasmodium. Inside the erythrocytes, the parasites multiply via schizogony, an unconventional cell division mode. The inner membrane complex (IMC), an organelle located beneath the parasite plasma membrane, serving as the platform for protein anchorage, is essential for schizogony. So far, the complete repertoire of IMC proteins and their localization determinants remain unclear. Here we used biotin ligase (TurboID)-based proximity labeling to compile the proteome of the schizont IMC of the rodent malaria parasite Plasmodium yoelii. In total, 300 TurboID-interacting proteins were identified. 18 of 21 selected candidates were confirmed to localize in the IMC, indicating good reliability. In light of the existing palmitome of Plasmodium falciparum, 83 proteins of the P. yoelii IMC proteome are potentially palmitoylated. We further identified DHHC2 as the major resident palmitoyl-acyl-transferase of the IMC. Depletion of DHHC2 led to defective schizont segmentation and growth arrest both in vitro and in vivo. DHHC2 was found to palmitoylate two critical IMC proteins CDPK1 and GAP45 for their IMC localization. In summary, this study reports an inventory of new IMC proteins and demonstrates a central role of DHHC2 in governing the IMC localization of proteins during the schizont development.

Staphylococcus aureus is an opportunistic human pathogen that is often involved in severe infections such as pneumonia and sepsis in which bacterial virulence factors play a key role. Infections caused by S. aureus are often difficult to eradicate, particularly when they are associated with biofilm. The physiological roles of the Crp/Fnr family regulator ArcR are elusive in S. aureus. In this study, it was found that the deletion of arcR increased the hemolytic ability and biofilm formation in S. aureus. Differential gene expression analysis by RNA-seq and real-time quantitative reverse transcription PCR showed that genes associated with hemolytic ability (hla and hlb) and biofilm formation (icaA, icaB, icaC and icaD) were significantly upregulated compared with those in the wild-type strain. The results revealed that ArcR regulated the expression of the hla and ica operon by binding to their promoter regions, respectively. This study provided new insights into the functional importance of ArcR in regulating the virulence and biofilm of S. aureus.

The various industries, sectors, and citizens’ daily lives have undergone significant changes after the outbreak of the COVID-19 pandemic. The researchers collected and analyzed PM2.5 samples including secondary inorganic ions (SO42−, NO3−, and NH4+, namely SNA), organic carbon (OC), elemental carbon (EC), and other 16 metal elements in Beijing in 2019 (before the pandemic) and 2020 (after the pandemic). The particulate matter (PM2.5) concentration in the autumn and winter of 2020 is 21.16 µg/m3 and 14.05 µg/m3 lower than in 2019, respectively. The contribution of six sources of pollution, including coal combustion, secondary sources, transportation-related sources, dust, Industrial I, and Industrial II, were analyzed using the Positive Matrix Factorization (PMF) model. Due to the impacts of the COVID-19 pandemic, more and more people are choosing private transportation, such as private cars, instead of public transportation. As a result, the contribution of PM2.5 pollution related to transportation increased after the pandemic. The metal elements measured during the sampling period represent only a very small fraction (1%) of PM2.5. However, their health risk to humans cannot be ignored because of the toxicity of some metallic elements, and the carcinogenic risks induced by metal elements in PM2.5 exceeded the safety threshold (>10−6) during the autumn and winter of 2019 and 2020. Arsenic (As) contributes the most to carcinogenic risk, so controlling arsenic emissions is the primary approach to reducing cancer risk in Beijing. Considering the contribution to the health risk from various sources obtained in PMF, coal combustion is the most significant contributor to cancer risk. Therefore, serious consideration should be given to controlling coal combustion at the local and regional levels to reduce health risks in Beijing.

Cattle are one of the six livestock species that have occupied an important place in Chinese history. Previous ancient DNA studies have indicated that Chinese taurine cattle (Bos taurus taurus) are exotic, but the exact route and diffusion by which they were introduced to China is unknown. In this study, we extracted the mitochondrial genomes of 34 cases of ancient taurine cattle (from the late Neolithic to Qin and Han dynasties) excavated from sites in northern China and the eastern Eurasian steppe, and successfully obtained 14 mitochondrial genome sequences. The results of ancient DNA analysis reveal that with cultural exchange and trade, there was close genetic exchange between domestic taurine cattle in different regions. The haplotypes shared by domestic cattle have genetic continuity, reflecting the strong cultural influence of the large capital city sites such as Taosi, Shimao and Erlitou on the surrounding areas. This study suggests that ancient northern Chinese taurine cattle may have accompanied the westward transmission of agricultural or painted pottery culture and thus had a maternal genetic contribution to modern Tibetan cattle.

Virtual water exerts an essential effect on water resources, yet such effect is rarely considered in current studies on water rights allocation in transboundary rivers. Hence, this paper ran a case study on Taihu Lake Basin, collecting data from 2017 to make clear the physical water rights of four regions—Jiangsu Province, Zhejiang Province, Anhui Province, and Shanghai City—in the Basin. After that, the multiregional input–output (MRIO) approach was utilized to measure the trade in value-added (TiVA) transfer and virtual water transfer (VWT) and construct an inequality index of VWT (VWI). Next, water efficiency coefficient was employed to convert the VWT into riparian level. Finally, VWT and VWI were incorporated into the water rights allocation model to form up a water rights allocation scheme for Taihu Lake Basin. Results showed: (1) Jiangsu enjoys the most allocated physical water rights, followed by Zhejiang, and Anhui ranks the lowest; (2) Anhui and Jiangsu are net virtual water exporters (2.259 billion m3 and 1.78 billion m3, respectively), while Zhejiang and Shanghai are net importers (2.344 billion m3 and 1.695 billion m3, respectively); (3) Anhui suffers the most inequality—0.4401—followed by 0.5076 of Jiangsu, while Zhejiang has the most equal environment—0.7012; (4) after the inclusion of virtual water, the quantity of water rights allocation changes, whereas Anhui experiences the largest growth—144 million m3—due to the dual effects from the highest VWT and inequality. In conclusion, the effect of virtual water is indispensable, so VWT and VWI should both be considered in the physical water rights allocation of transboundary rivers.

Total electron content (TEC) is a vital parameter for describing the state of the ionosphere, and precise prediction of TEC is of great significance for improving the accuracy of the Global Navigation Satellite System (GNSS). At present, most deep learning prediction models just consider TEC temporal variation, while ignoring the impact of spatial location. In this paper, we propose a TEC prediction model, ED-ConvLSTM, which combines convolutional neural networks with recurrent neural networks to simultaneously consider spatiotemporal features. Our ED-ConvLSTM model is built based on the encoder-decoder architecture, which includes two modules: encoder module and decoder module. Each module is composed of ConvLSTM cells. The encoder module is used to extract the spatiotemporal features from TEC maps, while the decoder module converts spatiotemporal features into predicted TEC maps. We compared the predictive performance of our model with two traditional time series models: LSTM, GRU, a spatiotemporal mode1 ConvGRU, and the TEC daily forecast product C1PG provided by CODE on a total of 135 grid points in East Asia (10°–45°N, 90°–130°E). The experimental results show that the prediction error indicators MAE, RMSE, MAPE, and prediction similarity index SSIM of our model are superior to those of the comparison models in high, normal, and low solar activity years. The paper also analyzed the predictive performance of each model monthly. The experimental results indicate that the predictive performance of each model is influenced by the monthly mean of TEC. The ED-ConvLSTM model proposed in this paper is the least affected and the most stable by the monthly mean of TEC. Additionally, the paper compared the predictive performance of each model during two magnetic storm periods when TEC changes sharply. The results indicate that our ED-ConvLSTM model is least affected during magnetic storms and its predictive performance is superior to those of the comparative models. This paper provides a more stable and high-performance TEC spatiotemporal prediction model.

The aim of the study was to optimize the conditions [inoculum size (4, 6, and 8%), fermentation temperature (31, 34, and 37 °C), and apple: tomato ratio (2:1, 1:1, and 1:2)] on the viable cell count and sensory evaluation in apple–tomato pulp by response surface methodology (RSM), and determine the physicochemical properties, antioxidant activity, and sensory properties during fermentation. The optimal treatment parameters obtained were an inoculum size of 6.5%, a temperature of 34.5 °C, and an apple: tomato ratio of 1:1. After fermentation, the viable cell count reached 9.02 lg(CFU/mL), and the sensory evaluation score was 32.50. During the fermentation period, the pH value, total sugar, and reducing sugar decreased by 16.67%, 17.15%, and 36.05%, respectively. However, the total titratable acid (TTA), viable cell count, total phenol content (TPC), and total flavone content (TFC) increased significantly by 13.64%, 9.04%, 21.28%, and 22.22%, respectively. The antioxidant activity [2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging ability, 2,2′-azino-di(2-ethyl-benzthiazoline-sulfonic acid-6) ammonium salt (ABTS) free-radical scavenging ability, and ferric-reducing antioxidant capacity power (FRAP)] also increased by 40.91%, 22.60%, and 3.65%, respectively, during fermentation. A total of 55 volatile flavour compounds were detected using HS-SPME-GC–MS among the uninoculated samples and fermented samples before and after fermentation. The results showed that fermentation increased the types and total amount of volatile components in apple–tomato pulp, and eight new alcohols and seven new esters were formed. Alcohols, esters, and acids were the main volatile components in apple–tomato pulp, accounting for 57.39%, 10.27%, and 7.40% of the total volatile substances, respectively.

Child hunger was prevalent during the COVID-19 pandemic, but the extent, determinants, and impact on pre-school children aged 6 months to 7 years old from Malaysian urban poor households are still unknown. This exploratory cross-sectional study was performed between July 2020 and January 2021 at the Lembah Subang People Housing Project, Petaling. The households’ food security status was assessed using the previously validated Radimer/Cornell questionnaire, and the children’s anthropometric measurements were taken. Food diversity score was assessed using the World Health Organization Infant and Young Children Feeding (under-2 children) or Food and Agriculture Organization Women’s Dietary Diversity (2-year-old-and-above children) systems. Overall, 106 households were recruited. The prevalence of child hunger is 58.4% (95% CI: 50.0, 67.4). Significant differences were found in breastfeeding and sugar-sweetened beverage consumption between under-2 and ≥2-year-old children. There were no significant differences between child hunger and other food-insecure groups in weight-for-age, height-for-age, and weight-for-height z-scores. Only a higher dietary diversity score was significantly protective against child hunger after adjusting for maternal age, paternal employment status, and the number of household children (ORadjusted: 0.637 (95% CI: 0.443, 0.916), p = 0.015)). Proactive strategies are warranted to reduce child hunger during the COVID-19 pandemic by improving childhood dietary diversity.

A covariance decomposition method is applied to a monthly global precipitation dataset to decompose the interannual variability in the seasonal mean time series into an unpredictable component related to “weather noise” and to a potentially predictable component related to slowly varying boundary forcing and low-frequency internal dynamics. The “potential predictability” is then defined as the fraction of the total interannual variance accounted for by the latter component. In tropical oceans (30° E–0° W, 30° S–30° N), the consensus is that the El Nino-Southern Oscillation (ENSO, with 4–8 year cycles) is a dominant driver of the potentially predictable component, while the Madden-Julian Oscillation (MJO, with 30–90 days cycles) is a dominant driver of the unpredictable component. In this study, the consensus is verified by using the Nino3-4 SST index and a popular MJO index. It is confirmed that Nino3-4 SST does indeed explain a significant part of the potential predictable component, but only limited variability of the unpredictable component is explained by the MJO index. This raises the question of whether the MJO is dominant in the variability of the unpredictable component of the precipitation, or the current MJO indexes do not represent MJO variability well.

Background: Foodborne pathogenic bacteria threaten worldwide public health, and simple bacterial detection methods are in urgent need. Here, we established a lab-on-a-tube biosensor for simple, rapid, sensitive, and specific detection of foodborne bacteria. Methods: A rotatable Halbach cylinder magnet and an iron wire netting with magnetic silica beads (MSBs) were used for simple and effective extraction and purification of DNA from the target bacteria, and recombinase-aided amplification (RAA) was combined with clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins12a(CRISPR-Cas12a) to amplify DNA and generate fluorescent signal. First, 15 mL of the bacterial sample was centrifuged, and the bacterial pellet was lysed by protease to release target DNA. Then, DNA-MSB complexes were formed as the tube was intermittently rotated and distributed uniformly onto the iron wire netting inside the Halbach cylinder magnet. Finally, the purified DNA was amplified using RAA and quantitatively detected by the CRISPR-Cas12a assay. Results: This biosensor could quantitatively detect Salmonella in spiked milk samples in 75 min, with a lower detection limit of 6 CFU/mL. The fluorescent signal of 102 CFU/mL Salmonella Typhimurium was over 2000 RFU, while 104 CFU/mL Listeria monocytogenes, Bacillus cereus, and E. coli O157:H7 were selected as non-target bacteria and had signals less than 500 RFU (same as the negative control). Conclusions: This lab-on-a-tube biosensor integrates cell lysis, DNA extraction, and RAA amplification in one 15 mL tube to simplify the operation and avoid contamination, making it suitable for low-concentration Salmonella detection.

In the current context of climate change and demographic expansion, one of the phenomena that humanity faces are the suburban wildfires. To prevent the occurrence of suburban forest fires, fire risk assessment and early fire detection approaches need to be applied. Forest fire risk mapping depends on various factors and contributes to the identification and monitoring of vulnerable zones where risk factors are most severe. Therefore, watchtowers, sensors, and base stations of autonomous unmanned aerial vehicles need to be placed carefully in order to ensure adequate visibility or battery autonomy. In this study, fire risk assessment of an urban forest was performed and the recently introduced 360-degree data were used for early fire detection. Furthermore, a single-step approach that integrates a multiscale vision transformer was introduced for accurate fire detection. The study area includes the suburban pine forest of Thessaloniki city (Greece) named Seich Sou, which is prone to wildfires. For the evaluation of the performance of the proposed workflow, real and synthetic 360-degree images were used. Experimental results demonstrate the great potential of the proposed system, which achieved an F-score for real fire event detection rate equal to 91.6%. This indicates that the proposed method could significantly contribute to the monitoring, protection, and early fire detection of the suburban forest of Thessaloniki.

The electromagnetic data observed with the CSES (China Seismo-Electromagnetic Satellite, also known as Zhangheng-1 satellite) contain numerous spatial disturbances. These disturbances exhibit various shapes on the spectrogram, and constant frequency electromagnetic disturbances (CFEDs), such as artificially transmitted very-low-frequency (VLF) radio waves, power line harmonics, and interference from the satellite platform itself, appear as horizontal lines. To exploit this feature, we proposed an algorithm based on computer vision technology that automatically recognizes these lines on the spectrogram and extracts the frequencies from the CFEDs. First, the VLF waveform data collected with the CSES electric field detector (EFD) are converted into a time–frequency spectrogram using short-time Fourier Transform (STFT). Next, the CFED automatic recognition algorithm is used to identify horizontal lines on the spectrogram. The third step is to determine the line frequency range based on the proportional relationship between the frequency domain of the satellite’s VLF and the height of the time–frequency spectrogram. Finally, we used the CSES power spectrogram to confirm the presence of CFEDs in the line frequency range and extract their true frequencies. We statistically analyzed 1034 orbit time–frequency spectrograms and power spectrograms from 8 periods (5 days per period) and identified approximately 200 CFEDs. Among them, two CFEDs with strong signals persisted throughout an entire orbit. This study establishes a foundation for detecting anomalies due to artificial sources, particularly in the study of short-term strong earthquake prediction. Additionally, it contributes to research on other aspects of spatial electromagnetic interference and the suppression and cleaning of electromagnetic waves.

Abstract Background To investigate the clinical efficacy of the MyoSure hysteroscopic tissue removal system in the treatment of endometrial and cervical polyps in women with an intact hymen. Methods Retrospective analysis was performed on the clinical data of 32 patients treated with the MyoSure hysteroscopic tissue removal system for endometrial and cervical polyps. Results All the patients successfully completed the procedure. No intraoperative complications, such as cervical trauma, uterine perforation or TURP syndrome, were reported. The surgical time ranged from 5 to 35 min, with an average time of 19.3 min, and the intraoperative blood loss ranged from 2 to 50 ml with an average blood loss of 10.8 ml. After surgery, all patients were shown to have intact hymens. No residual polyp tissues were observed under the microscope, and abnormal uterine bleeding was relieved. Conclusions The MyoSure hysteroscopic tissue removal system can be a safe and effective treatment for endometrial and cervical polyps in women with an intact hymen.

Objective: To investigate if routine audiometry in Bell’s palsy patients has prognostic value. Methods: Retrospective case review was conducted on all Bell’s palsy patients (n=191) seen at the tertiary otolaryngology specialist outpatient clinic from 2015 to 2017. Correlation of ipsilesional audiometric thresholds with patients’ time-to-recovery and initial clinical severity (measured by House-Brackmann (HB) scoring) were used for the prognostic outcome measure. Audiometry results were analyzed using three contiguous frequency pure-tone average (1kHz, 2kHz, 4kHz). Statistical analysis was done via Stata (v13.1), significance tests were 2-sided at 5% significance level. Results: There was no significant difference between audiometric thresholds between the ipsilesional ear and the contralateral ear (p=0.87). Time-to-recovery was significantly longer for patients with severe initial presentation as compared to mild and moderate severity (p

Abstract Ferroptosis is a novel type of programmed cell death, which is different from apoptosis and autophagic cell death. Recently, ferroptosis has been indicated to contribute to the in vitro neurotoxicity induced by isoflurane, which is one of the most common anesthetics in clinic. However, the in vivo position of ferroptosis in isoflurane-induced neurotoxicity as well as learning and memory impairment remains unclear. In this study, we mainly explored the relationship between ferroptosis and isoflurane-induced learning and memory, as well as the therapeutic methods in mouse model. Our results indicated that isoflurane induced the ferroptosis in a dose-dependent and time-dependent manner in hippocampus, the organ related with learning and memory ability. In addition, the activity of cytochrome c oxidase/Complex IV in mitochondrial electron transport chain (ETC) was increased by isoflurane, which might further contributed to cysteine deprivation-induced ferroptosis caused by isoflurane exposure. More importantly, isoflurane-induced ferroptosis could be rescued by both ferroptosis inhibitor (ferrostatin-1) and mitochondria activator (dimethyl fumarate), which also showed effective therapeutic action against isoflurane-induced learning and memory impairment. Taken together, our data indicate the close association among ferroptosis, mitochondria and isoflurane, and provide a novel insight into the therapy mode against isoflurane-induced learning and memory impairment.

Abstract In this study, 0, 0.5, 1, 1.5, 2, 4, 6 and 8 mg·kg−1 of cadmium were added to the cultivation materials. In order to study the effects of different concentrations of Cd stress on J1 and J77, the contents of antioxidant enzymes, proline and malondialdehyde, Cd content, agronomic traits and yield of fruiting bodies of Agaricus brasiliensis were determined, and the nutritional components such as polysaccharide, triterpene, protein, total sugar and total amino acid were determined. The results showed that the physiological indexes of strain J1 and J77 changed regularly under different concentrations of Cd stress. J1 was a high absorption and low tolerance variety, while J77 was a low absorption and high tolerance variety. Low concentration of Cd promoted the growth of strain J1, and higher concentration of Cd promoted the growth of strain J77. The contents of protein and total amino acids in the two strains changed greatly, followed by polysaccharides, which indicated that Cd stress had the greatest impact on the three nutrients, and other nutrients were not sensitive to Cd stress.

Introduction: Although persistent inhibition of HBV replication by antiviral therapy has shown to slow disease progression, cost-related access barriers to these essential medicines are becoming salient. The national volume-based procurement (NVBP) was piloted in China and led to substantial reduction in the list price of prescription drugs. To examine the impact of NVBP on selected antiviral medication costs per defined daily dose (DDD), procurement volumes, and spending.Methods: We employed an interrupted time series design to examine changes in cost per defined daily dose (DDD), procurement volumes, and spending for NVBP bid-winning antiviral medications (tenofovir disoproxil fumarate and entecavir) in 11 pilot cities from 2017 to 2020. Procurement transaction data were obtained from 9,454 hospitals in the Chinese Hospital Pharmaceutical Audit (CHPA) database. In the secondary analysis, the control group comprised two non-NVBP drugs (adefovir and lamivudine) procured in 11 cities not exposed to the NVBP.Results: Cost per DDD of the two hepatitis B virus (HBV) antiviral medications reduced by CNY1.598 (p = 0.002) immediately following the implementation of NVBP, dropping from an average cost of CNY16.483 per DDD at baseline to CNY6.420 at the end of the observation period. NVBP implementation resulted in a substantial reduction in daily costs of antivirals and an increase in monthly procurement volumes by 6.674 million DDDs (p = 0.017), while monthly spending was reduced by CNY138.26 million (p = 0.002). In the secondary ITS analysis with a control group, the average cost per DDD of the NVBP bid-winning antivirals declined by CNY4.537 (p < 0.001), monthly procurement volumes increased by 7.209 million DDDs (p = 0.002), and monthly spending dropped by CNY138.83 million (p < 0.001).Conclusion: Volume-based procurement piloted in China may be effective for reducing price and total expenditures and improving drug utilization, which is especially important for HBV patients who need constant access to antiviral therapies.

Both long-term exposure to air pollution and abnormal fasting blood glucose (FBG) are linked to dyslipidemia prevalence. However, the joint role of air pollution and FBG on dyslipidemia remains unknown clearly. In this study, we aimed to test whether abnormal FBG could enhance the risks of long-term exposure to air pollutants on dyslipidemia in general Chinese adult population. The present study recruited 8917 participants from 4 cities in Hebei province, China. Participants' individual exposure to air pollutants was evaluated by the Empirical Bayesian Kriging statistical model in ArcGIS10.2 geographic information system. Dyslipidemia was defined according to Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults. Subjects were grouped into normal, prediabetes, diabetes according to FBG level. Generalized linear models were applied to analyze the interaction of air pollutants and FBG on dyslipidemia prevalence. The prevalence of dyslipidemia was 43.83% in our investigation. After adjusting all covariates, we found the risk of four air pollutants (PM2.5, PM10, NO2, SO2) on dyslipidemia prevalence was stronger as higher FBG level, and the adjusted odd ratio of interaction (ORinter (95% CI)) between PM2.5, PM10, NO2, SO2 and FBG levels on dyslipidemia was 1.171 (1.162, 1.189), 1.119 (1.111, 1.127), 1.124 (1.115, 1.130), 1.107 (1.098, 1.115), respectively. Stratified analyses indicated the modifying effects of FBG on the association of air pollution with dyslipidemia were stronger among male, less than 65 years old, overweight/obesity (all Pinter

AimsThis study aimed to observe the efficacy and safety of anlotinib in the treatment of small cell lung cancer (SCLC) in the real world, as first-line maintenance therapy, second-line, and above.MethodsClinical data of 109 patients with SCLC treated with anlotinib and hospitalized at The First Affiliated Hospital of Zhengzhou University from June 2018 to June 2020 were retrospectively analyzed. Analysis of short-term efficacy and survival was performed, with p

Background: The rapid worldwide spread of the Omicron variant of SARS-CoV-2 has unleashed a new wave of COVID-19 outbreaks. The efficacy of molnupiravir, an approved drug, is still unknown in patients infected with the Omicron variant.Objective: Evaluated the antiviral efficacy and safety of molnupiravir in patients infected with SARS-CoV-2 Omicron variant, with symptom duration within 5 days.Methods: We conducted a randomized, controlled trial involving patients with mild or moderate COVID-19. Patients were randomized to orally receive molnupiravir (800 mg) plus basic treatment or only basic treatment for 5 days (BID). The antiviral efficacy of the drug was evaluated using reverse transcriptase polymerase chain reaction.Results: Results showed that the time of viral RNA clearance (primary endpoint) was significantly decreased in the molnupiravir group (median, 9 days) compared to the control group (median, 10 days) (Log-Rank p = 0.0092). Of patients receiving molnupiravir, 18.42% achieved viral RNA clearance on day 5 of treatment, compared to the control group (0%) (p = 0.0092). On day 7, 40.79%, and 6.45% of patients in the molnupiravir and control groups, respectively, achieved viral RNA clearance (p = 0.0004). In addition, molnupiravir has a good safety profile, and no serious adverse events were reported.Conclusion: Molnupiravir significantly accelerated the SARS-CoV-2 Omicron RNA clearance in patients with COVID-19.Clinical Trial Registration: [chictr.org.cn], identifier [ChiCTR2200056817].

BackgroundAccumulating evidence has shown that diabetes has an impact on bone metabolism with conflicting results. Furthermore, little is known about the relationship of prediabetes with bone mineral density (BMD). Therefore, we explored the association between BMD and glucometabolic status in adults in the US.MethodsIn this cross-sectional study, we extracted and analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. A total of 14610 subjects aged 40 ≥ years diagnosed with diabetes, prediabetes, or normal glucose regulation (NGR) and had available data on BMD were eligible.ResultsThe prevalence of prediabetes and diabetes in US adults aged 40 ≥ years were 39.2% and 26.4%, respectively. After multivariable adjustment, we found an increasing trend of BMD at the total hip, femoral neck, and lumbar spine with glucometabolic conditions from NGR and prediabetes to diabetes in adults aged ≥ 40 years in the US. This trend was more prominent in women than that in men. Fasting plasma glucose (FPG) and HbA1c levels were also positively correlated with BMD.ConclusionsGlucometabolic conditions were significantly associated with BMD values in US adults.

ObjectiveTo explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions.MethodsWe screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low-abundance plasma proteins encoded by miR-193b-3p target genes were explored in this study population. We further investigated the potential cellular functions of the differentially expressed miRNAs in HepG2 cells.ResultsmiR-193b-3p was differentially expressed in type 2 diabetes cases compared to healthy controls (fold change = 2.01, P = 0.006). Plasma levels of triosephosphate isomerase (TPI1, a protein involved in the glycolytic pathway) decreased in type 2 diabetes cases (fold change = 1.37, P = 0.002). The effect of miR-193b-3p on TPI1 was verified by transfection of miR-193b-3p into HepG2 cells. miR-193b-3p inhibited the expression of YWHAZ/14-3-3ζ in the PI3K-AKT pathway, subsequently altering the expression of FOXO1 and PCK1. After transfection, cells were incubated in glucose-free medium for another 4 h. Glucose levels in medium from cells with elevated miR-193b-3p levels were significantly higher than those in medium from negative control cells (P = 0.016). In addition, elevated miR-193b-3p reduced glucose uptake by inhibiting insulin receptor (IR) and GLUT2 expression.ConclusionPlasma miR-193b-3p levels increased in type 2 diabetes cases, and TPI1 levels decreased in both plasma and HepG2 cells with increased miR-193b-3p levels, while extracellular lactate levels did not significantly changed. Moreover, miR-193b-3p may affect glucose metabolism by directly targeting YWHAZ/14-3-3ζ and upregulating the transcription factor FOXO1 downstream of the PI3K-AKT pathway.

Objectives: Pharmacoeconomics evaluation (PE) is increasingly used in the healthcare decision-making process in China. Little is known about PE conducted in Chinese Herbal Medicines (CHMs). We aimed to systematically review trends, characteristics, and quality of PE of CHMS.Methods: We systematically searched both Chinese (CNKI, WanFang, and VIP) and English (Pubmed) databases. Studies were included if they were PE studies comparing both costs and outcomes between two or more interventions published in Chinese or English. Assessment of the quality of studies was conducted using the Quality of Health Economic Analyses (QHES) instrument. T-test and Chi-square tests were used to compare the studies before and after the first edition of China Guidelines for PE published in 2011, and between studies published in Chinese and English.Results: A total of 201 articles were included. There was an increasing trend of PE studies on CHMs during the study period. The top three studied diseases were central nervous system (CNS), mental, and behavioral disorders; cardiovascular diseases; and blood, immune and endocrine diseases. The average QHES score for the included studies was 63.37. Cost-effectiveness analysis (CEA) accounted for the majority (76.6%) of the included studies. Only a quarter of the articles (27.4%) were funded, and there were significantly more studies funded after the publication of China guidelines for PE. About 96.5% of studies did not specify evaluation perspectives and 89.6% of studies had a sample size of less than 300. Around half of the studies (55%) used incremental analysis, but only a few of them considered using a threshold. Half of the studies lacked sensitivity analysis. There was no significant improvement in the quality of studies published after the publication of China Guidelines for PE, and English articles had significantly higher quality than Chinese articles.Conclusion: This study identified several problems in PE studies on CHMs, including having small sample sizes, lacking necessary research elements, and using single evaluation methods. The quality of PE studies on CHMs was not sufficient. Researchers need to understand the standardized way to conduct PE studies and improve the quality and level of PE studies on CHMs.

Agrobacterium transfers T-DNA to plants where it may integrate into the genome. Non-homologous end-joining (NHEJ) has been invoked as the mechanism of T-DNA integration, but the role of various NHEJ proteins remains controversial. Genetic evidence for the role of NHEJ in T-DNA integration has yielded conflicting results. We propose to investigate the formation of T-circles as a proxy for understanding T-DNA integration. T-circles are circular double-strand T-DNA molecules, joined at their left (LB) and right (RB) border regions, formed in plants. We characterized LB-RB junction regions from hundreds of T-circles formed in Nicotiana benthamiana or Arabidopsis thaliana. These junctions resembled T-DNA/plant DNA junctions found in integrated T-DNA: Among complex T-circles composed of multiple T-DNA molecules, RB-RB/LB-LB junctions predominated over RB-LB junctions; deletions at the LB were more frequent and extensive than those at the RB; microhomology was frequently used at junction sites; and filler DNA, from the plant genome or various Agrobacterium replicons, was often present between the borders. Ku80 was not required for efficient T-circle formation, and a VirD2 ω mutation affected T-circle formation and T-DNA integration similarly. We suggest that investigating the formation of T-circles may serve as a surrogate for understanding T-DNA integration.

BackgroundIn our previous phase II study, nab-paclitaxel plus S-1 (NPS) showed encouraging objective response rate (ORR) as first-line treatment for advanced pancreatic adenocarcinoma (APAC). This study aimed to evaluate the effectiveness and safety of S-1 maintenance after NPS in APAC and to explore factors predicting survival benefits when using S-1 maintenance.MethodsBetween 2014 and 2018 a total of 182 patients with APAC, who were primarily treated with NPS, were included. For patients without progression or with treatment discontinuation due to any reasons within 4 months during NPS treatment, S-1 monotherapy was administrable as maintenance therapy at the physicians’ discretion based on the patients’ preference and performance status. Efficacy and safety of S-1 maintenance were investigated.ResultsIn 123 patients without progression within 4 months during NPS treatment, 74 received S-1 maintenance and had median progression-free survival of 9.6 months and median overall survival of 16.7 months. Multivariable analysis showed that in patients receiving S-1 maintenance after first-line NPS therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, non-metastatic disease, and complete or partial response as best response to NPS chemotherapy were independently associated with better survival. The most common all-grade hematological and non-hematological adverse events were neutropenia (82.4%) and peripheral neurotoxicity (66.2%), respectively, and the most common ≥Grade 3 hematological and non-hematological adverse events were neutropenia (40.5%) and peripheral neurotoxicity (6.8%), respectively in patients who received S-1 maintenance.ConclusionsOur real-world study showed that S-1 maintenance after tumor response or stable disease induced by first-line NPS treatment was effective and well-tolerated for some patients with APAC, which offers a promising alternative treatment strategy with encouraging survival for APAC.