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Abstract Ten cucurbitane-type triterpene glycosides, including five new compounds named charantosides H (1), J (2), K (3), momorcharacoside A (4), goyaglycoside-l (5), and five known compounds (6–10), were isolated from the EtOAc extract of Momordica charantia fruits. The chemical structures of these compounds were identified by 1D and 2D NMR and HRESIMS spectroscopic analyses. Configurations of new compounds were determined by ROESY correlations and comparison of their 13C NMR data with literature reported values. All compounds were evaluated for their inhibition against α-glucosidase, in which compounds 2, 5, 7, 8, 9 showed moderate inhibitory activities with IC50 values ranging from 28.40 to 63.26 μM comparing with the positive control (acarbose, IC50 87.65 ± 6.51 μM). Graphic Abstract

Existing literature shows that people living with physical impairment are systematically disadvantaged in the workforce and their voices are often silenced. With a perspective of intersectionality, this article looks into how disabled women suffer from multiple forms of discrimination and how social media may emerge as a tool of empowerment for them in both the workforce and their everyday lives. Drawing on five cases of Chinese disabled women in the cyber workforce, the study finds that the booming Internet economy enables more disabled women to financially support themselves. Social media appears as a cover for these women to disguise their disability identity and get more job opportunities. It serves as an aid in many cases to allow these women to increase social participation, to project their voice, and to form alliances. The risks and challenges that disabled women often encounter in the cyber workforce are also discussed.

Abstract Background Stroke is a major cause of death and disability worldwide. Over the years, traditional medicines for stroke treatment have undergone tremendous progress, but few bibliometric studies have been performed. This study explored the trends and issues relating to the application of traditional medicine in stroke research. Methods A bibliometric search was performed in the Web of Science Core Collection database to identify studies that investigated the application of traditional medicine in stroke management. CiteSpace VI and Excel 2016 were used to analyze information from the retrieved studies. Activity index and attractive index were used to explore the worldwide development modes. Results A total of 1083 English articles published between 2004 and 2018 were identified. Over the last 15 years, the developments in research occurred in three geographic clusters. The development modes were investigated and classified into 4 categories. In mainland China, the number and impact of research showed an increasing trend over the study period. The United States played a leading role in this topic. Three clusters of institutes and the majority of authors mainly came from South Korea, Taiwan and mainland China. Reperfusion injury and angiogenesis were identified as the potential topics likely to dominate future research in this field. Conclusion The progress of studies on traditional medicine for stroke could be explained by the global attention to traditional medicine, the geospatial proximity for research collabration, and the increasing resources invested. Based on a large amount of existing research, researchers engaged in this topic should objectively consider the influential studies to identify and solve the common issues worldwide.

Abstract Background Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. Methods Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. Results LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. Conclusions Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

Abstract Background During human pregnancy, placental trophectoderm cells release extracellular vesicles (EVs) into maternal circulation. Trophoblasts also give rise to cell-free DNA (cfDNA) in maternal blood, and has been used for noninvasive prenatal screening for chromosomal aneuploidy. We intended to prove the existence of DNA in the EVs (evDNA) of maternal blood, and compared evDNA with plasma cfDNA in terms of genome distribution, fragment length, and the possibility of detecting genetic diseases. Methods Maternal blood from 20 euploid pregnancies, 9 T21 pregnancies, 3 T18 pregnancies, 1 T13 pregnancy, and 2 pregnancies with FGFR3 mutations were obtained. EVs were separated from maternal plasma, and confirmed by transmission electronic microscopy (TEM), western blotting, and flow cytometry (FACS). evDNA was extracted and its fetal origin was confirmed by quantitative PCR (qPCR). Pair-end (PE) whole genome sequencing was performed to characterize evDNA, and the results were compared with that of cfDNA. The fetal risk of aneuploidy and monogenic diseases was analyzed using the evDNA sequencing data. Results EVs separated from maternal plasma were confirmed with morphology by TEM, and protein markers of CD9, CD63, CD81 as well as the placental specific protein placental alkaline phosphatase (PLAP) were confirmed by western blotting or flow cytometry. EvDNA could be successfully extracted for qPCR and sequencing from the plasma EVs. Sequencing data showed that evDNA span on all 23 pairs of chromosomes and mitochondria, sharing a similar distribution pattern and higher GC content comparing with cfDNA. EvDNA showed shorter fragments yet lower fetal fraction than cfDNA. EvDNA could be used to correctly determine fetal gender, trisomies, and de novo FGFR3 mutations. Conclusions We proved that fetal DNA could be detected in EVs separated from maternal plasma. EvDNA shared some similar features to plasma cfDNA, and could potentially be used to detect genetic diseases in fetus.

Based on our previous pulsed current and internal overvoltage test data and the experience of common commercial high power cables, a 100 kA coaxial pulsed power cable is designed and manufactured to adapt the coaxial electric energy breech transmission between the plasma generator and the pulsed power supply (PPS) in electrothermal-chemical (ETC) guns. The index parameters are analyzed and determined. Semi-conductor layers and a shield stiffener are introduced to prevent the deformation and burst of the pulsed power cable structurally. The semi-conductor layer can eliminate the air gap and balance the electric field in the cable. The shield stiffener can multiply the mechanical strength to restrain the strong electrodynamic force produced by the core dislocation of the outer conductor. The multi-coupling of electromagnetic field, stress field and thermal field analysis are established to assist in aided design of electrical strength, mechanical strength and temperature rise characteristics. Both a DC voltage withstand test and pulsed discharge tests are introduced to verify and inspect the performance and dynamic response of the pulsed power cable. The 25 kV/5min DC voltage withstand test result shows that the sample leakage current is nearly 3 μA and no abnormal phenomena of the pulsed power cable sample occurred. The pulsed discharge tests show that the sample can sustain the 100 kA peak current. Furthermore, this 100 kA coaxial pulsed power cable can satisfy the ETC test requirements. Keywords: Pulsed power cable, Pulsed power supply, Electrothermal-chemical launch, Coaxial structure

Abstract Background The growth plate is a special region of the cartilage that drives longitudinal growth of long bones. Proliferating chondrocytes in the growth plate, arranged in columns, divide perpendicular to the long axis of the growth plate then intercalate to re-align with parental columns. Which molecular partners maintain growth plate columnar structures and chondrocyte cytokinesis has not been fully revealed. It is reported that kinesin family member 3A (KIF3A), a subunit of kinesin-2, plays an important role in maintaining columnar organization in growth plates via controlling primary cilia formation and cell proliferation. Result Here we identify kinesin family member 5B (KIF5B), the heavy chain of kinesin-1, a ubiquitously expressed motor protein for anterograde intracellular transport along the microtubule network, as a key modulator of cytokinesis in chondrocytes via maintenance of central spindle organization. We show that KIF5B is concentrated in the central spindle during cytokinesis in both primary chondrocytes and chondrogenic ATDC5 cells. Conclusion The failure of cytokinesis in KIF5B null chondrocytes leads to incomplete cell rotation, disrupting proliferation and differentiation, and results in a disorganized growth plate.

Objective: To gain a deeper understanding of the hot topics and future prospects of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors treatment of cancer through scientometric analysis of the top-100 most cited clinical trials. Materials and methods: We searched the Web of Science Core Collection database from 1980 to June 2019. Two reviewers independently screened the top-100 most cited clinical trials that defined by the National Institutes of Health starting from the most cited article. Title, year of publication, citations, type of cancer, and focused aspects of outcomes were extracted from included clinical trials. VOSviewer software (version 1.6.9) and Excel 2016 were used to do statistical analysis. The evidence mapping was used to present the relationship between cancers, drugs, citations, and outcomes, etc. Results: The top-100 most cited clinical trials published from 2010 to 2018 in nine journals with high impact factor (IF) (IF2018:6.68–70.67), and Lancet Oncology (USA) published the most clinical trials (n = 29, IF2018 = 35.3856). The total number of citations of the top-100 most cited clinical trials was from 59 to 5606. 920 authors from 34 countries and 458 organizations participated in publishing the top-100 most cited clinical trials. The USA (n = 95) and Memorial Sloan-Kettering Cancer Center (n = 31) contributed the most publications. Based on the evidence mapping, there are 25 different types of cancers (e.g. lung cancer, melanoma, and renal cell cancer) and five focused aspects of outcomes (e.g. safety and efficacy). Conclusion: The USA was the dominant country. Anti-PD-1/PD-L1 drugs were widely used to treat lung cancer, melanoma, renal cell cancer, and Hodgkin lymphoma. More exploration should be done to explore the use of anti-PD-1/PD-L1 drugs to treat more type of cancers in future research.

Risperidone is an efficacious second-generation antipsychotic (SGA) to treat a wide spectrum of psychiatric diseases, whereas its active moiety (risperidone and 9-hydroxyrisperidone) concentration without a therapeutic reference range may increase the risk of adverse drug reactions. We aimed to establish a prediction model of risperidone active moiety concentration in the next therapeutic drug monitoring (TDM) based on the initial TDM information using machine learning methods. A total of 983 patients treated with risperidone between May 2017 and May 2018 in Beijing Anding Hospital were collected as the data set. Sixteen predictors (the initial TDM value, dosage, age, WBC, PLT, BUN, weight, BMI, prolactin, ALT, MECT, Cr, AST, Ccr, TDM interval, and RBC) were screened from 26 variables through univariate analysis (p < 0.05) and XGBoost (importance score >0). Ten algorithms (XGBoost, LightGBM, CatBoost, AdaBoost, Random Forest, support vector machine, lasso regression, ridge regression, linear regression, and k-nearest neighbor) compared the model performance, and ultimately, XGBoost was chosen to establish the prediction model. A cohort of 210 patients treated with risperidone between March 1, 2019, and May 31, 2019, in Beijing Anding Hospital was used to validate the model. Finally, the prediction model was evaluated, obtaining R2 (0.512 in test cohort; 0.374 in validation cohort), MAE (10.97 in test cohort; 12.07 in validation cohort), MSE (198.55 in test cohort; 324.15 in validation cohort), RMSE (14.09 in test cohort; 18.00 in validation cohort), and accuracy of the predicted TDM within ±30% of the actual TDM (54.82% in test cohort; 60.95% in validation cohort). The prediction model has promising performance to facilitate rational risperidone regimen on an individualized level and provide reference for other antipsychotic drugs' risk prediction.

Heavy metal(loid) contamination represents an immense challenge in sustainable agriculture. Arsenic, in particular, poses a great risk to the quality of agricultural products (e.g., rice grain). The sulfur amendment is recommended as an effective practice to remediate heavy metal(loid)–polluted soil, given its function in enhancing crop production and alleviating heavy metal(loid) accumulation in the plant. This study aims to investigate the roles of sulfur fertilizer on arsenic accumulation in rice and to explore the key mechanisms. In this study, Elemental sulfur (ES) and gypsum sulfur (GS) were chosen as sulfur fertilizers, with different application rates (0, 0.15, and 0.30 g S kg−1 soil). The results showed that ES and GS treatment significantly increased rice grain yield by 46.6–59.7% and significantly reduced the rice grain arsenic content by more than 39.1%. The sulfur treatment decreased soil pe + pH values. ES treatment increased the availability of arsenic in the bulk soil, whereas GS showed little effect. Sulfur application promoted the formation of iron and manganese plaques, which could suppress the migration of arsenic from soil to rice root. In addition, the sulfur treatment decreased the arsenic that migrating from rice roots to grains by 33.3–66.7%. This study indicates that sulfur application could increase arsenic availability in paddy soil; however, it can inhibit arsenic accumulation in rice grains via increasing the root plaques content and inhibiting the translocation of arsenic from roots to grains.

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic neoplasm with poor survival outcomes. However, the routine clinical features are not sufficient to accurately predict the prognosis of AML. The expression of hypoxia-related genes was associated with survival outcomes of a variety of hematologic and lymphoid neoplasms. We established an 18-gene signature-based hypoxia-related prognosis model (HPM) and a complex model that consisted of the HPM and clinical risk factors using machine learning methods. Both two models were able to effectively predict the survival of AML patients, which might contribute to improving risk classification. Differentially expressed genes analysis, Gene Ontology (GO) categories, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to reveal the underlying functions and pathways implicated in AML development. To explore hypoxia-related changes in the bone marrow immune microenvironment, we used CIBERSORT to calculate and compare the proportion of 22 immune cells between the two groups with high and low hypoxia-risk scores. Enrichment analysis and immune cell composition analysis indicated that the biological processes and molecular functions of drug metabolism, angiogenesis, and immune cell infiltration of bone marrow play a role in the occurrence and development of AML, which might help us to evaluate several hypoxia-related metabolic and immune targets for AML therapy.

Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations.Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples.Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults.Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors.

Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3′-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency.

A variety of needle-motion profiles are used in diesel injectors. However, it is unclear what the underlying mechanism is to determine the needle-motion profiles and how they affect the spray dynamics. It has been of significant interest to examine how the spray dynamics will change if only altering the needle valve opening speed or closing speed while all other parameters are kept the same. The different needle-motion profiles were obtained using a piezo nozzle (Nozzle #P) and a solenoid nozzle (Nozzle #S), which have identical nozzle geometry. By utilizing the X-ray imaging technique, it was observed that the average needle valve speed of Nozzle #P was 51% higher at the opening stage but 17% lower at the closing stage than Nozzle #S. When the needle valve lift is low (approximately 200 μm), the needle valve opening speed has a crucial effect on spray dynamics. The faster needle valve opening of Nozzle #P results in a 42% larger spray spreading angle and 34% lower spray velocity at the downstream field. The spray dynamics may be controllable by properly designing the needle-motion profiles in the scenarios of the low needle lifts. However, when the needle valve is sufficiently open (approximately over 200 μm), almost identical spray characteristics were observed regardless of the needle-motion profiles.

The reserve of the copper-oxide-bearing limonite ore (COBL ore) in Yulong Copper Co., Ltd. is up to 20 million tons with 1.79% of copper content. The characters of the copper resources in the COBL ore are high-proportioned oxidation state (99.98%) and combined state (84.83%). The combined copper oxide is mainly copper-oxide-bearing limonite, which has a copper content of more than 78%. Because of the high altitude and average annual temperature of 15 °C in Tibet, fire leaching cannot be adopted. The leaching efficiency of copper from COBL ore using direct leaching of sulfuric acid is only 40%, which is greatly influenced by temperature and time. Based on the characteristics of COBL ore, a novel combined method of magnetic separation and individual leaching has been proposed to efficient recover copper resources. Experimental results show that the magnetic concentrates and tailings were obtained by magnetic separation of COBL ore at 0.6 T with the yields were 59.65% and 40.35%, respectively. Due to the obvious leaching properties difference of the magnetic concentrates and tailings, individual leaching process routes were used to treat them. The magnetic concentrate was leached with stirring for 3 days at room temperature (20 °C), and the magnetic tailing was easily leached for 4 h at 40 °C. The recovery efficiency of total copper was 72%, which was about 32% higher than that of the single leaching of the COBL ore. The method proposed in this study achieves environmentally friendly, low energy consumption, and efficient extraction of refractory copper oxide ore.

Ruminants are mostly herbivorous animals that employ rumen fermentation for the digestion of feed materials, including dairy cows. Ruminants consume plant fibre as their regular diet, but lack the machinery for their digestion. For this reason, ruminants maintain a symbiotic relation with microorganisms that are capable of producing enzymes to degrade plant polymers. Various species of microflora including bacteria, protozoa, fungi, archaea, and bacteriophages are hosted at distinct concentrations for accomplishing complete digestion. The ingested feed is digested at a defined stratum. The polysaccharic plant fibrils are degraded by cellulolytic bacteria, and the substrate formed is acted upon by other bacteria. This sequential degradative mechanism forms the base of complete digestion as well as harvesting energy from the ingested feed. The composition of microbiota readily gets tuned to the changes in the feed habits of the dairy cow. The overall energy production as well as digestion is decided by the intactness of the resident communal flora. Disturbances in the homogeneity gastrointestinal microflora has severe effects on the digestive system and various other organs. This disharmony in communal relationship also causes various metabolic disorders. The dominance of methanogens sometimes lead to bloating, and high sugar feed culminates in ruminal acidosis. Likewise, disruptive microfloral constitution also ignites reticuloperitonitis, ulcers, diarrhoea, etc. The role of symbiotic microflora in the occurrence and progress of a few important metabolic diseases are discussed in this review. Future studies in multiomics provides platform to determine the physiological and phenotypical upgradation of dairy cow for milk production.

Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs).Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: 20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality.Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014–1.063]) and hospital (1.025 [1.005–1.046]) mortalities. As a categorical variable, mean VTC of 10–15 mg/L was not associated with reduced ICU (1.705 [0.975–2.981]) and hospital (1.235 [0.829–1.841]) mortalities. Mean VTC of 15–20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924–2.029]). Moreover, mean VTCs of 15–20 and >20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111–3.332]; 2.428 [1.385–4.258]), and mean VTC of >20 mg/L with higher hospital mortality (1.585 [1.053–2.387]) than mean VTC of

Background: Upper respiratory infections (URIs) are among the most common diseases. However, the related burden has not been comprehensively evaluated. Thus, we designed the present study to describe the global and regional burden of URIs from 1990 to 2019. Methods: A secondary analysis was performed on the incidence, mortality, and disability-adjusted life years (DALYs) of URIs in different sex and age groups, from 21 geographic regions, 204 countries and territories, between 1990 and 2019, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Countries and territories were categorized according to Socio-demographic Index (SDI) quintiles. Findings: Globally, the incident cases of URIs reached 17·2 (95% uncertainty interval: 15·4 to 19·3) billion in 2019, which accounted for 42·83% (40·01% to 45·77%) cases from all causes in the GBD 2019 study. The age-standardized incidence rate remained stable from 1990 to 2019, while significant decreases were found in the mortality and DALY rate. The highest age-standardized incidence rates from 1990 to 2019 and the highest age-standardized DALY rates after 2011 were observed in high SDI regions. Among all the age groups, children under five years old suffered from the highest incidence and DALY rates, both of which were decreased with increasing age. Fatal consequences of URIs occurred mostly in the elderly and children under five years old. Interpretation: The present study provided comprehensive estimates of URIs burden for the first time. Our findings, highlighting the substantial incidence and considerable DALYs due to URIs, are expected to attract more attention to URIs and provide future explorations in the prevention and treatment with epidemiological evidence. Funding: The study was funded by the National Natural Science Foundation of China (81770057).

Alzheimer disease (AD) is the most common cause of dementia in geriatric population. At present, no effective treatments exist to reverse the progress of AD, however, early diagnosis and intervention might delay its progression. The search for biomarkers with good safety, repeatable detection, reliable sensitivity and community application is necessary for AD screening and early diagnosis and timely intervention. Electroencephalogram (EEG) examination is a non-invasive, quantitative, reproducible, and cost-effective technique which is suitable for screening large population for possible AD. The power spectrum, complexity and synchronization characteristics of EEG waveforms in AD patients have distinct deviation from normal elderly, indicating these EEG features can be a promising candidate biomarker of AD. However, current reported deviation results are inconsistent, possibly due to multiple factors such as diagnostic criteria, sample sizes and the use of different computational measures. In this study, we collected two neurological tests scores (MMSE and MoCA) and the resting-state EEG of 30 normal control elderly subjects (NC group) and 30 probable AD patients confirmed by Pittsburgh compound B positron emission tomography (PiB-PET) inspection (AD group). We calculated the power spectrum, spectral entropy and phase synchronization index features of these two groups’ EEG at left/right frontal, temporal, central and occipital brain regions in 4 frequency bands: δ oscillation (1–4 Hz), θ oscillation (4–8 Hz), α oscillation (8–13 Hz), and β oscillation (13–30 Hz). In most brain areas, we found that the AD group had significant differences compared to NC group: (1) decreased α oscillation power and increased θ oscillation power; (2) decreased spectral entropy in α oscillation and elevated spectral entropy in β oscillation; and (3) decrease phase synchronization index in δ, θ, and β oscillation. We also found that α oscillation spectral power and β oscillation phase synchronization index correlated well with the MMSE/MoCA test scores in AD groups. Our study suggests that these two EEG features might be useful metrics for population screening of probable AD patients.

Pseudomonas aeruginosa is a Gram-negative pathogen that causes a variety of infections in humans and animals. Due to the inappropriate use of antibiotics, multi-drug resistant (MDR) P. aeruginosa strains have emerged and are prevailing. In recent years, cow mastitis caused by MDR P. aeruginosa has attracted attention. In this study, a microbial community analysis revealed that P. aeruginosa could be a cause of pathogen-induced cow mastitis. Five MDR P. aeruginosa strains were isolated from milk diagnosed as mastitis positive. To seek an alternative antibacterial agent against MDR, P. aeruginosa, a lytic phage, designated vB_PaeS_PAJD-1 (PAJD-1), was isolated from dairy farm sewage. PAJD-1 was morphologically classified as Siphoviridae and was estimated to be about 57.9 kb. Phage PAJD-1 showed broad host ranges and a strong lytic ability. A one-step growth curve analysis showed a relatively short latency period (20 min) and a relatively high burst size (223 PFU per infected cell). Phage PAJD-1 remained stable over wide temperature and pH ranges. Intramammary-administered PAJD-1 reduced bacterial concentrations and repaired mammary glands in mice with mastitis induced by MDR P. aeruginosa. Furthermore, the cell wall hydrolase (termed endolysin) from phage PAJD-1 exhibited a strong bacteriolytic and a wide antibacterial spectrum against MDR P. aeruginosa. These findings present phage PAJD-1 as a candidate for phagotherapy against MDR P. aeruginosa infection.

Mastitis caused by Escherichia coli (E. coli) remains a threat to dairy animals and impacts animal welfare and causes great economic loss. Furthermore, antibiotic resistance and the lagged development of novel antibacterial drugs greatly challenge the livestock industry. Phage therapy has regained attention. In this study, three lytic phages, termed vB_EcoM_SYGD1 (SYGD1), vB_EcoP_SYGE1 (SYGE1), and vB_EcoM_SYGMH1 (SYGMH1), were isolated from sewage of dairy farm. The three phages showed a broad host range and high bacteriolytic efficiency against E. coli from different sources. Genome sequence and transmission electron microscope analysis revealed that SYGD1 and SYGMH1 belong to the Myoviridae, and SYGE1 belong to the Autographiviridae of the order Caudovirales. All three phages remained stable under a wide range of temperatures or pH and were almost unaffected in chloroform. Specially, a mastitis infected cow model, which challenged by a drug resistant E. coli, was used to evaluate the efficacy of phages. The results showed that the cocktails consists of three phages significantly reduced the number of bacteria, somatic cells, and inflammatory factors, alleviated the symptoms of mastitis in cattle, and achieved the same effect as antibiotic treatment. Overall, our study demonstrated that phage cocktail may be a promising alternative therapy against mastitis caused by drug resistant E. coli.

In this study, based on the retrieval data from the Fengyun geostationary meteorological satellite and the Tropical Rainfall Measuring Mission satellite, a large-scale precipitation case in eastern China is selected to address the systematic deviations of deterministic forecasts for clouds and precipitation. A multi-physical ensemble transform Kalman filter (ETKF) is constructed in this research based on the Weather Research and Forecast model version 3.6, and its forecasting ability in terms of cloud-top height and temperature, hydrometeors, and precipitation is evaluated by quantitatively comparing three microphysical parameterization schemes (Lin, Morrison, and CAM5.1 schemes) and their corresponding multi-physical ensemble mean. The results show that the Lin, Morrison, and CAM5.1 schemes all underestimate the range of cloud systems and have different advantages and disadvantages in forecasting different elements, while the forecasting improvement of the multi-physical ensemble mean is limited. However, the multi-physical ETKF can effectively improve the forecast accuracy of the cloud system range. In addition, the multi-physical ETKF has the advantages of different physical parameterization schemes, which can dramatically improve the forecast accuracy of cloud hydrometeors, reduce precipitation forecast errors, and improve threat scores.

Douchi is a traditional fermented soya bean product that is popular for its smelled saltiness and unique flavor. In order to look for the relationship between smelled saltiness of volatiles and their saltiness-enhancing properties, gas chromatography-olfactometry/associated taste was used to select odorants associated with saltiness in Yongchuan Douchi. The enhancement effects of saltiness intensity by selected odorants were further verified by sensory evaluation analyses of 2-alternative forced-choice and odor-induced saltiness enhancement in a follow-up study. A total of 14 odorant compounds were selected for their odor-associated saltiness perception. The compounds of 2-ethyl-3,5-dimethyl pyrazine, 2,5-dimethyl pyrazine, dimethyl trisulfide, 3-(methylthio) propanol and 3-(methylthio) propanal could significantly enhance saltiness perception in salt solution. Among them, 2-ethyl-3,5-dimethyl pyrazine was reported for the first time to be able to improve the salty taste. The study suggested that salty food is an ideal material for selecting saltiness-enhancing odorants, which could provide more direct theoretical support for salt reduction in the food industry.

The aim of this study is to examine the thiol species for the high cadmium (Cd) tolerance of spinach and provide information for the improvement of soil utilization. The spinach was cultured in aqueous solution with concentrations of Cd ranging from 1 to 9 mg/L. The time responses of glutathione (GSH) and phytochelatins (PCs, PC2-PC4) in the tissues of spinach were monitored via HPLC–MS/MS, and the concentrations of Cd in the roots, shoots and leaves were detected by ICP–OES. Data were analyzed via one-way ANOVA and Spearman correlation to assess the relationships among the types of thiols and the changes between types of thiols and Cd. As Cd stress increased, Cd concentrations in tissues also increased. The total thiol contents responded to Cd stresses with correlations r ranging from 0.394 (root), 0.520 (shoot) to 0.771 (leaf) (p < 0.01). GSH and PC3 were dominant on most of the days under Cd stress. The correlation r between improvements in GSH and increments of Cd concentration in roots was −0.808 (p < 0.01), and r between changes in PC3 and changes in Cd concentrations in leaves was −0.503 (p < 0.01). No correlation can be found between GSH and the subtypes of PCs in shoots, but strong positive correlations within the subtypes of PCs. Thiols can be produced in different tissues of spinach, while the shoots are only a transport tissue for GSH.

High potential toxic element (PTE) concentrations in soils that exceed local regulatory threshold values have been reported in non-polluted mountainous areas worldwide. However, there have been few studies that have comprehensively investigated the contribution of natural factors including the parental material, pedogenesis processes and physiochemical properties of soils on the distribution of PTEs in these soils. Therefore, in this study, we studied the distribution of 13 PTEs in sloping farmland soils collected from a mountainous watershed in Guizhou Province, Southwest China. The contributions of natural influencing factors were analyzed using a geostatistical analysis and a geographic detector method. All of the PTEs were unevenly distributed, especially Sb, and the average contents of V, Cr, Co, Ni, Cu, Zn, As, Mo, Cd, Sb, Tl, Pb and Hg were 57.15, 36.20, 4.61, 12.61, 13.36, 63.50, 11.94, 0.78, 0.37, 6.44, 0.48, 27.42 and 0.36mg/kg, respectively. The proportion of samples with Cd, Hg and As exceeding the screening value of the soil pollution risk of agricultural land in China was 46.7%, 5.9% and 4.4%, respectively. Except for Cd and Pb, the q values of the PTEs calculated from the geographical detector were above 0.05, indicating that altitude changes, which affect the pedogenesis process, have a great impact on the spatial distribution. Stratigraphic factors contributed greatly to the distribution of Co, Ni and Cu, which indicates their similarity in parental material. The combined effect of clay content, topographic factors and agricultural land types had the strongest explanatory power for V, Cr, Mo and Pb. The distributions of As, Sb, Tl and Hg are strongly associated with a potential source of mercury ore, and their accumulation is also enhanced by the adsorption on soil clay. Agricultural As also contributes to its distribution.

Nano-hydroxyapatite (HA-NPs) coating on the surface of titanium is an effective way to improve the osteoinductivity of implants. However, particle agglomeration and uncontrollable structure of HA-NPs results in limited osteogenic capability. In this study, pulse electrochemical deposition method was used to drive PPy in situ, and HA-NPs as well as the osteoinductive drug Dex were introduced to PPy based on its doping characteristics to endow the titanium-based composite coating with long-term osteoinductivity during the osseointegration process. During the oxidative polymerization of PPy, PO43− and Dex− were doped into the main chain of PPy, and HA was formed due to the electrostatic interaction of PO43− and Ca2+, finally realizing the co-deposition of HA-NPs and Dex. Dex drug release experiments showed that the doping effect of PPy has reduced the release rate of Ca2+ from the coating and increased the physiological stability of the coating. The in vitro evaluation of osteoblasts and vascular endothelial cells showed that the number of cells increased steadily with good proliferation conditions, showing promising osteogenic ability and angiogenic property. In summary, a bioactive PPy@HA/Dex nanocomposite coating with sustained osteoinductivity was successfully constructed on the titanium surface using pulse electrochemical method.

Background: Lianhuaqingwen (LH) has been proven effective for influenza. However, the promotion of LH for the treatment of patients with COVID-19 remains controversial. Therefore, our study aimed to assess the efficacy and safety of Lianhuaqingwen (LH) in treating patients with COVID-19 by a systematic review and meta-analysis. Methods: We conducted the literature search using six electronic databases from December 1, 2019, to June 2, 2020. Cochrane Risk of Bias tool was used to assess the quality of randomized controlled trials. Newcastle-Ottawa Scale was used to assess the quality of case control studies. Agency for Healthcare Research and Quality checklist was used to assess the quality of case series. All analyses were conducted by RevMan 5.3. For outcomes that could not be meta-analyzed were performed a descriptive analysis. Results: Eight studies with 924 patients were included. Three studies were RCTs, three were case control studies, and two were case series. The quality of the included studies was poor. Compared with patients treated by conventional treatment, patients treated by LH combined with conventional treatment have a higher overall effective rate (RR = 1.16, 95%CIs: 1.04∼1.30, P = 0.01) and CT recovery rate (RR=1.21, 95%CIs: 1.02∼1.43, P = 0.03). Patients of LH groups have a lower incidence of diarrhea (5.6% vs.13.4%), and have statistically significant (P = 0.026). But the rate of abnormal liver function in the combined medication group is higher than that in the single LH group. Conclusion: LH combined with conventional treatment seems to be more effective for patients with mild or ordinary COVID-19.

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

Background Previous studies have suggested that sleep timing is associated with cardiovascular risk factors. However, there is no evidence on the relationship between sleep timing and congestive heart failure (CHF). We aimed to examine this relationship in this study. Methods and Results We recruited 4765 participants (2207 men; mean age, 63.6±11.0 years) from the SHHS (Sleep Heart Health Study) database in this multicenter prospective cohort study. Follow‐up was conducted until the first CHF diagnosis between baseline and the final censoring date. Sleep timing (bedtimes and wake‐up times on weekdays and weekends) was based on a self‐reported questionnaire. Cox proportional hazard models were constructed to investigate the association between sleep timing and CHF. During the mean follow‐up period of 11 years, 519 cases of CHF (10.9%) were reported. The multivariable Cox proportional hazards models revealed that participants with weekday bedtimes >12:00 am (hazard ratio [HR], 1.56; 95% CI, 1.15–2.11; P=0.004) and from 11:01 pm to 12:00 am (HR, 1.25; 95% CI, 1.00–1.56; P=0.047) had an increased risk of CHF compared with those with bedtimes from 10:01 pm to 11:00 pm. After stratified analysis, the association was intensified in participants with a self‐reported sleep duration of 6 to 8 hours. Furthermore, wake‐up times >8:00 am on weekdays (HR, 1.53; 95% CI, 1.07–2.17; P=0.018) were associated with a higher risk of incident CHF than wake‐up times ≤6:00 am. Conclusions Delayed bedtimes (>11:00 pm) and wake‐up times (>8:00 am) on weekdays were associated with an increased risk of CHF.

It is desirable to improve spatiotemporal control of light generated by synchrotron user facilities or table-top X-ray sources. Here the authors demonstrate manipulation of hard X-rays using microelectro mechanical systems (MEMS) oscillators on timescales of 300 ps, approaching the synchrotron pulse width.

Abstract Background Previous studies have found a connection between left coronary artery dominance and worse prognoses in patient with acute coronary syndrome, which remains a predominant cause of morbidity and mortality globally. The aim of this study was to investigate whether coronary dominance is associated with the incidence of acute inferior myocardial infarction (MI). Methods Between January 2011 and November 2014, 265 patients with acute inferior MI and 530 age-matched and sex-matched controls were recruited for a case-control study in the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. All participants underwent coronary angiography. The exclusion criteria included history of coronary artery bypass graft surgery, chronic or systemic diseases (including hepatic failure, kidney failure, hypothyroidism and Grave’s disease), ventricular fibrillation, and known allergy to iodinated contrast agent. Patients with left- or co-dominant anatomies were placed into the LD group and those with right-dominant anatomy were included in the RD group. The association of acute inferior MI and coronary dominant anatomy were assessed using multivariable conditional logistic regression, and to estimate the odds ratio (OR) and 95% confidence interval (95%CI). Results Distributions of right dominance were significantly different between the acute inferior MI group and control group (94.0% vs. 87.9%, P = 0.018). Univariable conditional logistic regression revealed that right dominance may be a risk factor for the incident acute inferior MI (OR: 2.137; 95% CI: 1.210–3.776; P = 0.009). After adjusting for baseline systolic blood pressure, heart rate, smoking status, diabetes mellitus, hypertension, hyperlipidaemia, and family history of coronary artery disease, results of multivariate conditional logistic regression showed that right dominance was associated with the incidence of acute inferior MI (OR: 2.396; 95% CI: 1.328–4.321; P = 0.004). Conclusions Right coronary dominance may play a disadvantageous role in the incidence of acute inferior MI. However, further studies are needed to verify our findings, especially with regard to the underlying mechanisms.

Objective: Using the traditional Chinese medicine theory of “Bi-zheng'' caused by kidney deficiency, combined with modern medical science and technology, this study assessed the relationships among organ weight, cytokines, pathological manifestations, and traditional Chinese medicine kidney deficiency syndrome in rats with rheumatoid arthritis. Methods: Sixty Sprague–Dawley rats were randomly divided into normal, collagen-induced arthritis (CIA) model, and kidney deficiency arthralgia model groups. Rats in the kidney deficiency arthritis group underwent removal of the testis or ovary and administration of an inflammatory agent. Rats in the control group solely received an inflammatory agent. Type II collagen-induced arthritis was induced within 1 week of the winter solstice or summer solstice, in order to sample organs and observe the mental state, posture, fur color, activity level, excrement, body weight, and organ weight of the rats. Results: Compared with the normal and CIA model groups, the kidney deficiency arthralgia model group showed fast and acute onset, prominent symptoms, most obvious potential joint swelling, worst general state, and least amount of weight gain. Compared with the normal group, the proportion of thymus, spleen, and adrenal glands of model rats were larger in winter, with varying degrees of hyperplasia and hypertrophy; these differences were statistically significant (P