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The objective of this simulation-based study was to assess how genes, environments, and genotype x environment (GxE) interaction affect the quantitative trait loci (QTL) mapping efficiency. The simulation software performed 50 samplings of 300 recombinant inbred lines (RILs) from a F2, which were assessed in six environments. The RILs were genotyped for 977 single nucleotide polymorphisms (SNP) and phenotyped for grain yield. The average SNP density was 2 cM. We defined six QTLs and 190 minor genes. The trait heritability ranged from 30 to 80%. We fitted the single QTL model and the multiple QTL model on multiple phenotypes. The environment and complex GxE interaction effects led to a low correlation between the QTL heritability and power. The single- and across-environment analyses allowed all QTLs be declared, with an average power of 28 to 100%. In the across-environment analysis, five QTLs showed average power in the range 46 to 82%. Both models provided a good control of the false positive rate (6%, on average) and a precise localization of the QTLs (bias of 2 cM, on average). The QTL power in each environment has a high positive correlation with the range between QTL genotypes for the sum of the additive, environment, and GxE interaction effects (0.76 to 0.96). The uncertainty about the magnitude and sign of the environment and GxE interaction effects makes QTL mapping in multi-environment trials unpredictable. Unfortunately, this uncertainty has no solution because the geneticist has no control over the magnitude and sign of the environment and GxE interaction effects. However, the single- and across-environment analyses are efficient even under a low correlation between QTL heritability and power. [ABSTRACT FROM AUTHOR]

Aquatic environments face frequent exposure to organophosphate pesticides, such as diazinon, which are frequently utilized in agriculture. The goal of this study was to evaluate the effects of diazinon exposure on fish and to investigate the potential of the HSP inducer (HSPi) in developing a defense mechanism. To achieve this, several factors were analyzed, including the HSP70 gene expression, levels of immunity markers (lysozyme, IgM, and C3), antioxidant status, and the activity of acetylcholine esterase (AChE). Stellate sturgeon (Acipenser stellatus) fry, was exposed to diazinon (25, 50, and 75% of 96h-LC50) for 6 days after pre-treatment with an HSP inducer (HSPi), TEX-OE® (a prickly pear cactus extract), for 4 hours. Two HSPi concentrations, 100 and 200 mg.L-1, were used. Pre-treatment with HSPi significantly enhanced HSP70 gene expression in the gill and liver, as well as immune markers in the blood of Acipenser stellatus. Diazinon-treated groups exhibited higher antioxidant activities of SOD, CAT, and T-AOC. Increased activity also observed in control fish pre-treated with HSPi. However, stellate sturgeon receiving both diazinon and HSPi+diazinon experienced a significant decrease in AChE activity in comparison with control group. Cortisol levels were elevated in the fish that were subjected to diazinon. Those subjected to diazinon after receiving HSPi showed a significant decrease in cortisol levels. In conclusion, the study suggests that HSPi-mediated HSP70 induction may have a protective effect. The presence of an HSP inducer offers a potential strategy to mitigate the consequences of diazinon exposure in stellate sturgeon. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the relationship between air temperature and the risk of hospitalization for genitourinary disorders. Methods: Distributed lag non-linear models (DLNM) were used to estimate the association between air temperature and the risk of hospitalization for genitourinary disorders, with subgroup analysis by gender and age to identify the susceptible population of temperature-sensitive genitourinary system diseases. Results: Low mean temperature (MT) (RR = 2.001, 95% CI: 1.856~2.159), high MT (RR = 2.884, 95% CI: 2.621~3.173) and low diurnal temperature range (DTR) (RR = 1.619, 95% CI: 1.508~1.737) were all associated with the increased risk of hospitalization for genitourinary disorders in the total population analysis, and the high MT effect was stronger than the low MT effect. Subgroup analysis found that high MT was more strongly correlated in male (RR = 2.998, 95% CI: 2.623~3.427) and those <65 years (RR = 3.003, 95% CI: 2.670~3.344), and low DTR was more strongly correlated in female (RR = 1.669, 95% CI: 1.510~1.846) and those <65 years (RR = 1.643, 95% CI: 1.518~1.780). Conclusions: The effect of high MT on the risk of hospitalization for genitourinary disorders is more significant than that of low MT. DTR was independently associated with the risk of hospitalization for genitourinary disorders. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the reasons behind the decline in the number of applicants and dropouts from N University's reformed program, which includes increased research experience, an optimized curriculum, and other benefits. The ultimate goal is to identify areas for improvement and make the program more appealing to potential students. Methods: This study utilized the Grounded Theory approach, conducting semi-structured in-depth interviews and applying data collection, coding, and the constant comparative method. As a result, a decision-making model for college students was constructed. Results: Following the initial stages of individual expectation formation, which include inducement and self-efficacy, and the subsequent stage of value assessment, individuals reach a decision. Throughout this process, the individual's circumstances and surroundings continue to influence their decision-making. Additionally, the decision-making procedure follows a Hierarchy Pyramid of Educational Needs. Our findings show that job prospects and continuing education are the primary factors influencing interviewees' decisions. However, it is important to note that individuals may place varying levels of importance on these factors. Additionally, the preferences and priorities of teachers, such as their commitment to research guidance, curriculum development, and maintaining fairness in examinations, can also play a role in shaping these decisions. Conclusion: To attract more talented individuals to research-oriented programs, universities should provide more job and higher education opportunities, reform the curriculum thoroughly, and enhance teachers' teaching devotion. [ABSTRACT FROM AUTHOR]

Background: The order Rickettsiales contains a group of vector-borne gram-negative obligate intracellular bacteria, which often cause human emerging infectious diseases and economic losses for dairy and meat industries. The purpose of this study is to investigate the distribution of the pathogens including Rickettsia spp., Anaplasma spp., and Ehrlichia spp. in the order Rickettsiales in ticks from Yueyang, a prefecture-level city of Hunan Province in Sothern China, and assess the potentiality of transovarial transmission of these rickettsial organisms. Methods: Ticks were collected from cattle in a farm in Yueyang City and the tick DNA was used as template to amplify the htrA, rrs, gltA, ompA and ompB genes of Rickettsia as well as rrs and groEL genes of Anaplasma and Ehrlichia. Results: All ticks (465) collected were the cattle tick, Rhipicephalus microplus. PCR showed the minimum infection rate (MIR) was 1.5% (7/465) for Candidatus Rickettsia xinyangensis, 1.9% (9/465) for C. Anaplasma boleense, 1.3% (6/465) for Anaplasma platys, 0.6% (3/465) for A. marginale, and 1.17% (2/465) for each of A. bovis, Ehrlichia minasensis, and a non-classified Ehrlichia sp. A human pathogen, C. Rickettsia xinyangensis and A. platys were detected in 100% (3/3) and 33.3% (2/6) laboratory-hatched larval pools from infected females respectively. Conclusion: Our study revealed a diversity of pathogenic rickettsial species in R. microplus ticks from Hunan Province suggesting a threat to people and animals in China. This study also provided the first molecular evidence for the potential transovarial transmission of C. Rickettsia xinyangensis and A. platys in R. microplus, indicating that R. microplus may act as the host of these two pathogens. Author summary: Spotted fever group rickettsiae, Anapalsma, and Ehrlichia are tick-borne bacteria, which can cause severe human and animal infection and/or extensive economic losses in animal husbandry. It has been well documented that some Ixodidae ticks are able to transmit Rickettsia, Anaplasma, and Ehrlichia, while the studies on transovarial transmission are limited. In this study, we detected 7 rickettsial species in the cattle tick Rhipicephalus microplus in Hunan Province of the Southern China. Among them, Candidatus Rickettsia xinyangensis and A. platys were also found in the tick eggs and laboratory-hatched larvae of R. microplus, suggesting the vertical transmission of these two pathogens in R. microplus. Our findings provide important information regarding the distribution and ecology of these tick-borne rickettsiae. [ABSTRACT FROM AUTHOR]

Water quality regulation is widely recognized as a highly effective strategy for disease prevention in the field of aquaculture, and it holds significant potential for the development of sustainable aquaculture. Herein, four water quality regulators, including potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS), and chitosan (CS), were added to the culture water of Oreochromis niloticus (GIFT tilapia) every seven days. Subsequently, the effects of these four water quality regulators on GIFT tilapia were comprehensively evaluated by measuring the water quality index of daily growth-related performance and immune indexes of GIFT tilapia. The findings indicated that implementing the four water quality regulators resulted in a decrease in the content of ammonia nitrogen, active phosphate, nitrite, total organic carbon (TOC), and chemical oxygen demand (COD) in the water. Additionally, these regulators were found to maintain dissolved oxygen (DO) levels and pH of the water effectively. Furthermore, using these regulators demonstrated positive effects on various physiological parameters of GIFT tilapia, including improvements in final body weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), feed conversion ratio (FCR), spleen index (SI), hepato-somatic index (HSI), immune cell count, the activity of antioxidant-related enzymes (Nitric oxide, NO and Superoxide dismutase, SOD), and mRNA expression levels of immunity-related factors (Tumor Necrosis Factor-alpha, TNF-α and Interleukin-1 beta, IL-1β) in the liver and spleen. Notably, the most significant improvements were observed in the groups treated with the BS and CS water quality regulators. Moreover, BS and CS groups exhibited significantly higher serum levels of albumin (ALB) and total protein (TP) (P < 0.05), whereas the other indicators showed no significant difference (P > 0.05) compared to the control group. However, the KMPS and THPS groups of GIFT tilapia exhibited significantly higher serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE) and blood urea nitrogen (BUN) (P < 0.05), whereas they exhibited significantly decreased HSI (P < 0.05). In addition, the partially pathological observations revealed the presence of cell vacuolation, nuclear shrinkage, and pyknosis within the liver. In conclusion, these four water quality regulators, mainly BS and CS, could improve the growth performance and immunity of GIFT tilapia to varying degrees by regulating the water quality and then further increasing the expression levels of immune-related factors or the activity of antioxidant-related enzymes of GIFT tilapia. On the contrary, the prolonged use of KMPS and THPS may gradually diminish their growth-enhancing properties and potentially hinder the growth of GIFT tilapia. [ABSTRACT FROM AUTHOR]

Aberrantly up-regulated activity of the type II transmembrane protease Matriptase-1 has been associated with the development and progression of a range of epithelial-derived carcinomas, and a variety of signaling pathways can mediate Matriptase-dependent tumorigenic events. During mammalian carcinogenesis, gain of Matriptase activity often results from imbalanced ratios between Matriptase and its cognate transmembrane inhibitor Hai1. Similarly, in zebrafish, unrestrained Matriptase activity due to loss of hai1a results in epidermal pre-neoplasms already during embryogenesis. Here, based on our former findings of a similar tumor-suppressive role for the Na+/K+-pump beta subunit ATP1b1a, we identify epithelial polarity defects and systemic hypotonic stress as another mode of aberrant Matriptase activation in the embryonic zebrafish epidermis in vivo. In this case, however, a different oncogenic pathway is activated which contains PI3K, AKT and NFkB, rather than EGFR and PLD (as in hai1a mutants). Strikingly, epidermal pre-neoplasm is only induced when epithelial polarity defects in keratinocytes (leading to disturbed Matriptase subcellular localization) occur in combination with systemic hypotonic stress (leading to increased proteolytic activity of Matriptase). A similar combinatorial effect of hypotonicity and loss of epithelial polarity was also obtained for the activity levels of Matriptase-1 in human MCF-10A epithelial breast cells. Together, this is in line with the multi-factor concept of carcinogenesis, with the notion that such factors can even branch off from one and the same initiator (here ATP1a1b) and can converge again at the level of one and the same mediator (here Matriptase). In sum, our data point to tonicity and epithelial cell polarity as evolutionarily conserved regulators of Matriptase activity that upon de-regulation can constitute an alternative mode of Matriptase-dependent carcinogenesis in vivo. Author summary: Deciphering the mechanisms of carcinogenesis is pivotal not only for the treatment of the disease, but also for identifying potential risk factors. Model systems can help to achieve this goal. Work with zebrafish has identified several evolutionarily conserved factors driving pre-neoplastic events in the epidermis already at embryonic stages. This study focuses on the oncogene ST14, encoding the type II transmembrane protease Matriptase-1 that upon hyperactivation—as for instance due to genetic loss of its cognate transmembrane inhibitor Hai1—can drive different carcinomas. Here, we identify two additional conditions promoting oncogenic Matriptase-1 hyperactivation: hypotonic stress and compromised epithelial cell polarity. Of note, these two conditions need to occur together for Matriptase-dependent induction of pre-neoplasms in the embryonic zebrafish epidermis, in line with the multi-factor concept of carcinogenesis. Hypotonicity increases the proteolytic activity of Matriptase, while epithelial polarity defects lead to a subcellular mis-localization of Matriptase in outer epidermal cells, bringing more of it into close contact to underlying basal cells and thus inducing oncogenic pathways in them. Together, our work identifies novel modes of oncogenic Matriptase hyperactivation and function in vivo, originating from cells of the tumor environment, rather than from the tumor cells themselves. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are highly prevalent in patients with age-related neurodegenerative diseases, which severely affect cognition and even lead to accumulated β-amyloid. Encouraging results from recent studies on transcranial direct current stimulation (tDCS) showed moderate positive effects on sleep quality in preclinical Alzheimer's disease (AD). Compared to tDCS, transcranial alternating current stimulation (tACS) enables the entrainment of neuronal activity with optimized focality through injecting electric current with a specific frequency and has significant enhancement effects on slow wave activities. Methods and design: This is a randomized, double-blind, sham-controlled clinical trial comparing 40 Hz tACS with tDCS in mild neurocognitive disorders due to AD with sleep disturbances. Magnetic resonance imaging (MRI) data is used to construct personalized realistic head model. Treatment outcomes, including sleep quality, cognitive performance and saliva Aβ levels will be conducted at baseline, 4th week, 8th week, 12th week and 24th week. Conclusions: It is expected that the repeated gamma-band tACS will show significant improvements in sleep quality and cognitive functions compared to tDCS and sham tDCS. The findings will provide high-level evidence and guide further advanced studies in the field of neurodegenerative diseases and sleep medicine. Trial registration: ClinicalTrials.gov Identifier: NCT05544201. [ABSTRACT FROM AUTHOR]

Background: The emergence and the spread of coronavirus disease (COVID-19) induced by the SARS-CoV-2 virus has multiple consequences in all countries around the world. Male germ cells of infertile patients which are shown to be vulnerable to many environmental conditions, could be particularly vulnerable to such an exceptional pandemic situation. We aimed through the current study to investigate the potential variations in sperm quality of infertile patients during the COVID-19 pandemic in Tunisia. Methods: This was a cohort study including 90 infertile patients addressed to Laboratory of Cytogenetics and Reproductive Biology of Monastir Department of Maternity and Neonatology in Monastir, during the two first COVID-19 waves in Tunisia and who already have a spermogram before the pandemic period. Results: We have pointed out a significant decrease in both total and progressive sperm motility during COVID-19 pandemic (p<0.0001 and p = 0.001 respectively). The percentage of morphologically abnormal spermatozoa increased from 90.99±7.38 to 93.67±4.55% during the pandemic (p< 0.001). The remaining sperm parameters were similar between the two compared timepoints. Interestingly, the univariate analysis didn't show any other associated factor to the observed impairment in sperm mobility and morphology. Conclusion: These data highlight the severe impact of the pandemic of the male reproductive health of hypofertile patients. Delaying infertility investigations and management after pandemic waves is recommended to hope a better gamete quality and hence to improve conception potential. [ABSTRACT FROM AUTHOR]

Thoracic ossification of the ligamentum flavum (TOLF) is characterized by ectopic bone formation in the ligamentum flavum and is considered to be a leading cause of thoracic spinal canal stenosis and myelopathy. However, the underlying etiology is not well understood. An iTRAQ proteomics was used to reveal the involvement of inflammation factors in TOLF. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of many human diseases. Protein profiling analysis showed that the protein level of TNF-α increased in the ossified ligamentum flavum of TOLF, which was confirmed by western blot. The effects of TNF-α on primary ligamentum flavum cells was examined. Cell proliferation assay demonstrated that primary cells from the ossified ligamentum flavum of TOLF grew faster than the control. Flow cytometry assay indicated that the proportions of cells in S phase of cell cycle of primary cells increased after TNF-α stimulation. To address the effect of TNF-α on gene expression, primary cells were derived from ligamentum flavum of TOLF patients. Culture cells were stimulated by TNF-α. RNA was isolated and analyzed by quantitative RT-PCR. G1/S-specific proteins cyclin D1 and c-Myc were upregulated after TNF-α stimulation. On the other hand, osteoblast differentiation related genes such as Bmp2 and Osterix (Osx) were upregulated in the presence of TNF-α. TNF-α activated Osx expression in a dose-dependent manner. Interestingly, a specific mitogen-activated protein kinase ERK inhibitor U0126, but not JNK kinase inhibitor SP600125, abrogated TNF-α activation of Osx expression. This suggests that TNF-α activates Osx expression through the mitogen-activated protein kinase ERK pathway. Taken together, we provide the evidence to support that TNF-α involves in TOLF probably through regulating cell proliferation via cyclin D1 and c-Myc, and promoting osteoblast differentiation via Osx. [ABSTRACT FROM AUTHOR]

For a long time, governments of all countries have attached great importance to the development of underground economic activities. The reason is that the characteristics of the underground economy are hidden and the information disclosure is not sufficient, which not only distorts the economic data indicators, but more importantly, the existence of the underground economy has led to the loss of a large amount of tax base, affecting the long-term economic development of the country. Whether raising the tax burden rate boosts the tax revenue or expand the scale of the underground economy. In this paper, we use Kuznet Tax Curve (KTC) method to analyze the relationship between GDP and TTR/DTR/ITR. We find that the tax base erosion rate of indirect tax is lower than that of direct tax. In addition, we explore the relationship among economic growth, tax rate and tax revenue and adopt SUR-OLS method and Threshold approach to estimate the response of economic growth on total tax revenue(TTR), direct tax revenue(DTR) and indirect tax revenue (ITR) in Taiwan from 1991-2020. Our empirical research shows that when DTR tax rates are between 12.59% and 13%, an increase in income leads to a decrease, not an increase, in DTR, leading to severe tax base erosion. That is, the relationship between GDP and DTR presents a N-shaped relationship. However, ITR does not exist any tax rate threshold effect. Obviously, with the increase of GDP, ITR also increases. This reflects that the difference of tax structure between direct tax and indirect tax plays a key role in the relationship between tax rate and tax base erosion. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases are a major threat to public health, causing serious medical consumption and casualties. Accurate prediction of infectious diseases incidence is of great significance for public health organizations to prevent the spread of diseases. However, only using historical incidence data for prediction can not get good results. This study analyzes the influence of meteorological factors on the incidence of hepatitis E, which are used to improve the accuracy of incidence prediction. Methods: We extracted the monthly meteorological data, incidence and cases number of hepatitis E from January 2005 to December 2017 in Shandong province, China. We employ GRA method to analyze the correlation between the incidence and meteorological factors. With these meteorological factors, we achieve a variety of methods for incidence of hepatitis E by LSTM and attention-based LSTM. We selected data from July 2015 to December 2017 to validate the models, and the rest was taken as training set. Three metrics were applied to compare the performance of models, including root mean square error(RMSE), mean absolute percentage error(MAPE) and mean absolute error(MAE). Results: Duration of sunshine and rainfall-related factors(total rainfall, maximum daily rainfall) are more relevant to the incidence of hepatitis E than other factors. Without meteorological factors, we obtained 20.74%, 19.50% for incidence in term of MAPE, by LSTM and A-LSTM, respectively. With meteorological factors, we obtained 14.74%, 12.91%, 13.21%, 16.83% for incidence, in term of MAPE, by LSTM-All, MA-LSTM-All, TA-LSTM-All, BiA-LSTM-All, respectively. The prediction accuracy increased by 7.83%. Without meteorological factors, we achieved 20.41%, 19.39% for cases in term of MAPE, by LSTM and A-LSTM, respectively. With meteorological factors, we achieved 14.20%, 12.49%, 12.72%, 15.73% for cases, in term of MAPE, by LSTM-All, MA-LSTM-All, TA-LSTM-All, BiA-LSTM-All, respectively. The prediction accuracy increased by 7.92%. More detailed results are shown in results section of this paper. Conclusions: The experiments show that attention-based LSTM is superior to other comparative models. Multivariate attention and temporal attention can greatly improve the prediction performance of the models. Among them, when all meteorological factors are used, multivariate attention performance is better. This study can provide reference for the prediction of other infectious diseases. [ABSTRACT FROM AUTHOR]

Low-cost and efficient dynamic monitoring of surface salinization information is critical in arid and semi-arid regions, we conducted a remote sensing inversion exercise for soil salinity in the Bosten Lake watershed in Xinjiang, Northwest China, with a total area of about 43,930 km2, a typical watershed in an arid area. Sentinel MSI and Landsat OLI data were combined with measured soil salinity data in July 2020, and optimal combination bands were selected based on characteristic bands to create a grid search-support vector machine (GS-SVM) inversion model of soil salt content. The maximum value of soil salt content in the Bosten Lake watershed was 11.8 g/kg. The minimum value was 0.41 g/kg, and the average value was 4.77 g/kg, soil salinization is serious. The results of previous studies were applied to the estimation of salt content in Bosten Lake watershed and could not meet the monitoring requirements of the study area, R2 < 0.3. The GS-SVM soil salinity monitoring model was established based on the optimal DI, RI, and NDI remote sensing indexes for the Bosten Lake watershed. After model verification, it was found that the optimal model of image data was the Landsat OLI first-derivative model with R2 of 0.64, RMSE of 3.12, and RPD of 1.64, indicating that the prediction ability of the model was high. We used the first-order derivative model of Landsat OLI data to map the soil salt content in the Bosten Lake watershed in arid area, and found that soil salt content in most of the study area was between 10 and 20 g/kg, indicating severe salinization. This study not only reveals the distribution characteristics of salinization in Bosten Lake watershed, but also provides a scientific basis for soil salinization monitoring in Central Asia to lay a foundation for further soil salinization monitoring in arid areas. [ABSTRACT FROM AUTHOR]

Visible disruptions of appropriate food distribution for end consumers during the onset of the COVID-19 pandemic prompted calls for an urgent, renewed look at how the U.S. agri-food system is impacted by and responds to pandemics, natural disasters, and human-made crises. Previous studies suggest the COVID-19 pandemic yielded uneven impacts across agri-food supply chain segments and regions. For a rigorously comparable assessment of the impact of COVID-19 on agri-food businesses, a survey was administered from February to April 2021 to five segments of the agri-food supply chain in three study regions (California, Florida, and the two-state region of Minnesota-Wisconsin). Results (N = 870) measuring the self-reported changes in quarterly business revenue in 2020 compared to businesses' typical experience pre-COVID-19 suggest significant differences across supply chain segments and regions. In the Minnesota-Wisconsin region, restaurants took the largest hit and the upstream supply chains were relatively unaffected. In California, however, the negative impacts were felt throughout the supply chain. Two factors likely contributed to regional differences: (1) regional disparities in pandemic evolution and governance and (2) structural differences in regional agri-food systems. Regionalized and localized planning and the development of best-practices will be necessary for the U.S. agri-food system to enhance preparedness for and resilience to future pandemics, natural disasters, and human-made crises. [ABSTRACT FROM AUTHOR]

Moss, was frequently found growing in litchi orchards. However, less known about whether it can be used as a visual bio-indicator for evaluating soil fertility and health. Therefore, soil chemical and biological properties, microbial community structures and the metabolic functions of microbes in soils between moss- and non-moss-growth areas were analyzed using traditional and high-throughput sequencing technologies. The results showed that pH and the contents of and available phosphorus (AP) in moss growth areas were significantly lower than those of non-moss growth areas, but the contents of alkali-hydrolyzable nitrogen (AN) and available potassium (AK) were significantly increased. In comparison with the soil of the non-moss-growth area, the abundances of hypotrophic microorganisms, such as Chloroflexi, Cyanobacteria and WPS-2 enriched in the soil of the moss-grown area. Moreover, the proportions of eutrophic microorganisms, such as Proteobacteria and Firmicutes also declined in the soils of the moss-growth area. Furthermore, the metabolic pathways of soil bacteria and fungi were also degraded in the moss-growth area. All above results indicated that not only lower soil fertility, but also soil microbial diversity also declined in moss growth area which compared to those of non-moss growth area. In one word, moss can be considered using as a visual bio-indicator for representing soil degradation in litchi orchards. [ABSTRACT FROM AUTHOR]

Background: Ticks act as important vectors of infectious agents, and several emerging tick-borne viruses have recently been identified to be associated with human diseases in northeastern China. However, little is known about the tick virome in northeastern China. Methods: Ticks collected from April 2020 to July 2021 were pooled for metagenomic analysis to investigate the virome diversity in northeastern China. Results: In total, 22 RNA viruses were identified, including four each in the Nairoviridae and Phenuiviridae families, three each in the Flaviviridae, Rhabdoviridae, and Solemoviridae families, two in the Chuviridae family, and one each in the Partitiviridae, Tombusviridae families and an unclassified virus. Of these, eight viruses were of novel species, belonging to the Nairoviridae (Ji'an nairovirus and Yichun nairovirus), Phenuiviridae (Mudanjiang phlebovirus), Rhabdoviridae (Tahe rhabdovirus 1–3), Chuviridae (Yichun mivirus), and Tombusviridae (Yichun tombus-like virus) families, and five members were established human pathogens, including Alongshan virus, tick-borne encephalitis virus, Songling virus, Beiji nairovirus, and Nuomin virus. I. persulcatus ticks had significant higher number of viral species than H. japonica, H. concinna, and D. silvarum ticks. Significant differences in tick viromes were observed among Daxing'an, Xiaoxing'an and Changbai mountains. Conclusions: These findings showed an extensive diversity of RNA viruses in ticks in northeastern China, revealing potential public health threats from the emerging tick-borne viruses. Further studies are needed to explain the natural circulation and pathogenicity of these viruses. Author summary: Ticks are important vectors to transmit many infectious agents. In recent years, many novel tick-borne viruses associated with human illness, including Alongshan virus, Songling virus, and Beiji nairovirus, have been identified in northeastern China. It is necessary to conduct routine surveillance of tick-borne viruses in ticks, however, little is known about the tick virome in northeastern China. In this study, we used metatranscriptomics to investigate the virome diversity in four tick species collected from northeastern China. In total, we identified 22 RNA viruses belonging to eight virus families (exclude an unclassified virus). Of these, five members were established human pathogens, eight viruses were of novel species, and six viruses had close relationship with pathogenic tick-borne viruses with potential public health threats. Moreover, we found that the viromes were significantly affected by the tick species and geographical location in the study. These findings revealed an extensive diversity of RNA viruses in ticks in northeastern China, which will lay the foundation for the prevention and control of emerging tick-borne diseases. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) is a useful molecular diagnostic tool for genetic diseases. However, due to the presence of highly homologous pseudogenes, it is challenging to use short-read NGS for analyzing mutations of the Shwachman-Bodian-Diamond syndrome (SBDS) gene. The SBDS mutation spectrum was analyzed in the Chinese population, which revealed that SBDS variants were primarily from sequence exchange between SBDS and its pseudogene at the base-pair level, predominantly in the coding region and splice junction of exon two. The c.258+2T>C and c.185_184TA>GT variants were the two most common pathogenic SBDS variants in the Chinese population, resulting in a total carrier frequency of 1.19%. When analyzing pathogenic variants in the SBDS gene from the NGS data, the misalignment was identified as a common issue, and there were different probabilities of misalignment for different pathogenic variants. Here, we present a novel mathematical method for identifying pathogenic variants in the SBDS gene from the NGS data, which utilizes read-depth of the paralogous sequence variant (PSV) loci of SBDS and its pseudogene. Combined with PCR and STR orthogonal experiments, SBDS gene mutation analysis results were improved in 40% of clinical samples, and various types of mutations such as homozygous, compound heterozygous, and uniparental diploid were explored. The findings effectively reduce the impact of misalignment in NGS-based SBDS mutation analysis and are helpful for the clinical diagnosis of SBDS-related diseases, the research into population variation, and the carrier screening. [ABSTRACT FROM AUTHOR]

This study was aimed to evaluate the effects of post-transportation vitamin E (VE) supplementation on health condition, blood biochemical parameters, blood antioxidant indices and blood metabolomics in yak. Five yaks were used in this study. After 2100 km of highway transportation from Riwoqe county to Rongchang County, Chongqing, blood was collected immediately after arrival and these samples served as the baseline (control, CON_VE). A VE injection (40 mg/kg) was then performed and blood samples were collected 10 days later. Injection of VE led to lower serum VE concentration. Relative to the CON_VE, VE injection led to greater concentrations of creatinine and lower concentrations of glutamate pyruvic transaminase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, indirect bilirubin, direct bilirubin, UREA and glucose. Compared with CON_VE, VE injection led the lower serum level of malondialdehydeand greater serum level of glutathione s-transferase, glutathione peroxidase, glutathione reductase and glutathione peroxidase 4. Based on metabolomics analysis, 119 differentially altered serum metabolites (P<0.05 and VIP>1.0) were identified with VE injection relative to CON_VE. VE injection resulted in changes of lysophosphatidylethanolamine, lysophosphatidylcholine, phosphocholine, choline, malate, citrate, α-Oxo-glutarate, phenylalanine, 3-Phenylpropanoic acid and 3-(3-Hydroxyphenyl) propanoic acid. These metabolites are associated with lipid metabolism, tricarboxylic acid cycle and oxidative stress. Overall, our study indicates that VE injection can alleviate transportation stress in yak partly through protecting liver and kidney, and improving antioxidant defense systems. [ABSTRACT FROM AUTHOR]

Litter pollution is a global environmental problem that occurs in virtually all ecosystems. Scientific research on anthropogenic litter and its environmental impacts focusses predominantly on plastics and the marine environment. Little empirical knowledge exists about the distribution and ecological impacts of litter in terrestrial environments, where most litter is produced. To start closing that knowledge gap, we investigated the distribution of litter in a cultural landscape in central Norway and in relation to land cover types. We registered and collected litter in 110 survey plots that were randomly stratified across various land cover types. Our results show that land cover type modulates the occurrence, abundance, fragments size, and that litter is most present and abundant in or near land cover types associated with high human activities. Plastic was by far the most common litter material type, although the litter community (in terms of materials type) was not independent from land cover type. This knowledge can help to inform and optimize litter management and clean-up activities in terrestrial landscapes. How and to what extent the spatial structure of the litter community mediates ecological effects across various land cover types remains unknown to a large extent and warrants further study. [ABSTRACT FROM AUTHOR]

Increasing evidence showed that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are common event in the pathophysiology of many vascular diseases, including atherosclerosis and restenosis after angioplasty. Among the underlying mechanisms, oxidative stress is one of the principal contributors to the proliferation and migration of VSMCs. Oxidative stress occurs as a result of persistent production of reactive oxygen species (ROS). Recently, the protective effects of peroxisome proliferator-activated receptor γ (PPARγ) against oxidative stress/ROS in other cell types provide new insights to inhibit the suggests that PPARγ may regulate VSMCs function. However, it remains unclear whether activation of PPARγ can attenuate oxidative stress and further inhibit VSMC proliferation and migration. In this study, we therefore investigated the effect of PPARγ on inhibiting VSMC oxidative stress and the capability of proliferation and migration, and the potential role of mitochondrial uncoupling protein 2 (UCP2) in oxidative stress. It was found that platelet derived growth factor-BB (PDGF-BB) induced VSMC proliferation and migration as well as ROS production; PPARγ inhibited PDGF-BB-induced VSMC proliferation, migration and oxidative stress; PPARγ activation upregulated UCP2 expression in VSMCs; PPARγ inhibited PDGF-BB-induced ROS in VSMCs by upregulating UCP2 expression; PPARγ ameliorated injury-induced oxidative stress and intimal hyperplasia (IH) in UCP2-dependent manner. In conclusion, our study provides evidence that activation of PPARγ can attenuate ROS and VSMC proliferation and migration by upregulating UCP2 expression, and thus inhibit IH following carotid injury. These findings suggest PPARγ may represent a prospective target for the prevention and treatment of IH-associated vascular diseases. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans. SARS-CoV-2 infection is mediated by the entry receptor ACE2, but cellular entry factors that inhibit viral entry are largely unknown. This study shows that human LRRC15 protein is expressed in pathological fibroblasts, directly binds to the receptor-binding domain of spike protein, and inhibits SARS-CoV-2 spike-mediated viral entry in neighboring cells. [ABSTRACT FROM AUTHOR]

Background & importance: This patient and public-involved systematic review originally focused on arachnoiditis, a supposedly rare "iatrogenic chronic meningitis" causing permanent neurologic damage and intractable pain. We sought to prove disease existence, causation, symptoms, and inform future directions. After 63 terms for the same pathology were found, the study was renamed Diseases of the Leptomeninges (DLMs). We present results that nullify traditional clinical thinking about DLMs, answer study questions, and create a unified path forward. Methods: The prospective PRISMA protocol is published at Arcsology.org. We used four platforms, 10 sources, extraction software, and critical review with ≥2 researchers at each phase. All human sources to 12/6/2020 were eligible for qualitative synthesis utilizing R. Weekly updates since cutoff strengthen conclusions. Results: Included were 887/14286 sources containing 12721 DLMs patients. Pathology involves the subarachnoid space (SAS) and pia. DLMs occurred in all countries as a contributor to the top 10 causes of disability-adjusted life years lost, with communicable diseases (CDs) predominating. In the USA, the ratio of CDs to iatrogenic causes is 2.4:1, contradicting arachnoiditis literature. Spinal fusion surgery comprised 54.7% of the iatrogenic category, with rhBMP-2 resulting in 2.4x more DLMs than no use (p<0.0001). Spinal injections and neuraxial anesthesia procedures cause 1.1%, and 0.2% permanent DLMs, respectively. Syringomyelia, hydrocephalus, and arachnoid cysts are complications caused by blocked CSF flow. CNS neuron death occurs due to insufficient arterial supply from compromised vasculature and nerves traversing the SAS. Contrast MRI is currently the diagnostic test of choice. Lack of radiologist recognition is problematic. Discussion & conclusion: DLMs are common. The LM clinically functions as an organ with critical CNS-sustaining roles involving the SAS-pia structure, enclosed cells, lymphatics, and biologic pathways. Cases involve all specialties. Causes are numerous, symptoms predictable, and outcomes dependent on time to treatment and extent of residual SAS damage. An international disease classification and possible treatment trials are proposed. [ABSTRACT FROM AUTHOR]

Salt and drought stresses are major environmental conditions that severely limit grape growth and productivity, while exogenous melatonin can alleviate the drought and salt damage to grapevines. N-acetylserotonin methyltransferase (ASMT) is the key enzyme in melatonin synthesis, which plays a critical role in regulating stress responses. However, the roles of ASMTs from grapevine under drought and salt stresses responses remain largely unclear. In this study, the VvASMT1 gene was isolated from grapevine, and its physiological functions in salt and mimic drought stress tolerance were investigated. Expression pattern analysis revealed that VvASMT1 was significantly induced by different salt and osmotic stresses. Ectopic expression of VvASMT1 in Nicotiana benthamiana significantly enhanced melatonin production in transgenic plants. Compared with wild-type plants, the transgenic lines exhibited a higher germination ratio, longer root length, lower degree of leaf wilting and relative water content (RWC) under salt and osmotic stresses. In addition, under salt and osmotic stresses, overexpression of VvASMT1 improved proline and malondialdehyde (MDA) contents, increased the activity of antioxidant enzymes and decreased the accumulation of reactive oxygen species (ROS). Taken together, our results demonstrate the explicit role of VvASMT1 in salt and osmotic stress responses, which provides a theoretical foundation for the genetic engineering of grapevine. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is a common microenvironment condition in most malignant tumors and has been shown to be associated with adverse outcomes of cervical cancer patients. In this study, we investigated the effects of hypoxia-related genes on tumor progress to characterize the tumor hypoxic microenvironment. Methods: We retrieved a set of hypoxia-related genes from the Molecular Signatures Database and evaluated their prognostic value for cervical cancer. A hypoxia-based prognostic signature for cervical cancer was then developed and validated using tumor samples from two independent cohorts (TCGA-CESC and CGCI-HTMCP-CC cohorts). Finally, we validated the hypoxia prediction of ccHPS score in eight human cervical cancer cell lines treated with the hypoxic and normoxic conditions, and 286 tumor samples with hypoxic category (more or less) from Gene Expression Omnibus (GEO) database with accession GSE72723. Results: A risk signature model containing nine hypoxia-related genes was developed and validated in cervical cancer. Further analysis showed that this risk model could be an independent prognosis factor of cervical cancer, which reflects the condition of the hypoxic tumor microenvironment and its remodeling of cell metabolism and tumor immunity. Furthermore, a nomogram integrating the novel risk model and lymphovascular invasion status was developed, accurately predicting the 1-, 3- and 5-year prognosis with AUC values of 0.928, 0.916 and 0.831, respectively. These findings provided a better understanding of the hypoxic tumor microenvironment in cervical cancer and insights into potential new therapeutic strategies in improving cancer therapy. [ABSTRACT FROM AUTHOR]

Bacillus cereus is a food contaminant with widely varying enterotoxic potential due to its virulence proteins. In this article, phylogenetic analysis of the amino acid sequences from the whole-genomes of 41 strains, evolutionary distance calculation of the amino acid sequences of the virulence genes, and functional and structural predictions of the virulence proteins were performed to reveal the taxonomically diverse distribution of virulence factors. The genome evolution of the strains showed a clustering trend based on the protein-coding virulence genes. The strains of B. cereus have evolved into non-toxic risk and toxic risk clusters with medium-high- and medium-low-risk subclusters. The evolutionary transfer distances of incomplete virulence genes relative to housekeeping genes were greater than those of complete virulence genes, and the distance values of HblACD were higher than those of nheABC and CytK among the complete virulence genes. Cytoplasmic localization was impossible for all the virulence proteins, and NheB, NheC, Hbl-B, and Hbl-L1 were predicted to be extracellular. Nhe and Hbl proteins except CytK had similar spatial structures. The predicted structures of Nhe and Hbl mainly showed 'head' and 'tail' domains. The 'head' of NheA and Hbl-B, including two α-helices separated by β-tongue strands, might play a special role in the formation of Nhe trimers and Hbl trimers, respectively. The 'cap' of CytK, which includes two 'latches' with many β-sheets, formed a β-barrel structure with pores, and a 'rim' balanced the structure. The evolution of B. cereus strains showed a clustering tendency based on the protein-coding virulence genes, and the complete virulence-gene operon combination had higher relative genetic stability. The beta-tongue or latch associated with β-sheet folding might play an important role in the binding of virulence structures and pore-forming toxins in B. cereus. [ABSTRACT FROM AUTHOR]

Breast cancer is regarded as the leading killer of women today. The early diagnosis and treatment of breast cancer is the key to improving the survival rate of patients. A method of breast cancer histopathological images recognition based on deep semantic features and gray level co-occurrence matrix (GLCM) features is proposed in this paper. Taking the pre-trained DenseNet201 as the basic model, part of the convolutional layer features of the last dense block are extracted as the deep semantic features, which are then fused with the three-channel GLCM features, and the support vector machine (SVM) is used for classification. For the BreaKHis dataset, we explore the classification problems of magnification specific binary (MSB) classification and magnification independent binary (MIB) classification, and compared the performance with the seven baseline models of AlexNet, VGG16, ResNet50, GoogLeNet, DenseNet201, SqueezeNet and Inception-ResNet-V2. The experimental results show that the method proposed in this paper performs better than the pre-trained baseline models in MSB and MIB classification problems. The highest image-level recognition accuracy of 40×, 100×, 200×, 400× is 96.75%, 95.21%, 96.57%, and 93.15%, respectively. And the highest patient-level recognition accuracy of the four magnifications is 96.33%, 95.26%, 96.09%, and 92.99%, respectively. The image-level and patient-level recognition accuracy for MIB classification is 95.56% and 95.54%, respectively. In addition, the recognition accuracy of the method in this paper is comparable to some state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. A growing number of studies have shown that competitive endogenous RNA (ceRNA) regulatory networks might play important roles during HCC process. The present study aimed to identify a regulatory axis of the ceRNA network associated with the development of HCC. The roles of SNX16 and PAPOLG in HCC were comprehensively analyzed using bioinformatics tools. Subsequently, the "mRNA-miRNA-lncRNA" model was then used to predict the upstream miRNAs and lncRNAs of SNX16 and PAPOLG using the miRNet database, and the miRNAs with low expression and good prognosis in HCC and the lncRNAs with high expression and poor prognosis in HCC were screened by differential expression and survival analysis. Finally, the risk-prognosis models of ceRNA network axes were constructed by univariate and multifactorial Cox proportional risk analysis, and the immune correlations of ceRNA network axes were analyzed using the TIMER and GEPIA database. In this study, the relevant ceRNA network axis GSEC/miR-101-3p/SNX16/PAPOLG with HCC prognosis was constructed, in which GSEC, SNX16, and PAPOLG were highly expressed in HCC with poor prognosis, while miR-101-3p was lowly expressed in HCC with good prognosis. The risk-prognosis model predicted AUC of 0.691, 0.623, and 0.626 for patient survival at 1, 3, and 5 years, respectively. Immuno-infiltration analysis suggested that the GSEC/miR-101-3p/SNX16/PAPOLG axis might affect macrophage polarization. The GSEC/miR-101-3p/SNX16/PAPOLG axis of the ceRNA network axis might be an important factor associated with HCC prognosis and immune infiltration. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy of Y-chromosome mini-STR-based next-generation sequencing (NGS) for non-invasive prenatal paternity testing (NIPPT). Methods: DNA was extracted from the plasma of 24 pregnant women, and cell-free fetal DNA (cffDNA) haplotyping was performed at 12 Y-chromosome mini-STR loci using the Illumina NextSeq 500 system. The cffDNA haplotype was validated by the paternal haplotype. Subsequentlly, the paternity testing parameters were attributed to each case quantitatively. Results: The biological relationship between the alleged fathers and infants in all 24 family cases were confirmed by capillary electrophoresis (CE). The Y-chromosome mini-STR haplotypes of all 14 male cffDNA were obtained by NGS without any missing loci. The alleles of cffDNA and paternal genomic DNA were matched in 13 cases, and a mismatched allele was detected at the DYS393 locus in one case and considered as mutation. No allele was detected in the 10 female cffDNA. The combined paternity index (CPI) and probability of paternity calculation was based on 6 loci Y-haplotype distributions of a local population. The probability of paternity was 98.2699–99.8828% for the cases without mutation, and 14.8719% for the case harboring mutation. Conclusions: Our proof-of-concept study demonstrated that Y-chromosome mini-STR can be used for NGS-based NIPPT with high accuracy in real cases, and is a promising tool for familial searching, paternity exclusion and sex selection in forensic and medical applications. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by protozoan parasites belonging to the genus Leishmania for which there are no approved human vaccines. Infections localise to different tissues in a species-specific manner with the visceral form of the disease caused by Leishmania donovani and L. infantum being the most deadly in humans. Although Leishmania spp. parasites are predominantly intracellular, the visceral disease can be prevented in dogs by vaccinating with a complex mixture of secreted products from cultures of L. infantum promastigotes. With the logic that extracellular parasite proteins make good subunit vaccine candidates because they are directly accessible to vaccine-elicited host antibodies, here we attempt to discover proteins that are essential for in vitro growth and host infection with the goal of identifying subunit vaccine candidates. Using an in silico analysis of the Leishmania donovani genome, we identified 92 genes encoding proteins that are predicted to be secreted or externally anchored to the parasite membrane by a single transmembrane region or a GPI anchor. By selecting a transgenic L. donovani parasite that expresses both luciferase and the Cas9 nuclease, we systematically attempted to target all 92 genes by CRISPR genome editing and identified four that were required for in vitro growth. For fifty-five genes, we infected cohorts of mice with each mutant parasite and by longitudinally quantifying parasitaemia with bioluminescent imaging, showed that nine genes had evidence of an attenuated infection although all ultimately established an infection. Finally, we expressed two genes as full-length soluble recombinant proteins and tested them as subunit vaccine candidates in a murine preclinical infection model. Both proteins elicited significant levels of protection against the uncontrolled development of a splenic infection warranting further investigation as subunit vaccine candidates against this deadly infectious tropical disease. Author summary: Leishmaniasis is a parasitic infectious disease that is responsible for many tens of thousands of human deaths per year, primarily in impoverished parts of the world. Although there are drugs to treat this parasite infection, resistance is emerging and there are no approved human vaccines. Extracellular parasite proteins can make good vaccine targets because they are directly accessible to host antibodies; however, not all parasite surface proteins can elicit protective immune responses. With the goal of identifying new vaccine targets, we selected over 90 genes that encode parasite cell surface and secreted proteins and used the latest CRISPR gene editing technology to individually target them. Using these mutant parasites, we identified four genes required for parasite growth in the laboratory. We expressed two of the proteins as subunit vaccines and a preclinical infection model was used to determine if they could elicit protective immune responses. We found that two of our candidates were able to confer significant levels of protection in a murine model of visceral leishmaniasis. Our study will contribute to the search for a highly effective vaccine against visceral leishmaniasis to improve the lives of people living in some of the poorest regions on the planet. [ABSTRACT FROM AUTHOR]

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is continuously evolving, and this poses a major threat to antibody therapies and currently authorized Coronavirus Disease 2019 (COVID-19) vaccines. It is therefore of utmost importance to investigate and predict the putative mutations on the spike protein that confer immune evasion. Antibodies are key components of the human immune system's response to SARS-CoV-2, and the spike protein is a prime target of neutralizing antibodies (nAbs) as it plays critical roles in host cell recognition, fusion, and virus entry. The potency of therapeutic antibodies and vaccines partly depends on how readily the virus can escape neutralization. Recent structural and functional studies have mapped the epitope landscape of nAbs on the spike protein, which illustrates the footprints of several nAbs and the site of escape mutations. In this review, we discuss (1) the emerging SARS-CoV-2 variants; (2) the structural basis for antibody-mediated neutralization of SARS-CoV-2 and nAb classification; and (3) identification of the RBD escape mutations for several antibodies that resist antibody binding and neutralization. These escape maps are a valuable tool to predict SARS-CoV-2 fitness, and in conjunction with the structures of the spike-nAb complex, they can be utilized to facilitate the rational design of escape-resistant antibody therapeutics and vaccines. [ABSTRACT FROM AUTHOR]

Many CRISPR/Cas platforms have been established for the detection of SARS-CoV-2. But the detection platform of the variants of SARS-CoV-2 is scarce because its specificity is very challenging to achieve for those with only one or a few nucleotide(s) differences. Here, we report for the first time that chimeric crRNA could be critical in enhancing the specificity of CRISPR-Cas12a detecting of N501Y, which is shared by Alpha, Beta, Gamma, and Mu variants of SARS-CoV-2 without compromising its sensitivity. This strategy could also be applied to detect other SARS-CoV-2 variants that differ only one or a few nucleotide(s) differences. [ABSTRACT FROM AUTHOR]

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains–including 191 T. pallidum subsp. pallidum–sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543–1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens. Author summary: Each year, millions of new cases of venereal and congenital syphilis, caused by the bacterium Treponema pallidum (T. pallidum) subsp. pallidum, are diagnosed worldwide, resulting in significant morbidity and mortality. Alongside endemic circulation of syphilis in low-income countries, disease resurgence in high-income nations has underscored the need for a vaccine. Due to prior technological limitations in culturing and sequencing the organism, the extent of the genetic diversity within modern strains of T. pallidum subsp. pallidum remains poorly understood, hampering development of a broadly protective vaccine. In this study, we obtained 196 near-complete T. pallidum genomes directly from clinical swabs from eight countries across six continents. Of these, 191 were identified as T. pallidum subsp. pallidum, including 90 Nichols clade genomes. Bayesian analysis revealed a high degree of variance in mutation rate among subclades. Interestingly, a Nichols subclade with a particularly high mutation rate harbors a non-synonymous mutation in a putative DNA repair helicase. Coupling sequencing data with protein structure prediction, we identified multiple novel amino acid variants in several proteins previously identified as potential vaccine candidates. Our data help inform current efforts to develop a broadly protective syphilis vaccine. [ABSTRACT FROM AUTHOR]

Working memory (WM) deficits have been widely documented in schizophrenia (SZ), and almost all existing studies attributed the deficits to decreased capacity as compared to healthy control (HC) subjects. Recent developments in WM research suggest that other components, such as precision, also mediate behavioral performance. It remains unclear how different WM components jointly contribute to deficits in schizophrenia. We measured the performance of 60 SZ (31 females) and 61 HC (29 females) in a classical delay-estimation visual working memory (VWM) task and evaluated several influential computational models proposed in basic science of VWM to disentangle the effect of various memory components. We show that the model assuming variable precision (VP) across items and trials is the best model to explain the performance of both groups. According to the VP model, SZ exhibited abnormally larger variability of allocating memory resources rather than resources or capacity per se. Finally, individual differences in the resource allocation variability predicted variation of symptom severity in PSZ, highlighting its functional relevance to schizophrenic pathology. This finding was further verified using distinct visual features and subject cohorts. These results provide an alternative view instead of the widely accepted decreased-capacity theory and highlight the key role of elevated resource allocation variability in generating atypical VWM behavior in schizophrenia. Our findings also shed new light on the utility of Bayesian observer models to characterize mechanisms of mental deficits in clinical neuroscience. Author summary: Working memory is a core cognitive function related to a broad range of cognitive domains such as problem-solving, attention, executive control, and IQ. Although working memory deficits have been well-documented in schizophrenia, the underlying mechanisms remain unclear. Conventional working memory theories attribute working memory deficits in schizophrenia to their reduced memory capacity, overlooking the potential roles of other memory components, such as precision. In this study, we take the approach of computational psychiatry and use computational modeling to uncover the major determinants of working memory deficits. We assess working memory performance of a large cohort of participants (60 schizophrenia patients and 61 demographic matched healthy controls) and evaluate multiple mainstream computational models of visual working memory. The variable precision model turns out to be the best model for both groups. We further find that the poorer performance of schizophrenia patients arises from heterogeneous distribution of memory resources when encoding items in memory. This resource allocation variability can also predict symptom severity in schizophrenia. Our study highlights the use of computational models in psychiatric researches. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3-dioxygenase 1 (IDO-1) is an immunosuppressive enzyme expressed in the placenta, neoplastic cells, and macrophages to reject T cells by converting tryptophan into kynurenine. However, the role of IDO-1 in brain immunity, especially in the meninges, is unclear. We aim to elucidate the distribution pattern of IDO-1+ macrophages/microglia in the human brain tissues, human glioblastoma, APP/PS1 mouse brains, and quinolinic acid model brains and explore the physiological and immunological roles of IDO-1+ macrophages/microglia. Here, we find that both human and mouse macrophages/microglia of the perivascular and subarachnoid space and in glioblastoma (GBM) expressed IDO-1 but not macrophages/microglia of parenchyma. Using IDO-1 inhibitors including 1-MT and INCB24360, we observed that inhibiting IDO-1 reduced the cellular size and filopodia growth, fluid uptake, and the macropinocytic and phagocytic abilities of human blood monocytes and RAW264.7/BV-2 cells. Inhibiting IDO-1 with 1-MT or INCB24360 increased IL-1β secretion and suppressed NLRP3 expression in RAW264.7/BV-2 cells. Our data collectively show that IDO-1 expression in perivascular and meninges macrophages/microglia increases cellular phagocytic capacity and might suppress overactivation of inflammatory reaction. [ABSTRACT FROM AUTHOR]

U2 snRNP is an essential component of the spliceosome. It is responsible for branch point recognition in the spliceosome A-complex via base-pairing of U2 snRNA with an intron to form the branch helix. Small molecule inhibitors target the SF3B component of the U2 snRNP and interfere with A-complex formation during spliceosome assembly. We previously found that the first SF3B inhibited-complex is less stable than A-complex and hypothesized that SF3B inhibitors interfere with U2 snRNA secondary structure changes required to form the branch helix. Using RNA chemical modifiers, we probed U2 snRNA structure in A-complex and SF3B inhibited splicing complexes. The reactivity pattern for U2 snRNA in the SF3B inhibited-complex is indistinguishable from that of A-complex, suggesting that they have the same secondary structure conformation, including the branch helix. This observation suggests SF3B inhibited-complex instability does not stem from an alternate RNA conformation and instead points to the inhibitors interfering with protein component interactions that normally stabilize U2 snRNP's association with an intron. In addition, we probed U2 snRNA in the free U2 snRNP in the presence of SF3B inhibitor and again saw no differences. However, increased protection of nucleotides upstream of Stem I in the absence of SF3A and SF3B proteins suggests a change of secondary structure at the very 5′ end of U2 snRNA. Chemical probing of synthetic U2 snRNA in the absence of proteins results in similar protections and predicts a previously uncharacterized extension of Stem I. Because this stem must be disrupted for SF3A and SF3B proteins to stably join the snRNP, the structure has the potential to influence snRNP assembly and recycling after spliceosome disassembly. [ABSTRACT FROM AUTHOR]

To promote the coordinated development between renewable energy and the distribution network, a capacity allocation model of battery energy storage systems (BESS) is proposed to achieve the coordinated optimization for active and reactive power flow, which can reduce the voltage deviation and improve the absorptive capacity for renewable energy. In addition, BESS with four-quadrant operation characteristics, on-load tap changer, and capacitor banks are treated as flexible devices to improve the adaptability for renewable energy fluctuations. In view of the uncertainties of renewable energy caused by the inaccuracy of historical sample data, a set of extreme scenarios with the characteristics of temporal and spatial correlation are considered to obtain a robust BESS configuration decision. The big-M approach and the second-order conic relaxation technique are utilized to convert the BESS capacity allocation model into a mixed-integer linear programming problem. Finally, the IEEE 33-node distribution system is taken as an example to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

In this work two kinds of smooth (compactons or cnoidal waves and solitons) and nonsmooth (peakons) solutions to the general Degasperis-Procesi (gDP) equation and its family (Degasperis-Procesi (DP) equation, modified DP equation, Camassa-Holm (CH) equation, modified CH equation, Benjamin-Bona-Mahony (BBM) equation, etc.) are reported in detail using different techniques. The single and periodic peakons are investigated by studying the stability analysis of the gDP equation. The novel compacton solutions to the equations under consideration are derived in the form of Weierstrass elliptic function. Also, the periodicity of these solutions is obtained. The cnoidal wave solutions are obtained in the form of Jacobi elliptic functions. Moreover, both soliton and trigonometric solutions are covered as a special case for the cnoidal wave solutions. Finally, a new form for the peakon solution is derived in details. As an application to this study, the fluid basic equations of a collisionless unmagnetized non-Maxwellian plasma is reduced to the equation under consideration for studying several nonlinear structures in the plasma model. [ABSTRACT FROM AUTHOR]

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that HlaH35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby HlaH35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by HlaH35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens. Author summary: Pore-forming toxins, a kind of exotoxins utilized by many pathogens as immune escaping weapons that targeting the immune cells and disturbing the immune system, are conventionally deemed as perfect antigens for vaccine development against infectious diseases. In this study, we reported that fusion of HlaH35A, a typical pore-forming toxin toxoid, to candidate protein antigens from different species resulted in improved immunogenicity and protective efficacy. The improvement was mainly due to the increased antigen uptake and activating of immune-associated signaling pathways, probably by targeting ADAM10, the receptor of Hla on host immune cells. The importance of this work was to demonstrate the possible mechanisms of that pore-forming toxin function as atypical carrier protein to improve the immunogenicity of other proteins and confirm the potential of non-conservative but highly immunogenic exotoxins derived from hyper-virulent clinical strains for application in rational antigen design and vaccines development. [ABSTRACT FROM AUTHOR]

Background: The population in Jiamusi has been reported to have the highest prevalence of colorectal cancer (CRC) in China. The genetic causal-effect for this occurrence among the residents remains unclear. Given the long cold seasons with people wearing more clothes and reduced UV exposure, we aimed to study the association between the vitamin D metabolism-related gene CYP24A1 polymorphism and CRC susceptibility. Method: A case-control study was conducted that included 168 patients with CRC and 710 age-matched healthy individuals as the control group. Plausible susceptible variations were sought and clinical phenotypic-genotype association analysis was performed. Results: Overall, two CYP24A1 polymorphisms, rs6013905 AX (P = 0.02, OR = 1.89, 95%CI: 1.09–3.29) and rs2762939 GX (P = 0.02, OR = 1.52, 95%CI: 1.08–2.13) were significantly associated with CRC in the Jiamusi population. In the female group, three CYP24A1 polymorphisms, rs6013905 AX (P = 0.04, OR = 2.59, 95%CI: 1.03–6.49), rs2762939 GX (P = 0.01, OR = 2.35, 95%CI: 1.25–4.42), and rs6068816 GG (P = 0.05, OR = 1.89, 95%CI: 0.99–3.59) carriers were significantly associated with CRC. In clinical phenotypic-genotype analysis, rs6013905 GG (P = 0.05, OR = 4.00, 95%CI: 0.92–17.48) and rs2762939 GX (P = 0.03, OR = 4.87, 95%CI: 1.00–23.69) carriers were significantly associated with poorly differentiated CRC, while CYP24A1 rs6068816 AX was significantly associated with the tumor type (P = 0.02, OR = 2.08, 95%CI: 1.10–3.96) and location (P = 0.04, OR = 2.24, 95%CI: 1.05–4.77). Conclusion: CYP24A1 gene polymorphism may be a genetic risk factor attributable to the highest prevalence of CRC in Jiamusi people. Individuals with CYP24A1 gene polymorphism may have an increased barrier for vitamin D absorption, thus contributing to the risk of CRC development. [ABSTRACT FROM AUTHOR]

A single insulin receptor (InR) gene has been identified and extensively studied in model species ranging from nematodes to mice. However, most insects possess additional copies of InR, yet the functional significance, if any, of alternate InRs is unknown. Here, we used the wing-dimorphic brown planthopper (BPH) as a model system to query the role of a second InR copy in insects. NlInR2 resembled the BPH InR homologue (NlInR1) in terms of nymph development and reproduction, but revealed distinct regulatory roles in fuel metabolism, lifespan, and starvation tolerance. Unlike a lethal phenotype derived from NlInR1 null, homozygous NlInR2 null mutants were viable and accelerated DNA replication and cell proliferation in wing cells, thus redirecting short-winged–destined BPHs to develop into long-winged morphs. Additionally, the proper expression of NlInR2 was needed to maintain symmetric vein patterning in wings. Our findings provide the first direct evidence for the regulatory complexity of the two InR paralogues in insects, implying the functionally independent evolution of multiple InRs in invertebrates. Author summary: The highly conserved insulin/insulin-like growth factor signaling pathway plays a pivotal role in growth, development, and various physiological processes across a wide phylogeny of organisms. Unlike a single InR in the model species such as the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, most insect lineages have two or even three InR copies. However, the function of the alternative InRs remains elusive. Here, we created a homozygous mutation for a second insulin receptor (InR2) in the wing-dimorphic brown planthopper (BPH), Nilaparvata lugens, using the clustered regularly interspaced palindromic repeats/CRISPR-associated (CRISPR/Cas9) system. Our findings revealed that InR2 possesses functions distinct from the BPH InR homologue (NlInR1), indicating that multiple InR paralogues may have evolved independently and may have functionally diversified in ways more complex than previously expected in invertebrates. [ABSTRACT FROM AUTHOR]

Background: Hepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by many factors, including schistosomes. Previous studies in our lab have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. Let-7b is a member of the let-7 microRNA family and plays an inhibitory role in a variety of diseases and inflammatory conditions. In this study, we investigated the role of let-7b in the inhibition of HSC activation by rSjP40. Methods: Expression of let-7b was detected by quantitative real-time PCR. A dual luciferase assay was used to confirm direct interaction between let-7b and collagen I. We also used western blot to assess protein levels of TGFβRI and collagen type I α1 (COL1A1). Results: We found that rSjP40 up-regulates expression of let-7b in HSCs. Let-7b inhibits collagen I expression by directly targeting the 3'UTR region of the collagen I gene. Furthermore, we discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40. Conclusion: Our research clarifies the role of let-7b in the inhibition of HSC activation by rSjP40 and will provide new insights and ideas for the inhibition of HSC activation and treatment of liver fibrosis. Author summary: Hepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by schistosomes. Our previous studies have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. In this study, we found that rSjP40 up-regulates expression of let-7b in HSCs. Let-7b is a member of the let-7 microRNA family and plays an inhibitory role in a variety of diseases and inflammatory conditions. Let-7b inhibits collagen I expression by directly targeting the 3'UTR region of the collagen I gene. Furthermore, we discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40. Our research clarifies the role of let-7b in the inhibition of HSC activation by rSjP40 and will provide new insights and ideas for the inhibition of HSC activation and treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Prior studies have reported inconsistent findings with regard to the effects of small-group student talk on developing individual students' English-as-a-foreign-language (EFL) writing ability. To further explore the question under discussion, we designed a quasi-experimental study that included a pretest, a posttest, and a delayed posttest, and implemented it in two English-major groups at a university in China. We randomly assigned the students to an intervention group and a comparison group to investigate whether employing structured small-group student talk as collaborative prewriting discussions would effectively facilitate individual students' EFL writing development and whether such effects could be retained. The immediate and sustained effects after the quasi-experimental study was completed were measured by the analytic scores on five components of the writing task (content, organization, vocabulary, language, and mechanics) and the holistic writing scores cumulated of all these components. Statistical analyses revealed that the two groups were significantly distinguished by their analytic and holistic scores, indicating that students in the intervention group outperformed their comparison group peers in writing performance. The effects of collaborative prewriting discussions in the form of structured small-group student talk were found statistically significant in facilitating students' writing improvement in the content, organization, vocabulary, and language use, but not mechanics. The effects on content, organization, and vocabulary were retained as seen from the delayed posttest, while those on language use were not. The comparison group showed little improvement in their writing performance across the three tests. We concluded this study with a discussion on the implications for English-as-a-second/foreign-language (L2) writing instruction. [ABSTRACT FROM AUTHOR]

The current study examined how emotional faces impact on attentional control at both involuntary and voluntary levels in children with and without autism spectrum disorder (ASD). A non-face single target was either presented in isolation or synchronously with emotional face distractors namely angry, happy and neutral faces. ASD and typically developing children made more erroneous saccades towards emotional distractors relative to neutral distractors in parafoveal and peripheral conditions. Remote distractor effects were observed on saccade latency in both groups regardless of distractor type, whereby time taken to initiate an eye movement to the target was longest in central distractor conditions, followed by parafoveal and peripheral distractor conditions. The remote distractor effect was greater for angry faces compared to happy faces in the ASD group. Proportions of failed disengagement trials from central distractors, for the first saccade, were higher in the angry distractor condition compared with the other two distractor conditions in ASD, and this effect was absent for the typical group. Eye movement results suggest difficulties in disengaging from fixated angry faces in ASD. Atypical disengagement from angry faces at the voluntary level could have consequences for the development of higher-level socio-communicative skills in ASD. [ABSTRACT FROM AUTHOR]

A diverse community of microorganisms inhabits various parts of a plant. Recent findings indicate that perturbations to the normal microbiota can be associated with positive and negative effects on plant health. In this review, we discuss these findings in the context of understanding how microbiota homeostasis is regulated in plants for promoting health and/or for preventing dysbiosis. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl− and HCO3−. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl− and HCO3− secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl− transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl− signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment. Author summary: Trichomonas vaginalis is a common sexually transmitted parasite that colonized the urogenital mucosa and causes trichomoniasis, a neglected sexually transmitted infection associated with multiple adverse reproductive outcomes in humans. However, the underlying mechanisms remain largely unknown. The epithelial cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel conducting both Cl− and HCO3−, which participates in the regulation of luminal fluid microenvironment conducive to the success of reproductive events. Prostaglandin E2 (PGE2), a bioactive molecule abundant in human seminal fluid, has been demonstrated to exhibit a robust pro-secretory action by activating CFTR in the female genital tract epithelial cells such as endometrial epithelium. These discoveries motivated the authors to investigate the effect of T. vaginalis infection on exogenous PGE2-induced transepithelial transport of electrolytes in vagina. Here, we found that in rat vaginal epithelium, luminal administration of PGE2 elicited a response of Cl− and HCO3− secretion mediated by cAMP-activated CFTR. However, T. vaginalis infection impaired transepithelial anion transport evoked by PGE2, which is probably related to the defective expression and function of CFTR. These outcomes may complement and expand our knowledge of the complex interaction between T. vaginalis and the infected host, providing a novel therapeutic strategy for disequilibrium in vaginal fluid microenvironment and infertility induced by T. vaginalis infection. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) represents one of major zoonotic diseases among cattle, it also affects the health of human, other domestic animals and wild life populations. Inhalation of infected aerosol droplets is considered as the most frequent route of the infection. This study aims to investigate the current forms of tuberculosis in cattle and identify the possible transmission modes in dairy farms of China. 13,345 cows from eight dairy farms in three provinces were comprehensively diagnosed by a multitude of assays, including SIT, CIT, IFN-γ assay and ELISA. It has been indicated that advanced infection of bTB was found in 752 (5.64%) cattle, suggesting a high prevalence of tuberculosis in these dairy farms. In the necropsy examination of 151 positive cattle, typical bTB lesions were observed in 131 cattle (86.75%), of which, notably, 90.84% lesions appeared in liver, spleen, mesenteric lymph nodes, mammary lymph nodes and other organs, taking up a large proportion among cattle with advanced bTB infection. 71.26% extrapulmonary tuberculosis (EPTB) was related to gastrointestinal system. M. bovis nucleic acid was further found in milk and feces samples and M. bovis was even isolated from milk samples. Phylogenetic analysis based on whole genome sequencing unraveled that six isolates were closely related to M. bovis AF2122/97 originated from UK, whereas four isolates shared close relation to M. bovis 30 from China, respectively. Our data demonstrate that the increase of EPTB transmitted by digestive tract is implicated in the current high prevalence rate of bTB in China, which also provides leads for bTB control in other countries with high prevalence of bTB in the future. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the knowledge, practices, and attitudes of medical professionals toward Traditional Chinese Medicine (TCM) for the prevention and treatment of coronavirus disease 2019 (COVID-19). All 401 medical professionals were surveyed using an anonymous with an investigator using the Questionnaire star APP. The participants answered 14 questions; of the 401 participants, 55.2% agreed with the statement "TCM can be used for the prevention and treatment of COVID-19," 40.4% remained neutral, and 4.4% disagreed. Moreover, 75.3% agreed with the statement "There is no specific drug for COVID-19," 67% agreed with the statement "TCM can develop immunity to COVID-19" and 62.1% agreed with "TCM can alleviate the symptoms of patients with COVID-19." Meanwhile, 69.1% were aware that TCM has been recommended for COVID-19 by the National Health Commission of the People's Republic of China. Regarding the selection of sources of knowledge on whether "TCM can be used for the prevention and treatment of COVID-19," There were 277, 123, 82, 369, and 17 participants selected sources from "Hospital training," "Academic journals," "Academic Conferences," "Social media platforms (such as WeChat)" and "Others," respectively. Further, 358 participants will take TCM for the prevention of COVID-19. Multiple logistic regression analysis showed that age, major and received TCM treatment within the last five years were independent factors affecting the participants' attitudes. In the absence of specific drugs for COVID-19, more than half of the participants agreed that TCM could be used for the prevention and treatment of COVID-19 and most participants are willing to take TCM to prevent COVID-19, although unsure about its effectiveness. The main information sources on TCM for the treatment and prevention of COVID-19 were social platforms and hospital training. [ABSTRACT FROM AUTHOR]

With the development of the economy and technology, people's requirement for communication is also increasing. Satellite communication networks have been paid more and more attention because of their broadband service capability and wide coverage. In this paper, we investigate the scheme of convolutional long short term memory (CLSTM) network and transfer learning (TL) based combined free/demand assignment multiple access (CFDAMA) scheme (CFDAMA-CLSTMTL), which is a new multiple access scheme in the satellite communication networks. Generally, there is a delay time T between sending a request from the user to the satellite and receiving a reply from the satellite. So far, the traditional multiple access schemes have not processed the data generated in this period. So, in order to transmit the data in time, we propose a new prediction method CLSTMTL, which can be used to predict the data generated in this period. We introduce the prediction method into the CFDAMA scheme so that it can reduce data accumulation by the way of sending the slots request which is the sum of slots requested by the user and the predicted slots generated in the delay time. A comparison with CFDAMA-PA and CFDAMA-PB is provided through simulation results, which gives the effect of the CFDAMA-CLSTMTL in a satellite communication network. [ABSTRACT FROM AUTHOR]

The outcome of Leishmania donovani infection depends upon the dynamic interchanges between M1 and M2 macrophages. Information of the involvement of microRNAs (miRNAs) and epigenetic modifiers in regulating macrophage plasticity during L. donovani infection is still elusive. Differential expression analysis of polarization-regulating miRNAs, revealed significant enrichment of miR146a-5p during Leishmania donovani infection. A sustained enrichment of miR146a-5p was observed in both infected bone marrow derived macrophages (BMDMs) and BALB/c mice organs. We found involvement of miR146a-5p in phagocytosis and survivability of parasites. Moreover, miR146a-5pgot enriched in interleukin 4- stimulated BMDMs, indicating its possible involvement in M2 polarization. Upon transfecting BMDMs with miRVANA anti-146a oligos, M2 markers (CCR7, YM-1, FIZZ-1, arginase-1, IL10 and IL4) and transcription factors (p-STAT6 and c/EBPβ) got depleted with concomitant augmentation of M1-polarizing transcription factors (p-STAT1, AP1 and IRF-1), miR146a target genes (TRAF6 and IRAK1), M1 cytokines (IL12 and TNFα), iNOS, nitric oxide, and nuclear translocation of phospho p-65 subunit. Neutralization of intracellular mature miR146a-5p pool in infected BALB/c mice lower organ parasite burden and expressions of M2 markers and IL10 with enrichment of M1 markers like iNOS and IL12. Additionally, we explored the novel role of super enhancer (SE), a cis-acting regulatory component, to enrich miR146a-5p expression during infection. Enhanced expression and nuclear retention of SE components like BET bromodomain 4 (BRD4) and p300 were found in infected BMDMs. Upon silencing BRD4, expressions of miR146a-5p and M2 markers were down regulated and TRAF6, IRAK1 and iNOS levels increased. STRING V.11 based predication and immune precipitation confirmed the strong interaction amongst BRD4, p300 and RNA pol II (RpbI). Chromatin immune precipitation studies suggested the recruitment of BRD4 at the enhancer loci of miR146a-5p gene during infection. Altogether, our findings revealed a novel role of BRD4/p300-depdendent super-enhancer in regulating miR146a expression during L. donovani infection which in turn mediates M2 polarization and immune-suppression. Author summary: Visceral leishmaniasis (VL), caused by protozoan parasites Leishmania donovani, is the most severe form of leishmaniasis and is highly lethal if left untreated. Major obstacle for successful therapy of VL originates from the life-long immune-suppression triggered in the post kala-azar dermal leishmaniasis (PKDL) patients during infection. Identification of molecular principles behind such immune-suppression will add success in VL therapeutics. L. donovani hijacks the host macrophages and converts them from pro-inflammatory M1 to immune-suppressive M2 type, which allows successful infection establishment. Herein, we explored the indispensable role of miRNA-146a-5p in conversion of M1 to M2 type during infection. Both in vitro and in vivo miRNA silencing established miR146a-5p as an imperative negative regulator ofM1 polarization. Computational analysis as well as immune precipitation based experiments authenticated that L. donovani induces super enhancer complex mediated transcriptional upregulation of miR146a-5p. BET bromodomain protein 4 (BRD4) forms this SE complex along with p300 histone acetyl transferase and RNA pol II. Silencing of BRD4 significantly abrogated miR146a-5p mediated M2 polarization. In short, our current findings established a previously unrecognized role of BRD4-depdendent super enhancers in orchestrating persistent transcription of macrophage miR146a-5p which in turn promotes M2 polarization during L. donovani infection. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a widespread neglected tropical disease transmitted by infected sand flies resulting in either benign cutaneous infection or fatal visceral disease. Leishmania donovani is the principal species responsible for visceral leishmaniasis, yet an atypical L. donovani has become attenuated in several countries including Sri Lanka and causes cutaneous leishmaniasis. Previous studies have identified 91 genes altered in the atypical cutaneous L. donovani compared to typical visceral disease associated L. donovani including mutations in the RagC and Raptor genes that are part of the eukaryotic conserved TOR pathway and its upstream sensing pathway. In the present study, we investigate whether the RagC R231C mutation present in atypical cutaneous L. donovani introduced into the virulent L. donovani 1S2D chromosome by CRISPR gene editing could affect virulence for survival in visceral organs. Through bioinformatic analysis, we further investigated the presence of sensing pathway components upstream of TOR in L. donovani including RagC complexing proteins, RagA and Raptor. L. donovani 1S2D edited to express mutant RagC R231C were viable in promastigote but had reduced visceral parasitemia in infected BALB/c mice. The RagC R231C mutant retained the ability to interact with RagA and gene knockout experiments revealed that although the RagA gene was essential, the RagC gene was not essential under promastigote culture conditions but was essential for survival in the liver of experimentally infected mice. These results provide evidence that the TOR associated sensing pathway plays a prominent role in L. donovani visceral disease and the RagC R231C mutation contributed to the atypical pathology of cutaneous L. donovani in Sri Lanka. Author summary: The Leishmania donovani parasite is transmitted by infected sandflies and is the principal causative agent of visceral leishmaniasis, a neglected tropical disease with no available vaccine. The infection normally spreads to the liver, spleen and bone marrow and is fatal if untreated. In Sri Lanka however, L. donovani causes only skin pathology at the site of the sandfly bite and does not cause visceral disease. Previous genetic analysis of this atypical attenuated strain identified 91 gene mutations including single amino acid mutations in the RagC and Raptor genes that are part of the conserved eukaryotic TOR regulatory pathway and upstream sensing complexes. This study investigated whether members of the TOR and associated sensing pathways could be identified by bioinformatic analysis and the potential role a RagC mutation plays in the attenuation of L. donovani in Sri Lanka for causing visceral disease. This study provides novel insight into the role of the TOR and associated sensing pathways and the RagC single nucleotide polymorphism in L. donovani virulence. [ABSTRACT FROM AUTHOR]