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Tao Zhou,1 Lei Jia,1 Yi-Feng Luo,2 Jun Xu,1 Ru-Hua Chen,2 Zhi-Jun Ge,2 Tie-Liang Ma,2 Hong Chen,2 Tao-Feng Zhu2 1Department of Physics and Chemistry, Henan Polytechnic University, Jiaozuo, Henan, 2The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, People’s Republic of China Abstract: A novel multifunctional halloysite nanotube (HNT)-based Fe3O4@HNT-polyethyleneimine-Tip-Eu(dibenzoylmethane)3 nanocomposite (Fe-HNT-Eu NC) with both photoluminescent and magnetic properties was fabricated by a simple one-step hydrothermal process combined with the coupling grafting method, which exhibited high suspension stability and excellent photophysical behavior. The as-prepared multifunctional Fe-HNT-Eu NC was characterized using various techniques. The results of cell viability assay, cell morphological observation, and in vivo toxicity assay indicated that the NC exhibited excellent biocompatibility over the studied concentration range, suggesting that the obtained Fe-HNT-Eu NC was a suitable material for bioimaging and biological applications in human hepatic adenocarcinoma cells. Furthermore, the biocompatible Fe-HNT-Eu NC displayed superparamagnetic behavior with high saturation magnetization and also functioned as a magnetic resonance imaging (MRI) contrast agent in vitro and in vivo. The results of the MRI tests indicated that the Fe-HNT-Eu NC can significantly decrease the T2 signal intensity values of the normal liver tissue and thus make the boundary between the normal liver and transplanted cancer more distinct, thus effectively improving the diagnosis effect of cancers. Keywords: halloysite nanotube, lanthanide complex, iron oxide, luminescence, contrast agent

one rare 15-nor-cadinane sesquiterpenoid (1), one new chromene amide derivative (2), and one new highly conjugated ergosterol steroid (3), along with three known compounds (4-6) were isolated from the marine-derived fungus Eutypella sp. F0219. Their chemical structures including absolute configurations were established by HR-ESIMS, extensive 1D and 2D NMR investigations, and electronic circular dichroism (ECD) calculations. All compounds were evaluated for their anti-influenza A virus and anti-influenza B virus activities against the A/PR/8/34 (H1N1), ZX1109 (H1N1, oseltamivir resistant virus), HK68 (H3N2), and B/Florida/78/2015 strains. Compounds 3 and 4 showed significant antiviral activities against those four virus strains with EC50 values ranging from 2.07 to 11.3 μM. Most notably, compound 3 exhibited potent anti-influenza B virus activity against B/Florida/78/2015 strain with EC50 value of 2.27±1.76 μM, versus the postive control (oseltamivir, EC50 = 7.14±1.94 μM)., (© 2024 Wiley‐VCH GmbH.)

Eco-friendly aquaculture technology has become a major global trend in recent years. This study's investigation and analysis revealed that eco-friendly aquaculture management technologies increased the production per unit area of the grouper and the fourfinger threadfin. From an economic perspective, it was estimated that the application of eco-friendly aquaculture management technology might increase grouper production by 18.6 metric tons/ha and the output value by US$7,106.9/ha per year, as well as decrease electricity consumption by 1,510.45 kWh/ha/month. It was estimated that for fourfinger threadfin, the use of eco-friendly aquaculture management technologies might increase the production by 10.1 tons/ha and the output value by US$5,031.8/ha each year, as well as reduce the electricity consumption by 257.18 kWh/ha/month. As such, eco-friendly aquaculture management technologies may increase the output value while reducing energy consumption and costs. Furthermore, regression analysis with dummy variables showed that factors affecting grouper production per unit area included applying eco-friendly aquaculture management technology, stocking density, and harvest specifications. However, no significant relationship was identified between breeding time and production per unit area, and the correlation coefficient was negative. The main factors positively affecting the production per unit area of the fourfinger threadfin were stocking density, the application of eco-friendly aquaculture management technology, and harvest specifications. However, a longer breeding time did not result in better production per unit area. This study showed that eco-friendly aquaculture management technology increased the production per unit area and reduced water consumption, electricity consumption, and operating costs to promote sustainable use of water and land resources and sustainable industrial operation and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones., Results: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways., Conclusion: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1 , Q 3 ) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI )] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all P non-linear >0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Ventricular remodeling after myocardial infarction(VRAMI) is a pathological phenomenon triggered by the abrupt occlusion of coronary arteries, leading to myocardial ischemia and hypoxia. This intricate process encompasses alterations in the dimensions, composition, and elasticity of the ventricular tissue and reflects pathophysiological reactions and self-repair after cardiomyocytes are damaged. The characteristic pathological manifestation of VRAMI is the presence of myocardial fibrosis(MF), wherein fibrotic cardiac tissue undergoes a loss of contractile and relaxation capacity, ultimately culminating in heart failure(HF) and significantly impacting the patient's prognosis. Endothelial-mesenchymal transition(EndMT) is a biological process in which endothelial cells, in response to diverse pathological stimuli such as ischemia and hypoxia in the embryonic development period, undergo morphological alterations and functional impairment, progressively acquiring mesenchymal cell properties and ultimately differentiating into mesenchymal cells. The ongoing advancement of the EndMT process will result in an excessive buildup of collagen, thereby inducing structural harm to the myocardium and exacerbating the processes of VRAMI and MF. Recent investigations have demonstrated the pivotal involvement of EndMT in the pathological advancement of VRAMI. Consequently, a targeted intervention aimed at effectively impeding VRAMI, safeguarding cardiac function, and potentially serving as a novel therapeutic target for the prevention and treatment of VRAMI. This article provides a comprehensive review of recent Chinese and international literature, focusing on the role and pathophysiological mechanisms of EndMT in VRAMI. Additionally, it discusses the research progress of innovative targeted interventions using both traditional Chinese and Western medicine, so as to offer new insights and a theoretical foundation for the clinical treatment of the disease.

Bacterial species within the Acinetobacter baumannii-calcoaceticus (Acb) complex are very similar and are difficult to discriminate. Misidentification of these species in human infection may lead to severe consequences in clinical settings. Therefore, it is important to accurately discriminate these pathogens within the Acb complex. Raman spectroscopy is a simple method that has been widely studied for bacterial identification with high similarities. In this study, we combined surfaced-enhanced Raman spectroscopy (SERS) with a set of machine learning algorithms for identifying species within the Acb complex. According to the results, the support vector machine (SVM) model achieved the best prediction accuracy at 98.33% with a fivefold cross-validation rate of 96.73%. Taken together, this study confirms that the SERS-SVM method provides a convenient way to discriminate between A. baumannii, Acinetobacter pittii, and Acinetobacter nosocomialis in the Acb complex, which shows an application potential for species identification of Acinetobacter baumannii-calcoaceticus complex in clinical settings in near future., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults., Methods: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression., Results: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP., Conclusions: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population., (© 2024. The Author(s).)

High level dissolved B, which poses risks to human health, has been widely observed in geothermal water. In the Guide Basin, NW China, a series of geothermal water samples along a fault show a wide range of B contents ranging from 3.14 to 8.33 mg/L, which are higher than the WHO Guideline value equaling 2.4 mg/L in drinking water. To identify the sources and fate of B, we conduct a comprehensive analysis of hydrochemistry and stable isotopes (D, 18 O and 11 B) of three thermal fields representing three stages of hydrogeochemical evolution (stages I, II and III). From stage I to III, there are trends of increasing mineral dissolution, which is supported by increasing mean reservoir temperature and concentrations of conservative elements (Cl, Na, K, Li and Si). Geothermal water in stage I with meteoric origin and the lowest reservoir temperature has the highest B/Na resulting from silicate dissolution and falls on the mixing line between granitoids and cold water on the plot of δ 11 B versus 1/B, showing the control of silicate dissolution. However, geothermal water in stage III has lower Ca, B Sr and B/Na than that in stage II. Because of the occurrence of other processes, geothermal water in stages II and III deviates from the LMWL. Compared with geothermal water in stage I, the increased Sr/Ca and decreased B/Ca show that B are removed by both coprecipitation and vapor separation. With the aid of B isotopes, we find vapor separation dominates in stage II, whereas carbonate precipitation dominates in stage III. Overall, a combined use of three isotopes (H, O and B) and three element ratios (B/Na, B/Ca and Sr/Ca) leads to a complete understanding of B cycle and hydrogeochemical evolution in hydrothermal systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q 1 , Q 3 ) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2 . The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2 , -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( P nonlinear <0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( P linear <0.001), hip circumference ( P linear <0.001), and calf circumference ( P linear <0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

We examined the global biogeography of the Scytodes thoracica group of spitting spiders based on 23 years of sampling at the species level (61 species in the thoracica group and 84 species of Scytodes ) using DNA data from six loci. Our results indicated that the thoracica group initially dispersed from Southeast Asia to East Africa between 46.5 and 33.0 million years ago, and dispersal events intensified between Southeast/South Asia and East/South Africa from the early to late Miocene. The timing of these events indicates that Asian-African faunal exchange of the thoracica group was driven by the Indian monsoon, and the pattern of dispersal suggests that colonialization took root when the Indian monsoon shifted from a North-South direction to an East-West direction from the middle Eocene.

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR =1.22, 95% CI : 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR =0.67, 95% CI : 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K&#95;m value was 209.90 μmol·L~(-1) and k&#95;(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.

Corydalis yanhusuo W. T. Wang, also known as yanhusuo, yuanhu, yanhu and xuanhu, is one of the herb components of many Chinese Traditional Medicine prescriptions such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was traditionally used to relieve pain and motivate blood and Qi circulation. Now there has been growing interest in pharmacological effects of alkaloids, the main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. yanhusuo are its important bioactive components and can be characterized into protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and proper extraction or co-administration methods modulate their contents and efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the nervous system, cardiovascular system, cancer and others through multiple molecular mechanisms such as modulating neurotransmitters, ion channels, gut microbiota, HPA axis and signaling pathways and are potential treatments for many diseases. Plenty of novel drug delivery methods such as autologous red blood cells, self-microemulsifying drug delivery systems, nanoparticles and others have also been investigated to better exert the effects of alkaloids from C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo, their pharmacological effects and mechanisms, and methods of drug delivery to lay a foundation for future investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: How parents think and feel about their children's use of technology can influence how their kids behave online. The family's socioeconomic status (SES) may also affect this influence. In light of this, this research emphasizes the need for more investigation into parental attitudes and the role of SES in shaping how children consume media., Methods: This study surveyed 629 Taiwanese parents to explore their attitudes toward their young children's use of information communication technology (ICT), usage patterns, and the interplay with socioeconomic status., Results: The findings revealed a significant disconnect: although approximately 50% of parents considered above six years old to be a suitable age for children to start ICT, over 80% of children had already engaged with ICT before that age, indicating a large disparity between parental expectations and actual initiation. Furthermore, parents highlighted "learning interest" and "various content" as the most positive impacts of children's ICT use, while "addiction and overreliance" emerged as their primary concern. Notably, parents, as a whole, tended to perceive their child's ICT use more negative than positively, with fathers displaying greater acceptance of negative viewpoints than mothers. Parental attitudes toward children's ICT use were categorized into five clusters, ranging from balanced and optimistic views to value emphasis, conservatism, and negative doubts. This classification underscores the intricate and multifaceted nature of parental perspectives, encompassing both positive and negative outlooks on children's ICT utilization., Discussion: The findings underscore the nuanced character of parents' attitudes toward technology, shaped by the intricacies and challenges posed by the digital era. These insights emphasize that parental attitudes go beyond a simplistic positive-negative divide, reflecting a comprehensive response to the opportunities and complexities inherent in the digital age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Yang, Chou and Lee.)

Objective: To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease. Methods: Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform. Results: The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M ( Q 1 , Q 3 ) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type Ⅱb clade, B.1.3 lineage. Conclusions: Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74 -/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PL PNs -dSTR FSIs ) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PL PNs -BLA PNs ) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity., (© 2023. The Author(s).)

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO 2 ) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO 2 was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO 2 for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO 2 as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO 2 and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO 2 concentration was (32.18±10.36) μg/cm 3 . The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR( 95% CI ) value of 0.959(0.928-0.992). Compared with the T 1 group of NDVI, the risk of hypertension was lower in the T 3 group, with the OR (95% CI ) value of 0.852(0.769-0.944), and the trend test was statistically significant( P <0.05). Compared with the T 1 group of NO 2 , the risk of hypertension was higher in the T 2 and T 3 groups, with OR (95% CI ) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant ( P <0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO 2 was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO 2 had a negative multiplicative interaction on the risk of hypertension, with OR (95% CI ) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO 2 are associated with hypertension in older adults.

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95% CI ) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95% CI ) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.

Objective: To investigate the location and anatomical structure of "Shaochong"(HT9), "Shaofu"(HT8), "Shenmen"(HT7), "Lingdao"(HT4) and "Shaohai"(HT3) in the rabbit's forelimb., Methods: Sixteen rabbits (half male and half female) were used in the present study. By referring to the national standards on the location of acupoints in the human body and the literature about the location of acupoints in the rabbit, and by using the method of comparative anatomy, the location and needling operation of the Five-shu acupoints of Shaoyin Heart Meridian on the rabbit's forelimb were defined, and these acupoints were needled and CT three-dimensional reconstruction were conducted. Then, the rabbits were killed, and intravascular perfusion was performed, followed by inserting acupuncture needles into these five acupoints for observing the anatomical relationship between the inserted acupuncture needle and the structure of surrounding tissues., Results: HT9 is located at the medial side of the little finger of forelimb, about 1 mm beside the nail root, and is adjacent to the superficial flexor tendon of the finger, the dorsal branches of the proper palmar digital artery and vein, and the endings of dorsal branch of palmar digital proper nerve of the ulnar nerve on the fifth finger side. HT8 is located at the palm side of the forelimb, horizontally parallel to the proximal end of the 5th metacarpophalangeal joint and between the 4th and 5th metacarpal bones, and is adjacent to the lumbricalis, the 4th and 5th interossei, and common palmar digital artery and vein and the palmar digital proper nerve of the ulnar nerve. HT7 is located at the medial margin of the extensor carpal tendon on the ulnar side, between the distal end of the ulna and the ulnar carpal bone, and is adjacent to the tendons of flexor carpi ulnaris and extensor carpi ulnaris, ulnar artery, ulnar vein and ulnar nerve. HT4 is located at the medial border of the ulnar flexor tendon, about 1.5 cun superior to HT7, and is adjacent to extensor carpi ulnaris, flexor carpi ulnaris, flexor digitorum superficialis, flexor digitorum profundus, ulnar artery, vein and ulnar nerve. HT3 is located at the depression, medial to the condyle of humerus when the elbow is bent at 90°, its neighbor structure is composed of pronator teres, biceps brachii, brachial artery and vein, radial collateral artery, radial collateral vein, medial antebrachial cutaneous nerve and median nerve., Conclusion: In the rabbit, there is a close relationship between HT9, HT8, HT7, HT4 and HT3 regions and brachial vascular and its branches, cephalic vein and its branches, medial antebrachial cutaneous nerve, median nerve and ulnar nerve, which is the morphological basis of the Five-shu acupoints of Shaoyin Heart Meridian for treating some related clinical disorders.

Background: The advancement of digital technology implies the importance of polychronic learning. Since polychronicity is not equivalent to multitasking behavior, they need to be considered separately. However, less research has been explored on how polychronicity is related to multitasking behavior in the educational field., Objective: To explore the relationships among polychronicity, multitasking behavior and learning performance (including knowledge acquisition and learning satisfaction) in an online learning environment., Methods: The relationship among variables was analyzed from 865 responses obtained from a questionnaire survey, and independent sample t tests and SEM analysis were used to examine the research hypotheses., Results: College students showed a higher frequency of multitasking behavior, time tangibility and scheduling preference, and learning satisfaction in multitasking online learning environments than high school students. Additionally, college students were different from high school students on the paths of involvement with people to multitasking behavior (Δ  χ 2 = 5.42, p  = 0.02) and scheduling preference to learning satisfaction (Δ χ 2  = 9.54, p  = 0.002)., Conclusion: The relationship among polychronicity, multitasking behavior and perceived learning performance in an online learning environment varies by student educational stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Kang, Yang and Lu.)

Previous observational studies on the relationship between sleep characteristics and fracture have yielded contradictory results. The goal of this study was to replicate the findings in a large longitudinal cohort and then conduct a Mendelian randomization (MR) analysis to infer the causality between sleep behaviors and fracture risk. Based on data from the China Health and Retirement Longitudinal Study (CHARLS) including 17,708 participants, we found that individuals with short sleep duration (<5 h) (OR [odds ratio] = 1.62, 95% CI: 1.07-2.44) or restless sleep (OR = 1.55, 95% CI: 1.10-2.19) have a higher risk of hip fracture. A U-shaped relationship between nighttime sleep duration and hip fracture risk ( p -nonlinear = 0.01) was observed using restricted cubic spline regression analysis. Through joint effect analysis, we found that participants with short sleep duration (<5 h) combined with midday napping could significantly decrease hip fracture incidence. We further inferred the causal relationship between self-reported sleep behaviors and hip fracture using the MR approach. Among four sleep phenotypic parameters (sleep duration, daytime napping, chronotype, and insomnia), we found a modest causal relationship between sleep duration and fracture (OR = 0.69, 95% CI: 0.48 to 0.99, p = 0.04). However, no causal relationship was observed for other sleep traits. In conclusion, our findings suggest that short sleep duration has a potential detrimental effect on hip fracture. Improving sleep patterns is of significance for developing hip fracture preventive strategies in the middle-aged and the elderly populations.

Shigella and enterotoxigenic Escherichia coli (ETEC) are major bacterial pathogens of diarrheal disease that is the second leading cause of childhood mortality globally. Currently, it is well known that Shigella spp., and E . coli are very closely related with many common characteristics. Evolutionarily speaking, Shigella spp., are positioned within the phylogenetic tree of E . coli . Therefore, discrimination of Shigella spp., from E . coli is very difficult. Many methods have been developed with the aim of differentiating the two species, which include but not limited to biochemical tests, nucleic acids amplification, and mass spectrometry, etc. However, these methods suffer from high false positive rates and complicated operation procedures, which requires the development of novel methods for accurate and rapid identification of Shigella spp., and E . coli . As a low-cost and non-invasive method, surface enhanced Raman spectroscopy (SERS) is currently under intensive study for its diagnostic potential in bacterial pathogens, which is worthy of further investigation for its application in bacterial discrimination. In this study, we focused on clinically isolated E . coli strains and Shigella species (spp.), that is, S . dysenteriae , S . boydii , S . flexneri , and S . sonnei , based on which SERS spectra were generated and characteristic peaks for Shigella spp., and E . coli were identified, revealing unique molecular components in the two bacterial groups. Further comparative analysis of machine learning algorithms showed that, the Convolutional Neural Network (CNN) achieved the best performance and robustness in bacterial discrimination capacity when compared with Random Forest (RF) and Support Vector Machine (SVM) algorithms. Taken together, this study confirmed that SERS paired with machine learning could achieve high accuracy in discriminating Shigella spp., from E . coli , which facilitated its application potential for diarrheal prevention and control in clinical settings. Graphical abstract., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Tang, Mou, Lyu, Di, Liao, Luo, Li, Wu and Wang.)

Background: Vascular dementia (VD) is a disease that affects brain function through cerebrovascular disease. Due to its complex pathogenesis, there is no effective drug treatment for VD. The present study aimed to evaluate the role of acupoint catgut embedding in the treatment of rats with VD and its possible molecular mechanism., Methods: A modified 4 vessel occlusion (4-VO) method was used to establish a VD model rat, and spatial learning and memory ability was assessed using the Morris water maze (MWM) test. The protein expression levels were detected by Western blot. Hematoxylin and eosin (HE) staining was used for histological analysis and enzyme-linked immunosorbent assay (ELISA) was applied for analysis of serum inflammatory factors., Results: We successfully constructed VD model rats with spatial learning and memory impairment, hippocampus injury, and high inflammatory response. Treatment of VD rats with acupoint catgut embedding significantly reduced escape latency and increased the time in the target quadrant and platform crossing times. VD-mediated hippocampal tissue damage and inflammatory reaction [down-regulating interleukin-1β (IL-1β), interleukin-6 (IL-6)] were significantly alleviated by acupoint catgut embedding treatment. In addition, further mechanism exploration found that acupoint catgut embedding treatment could improve the activity of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. In summary, acupoint catgut embedding treatment improved spatial learning and memory loss, alleviated pathological damage of the hippocampus, and inhibited inflammation response in VD rats, which was probably related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway., Conclusions: Acupoint catgut embedding may warrant further study as an adjuvant therapy for the treatment of VD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6402/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Cerebral small vessel disease (CSVD) has not been systematically studied in patients with multiple system atrophy (MSA)., Objective: We sought to explore whether MSA patients suffer from a heavier CSVD burden relative to healthy individuals and whether CSVD has a relationship with motor, cognitive, and emotional dysfunction in patients with MSA., Methods: This study consecutively recruited 190 MSA patients and 190 matched healthy controls whose overall CSVD burden and single CSVD imaging markers (including white matter hyperintensity (WMH), microbleeds, lacunes, and enlarged perivascular spaces (EPVS)) were measured. Of the MSA patients, 118 completed multi-dimensional outcome assessments. Spearman's correlations and multivariable linear regressions were performed., Results: We observed a greater burden of overall CSVD, WMH, and EPVS in MSA patients compared with controls, but not for microbleeds and lacunes. Motor dysfunction and cognitive impairment were significantly worse in subjects with severe CSVD than those with none-to-mild CSVD. In patients with MSA, the severity of CSVD burden was positively associated with motor impairments as measured by the Unified Multiple System Atrophy Rating Scale-II (β= 2.430, p = 0.039) and Scale for the Assessment and Rating of Ataxia (β= 1.882, p = 0.015). Of CSVD imaging markers, different associations with MSA outcomes were displayed. WMH was associated with motor, cognitive, and emotional deficits, while the EPVS in the centrum semiovale, basal ganglia, and hippocampus regions was correlated only with motor severity, anxiety, and cognition, respectively. Similar findings were noted in MSA-cerebellar and MSA-parkinsonian patients., Conclusions: Concomitant CSVD may be correlated with worse multi-dimensional dysfunction in patients with MSA.

The properties and functions of BMSCs were altered by the diabetic microenvironment, and its mechanism was not very clear. In recent years, the regulation of the function of BMSCs by microRNA has become a research hotspot, meanwhile, HOX genes also have been focused on and involved in multiple functions of stem cells. In this study, we investigated the role of miR-139-5p in diabetes-induced BMSC impairment. Since HOXA9 may be a target gene of miR-139-5p, we speculated that miR-139-5p/HOXA9 might be involved in regulating the biological characteristics and the function of BMSCs in diabetes. We demonstrated that the miR-139-5p expression was increased in BMSCs derived from STZ-induced diabetic rats. MiR-139-5p mimics were able to inhibit cell proliferation, and migration and promoted senescence and apoptosis in vitro. MiR-139-5p induced the down-regulated expression of HOXA9 and c-Fos in BMSCs derived from normal rats. Moreover, miR-139-5p inhibitors reversed the tendency in diabetic-derived BMSCs. Further, gain-and-loss function experiments indicated that miR-139-5p regulated the functions of BMSCs by targeting HOXA9 and c-Fos. In vivo wound model experiments showed that the downregulation of miR-139-5p further promoted the epithelialization and angiogenesis of diabetic BMSC-mediated skin. In conclusion, induction of miR-139-5p upregulation mediated the impairment of BMSCs through the HOXA9/c-Fos pathway in diabetic rats. Therefore, miR-139-5p/HOXA9 might be an important therapeutic target in treating diabetic BMSCs and diabetic complications in the future., (© 2022 Federation of American Societies for Experimental Biology.)

Koumine, an alkaloid, exerts therapeutic effects against rheumatoid arthritis (RA), and thus may have a potential application in novel treatment strategies against this disease. Herein, we investigated the regulatory effect of koumine on Th cell polarization using a "pyramid" structure model to elucidate the mechanism underlying its therapeutic effect on RA. The third layer of the model comprises the cytokine secretion layer, in which the effects of koumine on the balance of Th-related cytokines were investigated in mice with collagen-induced arthritis (CIA). Koumine showed significant therapeutic effects and reversed the imbalance of Th1/Th2 and Th17/Treg cytokines. In the Th cell polarization layer, the effects of koumine on the relative numbers of Th cell subsets in splenocytes of rats with CIA were examined. Koumine attenuated both of the increased Th1/Th2 and Th17/Treg subset ratios accompanied with its therapeutic effects. Finally, the primary cultured splenocytes from BALB/c mice were used to further investigate the effect of koumine on Th cell activation by evaluating cell proliferation induced by concanavalin A (Con A), lipopolysaccharides (LPS) and phytohemagglutinin (PHA). Koumine inhibited the cell proliferation responses and its effects on proliferation induced by Con A and PHA were greater than those by LPS, showing the relatively selective inhibition on the proliferation of Th cells. Our results suggest that koumine might restore the homeostasis of the network system with Th subsets and cytokines by inhibiting the activation of T cells, subsequently regulating the polarization of Th subsets and the downstream imbalance of pro/anti-inflammatory cytokines in RA., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Parathyroidectomy (PTX) is a treatment for hyperparathyroidism (HPT) and has uncertain risks and benefits. The aim of this study was to evaluate the effect of PTX versus nonoperative treatment among nondiabetic hemodialysis patients., Methods: A retrospective matched cohort study was performed. Each PTX patient was matched with one patient who had severe HPT but rejected PTX. The patients were matched by sex, birth date, date of first dialysis, nondiabetic status, and left ventricular ejection fraction. The serum markers, survival, main adverse cardiovascular and cerebrovascular event (MACCE) rates, and hospitalization were compared between the PTX patients and matched non-PTX patients., Results: There were 1143 patients at our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2020. Of these, 75 PTX patients were matched with 75 non-PTX patients. Rapid decreases in the mean intact parathyroid hormone, calcium and phosphorus concentrations, and a gradual increase in hemoglobin concentration were observed in the PTX group. The mortality was 2.9 per 100 patient-years in the PTX group and 10.9 per 100 patient-years in the non-PTX group ( p  < 0.001). Compared with non-PTX patients, PTX patients had an adjusted HR for death of 0.236 (95% CI 0.108-0.518). The cumulative MACCE rates were 6.7 per 100 patient-years in the PTX group and 15.2 per 100 patient-years in the non-PTX group ( p  < 0.001). The adjusted HR of the occurrence of first MACCE for PTX patients compared with non-PTX patients was 0.524 (95% CI 0.279-0.982). The cumulative hospitalization rates were 50.3 per 100 patient-years in the PTX group and 66.5 per 100 patient-years in the matched non-PTX group ( p  < 0.001)., Conclusions: Compared with non-PTX patients, PTX was associated with an improvement in the biochemical measures and patient-level outcomes in nondiabetic hemodialysis patients with severe HPT.

Purpose: Problem solving has been defined as "a goal-directed sequence of cognitive and affective operations as well as behavioural responses to adapting to internal or external demands or challenges. Studies have shown that some nurses lack rational thinking and decision-making ability to identify patients' health problems and make clinical judgements, and have poor cognition and response to some clinical problems, easy to fall into problem-solving dilemma. This study aimed to understand the influencing factors of clinical nurses' problem solving dilemma, to provide a basis for developing training strategies and improving the ability of clinical nurses in problem solving., Methods: A qualitative research was conducted using in-depth interviews from August 2020 to December 2020. A total of 14 participants from a tertiary hospital in Shanghai, China were recruited through purposive sampling combined with a maximum variation strategy. Data were analysed with the conventional content analysis method., Results: Three themes and seven subthemes were extracted: nurse's own factors (differences in knowledge structure and thinking, differences in professional values, poor strain capacity); improper nursing management (low sense of organizational support, contradiction between large workload and insufficient manpower allocation); patient factors (the concept of emphasizing medicine and neglecting to nurse, individual differences of patients)., Conclusion: The influencing factors of clinical nurses' problem-solving dilemma are diverse. Hospital managers and nursing educators should pay attention to the problem-solving of clinical nurses, carry out a series of training and counselling of nurses by using the method of situational simulation, optimize the nursing management mode, learn to use new media technology to improve the credibility of nurses to provide guarantee for effective problem-solving of clinical nurses.

Background: Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT., Methods: A total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented., Results: Nine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p < 0.001) than the high-risk group. Patients in the low-risk group had better baseline FEV1/FVC% (96.3% vs. 85.9%, p = 0.046), less Grade ≥ 3 lymphopenia during CCRT (63.2% vs. 83.3%, p = 0.031), better recovery of lymphopenia from CCRT (71.4% vs. 27.8%, p < 0.001), lower incidence of Grade ≥ 2 radiation-induced pneumonitis (31.6% vs. 53.3%, p = 0.040), superior tumor remission (84.2% vs. 66.7%, p = 0.003)., Conclusion: Pretreatment radiomics features from tumor and TOE could boost the long-term survival forecast accuracy in LANSCLC patients, and the predictive results could be utilized as an effective indicator for survival risk stratification. Low-risk patients might benefit more from radical CCRT and further adjuvant immunotherapy., Trial Registration: retrospectively registered., (© 2022. The Author(s).)

An efficient one-pot reaction of propargylamides, isocyanides, and water catalyzed by zinc was developed for the rapid construction of 2-oxazolines with a wide functional group tolerance. The methylene-3-oxazoline was proven to play a vitally important role to start the tandem cascade transformation through unfunctionalized alkynes with sequential nucleophilic addition approaches of isocyanide and water. Notably, with a slight alteration of the reaction temperature and the addition of one molecule of water, various β-amino amide derivatives were synthesized in good to excellent yields.

In order to explore the impact of optimized land use allocation on phosphorus loss in the runoff process of a small watershed in the Three Gorges Reservoir area, a traditional agricultural model catchment area (CG) and a catchment area after optimized land use allocation in the Shipanqiu watershed in Zhong County, Chongqing (EG) were selected as the research object, sampling at the outlets of the two catchment areas, respectively, to monitor the runoff process and different forms of phosphorus in rainfall events and to analyze the influence of land use configuration on the law of phosphorus loss. The results showed that:① in the 10 monitored rainfall and runoff processes, the ρ [total phosphorus (TP)] of EG was lower than that of CG, and the ranges of the two were 0.09-0.75 mg·L -1 and 0.13-2.82 mg·L -1 , respectively. Compared with that of CG, EG significantly reduced the peak value of TP. ② The average EMC of TP, total dissolved phosphorus (TDP), dissolved inorganic phosphorus (DIP), and particulate phosphorus (PP) in the process of rainfall and runoff was lower than that of CG, and EG and CG showed significant differences in EMC of TP, TDP, and DIP ( P <0.05); the main form of phosphorus loss in the two catchment areas in the process of rainfall and runoff was TDP, but the average TDP/TP of EG was larger. ③ The output load of EG was 45%, 43%, 57%, and 47% lower than that of the TP, TDP, DIP, and PP in CG. The output load of EG and CG of various forms of phosphorus was significantly correlated with the total runoff ( P <0.01). In addition, the slope of the linear fitting of various phosphorus forms in the CG catchment area to the total amount of runoff was 1.66 to 1.75 times that of EG. The output load of various phosphorus forms of CG was more sensitive to runoff than that of EG, and the output per unit area in the process of rainfall and runoff was more sensitive than that of EG. The amount of sand could have caused the difference in phosphorus concentration and output load more than the output per unit area. Optimizing land use configuration can effectively reduce the loss of various forms of phosphorus and provide a reference for the prevention and control of phosphorus loss in small watersheds in the Three Gorges Reservoir area.

Objective: To investigate the longitudinal changes of white matter microstructural based on diffusion tensor imaging in parents who lost their only child without psychiatric disorders and its relationship with symptoms of posttraumatic stress disorder (PTSD). Methods: Parents who had who lost their only child and without psychiatric disorders in Jiangsu Province, from September 2016 to March 2017, were retrospectively collected (TENP group, 32). MRI scans were performed at baseline and at the end of 5-year follow-up, and the Clinician Administered PTSD Scales (CAPS) were used for assessing the severity of symptoms. Additionally, sex, age and education level matched healthy subjects were recruited as healthy controls (control group, 27) and underwent MRI scanning using the same protocol. The differences of fractional anisotropy (FA) values between TENP group and control group at baseline were analyzed by using Tract-based spatial statistics method, and the brain areas of lateral differences were used as the regions of interest for longitudinal follow-up analysis of TENP group. Partial correlation analysis was used to evaluate the relationship between FA values changes in longitudinal differences in brain regions and CAPS scores. Results: Compared with the control group, FA values of the right cingulate gyrus, Uncinate fasciculus, superior longitudinal fasciculus, corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major in TENP group were decreased at baseline ((0.613±0.032) vs (0.631±0.034), (0.539±0.048) vs (0.563±0.045), (0.534±0.033) vs (0.558±0.039), (0.560±0.038) vs (0.580±0.030), (0.519±0.023) vs(0.549±0.024), (0.489±0.038) vs (0.518±0.027), (0.499±0.027) vs (0.533±0.032); all P <0.05). From baseline to follow-up, scores of trauma reexperience symptoms and avoidance/numbness symptoms were decreased ((5.2±2.8) vs (8.1±4.9), (4.0±3.2) vs (6.6±5.4); all P <0.05); FA values of the right corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major were decreased ((0.523±0.049) vs (0.537±0.049), (0.568±0.052) vs (0.590±0.050), (0.540±0.063) vs (0.559±0.059), (0.520±0.059) vs (0.547±0.059); all P <0.05); The decrease of FA values of the right Inferior fronto-occipital fasciculus and right Inferior longitudinal fasciculus was negatively correlated with the decrease of avoidance/numbness symptoms scores ( r =-0.458, -0.374, respectively, all P <0.05). Conclusions: The trauma of parents who lost their only child can result in impaired microstructural integrity of white matter. As the post-traumatic time goes by, parents who have lost their only child do not develop to PTSD and other psychiatric disorders, and the clinical symptoms are alleviated, the damage of the white matter microstructure continued to progress.

This study aims to explore the impact of gender and anxiety on various preventative health behaviors, and the relationships among these preventative health behaviors, individual well-being and depression, from the perspective of altruism. This study employed an online questionnaire survey, and 136 males and 204 females participated in the survey. The results of this study showed that females exhibited better preventative health behaviors than males, including hygiene habits, social distancing and behaviors intended to help others mitigate the epidemic. Anxiety regarding COVID-19 infection encouraged individuals to adopt hygienic habits and social distancing measures rather than to help others mitigate the epidemic. Hygiene habits improved the individual's psychological well-being. Helping others mitigate the epidemic improved the individual's psychological well-being and social well-being and contributed to reducing individual depression. However, the preventative health behavior involved in social distancing was not conducive to emotional well-being or social well-being. Affective elements are related to individual behaviors. Therefore, the use of prosocial, altruistic language may play an important role with respect to encouraging people to comply with preventative health behaviors in the context of COVID-19. In addition, it is worth noting that different preventative health behaviors may have different effects on people's mental health, especially when implementing social distancing-related epidemic mitigation behaviors. The question of how to prevent negative psychological effects in restricted actors must be answered, and the degree of life satisfaction experienced by those actors must also be taken into account.

The research aims to explore the influence mechanism of proactive personality on the entrepreneurial intentions of college students. Adopting proactive personality scale, social capital scale, human capital scale, and entrepreneurial intention scale, this research tested valid samples of 300 Chinese college students. The results revealed that proactive personality exerted a significant and positive impact on the entrepreneurial intentions. Social capital played a partial mediating role between the proactive personality and the entrepreneurial intentions. Human capital also played a partial mediating role between proactive personality and entrepreneurial intentions. Social capital and human capital exerted a chain mediation effect between proactive personality and entrepreneurial intentions. The result of this research offers valuable insights to the study of the influence of college students' proactive personality on entrepreneurial intentions and provides entrepreneurship education management in colleges with specific practical suggestions so as to improve entrepreneurial intentions among college students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Huang and Gao.)

sfgA is known as a key negative transcriptional regulator gene of asexual sporulation and sterigmatocystin production in Aspergillus nidulans . However, here, we found that the homolog sfgA gene shows a broad and complex regulatory role in governing growth, conidiation, sclerotia formation, secondary metabolism, and environmental stress responses in Aspergillus flavus . When sfgA was deleted in A. flavus , the fungal growth was slowed, but the conidiation was significantly increased, and the sclerotia formation displayed different behavior at different temperatures, which increased at 30 °C but decreased at 36 °C. In addition, sfgA regulated aflatoxin biosynthesis in a complex way that was associated with the changes in cultured conditions, and the increased production of aflatoxin in the ∆ sfgA mutant was associated with a decrease in sclerotia size. Furthermore, the ∆ sfgA mutant exhibited sensitivity to osmotic, oxidative, and cell wall stresses but still produced dense conidia. Transcriptome data indicated that numerous development- and secondary-metabolism-related genes were expressed differently when sfgA was deleted. Additionally, we also found that sfgA functions downstream of fluG in A. flavus , which is consistent with the genetic position in FluG-mediated conidiation in A. nidulans . Collectively, sfgA plays a critical role in the development, secondary metabolism, and stress responses of A. flavus, and sfgA renders A. flavus more stable to the external environment.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Palmitoylation may be relevant to the processes of learning and memory, and even disorders, such as post-traumatic stress disorder and aging-related cognitive decline. However, underlying mechanisms of palmitoylation in these processes remain unclear. Herein, we used acyl-biotin exchange, coimmunoprecipitation and biotinylation assays, and behavioral and electrophysiological methods, to explore whether palmitoylation is required for hippocampal synaptic transmission and fear memory formation, and involved in functional modification of synaptic proteins, such as postsynapse density-95 (PSD-95) and glutamate receptors, and detected if depalmitoylation by specific enzymes has influence on glutamatergic synaptic plasticity. Our results showed that global palmitoylation level, palmitoylation of PSD-95 and glutamate receptors, postsynapse density localization of PSD-95, surface expression of AMPARs, and synaptic strength of cultured hippocampal neurons were all enhanced by TTX pretreatment, and these can be reversed by inhibition of palmitoylation with palmitoyl acyl transferases inhibitors, 2-bromopalmitate and N-(tert-butyl) hydroxylamine hydrochloride. Importantly, we also found that acyl-protein thioesterase 1 (APT1)-mediated depalmitoylation is involved in palmitoylation of PSD-95 and glutamatergic synaptic transmission. Knockdown of APT1, not protein palmitoyl thioesterase 1, with shRNA, or selective inhibition, significantly increased AMPAR-mediated synaptic strength, palmitoylation levels, and synaptic or surface expression of PSD-95 and AMPARs. Results from hippocampal tissues and fear-conditioned rats showed that palmitoylation is required for synaptic strengthening and fear memory formation. These results suggest that palmitoylation and APT1-mediated depalmitoylation have critical effects on the regulation of glutamatergic synaptic plasticity, and it may serve as a potential target for learning and memory-associated disorders. SIGNIFICANCE STATEMENT Fear-related anxiety disorders, including post-traumatic stress disorder, are prevalent psychiatric conditions, and fear memory is associated with hyperexcitability in the hippocampal CA1 region. Palmitoylation is involved in learning and memory, but mechanisms coupling palmitoylation with fear memory acquisition remain poorly understood. This study demonstrated that palmitoylation is essential for postsynapse density-95 clustering and hippocampal glutamatergic synaptic transmission, and APT1-mediated depalmitoylation plays critical roles in the regulation of synaptic plasticity. Our study revealed that molecular mechanism about downregulation of APT1 leads to enhancement of AMPAR-mediated synaptic transmission, and that palmitoylation cycling is implicated in fear conditioning-induced synaptic strengthening and fear memory formation., (Copyright © 2022 the authors.)

Immunotherapy targeting programmed death ligand-1/programmed cell death protein-1 (PD-L1/PD-1) has achieved great success in multiple cancers, but only a small subset of patients showed clinical responses. Recent evidences have shown that post-translational modification of PD-L1 protein could regulate its protein stability and interaction with cognate receptor PD-1, thereby affecting anticancer immunotherapy in several solid tumors. However, the molecular mechanisms underlying how PD-1/PD-L1 expression is regulated still remain unclear in nasopharyngeal carcinoma (NPC). Here, we found N-glycosylation of PD-L1 in NPC cells and tissues. Mechanistically, we showed that STT3A transferred N-linked glycans to PD-L1, and TGF-β1 could positively regulate STT3A expression through activating c-Jun to bind to STT3A promoter. Functional assays showed that inhibition of TGF-β1 resulted in a decrease of glycosylated PD-L1 and enhanced cytotoxic T-cell function against NPC cells. Analysis of clinical specimens revealed that the expression of STT3A was positively correlated with TGF-β1 and c-Jun, and high STT3A expression was positively correlated with a more advanced clinical stage. Altogether, TGF-β1 activated c-Jun/STT3A signaling pathway to promote N-glycosylation of PD-L1, thus further facilitating immune evasion and reducing the efficacy of cancer immunotherapy. As such, all these data suggested that targeting TGF-β1 pathway might be a promising approach to enhance immune checkpoint blockade, and simultaneous blockade of PD-L1 and TGF-β1 pathways might elicit potent and superior antitumor activity relative to monotherapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ma, Luo, Zeng, Su, Liu, Li and Lu.)

Purpose: Knowledge, attitude, and practice (KAP) models are often used by researchers in the field of public health to explore people’s healthy behaviors. Therefore, this study mainly explored the relationships among participants’ sociodemographic status, COVID-19 knowledge, affective attitudes, and preventive behaviors. Method: This study adopted an online survey, involving a total of 136 males and 204 females, and used a cross-sectional study to investigate the relationships between variables including gender, age, COVID-19 knowledge, positive affective attitudes (emotional wellbeing, psychological wellbeing, and social wellbeing), negative affective attitudes (negative self-perception and negative perceptions of life), and preventive behaviors (hygiene habits, reducing public activities, and helping others to prevent the epidemic). Results: The majority of participants in the study were knowledgeable about COVID-19. The mean COVID-19 knowledge score was 12.86 (SD = 1.34, range: 7−15 with a full score of 15), indicating a high level of knowledge. However, the key to decide whether participants adopt COVID-19 preventive behaviors was mainly their affective attitudes, especially positive affective attitudes (β = 0.18−0.25, p< 0.01), rather than COVID-19 disease knowledge (β = −0.01−0.08, p > 0.05). In addition, the sociodemographic status of the participants revealed obvious differences in the preventive behaviors; females had better preventive behaviors than males such as cooperating with the epidemic prevention hygiene habits (t = −5.08, p< 0.01), reducing public activities (t = −3.00, p< 0.01), and helping others to prevent the epidemic (t = −1.97, p< 0.05), while the older participants were more inclined to adopt preventive behaviors including epidemic prevention hygiene habits (β = 0.18, p = 0.001, R2 = 0.03), reducing public activities (β = 0.35, p< 0.001, R2 = 0.13), and helping others to prevent the epidemic (β = 0.27, p< 0.001, R2 = 0.07). Conclusions: Having adequate COVID-19 knowledge was not linked to higher involvement in precautionary behaviors. Attitudes toward COVID-19 may play a more critical function in prompting individuals to undertake preventive behaviors, and different positive affective attitudes had different predictive relationships with preventive behaviors.

Objectives: To investigate the prevalence of diabetes mellitus (DM) among Uygur children in Hotan Prefecture of Xinjiang, China, as well as the factors influencing the development of DM., Methods: The cluster random sampling method was used to select 5 308 children, aged 4-18 years, from the middle and primary schools and kindergartens in Hotan Prefecture of Xinjiang. The survey methods included questionnaire survey and the measurement of height and weight. All subjects were tested for fasting fingertip blood glucose to investigate the prevalence of DM and impaired fasting glucose (IFG)., Results: A total of 5 184 valid questionnaires were collected. Fourteen children (0.27%) were found to have DM, among whom 8 had type 1 DM, 2 had type 2 DM, and 4 had unclassified DM. Twenty-nine children (0.56%) were found to have IFG. There was no significant difference in the prevalence rate of DM and IFG between boys and girls ( P >0.05). The prevalence rate of DM was 0.18% in the 4-<10 years group, 0.47% in the 10-<15 years group, and 0.07% in the 15-18 years group ( P =0.072).The prevalence rate of IFG in the above three age groups was 0.18%, 0.94%, and 0.42%, respectively, with a significant difference among groups ( P =0.007). The proportion of family history of DM and the proportion of overweight/obesity in children with DM were significantly higher than those in children without DM ( P <0.05), while the proportion of children with DM who preferred coarse grains was significantly lower than that in children without DM ( P <0.05)., Conclusions: The prevalence of DM and IFG in Uyghur children in Hotan Prefecture of Xinjiang is relatively low. There is no significant difference in the prevalence of DM among children of different genders or age groups, but the prevalence of IFG in children of different age groups is different. A family history of DM, overweight or obesity, and low intake of coarse grains might be associated with the development of DM.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness. Questionnaires such as modified Medical Research Council (mMRC) dyspnea scale and COPD assessment test (CAT) are useful for COPD condition and life quality assessment. These questionnaires reflect how respiratory disorder affects daily life. Breathing and autonomic nervous system (ANS) usually regulate each other. Few studies discussed the ANS activity and daily life quality in patients with COPD. Therefore, this study aimed to find the relationship between daily life quality assessed by mMRC or CAT and ANS assessed by a novel method, instantaneous pulse rate variability (iPRV), a method indicating not only the ANS activity but also the peripheral response. The result showed that the change in mMRC and the change in low frequency power to high frequency power ratio, which usually represents the sympathetic activity in conventional heart rate variability analysis, had significant correlation ( r  = 0.63; p < 0.05). The change in CAT and the change in high frequency power (regulated by vagal nervous and respiratory system) or very high frequency power (new frequency band can be indicated in iPRV spectrum) had significant negative correlation ( r  = -0.64 and -0.55, respectively; p < 0.05 for both). This study showed the change in iPRV indices when the condition of COPD was improvement or exacerbation. This study presents a possible way to show how cardiovascular activity affects daily life quality in patients with COPD. Increase in LF or decrease in HF and VHF would cause poorer quality of daily life in patients with COPD. The result can also be a reference for patients with COPD to choose the breathing type to adjust rehabilitation and therapy program for ANS regulation to indicate or improve their daily life quality., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Po-Hsun Huang et al.)

Friedelin, the most rearranged pentacyclic triterpene, also exhibits remarkable pharmacological and anti-insect activities. In particular, celastrol with friedelin as the skeleton, which is derived from the medicinal plant Tripterygium wilfordii , is a promising drug due to its anticancer and antiobesity activities. Although a previous study achieved friedelin production using engineered Saccharomyces cerevisiae , strains capable of producing high-level friedelin have not been stably engineered. In this study, a combined strategy was employed with integration of endogenous pathway genes into the genome and knockout of inhibiting genes by CRISPR/Cas9 technology, which successfully engineered multiple strains. After introducing an efficient Tw OSC1 T502E , all strains with genetic integration ( tHMG1 , ERG1 , ERG20 , ERG9 , POS5 , or UPC2.1 ) showed a 3.0∼6.8-fold increase in friedelin production compared with strain BY4741. Through further double knockout of inhibiting genes, only strains GD1 and GD3 produced higher yields. Moreover, strains GQ1 and GQ3 with quadruple mutants ( bts1 ; rox1 ; ypl062w ; yjl064w ) displayed similar increases. Finally, the dominant strain GQ1 with Tw OSC1 T502E was cultured in an optimized medium in shake flasks, and the final yield of friedelin reached 63.91 ± 2.45 mg/L, which was approximately 65-fold higher than that of the wild-type strain BY4741 and 229% higher than that in ordinary SD-His-Ura medium. It was the highest titer for friedelin production to date. Our work provides a good example for triterpenoid production in microbial cell factories and lays a solid foundation for the mining, pathway analysis, and efficient production of valuable triterpenoids with friedelin as the skeleton., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors LH., (Copyright © 2022 Gao, Zhao, Hu, Jiang, Xia, Zhang, Lu, Liu, Yin, Chen, Luo, Zhou, Wang, Gao, Gao and Huang.)

Structurally unique 2,2-disubstituted indolin-3-ones with a quaternary carbon center have been constructed through a novel C-C bond formation at the C3 position of Ugi N -acylamino amide adducts employing an organic base-mediated Dieckmann condensation. This facile, flexible protocol can be fine-tuned to construct drug-like pyrazino[1,2- a ]indole fragments with the same quaternary carbon center only through the variation of the acid part in Ugi input. This novel and expeditious methodology has a broad scope and can rapidly generate the drug-like indolin-3-one core.

Background: The mechanistic target of rapamycin complex 1 (mTORC1) signaling has served as a promising target for therapeutic intervention of major depressive disorder (MDD), but the mTORC1 signaling underlying MDD has not been well elucidated. In the present study, we investigated whether mTORC1 signaling pathway mediates synapse loss induced by chronic stress in the hippocampus. Methods: Chronic restraint stress-induced depression-like behaviors were tested by behavior tests (sucrose preference test, forced swim test and tail suspension test). Synaptic proteins and alternations of phosphorylation levels of mTORC1 signaling-associated molecules were measured using Western blotting. In addition, mRNA changes of immediate early genes (IEGs) and glutamate receptors were measured by RT-PCR. Rapamycin was used to explore the role of mTORC1 signaling in the antidepressant effects of fluoxetine. Results: After successfully establishing the chronic restraint stress paradigm, we observed that the mRNA levels of some IEGs were significantly changed, indicating the activation of neurons and protein synthesis alterations. Then, there was a significant downregulation of glutamate receptors and postsynaptic density protein 95 at protein and mRNA levels. Additionally, synaptic fractionation assay revealed that chronic stress induced synapse loss in the dorsal and ventral hippocampus. Furthermore, these effects were associated with the mTORC1 signaling pathway-mediated protein synthesis, and subsequently the phosphorylation of associated downstream signaling targets was reduced after chronic stress. Finally, we found that intracerebroventricular infusion of rapamycin simulated depression-like behavior and also blocked the antidepressant effects of fluoxetine. Conclusion: Overall, our study suggests that mTORC1 signaling pathway plays a critical role in mediating synapse loss induced by chronic stress, and has part in the behavioral effects of antidepressant treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Luo, Ye, Fang, Li, Xia, Liu, Lin, Huang, Zhu, Huang, Tan, Zhang, Liu, Zhou and Shen.)

The COVID-19 epidemic has been confirmed as the largest scale outbreak of atypical pneumonia since the outbreak of severe acute respiratory syndrome (SARS) in 2003 and it has become a public health emergency of international concern. It exacerbated public confusion and anxiety, and the impact of COVID-19 on people needs to be better understood. Indeed, prior studies that conducted meta-analysis of longitudinal cohort research compared mental health before versus during the COVID-19 pandemic and proved that public health polices (e.g., city lockdowns, quarantines, avoiding gatherings, etc.) and COVID-19-related information that circulates on new media platforms directly affected citizen's mental health and well-being. Hence, this research aims to explore Taiwanese people's health status, anxiety, media sources for obtaining COVID-19 information, subjective well-being, and safety-seeking behavior during the COVID-19 epidemic and how they are associated. Online surveys were conducted through new media platforms, and 342 responses were included in the analysis. The research results indicate that the participants experienced different aspects of COVID-19 anxiety, including COVID-19 worry and perceived COVID-19 risk. Among the given media sources, the more participants searched for COVID-19 information on new media, the greater they worried about COVID-19. Furthermore, COVID-19 worry was positively related to safety-seeking behavior, while perceived COVID-19 risk was negatively related to subjective well-being. This paper concludes by offering some suggestions for future studies and pointing out limitations of the present study.