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Abstract Intestinal microbiota imbalance plays an important role in the progression of obstructive sleep apnea (OSA), and is considered to be the main mediator that triggers metabolic comorbidities. Here, we analyzed the changes in intestinal microbiota in patients with different severities of OSA based on apnea hypopnea index (AHI) classification, and explored the role of intestinal microbiota in the severity of OSA. This study included 19 healthy volunteers and 45 patients with OSA [5 ≤ AHI

Based on meteorological data collected over nearly 60 years (1960–2017) from four national meteorological stations along the margins of the Badain Jaran Desert, this study analyzed the spatiotemporal variations in evaporation from water surfaces and identified the dominant controlling factors. Methods used included linear trend analysis, linear tendency estimation, the departure method, the rank correlation coefficient-based method, and Multiple Linear Regression (MLR). Results indicate notable spatiotemporal differences in evaporation distribution and evolution. Spatially, average annual evaporation exhibited a pronounced altitude effect, decreasing at a rate of about 8.23 mm/m from east to west with increasing altitude. Temporally, annual evaporation showed significant upward trends after 1996 at the northeastern (Guaizi Lake) and western (Dingxin) margins, with rates of 132 mm/10a and 105 mm/10a, respectively. Conversely, along the northwestern (Ejina Banner) and southern (Alxa Right Banner) margins of the desert, an evaporation paradox was observed, with annual evaporation trending downward at rates of 162 mm/10a and 187 mm/10a, respectively, especially after 1987. The dominant factors controlling evaporation varied spatially: Average annual temperature and relative humidity influended the western margin (Dingxin), average annual temperature was the key factor for the northeastern margin (Guaizi Lake), and average wind speed was crucial for the northern (Ejina Banner) and southern (Alxa Right Banner) margins.

Abstract Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next‐generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26–2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67–4.50) and in a biobank meta‐analysis (OR, 1.16; 95% CI, 1.04–1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9‐edited HEK293T cell lines show that loss‐of‐function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/− mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein‐stimulated pancreatitis models, Sec16a+/− mice display heightened pancreatic inflammation and fibrosis compared to wild‐type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Abstract Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched‐chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high‐fat diet/low‐dose streptozotocin (HFD/STZ)‐induced T2DM and leptin receptor‐deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label‐free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L‐type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA‐deficiency‐induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Background/Objective: This study examined sedentary volume and bouts of Chinese primary and middle school students during different segments of a school day and determined whether gender and school level are associated with their sedentary volume and bouts. Methods: A total of 472 students participated in this study. Accelerometers were used to measure the sedentary volume and sedentary bouts of different durations (i.e., 1–4 min, 5–9 min and ≥10 min) during all segments. Results: The participants spent the majority of their time in sitting (61.7%) and sitting bouts of ≥10 min (37.3%). They spent higher percentages of time in sitting during regular classes (76.7%) and out-of-school time (54.5%), and lower during physical education (PE) classes (32.2%), lunch break (35.4%) and recess (38.0%). The highest proportions of time were in sedentary bouts of ≥10 min during regular classes (50.2%), out-of-school time (28.0%) and lunch break (18.8%), while the greatest percentages occurred in sitting bouts of 1–4 min during PE class (16.4%) and recess (18.6%). Girls and middle school students had higher percentages of sedentary volume than boys and primary school students during most segments. They spent greater proportions of time in sitting bouts of ≥10 min during regular classes, lunch break, and out-of-school time, and higher proportions in sedentary bouts of 1–4 min than boys and primary students during PE classes. Conclusion: Regular class and out-of-school time were identified as key segments for reducing sedentary volume and breaking up prolonged sitting. Interventions on interrupting prolonged sitting during lunch break should also be explored. Girls and middle school students should receive more attention in future interventions.

Precipitation infiltration serves as a significant source of groundwater in the Badain Jaran Desert. To investigate variations in precipitation infiltration within the desert, this study collected data on moisture content and temperature from the vadose zone through in-situ field monitoring. Utilizing these data, a numerical model is employed to explore the mechanism of groundwater recharge via precipitation. The results are as follows: (1) Moisture content and temperature in the shallow vadose zone exhibit significant seasonal variations, with moisture content diminishing with increasing depth; (2) Groundwater recharge via precipitation infiltration initially increases and then decreases with groundwater level depth (GWD). Peak groundwater recharge via precipitation occurs at a GWD of 0.75 m, decreasing to merely 0.012 cm at GWDs exceeding 2 m; (3) Groundwater is no longer susceptible to phreatic water evaporation when the GWD reaches approximately 3.7 m. Therefore, GWD plays a crucial role in governing groundwater recharge via precipitation in the Badain Jaran Desert.

Abstract Background Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. Methods A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects’ blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. Results After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (

Abstract Background Little is known about the impact of the COVID-19 pandemic on patients with Parkinson’s disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. Methods This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. Results A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient’s life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/β-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

Abstract Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.

Purposes: This cross-sectional study aimed to examine the associations between the 24-h movement behaviours and body mass index (BMI) of students from China by using compositional data analysis. Methods: A total of 389 students aged 6–16 years participated in this study. Accelerometers were used to measure moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SED), and sleep. Weight and height were objectively measured. The association between 24-h movement and BMI was analyzed by using compositional data analysis. Results: Time reallocation using minutes and proportions created major differences to the results. Reallocating 10 min from other movement behaviours to MVPA was associated with decreased BMI z-score of 1.372 to 0.158 among primary-school students. Reallocating 10 min from sleep and SED to MVPA, and from sleep and SED to LPA were associated with decreased BMI z-score of 0.505 to 0.017 among middle-school students. Reallocating 10% of time from all other components to SED and sleep were associated with a higher BMI z-score by 0.148 (95%CI: 0.020; 0.276) and 0.125 (95%CI: 0.046; 0.204), while reallocating time to MVPA was associated with a decrease in BMI z-scores of 0.132 (95%CI: -0.193; −0.070) among primary-school students. Reallocating 10% of time from all other components to SED was associated with a higher BMI z-score of 0.254 (95%CI: 0.165; 0.345), whereas reallocating time to MVPA and LPA was associated with a decrease in BMI z-scores of 0.039 (95%CI: -0.073; −0.005) and 0.093 (95%CI: -0.153; −0.033) among middle-school students. Conclusion: Research results of 10-min one-to-one reallocation may be treated cautiously due to uneven distribution of time in 24-h movement behaviours. Based on the results of 10% one-to-remaining reallocation, replacing SED with MVPA may be an appropriate target for adiposity intervention in primary-school students, while increasing MVPA or LPA at the expense of SED may be effective in controlling adiposity of middle-school students in China.

Finding new cost-effective and environmentally friendly anti-corrosion materials is a never-ending task. Herein, the main objective is to prepare a new formulation based on piroxicam-cyclodextrin inclusion complex (PX@β-CD) as an efficient green inhibitor to protect mild steel against corrosion in 1 M HCl. The inhibition performance of PX@β-CD was determined by electrochemical tests coupled with theoretical study like as DFT calculation to assess the reactivity and interaction mechanisms between PX@β-CD and Fe. The obtained results revealed that PX@β-CD performs excellently inhibition performance where its inhibition efficiency reached 98.65% at 0.4 mM, and it acted as a mixed type inhibitor with anodic predominance. SEM and contact angle analysis showed the formation of compact PX@β-CD film on steel surface. The adsorption of PX@β-CD inhibitor followed the Langmuir adsorption model according to the gravimetric corrosion measurement. Thermodynamic analysis and DFT calculations revealed the chemisorption of the inhibitors on the steel surface.

Abstract Pervasive environmental contamination due to the uncontrolled dispersal of 2,4‐dinitrotoluene (2,4‐DNT) represents a substantial global health risk, demanding urgent intervention for the removal of this detrimental compound from affected sites and the promotion of ecological restoration. Conventional methodologies, however, are energy‐intensive, susceptible to secondary pollution, and may inadvertently increase carbon emissions. In this study, a 2,4‐DNT degradation module is designed, assembled, and validated in rice plants. Consequently, the modified rice plants acquire the ability to counteract the phytotoxicity of 2,4‐DNT. The most significant finding of this study is that these modified rice plants can completely degrade 2,4‐DNT into innocuous substances and subsequently introduce them into the tricarboxylic acid cycle. Further, research reveals that the modified rice plants enable the rapid phytoremediation of 2,4‐DNT‐contaminated soil. This innovative, eco‐friendly phytoremediation approach for dinitrotoluene‐contaminated soil and water demonstrates significant potential across diverse regions, substantially contributing to carbon neutrality and sustainable development objectives by repurposing carbon and energy from organic contaminants.

2,4-Dinitrotoluene (2,4-DNT) as a common industrial waste has been massively discharged into the environment with industrial wastewater. Due to its refractory degradation, high toxicity, and bioaccumulation, 2,4-DNT pollution has become increasingly serious. Compared with the currently available physical and chemical methods, in situ bioremediation is considered as an economical and environmentally friendly approach to remove toxic compounds from contaminated environment. In this study, we relocated a complete degradation pathway of 2,4-DNT into Escherichia coli to degrade 2,4-DNT completely. Eight genes from Burkholderia sp. strain were re-synthesized by PCR-based two-step DNA synthesis method and introduced into E. coli. Degradation experiments revealed that the transformant was able to degrade 2,4-DNT completely in 12 h when the 2,4-DNT concentration reached 3 mM. The organic acids in the tricarboxylic acid cycle were detected to prove the degradation of 2,4-DNT through the artificial degradation pathway. The results proved that 2,4-DNT could be completely degraded by the engineered bacteria. In this study, the complete degradation pathway of 2,4-DNT was constructed in E. coli for the first time using synthetic biology techniques. This research provides theoretical and experimental bases for the actual treatment of 2,4-DNT, and lays a technical foundation for the bioremediation of organic pollutants.

Abstract Aim The primary objective of this study was to assess the patient safety culture in a general hospital in Shanghai, China, through a modified Manchester Patient Safety Framework (MaPSaF). Design This study has a qualitative interview design. Data were collected through group interviews and analyses performed through content analysis. Methods The MaPSaF was translated into Chinese and used to assess the patient safety culture in a large general hospital in Shanghai, China. Group interviews using the MaPSaF were conducted with 15 nurses in the obstetric ward. Participants rated their safety practice individually on each of the nine MaPSaF safety culture dimensions. The dimensions and scores were then collectively discussed and a practice‐wide consensus score for each dimension was agreed. Discussions were recorded, transcribed and analysed to assess patient safety in the obstetric ward. Results It took about 2 hr to complete the discussion focusing on patients' safety employing the MaPSaF. Most participants recognized the process as acceptable and useful. The MaPSaF directed team discussion about patient safety issues and facilitated communication, prompting some practice changes. All participants responded positively to the discussion and perceived MaPSaF as a good safety culture assessment tool, with clear, comprehensive and understandable entries. The process demonstrated that the department of obstetrics in the hospital already had a positive patient safety culture, but certain areas were highlighted as still needing improvement. Based on participants' positive experience and perception of the MaPSaF, it can be concluded that there is potential benefit in its adaptation and use in obstetrics wards of Chinese hospitals. The MaPSaF has the potential to strengthen existing safety cultures and improve general safety through collaborative measures.

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

Abstract Background Production of vitamin C has been traditionally based on the Reichstein process and the two-step process. However, the two processes share a common disadvantage: vitamin C cannot be directly synthesized from D-glucose. Therefore, significant effort has been made to develop a one-step vitamin C fermentation process. While, 2-KLG, not vitamin C, is synthesized from nearly all current one-step fermentation processes. Vitamin C is naturally synthesized from glucose in Arabidopsis thaliana via a ten-step reaction pathway that is encoded by ten genes. The main objective of this study was to directly produce vitamin C from D-glucose in Escherichia coli by expression of the genes from the A. thaliana vitamin C biosynthetic pathway. Results Therefore, the ten genes of whole vitamin C synthesis pathway of A. thaliana were chemically synthesized, and an engineered strain harboring these genes was constructed in this study. The direct production of vitamin C from D-glucose based on one-step fermentation was achieved using this engineered strain and at least 1.53 mg/L vitamin C was produced in shaking flasks. Conclusions The study demonstrates the feasibility of one-step fermentation for the production of vitamin C from D-glucose. Importantly, the one-step process has significant advantages compared with the currently used fermentation process: it can save multiple physical and chemical steps needed to convert D-glucose to D-sorbitol; it also does not involve the associated down-streaming steps required to convert 2-KLG into vitamin C.

Abstract Background and objective The high prevalence of obesity is a serious problem, and sleep is considered to be a factor for obesity. This study aimed to examine the relationship between sleep duration, sleep quality, and weight status among children and adolescents in China and to explore whether the relationship between sleep duration and weight status is independent of sleep quality. Sex and age differences were also explored. Methods A cross-sectional research was conducted among 2019 children and adolescents (1029 boys and 990 girls) aged 8–16 years in Shanghai. An open-question was used to obtain data on sleep duration, which was categorized into the following four groups based on the age-specific National Sleep Foundation Sleep Duration Recommendations: 1) very short, 2) short, 3) recommended, and 4) long. The Pittsburgh Sleep Quality Index was used to assess sleep quality. Weight and height were measured for all participants. The variable weight status was estimated with the Chinese children and adolescent age- and sex-specific body mass index (BMI) and was categorized into overweight/obesity and normal weight. Results Short sleep duration (7–8 and 6–7 h for 6–13 and 14–16 years old, respectively) significantly increased odds of overweight/obesity (OR = 1.32, 95% CI: 1.06–1.64) compared with that of the recommended sleep duration (9–11 and 8–10 h for 6–13 and 14–16 years old, respectively). The relationship between the two variables existed independent of sleep quality. No significant relationship was found between sleep quality and overweight/obesity of children and adolescents. Sleep quality (OR = 1.07, 95% CI: 1.01–1.14) and short sleep duration (OR = 1.51, 95% CI: 1.06–2.13) increased the risk for overweight/obesity among girls, whereas no significant relationships between sleep duration, sleep quality, and overweight/obesity were found among boys. Short sleep duration increased the risk of overweight/obesity in children aged 8–13 years (OR = 1.34, 95% CI: 1.05–1.71), independent of sleep quality, but no significant relationships between these two variables existed for adolescents aged 14–16 years. Conclusions Overall, short sleep duration increased the risks of overweight/obesity in children and adolescents in China, independent of sleep quality. This relationship is significant for girls and children aged 8–13 years instead of boys and adolescents aged 14–16 years. Interventions to extend the sleep duration of children and adolescents, especially girls and children aged 8–13 years in China, are necessary to improve their weight status.

Methionine is an essential sulfur-containing amino acid that finds widespread applications in agriculture, medicine, and the food industry. However, the complex and multibranched biosynthetic pathway of methionine has posed significant challenges to its efficient fermentation production. In this study, we employed a modularized synthetic biology strategy to improve the weakest branched pathway of methionine biosynthesis. Three exogenous modules were constructed and assembled to provide methyl donors, which are the primary limiting factors in methionine biosynthesis. The first module utilized added methanol, which was converted into 5,10-methylene-tetrahydrofolate for methionine production but was hindered by the toxicity of methanol. To circumvent this issue, a non-toxic formate module was constructed, resulting in a visible improvement in the methionine titer. Finally, an exogenous betaine module was constructed, which could directly deliver methyl to methionine. The final strain produced 2.87 g/L of methionine in a flask, representing a 20% increase over the starting strain. This study presents a novel strategy for improving and balancing other metabolites that are synthesized through complex multibranched pathways.

Background/aim: Patients with elevated intracranial pressure (ICP) tend to have optic disc edema and a thicker optic nerve sheath diameter (ONSD). However, the cut-off value of the optic disc height (ODH) for evaluating elevated ICP is not clear. This study was conducted to evaluate ultrasonic ODH and to investigate the reliability of ODH and ONSD for elevated ICP.Methods: Patients suspected of having increased ICP and who underwent a lumbar puncture were recruited. ODH and ONSD were measured before lumbar puncture. Patients were divided according to elevated and normal ICP. We analyzed the correlations between ODH, ONSD, and ICP. ODH and ONSD cut-off points for the identification of elevated ICP were determined and compared.Results: There were a total of 107 patients recruited for this study, 55 patients with elevated ICP and 52 with normal ICP. Both ODH and ONSD in the elevated ICP group were higher than in the normal group [ODH: median 0.81 (range 0.60–1.06) mm vs. 0.40 [0–0.60] mm, p < 0.001; ONSD: 5.01 ± 0.37 mm vs. 4.20 ± 0.38 mm, p < 0.001]. ICP was positively correlated with ODH (r = 0.613; p < 0.001) and ONSD (r = 0.792; p < 0.001). The cut-off values of ODH and ONSD for evaluating elevated ICP were 0.63 mm and 4.68 mm, respectively, with 73% and 84% sensitivity and 83% and 94% specificity, respectively. ODH combined with ONSD showed the highest value under the receiver operating characteristic curve of 0.965 with a sensitivity of 93% and a specificity of 92%.Conclusion: Ultrasonic ODH combined with ONSD may help monitor elevated ICP non-invasively.

ObjectiveTo examine characteristics of pathogens identified among patients with fever and rash syndrome (RFIs) in Gansu province from 2009 to 2019, and to provide a reference for implementing targeted prevention measures and conducting pathogen surveillance. Methods Sentinel surveillance data on 5 822 RFIs cases reported in Gansu province from 2009 through 2019 were extracted from the Information Management System for Prevention and Treatment of AIDS and Viral Hepatitis and other Major Infectious Diseases. Multiple correspondence analysis was adopted to analyze characteristics of pathogens isolated from the RFIs patients. Results Enterovirus infection was confirmed in 1 653 (28.39%) of the all RFIs patients reported during the period and the number (proportion) of the patients confirmed with other pathogen infections were 548 (9.41%) for measles virus, 201 (3.45%) for rubella virus, and 495 (8.50%) for varicella-zoster virus, respectively. No pathogen infection was confirmed in 2 925 (50.24%) RFIs patients. The results of multiple correspondence analysis showed that enteroviruses infection was more frequently diagnosed in hospitalized cases in western and central Gansu province, during summer/autumn season, among scattered children aged ≤ 5 years and kindergarten children, among patients hospitalized in provincial and county-level hospitals; measles virus infection was more frequently confirmed among the patients in eastern and southern areas of Gansu province, during winter/spring season, in the adults (≥ 18 years) with some specific occupations, and among patients seeking medication at municipal hospitals; and more varicella-zoster virus and rubella virus infections were detected among the students aged 6 to 17 years. No pathogen infection was identified among the majority of the RFIs patients visiting doctors in outpatient/emergency departments. Conclusion The main pathogens inducing RFIs incidents in Gansu province from 2009 to 2019 include enterovirus, measles virus, varicella-zoster virus and rubella virus, and there were disparities in the detection rate of the pathogens among various populations, in different seasons and in various geographical areas.

Abstract Background Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. Methods A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. Results Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. Conclusions A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.

Objectives: Stroke patients with high intracranial pressure (ICP) may have poor prognosis. Non-invasive ultrasonic optic nerve sheath diameter (ONSD) could evaluate increased ICP. To investigate whether ONSD is valuable for prognosis of patients with acute ischemic stroke (AIS).Methods: AIS receiving intensive care were recruited with the Glasgow Coma Scale (GCS) score. Patients in group A underwent ultrasonic ONSD to assess ICP voluntarily, whereas group B without ONSD. Patients were followed up at discharge and once a week for 3 months with Glasgow Outcome Scale (GOS) score (four to five scores indicated good prognosis and one to three scores indicated poor prognosis).Results: Forty-nine patients were included. GCS scores did not differ significantly between groups A (26 patients) and B (8 ± 3 vs. 7 ± 3, p < 0.05). In group A, ONSD was 5.01 ± 0.48 mm, which correlated with GCS score (p < 0.05). At discharge, the GOS score was higher in group A than in group B (3.35 ± 1.35 vs. 2.57 ± 1.121, p = 0.034). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 13.0%, p = 0.006). At discharge and after 3 months of follow-up, ONSD at admission was correlated with the GOS score in group A (r = -0.648 [p < 0.05] and -0.731 [p < 0.05], respectively). After 3 months of follow-up, the GOS score was higher in group A than group B (3.00 ± 1.673 vs. 2.04 ± 1.430, p < 0.05). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 21.2%, p = 0.039). The Kaplan-Meier curve showed a higher rate of good prognosis in group A than in group B. ONSD (p < 0.05) was an independent predictor of poor prognosis.Conclusion: Non-invasive ultrasonic ONSD could be useful in improving the prognosis of patients with AIS receiving intensive care.

The Badain Jaran Desert is the third largest desert in China, covering an area of 50000 km2. It lies in Northwest China, where the arid and rainless natural environment has a great impact on the climate, environment, and human living conditions. Based on the results of 1∶250000 regional hydrogeological surveys and previous researches, this study systematically investigates the circulation characteristics and resource properties of the groundwater as well as the evolution of the climate and ecological environment since the Quaternary in the Badain Jaran Desert by means of geophysical exploration, hydrogeological drilling, hydrogeochemistry, and isotopic tracing. The results are as follows. (1) The groundwater in the Badain Jaran Desert is mainly recharged through the infiltration of local precipitation and has poor renewability. The groundwater recharge in the desert was calculated to be 1.8684×108 m3/a using the water balance method. (2) The Badain Jaran Desert has experienced four humid stages since the Quaternary, namely MIS 13-15, MIS 5, MIS 3, and the Early–Middle Holocene, but the climate in the desert has shown a trend towards aridity overall. The average annual temperature in the Badain Jaran Desert has significantly increased in the past 50 years. In detail, it has increased by about 2.5°C, with a higher rate in the south than in the north. Meanwhile, the precipitation amount has shown high spatial variability and the climate has shown a warming-drying trend in the past 50 years. (3) The lakes in the hinterland of the Badain Jaran Desert continuously shrank during 1973–2015. However, the vegetation communities maintained a highly natural distribution during 2000–2016, with the vegetation cover has increased overall. Accordingly, the Badain Jaran Desert did not show any notable expansion in that period. This study deepens the understanding of groundwater circulation and the climate and ecological evolution in the Badain Jaran Desert. It will provide a scientific basis for the rational exploitation of the groundwater resources and the ecological protection and restoration in the Badain Jaran Desert.© 2021 China Geology Editorial Office.

BackgroundGestational trophoblastic neoplasia (GTN) is a group of clinically rare tumors that develop in the uterus from placental tissue. Currently, its satisfactory curability derives from the timely and accurately classification and refined management for patients. This study aimed to discover biomarkers that could predict the outcomes of GTN patients after first-line chemotherapy.MethodsA total of 65 GTN patients were included in the study. Patients were divided into the good or poor outcome group and the clinical characteristics of the patients in the two groups were compared. Furthermore, the serum peptide profiles of all patients were uncovered by using weak cation exchange magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Feature peaks were identified by three machine learning algorithms and then models were constructed and compared using five machine learning methods. Additionally, liquid chromatography mass spectrometry was used to identify the feature peptides.ResultsMultivariate logistic regression analysis showed that the International Federation of Gynecology and Obstetrics (FIGO) risk score was associated with poor outcomes. Eight feature peaks (m/z =1287, 2042, 2862, 2932, 2950, 3240, 3277 and 6626) were selected for model construction and validation by the three algorithms. Based on the panel combining FIGO risk score and peptide serum signatures, the neural network (nnet) model showed promising performance in both the training (AUC=0.9635) and validation (AUC=0.8788) cohorts. Peaks at m/z 2042, 2862, 2932, 3240 were identified as the partial sequences of transthyretin, fibrinogen alpha chain (FGA), beta-globin and FGA, respectively.ConclusionWe combined FIGO risk score and serum peptide signatures using the nnet method to construct the model which can accurately predict outcome of GTN patients after first-line chemotherapy. With this model, patients can be further classified and managed, and those with poor predicted outcomes can be given more attention for developing treatment failure.

PurposeTo investigate the association between subtypes of metabolic syndrome (MetS) and prognosis of patients with stage I endometrioid adenocarcinoma.Patients and methodsPatients with stage I endometrioid adenocarcinoma who received surgical treatment as primary therapy at the Department of Gynecology of the Sun Yat-sen Memorial Hospital between June 2015 and December 2019 were retrospectively enrolled. According to the diagnosis criteria of MetS, the patients were categorized as patients without MetS, patients with MetS but without raised fasting plasma glucose (FPG, including previously diagnosed diabetes), and patients with MetS and raised FPG. All the included patients were followed from the dates of surgery until death, June 2021, or loss to follow-up, whichever came first, and cancer recurrence (including metastasis) was studied as the main outcome. Cox regression was used to evaluate the associations between subtypes of MetS and the study outcome adjusting for potential confounding factors.ResultsAmong the included 387 patients with stage I endometrioid adenocarcinoma, 193 (49.9%) were without MetS, 65 (16.8%) were with FPG not involving MetS, and 129 (33.3%) were with raised FPG involved MetS. With a median follow-up of 1,253 days, the cumulative incidence of cancer recurrence was 8.76% (95% confidence interval (CI) 2.5%–14.62%), 28.31% (95% CI 2.33%–47.38%), and 7.54% (95% CI 1.54%–13.17%), respectively. After adjusting for age, menopause, histological grade, tumor size, lymph-vascular space invasion, deep myometrial invasion, and treatments, comorbid FPG not involving MetS is a stronger risk factor of cancer recurrence than comorbid raised FPG involving MetS (hazard ratio 2.82 (95% CI 1.10–7.24) versus 1.18 (95% CI 0.45–3.13)) when compared to patients without MetS.ConclusionComorbid MetS generally presents as a risk factor of poor prognosis in patients with stage I endometrioid adenocarcinoma after surgical treatment, but the magnitude of the association may vary between subtypes, in which FPG not involving MetS appears to be predominant.

Nitrobenzene is widely present in industrial wastewater and soil. Biodegradation has become an ideal method to remediate organic pollutants due to its low cost, high efficiency, and absence of secondary pollution. In the present study, 10 exogenous genes that can completely degrade nitrobenzene were introduced into Escherichia coli, and their successful expression in the strain was verified by fluorescence quantitative polymerase chain reaction and proteomic analysis. The results of the degradation experiment showed that the engineered strain could completely degrade 4 mM nitrobenzene within 8 h. The formation of intermediate metabolites was detected, and the final metabolites entered the E. coli tricarboxylic acid cycle smoothly. This process was discovered by isotope tracing method. Results indicated the integrality of the degradation pathway and the complete degradation of nitrobenzene. Finally, further experiments were conducted in soil to verify its degradation ability and showed that the engineered strain could also degrade 1 mM nitrobenzene within 10 h. In this study, engineered bacteria that can completely degrade nitrobenzene have been constructed successfully. The construction of remediation-engineered bacteria by synthetic biology laid the foundation for the industrial application of biological degradation of organic pollutants.

Abstracts Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Abstract Background Hyperthermic intraperitoneal chemotherapy (HIPEC) is an important treatment for ovarian cancer. A certain portion of cisplatin exits the body via the perfusate at the end of HIPEC, so full-dose utilization cannot be achieved. Herein, we sought to explore how much cisplatin is actually utilized and its prognostic influence. Methods Cisplatin (70 mg/m2) was given at 43 °C for 90 min. The actually utilized dose (AD) of cisplatin was calculated using the following formula: AD (mg) = total dose (TD) (mg)-losing dose (LD) (mg); LD = volume (ml) of the perfusate (VPretained) that was retained in the HIPEC treatment system at the end of HIPEC * concentration of cisplatin in the perfusate (mg/ml). Result Sixty-two ovarian cancer patients were included. The median TD, median LD and median AD were 95 mg, 20.7 mg and 75.8 mg, respectively. The utility rate of cisplatin (AD/TD ratio) was 79.2%. On simple linear regression analysis, the TD and VPretained were found to significantly predict the AD. Based on these two factors, multiple linear regression analysis was conducted, and a significant regression equation was formulated [F (2, 59) = 71.419, P

Abstract The aim of this study was to reveal the effect of let‐7b on osteoporosis (OP). Synthetic let‐7b mimics or inhibitors were transfected into MC3T3‐E1 cells. The expression of let‐7b in MC3T3‐E1 and its effect on cell viability, apoptosis, and the apoptosis‐related proteins (Bcl‐2, Bax, and cleaved caspase‐9) were tested by CCK‐8 assay, flow cytometry and Western blot, severally. The osteogenic differentiation markers (Runx2 and Osterix) and Wnt/β‐catenin pathway related markers (β‐catenin and C‐myc) were detected by qRT‐PCR and Western blot. The relationships between let‐7b and cyclin D1 (CCND1) were confirmed by luciferase reporter assay. The differentiation and mineralization of MC3T3‐E1 cells were analyzed by alkaline phosphatase (ALP) activity assay and alizarin red staining. The outcomes indicated that overexpression/ablation of let‐7b repressed/facilitated MC3T3‐E1 cell viability and accelerated/suppressed MC3T3‐E1 cell apoptosis. Besides, a remarkable decrease/augment of Bcl‐2 protein expression and the distinct fortify/reduction of Bax and cleaved caspase‐9 expression levels were observed in let‐7b mimics/inhibitors group in MC3T3‐E1 cells. Moreover, we discovered that let‐7b overexpression/ablation retrained/facilitated the mRNA and protein expression of Runx2 and Osterix. It was confirmed that CCND1 was a downstream target of let‐7b and was negatively modulated by let‐7b. In addition, high‐expression/deficiency of let‐7b inhibited/increased the expression levels of β‐catenin and C‐myc in MC3T3‐E1 cells. Taken together, our study revealed that let‐7b overexpression/depletion repressed/accelerated MC3T3‐E1 cell proliferation, differentiation, and mineralization while promoted/suppressed MC3T3‐E1 cell apoptosis through targeting CCND1, which might be adjusted by Wnt/β‐catenin pathway. Our findings might offer a basis for developing novel targets for OP treatment.

Abstract Oocyte activation inefficiency is one of the reasons for female infertility and Ca2+ functions play a critical role in the regulation of oocyte activation. We used various inhibitors of Ca2+ channels located on the membrane, including sarcoplasmic/ endoplasmic reticulum Ca2+ATPases (SERCAs, the main Ca2+ pumps which decrease the intracellular Ca2+ level by refilling Ca2+ into the sarcoplasmic reticulum), transient receptor potential (TRP) ion channel subfamily member 7 (TRPM7, a Ca2+/Mg2+-permeable non-selective cation channel), T-type Ca2+ channels and calcium channel Orai1, to investigate their roles in [Ca2+]i oscillation patterns and mitochondrial membrane potential during oocyte activation by real-time recording. Our results showed that SERCAs, TRPM7 and T-type Ca2+ channels were important for initiation and maintenance of [Ca2+]i oscillations, which was required for mitochondrial membrane potential elevation during oocyte activation, as well as oocyte cytoskeleton stability and subsequent embryo development. Increasing the knowledge of calcium transport may provide a theoretical basis for improving oocyte activation in human assisted reproduction clinics.

Introduction The aim was to observe the effect of Toll-like receptor 4 (TLR4) deficiency on clinical severity and expression of Th1/Th2/Th17-associated cytokines in experimental autoimmune neuritis (EAN). Material and methods We selected C57BL/10 wild type (WT) mice and TLR4 knockout (KO) mice with the C57BL/10 background for induction of the EAN model by immunizing mice twice (days 0 and 8) via subcutaneous injection of 180 µg P0 peptide 180–199 emulsion in 25 µl of PBS and 0.5 mg Mycobacterium tuberculosis (Difco, USA) in 25 µl of Freund’s incomplete adjuvant into the back of mice. The concentrations of serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) were determined using the Ms Th1/Th2/Th17 CBA kit. Results We found that TLR4 deficiency could attenuate the clinical severity and delay the onset of EAN. Moreover, our data showed that the sera levels of IFN-γ, TNF, IL-6 and IL-17A were elevated in the WT mice with EAN when compared with the naive WT mice, but only the production of IL-17A was significantly lower in the TLR4 KO mice with EAN than in their WT counterparts. Conclusions Based on these findings, TLR4 may contribute to the pathogenesis of EAN by regulating Th17 cells and the production of Th17-associated factors. However, the exact mechanism remains unclear and more evidence is needed to elucidate its role in EAN.

Abstract Ultrasonographically measured optic nerve sheath diameter measurement has become a common noninvasive approach for detecting elevated intracranial pressure. We present a case of aneurysmal subarachnoid hemorrhage with elevated intracranial pressure. Postoperative arachnoiditis developed, and lumbar puncture revealed low intracranial pressure. However, ultrasonography revealed a dilated optic nerve sheath, denoting elevated intracranial pressure. This was confirmed by computed tomography showing ventricular dilation. Ophthalmoscopy revealed papilledema and hemorrhage. This case study demonstrated that noninvasive bedside ultrasonographic optic nerve sheath diameter measurement can detect elevated intracranial pressure more accurately than lumbar puncture, especially in cases with intracranial infection.

Abstract Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear “start point” for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.

Background/Aim: To study the impact of computer-aided detection (CADe) system on the detection rate of polyps and adenomas in colonoscopy. Materials and Methods: A total of 1026 patients were prospectively randomly scheduled for colonoscopy with (the CADe group, CADe) or without (the control group, CON) the aid of the CADe system, together with visual notification and voice alarm, so as to compare the detection rate of polyp. Results: Compared with group CON, the detection rate of adenomas increased in group CADe, the average number of adenomas increased, the number of small adenomas increased, the number of proliferative polyps increased, and the differences were statistically significant (P < 0.001), but the comparison for the number of larger adenomas showed no significant difference between the groups (P> 0.05). Conclusions: The CADe system is feasible for increasing the detection of polyps and adenomas in colonoscopy.

Background: Invasive intracranial pressure (ICP) can result in complications, pain, or even aggravate intracranial hypotension (IH) or headache in patients with IH. Objective: To investigate whether ultrasonographic measurements of optic nerve sheath diameter (ONSD) could serve as a noninvasive IH marker. Methods: Ultrasonographic ONSD was measured prior to lumbar puncture (LP) and ONSD measurements compared to LP’s opening pressure. We analyzed correlations between ONSD and ICP and determined the optimal ONSD cut-off point for IH. According to their LP on admission, patients were divided into three groups: IH group, normal ICP group, and elevated ICP group. Correlations between ONSD and ICP were analyzed using Pearson’s correlation. A receiver operating characteristic (ROC) curve was generated to determine the optimal cut-off point for IH. Results: In total, 136 subjects (75 men, 55.1% men) were included, and 1088 ONSDs were measured. The ONSD of the IH group (2.96 ± 0.15 mm) was significantly lower than that of the normal (3.59 ± 0.33 mm) and elevated ICP groups (4.90 ± 0.42 mm, p

2,4,6-trinitrotoluene (TNT) and cobalt (Co) contaminants have posed a severe environmental problem in many countries. Phytoremediation is an environmentally friendly technology for the remediation of these contaminants. However, the toxicity of TNT and cobalt limit the efficacy of phytoremediation application. The present research showed that expressing the Acidithiobacillus ferrooxidans single-strand DNA-binding protein gene (AfSSB) can improve the tolerance of Arabidopsis and tall fescue to TNT and cobalt. Compared to control plants, the AfSSB transformed Arabidopsis and tall fescue exhibited enhanced phytoremediation of TNT and cobalt separately contaminated soil and co-contaminated soil. The comet analysis revealed that the AfSSB transformed Arabidopsis suffer reduced DNA damage than control plants under TNT or cobalt exposure. In addition, the proteomic analysis revealed that AfSSB improves TNT and cobalt tolerance by strengthening the reactive superoxide (ROS) scavenging system and the detoxification system. Results presented here serve as strong theoretical support for the phytoremediation potential of organic and metal pollutants mediated by single-strand DNA-binding protein genes. Summarizes: This is the first report that AfSSB enhances phytoremediation of 2,4,6-trinitrotoluene and cobalt separately contaminated and co-contaminated soil.

Rab GTPases are the subfamily of the small guanosine triphosphate (GTP)-binding proteins which participated in the regulation of various biological processes. Recent studies have found that plant Rabs play some specific functions. However, the functions of Rabs in xylem development in trees remain unclear. In this study, functional identification of PagRabE1b in Populus was performed. Quantitative reverse transcription PCR (qRT-PCR) results showed that PagRabE1b was highly accumulated in stems, especially in phloem and xylem tissues. Overexpression of PagRabE1b in poplar enhanced programmed cell death (PCD) and increased the growth rate and the secondary cell wall (SCW) thickness. Quantitative analysis of monosaccharide content showed that various monosaccharides were significantly increased in secondary xylem tissues of the overexpressed lines. Flow cytometry analysis revealed that the number of apoptotic cells in PagRabE1b-OE lines is more than a wild type (WT), which indicated that PagRabE1b may play an important role in PCD. Further studies showed that overexpression of PagRabE1b increased the expression level of genes involved in SCW biosynthesis, PCD, and autophagy. Collectively, the results suggest that PagRabE1b plays a positive role in promoting the xylem development of poplar.

Abstract In the present study, we examined the factors affecting survival of women with inflammatory breast cancer (IBC) and constructed and validated a nomogram to predict overall survival (OS) in these patients. The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program between 1 January 2004 and 31 December 2013. Univariate and multivariate Cox proportional hazards regression models were constructed. A nomogram was developed based on significant prognostic indicators of OS. The discriminatory and predictive capacities of the nomogram were assessed using Harrell's concordance index (C‐index) and calibration plots. A total of 1651 eligible patients were identified, with a median survival time of 31 months (range 0‐131 months), and the 3‐ and 5‐year OS rates were 52.8% and 39.5%, respectively. Multivariate analysis revealed that race (P

The prediction skill of Arctic Oscillation (AO) in the decadal experiments with the Beijing Climate Center Climate System Model version 1.1 (BCC_CSM1.1) is assessed. As compared with the observations and historical experiments, the contribution of initialization for climate model to predict the seasonal scale AO and its interannual variations is estimated. Results show that the spatial correlation coefficient of AO mode simulated by the decadal experiment is higher than that in the historical experiment. The two groups of experiments reasonably reproduce the characteristics that AO indices are the strongest in winter and the weakest in summer. Compared with historical experiments, the correlation coefficient of the monthly and winter AO indices are higher in the decadal experiments. In particular, the correlation coefficient of monthly AO index between decadal hindcast and observation reached 0.1 significant level. Furthermore, the periodicity of the monthly and spring AO indices are achieved only in the decadal experiments. Therefore, the initial state of model is initialized by using sea temperature data may help to improve the prediction skill of AO in the decadal prediction experiments to some extent. Keywords: BCC_CSM1.1, Climate model, Decadal, Arctic oscillation, Hindcast

The conversion of cellular prion protein (PrPC) to disease-provoking conformer (PrPSc) is crucial in the pathogenesis of prion diseases. Heparin has been shown to enhance mammalian prion protein misfolding. As spontaneous prion disease has not been reported in non-mammalian species, such as chicken, it is interesting to explore the influence of heparin on the conversion of chicken prion protein (ChPrP). Herein, we investigated the influences of heparin on biochemical properties of full-length recombinant ChPrP, with murine prion protein (MoPrP) as control. The results showed that at low heparin concentration (10 μg/mL), a great loss of solubility was observed for both MoPrP and ChPrP using solubility assays. In contrast, when the concentration of heparin was high (30 μg/mL), the solubility of MoPrP and ChPrP both decreased slightly. Using circular dichroism, PK digestion and transmission electron microscopy, significantly increased β-sheet content, PK resistance and size of aggregates were observed for MoPrP interacted with 30 μg/mL heparin, whereas 30 μg/mL heparin-treated ChPrP showed less PK resistance and slight increase of β-sheet structure. Therefore, heparin can induce conformational changes in both MoPrP and ChPrP and the biochemical properties of the aggregates induced by heparin could be modified by heparin concentration. These results highlight the importance of concentration of cofactors affecting PrP misfolding.

BackgroundCancer stem cells (CSCs), responsible for cancer metastasis and recurrence, are generated from non-CSCs after chemo-radiation therapy. This study investigated the induction of CSC potential in non-stem breast cancer cells and the underlying molecular mechanisms in detachment culture.MethodsBulk breast cancer cells, or sorted non-CSCs and CSCs were cultured under an attached or detached condition to assess CSC numbers, ability to form tumor spheres, expression of stemness markers, and chemoresistance. Lentivirus carrying CD147 shRNA or cDNA was used to manipulate CD147 expression, while CD147 ligand recombinant cyclophilin A (CyPA) or its inhibitor was used to activate or inhibit CD147 signaling.ResultsDetachment promoted anoikis resistance, chemoresistance, sphere formation, self-renewal, and expression of stemness markers in breast cancer cells. Detachment increased functional ALDH+ or CD44highCD24–/low CSCs, and induced CSC potential in ALDH– or CD44lowCD24high non-CSCs. Upon detachment, both CD147 expression and CyPA secretion were enhanced, and CyPA-CD147 activation mediated detachment induced CSC potential in non-CSCs via STAT3 signaling. Clinically, CD147 and pSTAT3 were highly co-expressed and correlated with poor overall survival and tumor recurrence in breast cancer patients.ConclusionThis study demonstrates that detachment induces the generation of CSCs from non-stem breast cancer cells via CyPA-CD147 signaling, indicating that targeting CD147 may serve as a potential novel therapeutic strategy for lethal metastatic breast cancer by eliminating induced CSCs.

In vivo cell fate reprogramming has emerged as a new method for understanding cell plasticity and as potential treatment for tissue regeneration. Highly efficient and precise reprogramming requires fully understanding of the transcriptomes which function within different cell types. Here, we adopt weighted gene co-expression network analysis (WGCNA) to explore the molecular mechanisms of self-renewal in several well-known stem cell types, including embryonic stem cells (ESC), primordial germ cells (PGC), spermatogonia stem cells (SSC), neural stem cells (NSC), mesenchymal stem cells (MSC), and hematopoietic stem cells (HSC). We identified 37 core genes that were up-regulated in all of the stem cell types examined, as well as stem cell correlated gene co-expression networks. The validation of the co-expression genes revealed a continued protein-protein interaction network that included 823 nodes and 3113 edges. Based on the topology, we identified six densely connected regions within the continued protein-protein interaction network. The SSC specific genes Itgam, Cxcr6, and Agtr2 bridged four densely connected regions that consisted primarily of HSC-, NSC-, and MSC-correlated genes. The expression levels of identified stem cell related transcription factors were confirmed consistent with bioinformatics prediction in ESCs and NSCs by qPCR. Exploring the mechanisms underlying adult stem cell self-renewal will aid in the understanding of stem cell pool maintenance and will promote more accurate and efficient strategies for tissue regeneration and repair.

Abstract Background To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC). Methods A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A1c (HbA1c) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models. Results In total, 388 patients were included and had a median follow-up time of 39 months (range: 4–67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA1c

Background: Successful antiretroviral therapy (ART) has been demonstrated to be effective in reducing the infectivity of human immunodeficiency virus (HIV). We conducted a study to predict the potential effect of ART on the spread of HIV in Chaoyang District, Beijing, China, using the Asian Epidemic Model (AEM). Methods: The AEM baseline workbook was used to determine the current infection status and to project the future spread of HIV under current conditions. We changed the input on the ART coverage from 2014 to 2025 and also modified the treatment eligibility in the AEM intervention workbook, in order to allow for analysis of the projected downstream impact of ART. Results: By gradually increasing the ART coverage rate from 29.7% (rate of 2013) to 40.0%, 50.0%, 60.0%, 70.0%, 80.0%, and 90.0% (at CD4+ ≤350 cells/μl), and by changing the dates of coverage from 2014 to 2020, the number of new infections showed a cumulative decline of 0.60%, 1.59%, 2.94%, 5.33%, 9.32%, and 14.98%, respectively. After 2020, the projected rates of infection rebounded slightly, so with the exception of the years with very high coverage (90.0%), new infections continued to decrease. When we changed the initial threshold of therapy to CD4+ cell counts ≤500 cells/μl, new infections decreased 6.00%, 11.64%, 15.92%, 21.11%, 26.92%, 33.05%, and 38.75%, respectively, under varying ART coverages. Conclusion: Our study demonstrates that the early initiation of ART for people living with HIV/acquired immune deficiency syndrome (AIDS) has a positive effect in slowing the spread of HIV.