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Purpose: There is no consensus on whether cognitive measures among attention deficit hyperactivity disorder (ADHD) subtypes exhibit more similarities or differences, and most of them have been conducted on English-speaking subjects, lacking cross-cultural perspectives. The present study was aimed at investigating the intelligence structures of school-age children with ADHD who speak Chinese, using a multicenter and large sample size approach, offering some references for clinicians., Patients and Methods: 772 children aged 6 to 12 years with ADHD took part in the cross-sectional study. All participants underwent the Chinese Wechsler Intelligence Scale for Children-Third Edition assessment. Statistical Package for the Social Sciences (SPSS) Statistics 24 was used for statistical analyses., Results: No significant differences were found in full intelligence quotient (FIQ), verbal IQ (VIQ), performance quotient (PIQ), as well as most subtest scores among ADHD subtypes. The analysis of variance showed that the boys' scores were higher than girls' scores in PIQ ( P < 0.05), information ( P < 0.01), vocabulary ( P < 0.05) and block design ( P <0.01) from the perspective of sex, but lower in the coding ( P < 0.01). From the perspective of age, the senior group (aged 9-12) scored higher in block design ( P < 0.01) and object assembly ( P < 0.05) than the junior one (aged 6-8), but lower in VIQ ( P < 0.05) and verbal comprehension (VC) factor., Conclusion: Our study supported that ADHD substyles shared more similarities in intelligence structures. Boys outperformed girls in PIQ and some subtests, suggesting that the importance to consider the gender differences and the distribution of intellectual strengths and weaknesses. Older children outperformed in block design and object assembly, but underperformed in VIQ and VC factor. This indicated the need to focus on language development and screen for specific learning disabilities in managing school-age children with ADHD., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 Zhu et al.)

Mycotoxins are secondary metabolites produced by fungi with harmful effects such as carcinogenicity, teratogenicity, nephrotoxicity, and hepatotoxicity. They cause widespread contamination of plant products such as crops, food, and feed, posing serious threats to the life and health of human beings and animals. It has been found that many traditionally synthesized and natural compounds are capable of inhibiting the growth of fungi and their secondary metabolite production. Natural compounds have attracted much attention due to their safety, environmental, and health friendly features. In this paper, compounds of plant origin with inhibitory effects on ochratoxins, aflatoxins, Fusarium toxins, and Alternaria toxins, including cinnamaldehyde, citral, magnolol, eugenol, pterostilbene, curcumin, and phenolic acid, are reviewed, and the inhibitory mechanisms of different compounds on the toxin production of fungi are also elucidated, with the aim of providing application references to reduce the contamination of fungal toxins, thus safeguarding the health of human beings and animals., (© 2024. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

Although positive attitudes toward own aging (ATOA) have been shown to be associated with higher levels of quality of life (QoL) among older adults, the potential interrelationship between ATOA and QoL has not been fully explored. A sample of 2129 older adults aged 60 and above who participated in the three waves of the Chinese longitudinal healthy longevity survey was used. QoL was measured using three indicators, including self-rated health, loneliness, and life satisfaction. The cross-lagged analysis results showed that the bidirectional association between ATOA and QoL was not significant, while positive ATOA predicted better self-rated health, higher life satisfaction, and less loneliness. And there are no gender or age differences in the above relationships. In addition, economic status, sleep quality, and activity participation were common influences on self-rated health, life satisfaction, and loneliness, as well as important factors affecting ATOA. Several variables, such as demographic characteristics, health behaviors, and health status, also influenced QoL and ATOA. Measures to promote positive ATOA can help improve QoL. In addition, emphasis should be placed on improving economic status, sleep quality, and activity participation levels to enhance QoL and ATOA in older adults, with appropriate interventions targeting other factors affecting QoL and ATOA., (© 2024 International Association of Applied Psychology.)

Background: Nursing shortage is a global issue. Turnover intention and life satisfaction are significant predictors of turnover. The specific nature of nursing and stressful work schedules lead to impaired professional quality of life (ProQOL), and existing studies have confirmed the effect of a dimension of ProQOL (such as secondary trauma stress, burnout and compassion satisfaction) on turnover intention and life satisfaction. Yet the heterogeneity of ProQOL across individuals is not known. A lack of research on the relationship between potential ProQOL subgroups and turnover intention and life satisfaction, and the mechanisms underlying this relationship remain understudied. The study aimed to determine different ProQOL profiles, and their cross-sectional and longitudinal effects on turnover intention and life satisfaction, while exploring the mediating roles of job satisfaction and work engagement within the relationship., Methods: Data were collected at a tertiary hospital in a northeastern province of China. An online questionnaire was administered twice over the course of six months. 1832 and 900 participates provided cross-sectional and longitudinal data respectively. We used latent profile analysis (LPA) and K-means clustering to identify ProQOL profiles, and used the PROCESS macro program to conduct mediation analysis., Results: The LPA results supported a 4-profile solution, including balanced protection, good quality, traumatic satisfaction and burnout problem. ProQOL profiles directly predicted nurses' current and subsequent turnover intention and life satisfaction. In addition, job satisfaction and work engagement mediated the effects of ProQOL profiles on turnover intention and life satisfaction in cross-sectional sample, and mediated the effects of ProQOL profiles on turnover intention in longitudinal sample., Conclusion: The findings suggest that nurses' ProQOL has distinct categorical characteristics and is strongly associated with turnover intention and life satisfaction. Hospital administrators should implement individualized, join management and interventions according to each profile. Furthermore, more attentions should focus on improving nurses' job satisfaction and work engagement levels to promote good work and life outcomes., (© 2024. The Author(s).)

Ceramic aerogels are promising materials for thermal insulation and protection under harsh environments. Yet current synthesis methods fail to provide an energy-, time-, and cost-effective route for high-throughput production and large-scale applications, especially for non-oxide ceramic aerogels. Here we reported a way to synthesize SiC aerogels within seconds and over liter scale, with a demonstrated throughput of ~16 L min -1 in a typical lab experiment. The key lies in renovated combustion synthesis and a fast expansion from powder reactants to aerogel products over 1000% in volume. The synthesis process is self-sustainable and requires minimal energy input. The product is very cheap, with an estimated price of ~$0.7 L -1 (~$7 kg -1 ). The obtained SiC aerogels have excellent thermo-mechanical properties, including low thermal conductivity, high elasticity, and damage tolerance. Our invention not only offers a practical pathway for large-scale applications of ceramic aerogels, but also calls for rethinking of combustion synthesis in one-step conversion from raw chemicals to bulk products ready for practical applications., (© 2024. The Author(s).)

This study investigated the occurrence, stereoisomeric behavior, and potential sources of hexabromocyclododecanes (HBCDs) in topsoil and terrestrial vegetation from Svalbard and ocean sediment samples from Kongsfjorden, an open fjord on the west coast of Spitsbergen. The mean levels of total concentrations (Σ 3 HBCDs) were comparable to those in other remote regions and were lower than those in source regions. Elevated proportions of α-HBCD with an average of 41% in the terrestrial samples and 25% in ocean sediments compared to those in commercial products (10-13% for α-HBCD) were observed, implying isomerization from γ- to α-HBCD in the Arctic environment. In addition, the extensive deviations of enantiomeric fractions (EFs) from the racemic values reflected the effect of biotransformation on HBCD accumulation. Linear correlation analysis, redundancy analysis, and back-trajectory were combined to infer possible HBCD sources, and the results showed the important role of global production and long-range environmental transport (LRET) for the entry of HBCDs into the Arctic at an early stage. To the best of our knowledge, this study represents the first report on the diastereoisomer- and enantiomer-specific profiles of HBCDs in the Arctic terrestrial environment and sheds light on the transport pathways and environmental fate for more effective risk management related to HBCDs in remote regions., 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 B.V. All rights reserved.)

Objective: The present study aimed to investigate the long-term effects of parent-child separation during infancy and early childhood on depression, social relationships including parent-child and peer relationships, and academic performance during adolescence and early adulthood., Methods: Data from the China Family Panel Studies (CFPS) were analyzed, which included a sample of 3829 children aged 4-15 years from 25 provinces over a period of 8 years. The study examined the association between early parent-child separation and outcomes related to depression, social and academic performance, comparing outcomes between individuals with and without early separation experiences. A series of subgroup analyses were conducted to further explore these associations., Results: Parent-child separation lasting 3 months or longer was found to be associated with moderate to severe levels of depression and impaired social relationships during adolescence and early adulthood, particularly among males, adolescents, urban dwellers, and those with less educated mothers. Children who experienced parent-child separation for 3 months or longer showed a positive correlation between separation duration and depression. Short-term separations under 3 months did not show this association. The duration of separation also had a negative correlation with parent-child and peer relationships, as well as academic performance., Conclusion: Early parent-child separation has significant adverse effects on the mental health, social and academic performance of adolescents and early adulthood, especially among males, adolescents, urban residents, and those with lower maternal education. The severity of depression was found to be related to the duration of separation, highlighting the importance of minimizing separation to less than 3 months for children under the age of 3. These findings underscore the critical role of early parental care and the need for targeted interventions for high-risk populations., (© 2024. The Author(s).)

General movements (GMs) have been widely used for the early clinical evaluation of infant brain development, allowing immediate evaluation of potential development disorders and timely rehabilitation. The infants' general movements can be captured digitally, but the lack of quantitative assessment and well-trained clinical pediatricians presents an obstacle for many years to achieve wider deployment, especially in low-resource settings. There is a high potential to explore wearable sensors for movement analysis due to outstanding privacy, low cost, and easy-to-use features. This work presents a sparse sensor network with soft wireless IMU devices (SWDs) for automatic early evaluation of general movements in infants. The sparse network consisting of only five sensor nodes (SWDs) with robust mechanical properties and excellent biocompatibility continuously and stably captures full-body motion data. The proof-of-the-concept clinical testing with 23 infants showcases outstanding performance in recognizing neonatal activities, confirming the reliability of the system. Taken together with a tiny machine learning algorithm, the system can automatically identify risky infants based on the GMs, with an accuracy of up to 100% (99.9%). The wearable sparse sensor network with an artificial intelligence-based algorithm facilitates intelligent evaluation of infant brain development and early diagnosis of development disorders., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

In this review, 72 compounds isolated from marine-derived Penicillium fungi and their antimicrobial activities are reviewed from 2020 to 2023. According to their structures, these compounds can be divided into terpenoids, polyketides, alkaloids and other structural compounds, among which terpenoids and polyketides are relatively large in number. Some compounds have powerful inhibitory effects against different pathogenic bacteria and fungi. This review aims to provide more useful information and enlightenment for further efficient utilization of Penicillium spp. and their secondary metabolites., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Donor lymphocyte infusion (DLI) cures relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation through the graft-versus-tumor (GVT) effect. Although the important role of magnesium in enhancing immunity has been mentioned in studies, limited clinical data have explored how magnesium affects the efficacy of DLI. Besides, although laboratory data demonstrate that magnesium can enhance CD8 + T cells effector function, whether magnesium regulates the tumor killing effect of peripheral blood mononuclear cells (PBMCs) remains to be explored. Here, for the retrospective study, we collected clinical data of relapsed patients receiving DLI and explored the relationship between different serum magnesium levels and patient outcomes. For in vitro studies, we investigated the effect of magnesium on the cytotoxicity of DLI cells which were PBMCs and preliminarily explored the mechanism. Eighty-one patients were enrolled in this study. It was found that the high post-DLI magnesium level was significantly associated with a higher incidence of complete remission (CR) or partial remission (CR/PR) and a higher possibility of survival. The magnesium level after DLI was an independent risk factor of overall survival. In vitro studies proved that increased magnesium enhanced the cytotoxic function of PBMCs on hematologic malignancies. Besides, magnesium modulated LFA-1 headpiece opening. When blocking the integrin-ligand interaction between LFA-1 and ICAM-1, the regulation effect of magnesium on PBMCs was weakened. Therefore, it was possible that magnesium regulated PBMCs effector function by stimulating LFA-1. These results show that serum magnesium levels affect immunological responses mediated by donor lymphocytes in hematologic malignancies., (© 2023 John Wiley & Sons Ltd.)

As living standards advance, an escalating emphasis is placed on health, particularly in relation to prevalent chronic metabolic disorders. It is necessary to explore safe and effective functional foods or drugs. Fu brick tea (FBT) is a kind of dark tea fermented by fungi. The extracts are rich in compounds that can effectively relieve metabolic diseases such as hyperglycemia and hyperlipidemia, protect the liver, improve human immunity, enhance antioxidant activity, and regulate intestinal flora. This paper summarizes the biological activities and mechanisms of the extracts, polysaccharides, and small molecular compounds of FBT, which provides a certain theoretical basis for the rational, systematic, comprehensive development and utilization of the FBT resources. It is expected to develop and apply these active substances in health care products and natural medicines and provide more beneficial and diversified FBT products for human beings., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Objectives: To explore the differences between low kiloelectron volt (keV) virtual monoenergetic images (VMIs) using IQon spectral CT and conventional CT (120 kVp) in the diagnosis of osteoporosis., Methods: This retrospective study included 317 patients who underwent IQon spectral CT and dual-energy X-ray absorptiometry (DXA) examination. Commercial deep learning-based software was used for the fully automated extraction of the CT values of the first to fourth lumbar vertebrae (L1-L4) from two different low-keV levels (including 40/70 keV) VMIs and conventional 120 kVp images. The DXA examination results served as the standard of reference (normal [T-score ≥ -1], osteopenia [-2.5 < T-score < -1], and osteoporosis [T-score < -2.5]). Osteoporosis diagnosis models were constructed using machine learning classifiers (logistic regression, support vector machine, random forest, XGBoost, and multilayer perceptron) based on the average CT values of L1-L4. The area under the receiver operating characteristic curve (AUC) and DeLong test were performed to compare differences in the performance of the osteoporosis diagnosis model between virtual low-keV VMIs and standard 120 kVp images., Results: Random forest-based prediction model obtained good overall performance among all classifiers, and macro/micro average AUC values of 0.820/840, 0.834/853, and 0.831/852 were obtained based on 40/70 keV and 120 kVp images, respectively. The model presented no significant difference between low-keV VMIs and standard 120 kVp images for the diagnosis of osteoporosis (p > 0.05)., Conclusions: The performance of the osteoporosis diagnosis model using IQon spectral CT simulating the low tube voltage scanning condition (less than 120 kVp) was also satisfactory. Bone density screening evaluation can be performed with a combination of low-dose lung scanning CT, greatly reducing the radiation dose without affecting the diagnosis., Competing Interests: 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., (© 2023 The Authors.)

Baijiu, a prevalent alcoholic beverage, boasts over 2000 aroma compounds, with sulfur-containing compounds being the most influential in shaping its flavor. Benzenemethanethiol, a distinctive odorant in baijiu, is known to enhance the holistic flavor profile of baijiu. Despite its importance, there is very little literature on the biotransformation mechanism of benzenemethanethiol. Thus, extensive research efforts have been made to elucidate the formation mechanism of this compound in order to improve baijiu production. In this study, 12 yeast strains capable of generating benzenemethanethiol were isolated from baijiu daqu, and the Saccharomyces cerevisiae strain J14 was selected for further investigation. The fermentation conditions were optimized, and it was found that the optimal conditions for producing benzenemethanethiol were at 28 °C for 24 h with a 4% ( v/v ) inoculum of 3.025 g/L L-cysteine. This is the first time that yeast has been shown to produce benzenemethanethiol isolated from the baijiu fermentation system. These findings also suggest that benzenemethanethiol can be metabolized by yeast using L-cysteine and benzaldehyde as precursor substrates.

Secondary metabolites from marine organisms are diverse in structure and function. Marine Aspergillus is an important source of bioactive natural products. We reviewed the structures and antimicrobial activities of compounds isolated from different marine Aspergillus over the past two years (January 2021-March 2023). Ninety-eight compounds derived from Aspergillus species were described. The chemical diversity and antimicrobial activities of these metabolites will provide a large number of promising lead compounds for the development of antimicrobial agents.

Chemotherapy followed by donor lymphocyte infusion (DLI) is a promising treatment for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the best strategy for administering this therapy is still unclear. This study sought to explore the efficacy and safety of chidamide and CAG (cytarabine, aclarubicin, and granulocyte colony-stimulating factor) (CCAG) regimen followed by DLI in relapsed AML/MDS after allo-HSCT. This was a single-arm, phase II trial in patients with relapsed AML/MDS after allo-HSCT. CCAG regimen followed by DLI was given according to the inclusion and exclusion criteria. Twenty adult patients were enrolled. The median follow-up time was 12 months. The complete remission (CR) rate was 45% and the partial remission (PR) rate was 5%. The 1-year overall survival (OS) was 56.7% (95% confidence interval (95% CI), 31.6-75.6%), and the median OS was 19 months. The 1-year relapse-free survival (RFS) was 83.3% (95% CI, 27.3-97.5%). Patients relapsing more than 6 months after HSCT and achieving CR/PR after CCAG plus DLI regimen attained significantly higher survival rates. The cumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD) was 9.4%. There was no treatment-related mortality (TRM). These data suggest that CCAG plus DLI regimen is safe and induces durable remission and superior survival in patients with relapsed AML/MDS after allo-HSCT. Trial registration number: ChiCTR.org identifier: ChiCTR1800017740 and date of registration: August 12, 2018., (© 2023. The Author(s).)

Fuzhuan brick tea (FBT), a type of black tea, is a traditional beverage in China, especially popular among frontier ethnic groups. FBT is well-known for its health benefits, such as hypoglycemic, anti-hypertensive, anti-inflammatory, diuretic, and detoxification effects. Nevertheless, the underlying mechanisms on the molecular level are still elusive and the key compounds responsible for the health benefits are unidentified. Previous studies have mainly focused on functional studies of the water extract. However, FBT is typically cooked with butter or milk. Therefore, we hypothesized that some lipophilic components in FBT, which can be absorbed through the co-consumption of butter or milk, may play an important role in the health benefits. The present study aimed to investigate whether the liposoluble extract of FBT alleviates symptoms related to metabolic diseases and to identify the active compounds involved. By comparing the high-performance liquid chromatography (HPLC) profiles of water, milk and hexane extract, some low polarity peaks were observed in the milk and hexane extracts. Furthermore, the hexane extract treatment alleviated body weight gain, serum total cholesterol and triglyceride levels, and inhibited the accumulation of hepatic fat granules in a high-fat diet (HFD)-induced C57BL/6N mouse model. In order to identify the key functional lipophilic compounds in FBT, the hexane extract of FBT was subjected to chemical characterization. Four phenol analogs were characterized, namely, isodihydroauroglaucin (1), dihydroauroglaucin (2), tetrahydroauroglaucin (3), and flavoglaucin (4). Compounds 1 and 4 reduced the levels of total cholesterol and triglyceride in vivo. Both compounds also inhibited the high-fat diet-induced body weight gain and accumulation of fat granules in the liver of C57BL/6N mice. Isodihydroauroglaucin and flavoglaucin have therefore been identified as bioactive ingredients that contribute to the health benefits of FBT.

Polychlorinated dibenzo-p-dioxins and dibenzofurans and polychlorinated biphenyls were measured in the surface sediments of Liangshui River, the second largest drainage river in Beijing, China. The sum concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans and polychlorinated biphenyls ranged from 3.5 to 3019 (mean value: 184) pg g -1 dry weight and from 319 to 5949 (mean value: 1958) pg g -1 dry weight, and the corresponding World Health Organization toxic equivalent quantity values were 0.0011-5.1 pg TEQ g -1 dry weight and 0.0074-1.4 pg TEQ g -1 dry weight, respectively. The spatial distributions of polychlorinated dibenzo-p-dioxins and dibenzofurans and polychlorinated biphenyls showed increasing trends from urban area and development area to suburb. Principal component analysis revealed that polychlorinated dibenzo-p-dioxins and dibenzofurans contamination in the sediments may originate from pentachlorophenol and sodium pentachlorophenate and municipal solid waste incineration. Regarding polychlorinated biphenyls, the steel industry, combustion processes and usage of some commercial polychlorinated biphenyl products were identified as the major sources. The emission from a former steel plant could be the main contributor to polychlorinated biphenyls in urban areas. The mean value of the total toxic equivalent quantities in the sediment samples exceeded the Canadian interim sediment quality guidelines. Long-term wastewater irrigation increases the load of sediment-bound pollutants in agricultural soil and may pose potential ecological risks to crops and human health.

Microorganism-mediated Mn(Ⅱ) removal has gained increasing attention as a valuble bioremediation approach. In this study, a novel strain Stenotrophomonas sp. MNB17 - obtained from marine sediments - was found to show Mn(Ⅱ) removal efficiencies of 98.51-99.38% within 7 days and 92.24% within 20 days at Mn(Ⅱ) concentrations of 10-40 mM and 50 mM, respectively. On day 7, 80.44% of 50 mM Mn(Ⅱ) was oxidized to Mn(Ⅲ/Ⅳ), whereas only 2.11-2.86% of 10-40 mM Mn(Ⅱ) was oxidized. This difference in the proportion of Mn-oxides suggested that the strain MNB17 could remove soluble Mn(Ⅱ) via distinct mechanisms under different Mn(Ⅱ) concentrations. At 10 mM Mn(Ⅱ), indirect mechanisms were employed by strain MNB17 to remove Mn(Ⅱ). The sufficient energy generated by increased cellular respiration led to enhanced ammonification, and MnCO 3 was the main component of the Mn-precipitates (97.27%). Meanwhile, intracellular fatty acids were degraded and served as an important carbon source for respiration. At 50 mM Mn(Ⅱ), most of the soluble Mn(Ⅱ) was oxidized, and Mn-oxides dominated the Mn-precipitates (80.44%). Mn(Ⅱ) oxidation likely contributed to electrons for energy production, as the down-regulation of respiratory pathways resulted in a deficit of electron supply, which warrants futher study. The exogenous addition of tricarboxylic acid cycle substrates (malate, α-ketoglutarate, oxaloacetate, succinate, and fumarate) was found to accelerate Mn(Ⅱ) removal as MnCO 3 at a concentration of 50 mM. Overall, this study reports a novel strain MNB17 with the biotechnological potential of Mn(Ⅱ) removal and elucidates the function of cellular energy metabolism during the Mn(Ⅱ) removal process. In addition, it demonstrates the potential of aerobic respiration-related substrates in accelerating the removal of high concentrations of Mn(Ⅱ) for the first time., 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 © 2022 Elsevier Ltd. All rights reserved.)

Bacteria possess protective mechanisms against excess Mn(Ⅱ) to reduce its toxicity. Stenotrophomonas sp. MNB17 showed high Mn(Ⅱ) removal capacity (92.24-99.16 %) by forming Mn-precipitates (MnCO 3 and Mn-oxides), whose Mn-oxides content increased with increasing Mn(Ⅱ) concentrations (10-50 mM). Compared with 0 mM Mn(Ⅱ)-stressed cells, transcriptomic analysis identified genes with the same transcriptional trends in 10 mM and 50 mM Mn(Ⅱ)-stressed cells, including genes involved in metal transport, cell envelope homeostasis, and histidine biosynthesis, as well as genes with different transcriptional trends, such as those involved in oxidative stress response, glyoxylate cycle, electron transport, and protein metabolism. The upregulation of histidine biosynthesis and oxidative stress responses were the most prominent features of these metabolisms under Mn(Ⅱ) stress. We confirmed that the increased level of reactive oxygen species was one of the reasons for the increased Mn-oxides formation at high Mn(Ⅱ) concentrations. Metabolite analysis indicated that the enhanced histidine biosynthesis rather than the tricarboxylic acid cycle resulted in an elevated level of α-ketoglutarate, which helped eliminate reactive oxygen species. Consistent with these results, the exogenous addition of histidine significantly reduced the production of reactive oxygen species and Mn-oxides and enhanced the removal of Mn(Ⅱ) as MnCO 3 . This study is the first to correlate histidine biosynthesis, reactive oxygen species, and Mn-oxides formation at high Mn(Ⅱ) concentrations, providing novel insights into the molecular regulatory mechanisms associated with Mn(Ⅱ) removal in bacteria., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Candida albicans is an endogenous opportunistic pathogenic fungus that is harmless when the host system remains stable. However, C . albicans could seriously threaten human life and health when the body's immune function declines or the normal flora is out of balance. Due to the increasing resistance of candidiasis to existing drugs, it is important to find new strategies to help treat this type of systemic fungal disease. Biological control is considered as a promising strategy which is more friendly and safer. In this review, we compare the bacteriostatic behavior of different antagonistic microorganisms (bacteria and fungi) against C. albicans . In addition, natural products with unique structures have attracted researchers' attention. Therefore, the bioactive nature products produced by different microorganisms and their possible inhibitory mechanisms are also reviewed. The application of biological control strategies and the discovery of new compounds with antifungal activity will reduce the resistance of C. albicans , thereby promoting the development of novel diverse antifungal drugs.

Vitamin D (VD) deficiency during pregnancy and early brain development is an important environmental risk factor for autism spectrum disorder (ASD). Its specific mechanism of action is still unclear. However, one study on the correlation between metabolomics and VD levels in children with ASD has found that the whole-blood arginine (Arg) levels of children with ASD are significantly negatively correlated with serum VD levels, suggesting that the effect of VD on ASD may be related to the signaling pathway involving Arg. Arg is a precursor of nitric oxide (NO), and changes in its levels most directly affect NO levels and signal transduction pathways. NO, a biologically active free radical, is both a neurotransmitter and a neuromodulator in the central nervous system and is related to the pathogeneses of various neurological diseases. The NO signaling pathway is not only affected by VD levels but also closely related to ASD through a series of mechanisms, such as neurotransmitter imbalance, immune disorders, and oxidative stress. Therefore, the effect of VD on ASD may be achieved via regulation of the NO signaling pathway. The current review discusses the relationship among VD, NO, and ASD as suggested by a large body of evidence in the literature in an effort to provide clues for researchers on the pathogenesis of ASD and the mechanism of VD's impact on ASD., 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 Wang, Dong, Li, Yue and Xie.)

Purpose: To investigate the epidemiology, causative pathogen antibiotic susceptibility, and mortality risk factors of bloodstream infection (BSI) in patients with hematological malignancies (HMs)., Methods: Single-center retrospective analysis of BSI cases in patients with HMs in a Chinese tertiary hospital from 2012-2019., Results: Among 17,796 analyzed admissions, 508 BSI episodes (2.9%; 95% confidence interval: 2.6%-3.2%) were identified. Of 522 resulting isolates, 326 (62.5%) were Gram-negative, 173 (33.1%) were Gram-positive. The BSI incidence among patients with different HMs (severe aplastic anemia: 6.7%; acute leukemia: 6.2%; myelodysplastic syndrome: 3.2%; multiple myeloma: 1.3%; and lymphoma: 1.0%) differed significantly ( p < 0.001). The BSI incidence was significantly higher in the hematopoietic stem cell transplantation (HSCT) group (10.2%) than in the non-HSCT group (2.5%; p < 0.001). Escherichia coli (30.7%, 160/522) was the most common pathogen, followed by Coagulase-negative staphylococci (19.4%, 101/522) and Klebsiella pneumoniae (10.0%, 52/522) . , The rates of imipenem resistance for E. coli, K. pneumoniae, Pseudomonas aeruginosa , and Acinetobacter baumannii were 6.4%, 15.0%, 27.8%, and 79.0%, respectively. All the Gram-positive pathogens were linezolid susceptible. Three vancomycin-resistant Enterococcus species were isolated. The overall 14-day mortality was 9.8% (95% confidence interval: 7.2%-12.4%). A multivariate analysis showed that HM subtype severe aplastic anemia, A. baumannii , and malignancy non-remission were independent 14-day mortality risk factors., Conclusions: Gram-negative bacteria were the most common pathogens, with E. coli as the predominant strain, causing BSIs in HM patients. A carbapenem-resistant A. baumanni with a high mortality rate in HM patients made empirical antimicrobial choice a highly challenging issue., (© 2022 Published by Elsevier Ltd on behalf of Tsinghua University Press.)

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibrogenic factors Lum, CIV, CXI and Tgfbi participated in the synovial inflammation, fibrosis and hyperplasia in CIA. Based on KOG function class analysis, the proteins involved in the events of the central dogma was explored. They might be hyperplasia related proteins for most of them are related to the proliferation of cancer. ETD significantly attenuated synovial inflammation, fibrosis and hyperplasia in CIA rats by downregulating these proteins. Several proteins have not been observed in RA so far, such as Tmsb4x, Pura, Nfic, Ruvbl1, Snrpd3, U2af2, Srrm2, Srsf7, Elavl1, Hnrnph1, Wars, Yars, Bzw2, Mcts1, Eif4b, Ctsh, Lamp1, Dpp7, Ptges3, Cdc37 and Septin9, they might be potentials targets for RA. Blood biochemistry tests showed the safety of 7 months use of ETD on rats. In conclusion, present study displayed a comprehensive mechanism of synovial hyperplasia in CIA rats, on this basis, the clinical value of ETD in the treatment of RA was well confirmed., (© 2021. The Author(s).)

Melanoma is aggressive and can metastasize in the early stage of tumor. It has been proved that dihydroartemisinin (DHA) positively affects the treatment of tumors and has no apparent toxic and side effects. Our previous research has shown that DHA can suppress the formation of melanoma. However, it remains poorly established how DHA impacts the invasion and metastasis of melanoma. In this study, B16F10 and A375 cell lines and metastatic tumor models will be used to investigate the effects of DHA. The present results demonstrated that DHA inhibited the proliferative capacity in A375 and B16F10 cells. As expected, the migration capacity of A375 and B16F10 cells was also reduced after DHA administration. DHA alleviated the severity and histopathological changes of melanoma in mice. DHA induced expansion of CD8 + CTL in the tumor microenvironment. By contrast, DHA inhibited Treg cells infiltration into the tumor microenvironment. DHA enhanced apoptosis of melanoma by regulating FasL expression and Granzyme B secretion in CD8 + CTLs. Moreover, DHA impacts STAT3-induced EMT and MMP S in tumor tissue. Furthermore, Metabolomics analysis indicated that PGD2 and EPA significantly increased after DHA administration. In conclusion, DHA inhibited the proliferation, migration and metastasis of melanoma in vitro and in vivo . These results have important implications for the potential use of DHA in the treatment of melanoma in humans., 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 Zhang, Jin, Jin, Wei, Sun, Yue, Liu, Li, Li, Ren and Jin.)

Early classification and risk assessment for COVID-19 patients are critical for improving their terminal prognosis, and preventing the patients deteriorate into severe or critical situation. We performed a retrospective study on 222 COVID-19 patients in Wuhan treated between January 23rd and February 28th, 2020. A decision tree algorithm has been established including multiple factor logistic for cluster analyses that were performed to assess the predictive value of presumptive clinical diagnosis and features including characteristic signs and symptoms of COVID-19 patients. Therapeutic efficacy was evaluated by adopting Kaplan-Meier survival curve analysis and cox risk regression. The 222 patients were then clustered into two groups: cluster I (common type) and cluster II (high-risk type). High-risk cases can be judged from their clinical characteristics, including: age > 50 years, chest CT images with multiple ground glass or wetting shadows, etc. Based on the classification analysis and risk factor analysis, a decision tree algorithm and management flow chart were established, which can help well recognize individuals who needs hospitalization and improve the clinical prognosis of the COVID-19 patients. Our risk factor analysis and management process suggestions are useful for improving the overall clinical prognosis and optimize the utilization of public health resources during treatment of COVID-19 patients.

Background: Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients., Methods: The 24-week multicenter, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized in a 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer's Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL, and NPI at 24 weeks after treatment compared with baseline. A subgroup study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements., Results: Comparing with the placebo group (n = 83, change - 1.45), the ADAS-cog12 score change in the GV-971 600-mg group (n = 76) was - 1.39 (p = 0.89) and the GV-971 900-mg group (n = 83) was - 2.58 (p = 0.30). The treatment responders according to CIBIC-Plus assessment were significantly higher in the GV-971 900-mg group than the placebo group (92.77% vs. 79.52%, p < 0.05). The GV-971 900-mg subgroup showed a lower decline of cerebral metabolic rate for glucose than the placebo subgroup at the left precuneus, right posterior cingulate, bilateral hippocampus, and bilateral inferior orbital frontal at uncorrected p = 0.05. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%., Conclusions: GV-971 was safe and well tolerated. GV-971 900 mg was chosen for phase III clinical study., Trial Registration: ClinicalTrials.gov, NCT01453569 . Registered on October 18, 2011.

The implication of different dietary n-3/n-6 polyunsaturated fatty acids (PUFAs) ratios has been investigated in some neurodevelopmental disorders (including autism and depression). However, the mechanisms underlying the effects of different PUFAs ratios on the autism are still poorly understood. In the present study, a valproic acid (VPA) rat model of autism was used to study the effects of diet with different n-3/n-6 PUFA ratios on the autism, and the underlying mechanisms explored. Our results showed that rats with prenatal administration of VPA took less response time to sniff three odorants in the olfactory habituation/dishabituation tests, had lower frequency of pinning and following patterns, and had decreased hippocampal 5-hydroxytryptamine (5-HT), increased serum 5-HT and downregulated expression of tight junction protein (occludin and claudin-1) in the colon. However, supplementation of n-3/n-6 PUFAs (1:5) in the VPA treated rats ameliorated the autistic behaviors, increased hippocampal 5-HT and tight junction expression in the colon, and decreased serum 5-HT. In conclusion, dietary supplementation of n-3/n-6 PUFAs (1:5) significantly improves VPA-induced autism-like behaviors in rats, which may be, at least partially, related to the increased hippocampal 5-HT. Furthermore, this diet can increase the expression of tight junction proteins to improve intestinal barrier impairment., (Copyright © 2020 Wang, Zheng, Zhou, Xing, Li, Li, Zhang, Zhang and Li.)

Background: It has been shown that dihydroartemisinin (DHA) is effective in the treatment of malaria. Recently studies have demonstrated that DHA also regulates tumor cell growth, angiogenesis, T cell differentiation and generation. However, how DHA affects melanoma development remains poorly defined., Objectives: To investigate the effects of DHA on the proliferation and migration of melanoma in vivo and in vitro, and to explore its possible mechanism., Methods: B16F10 cells and melanoma-bearing BALB/c mice were used to investigate the effects of DHA on melanoma., Results: DHA had inhibitory effect on melanoma proliferation in a time-and dose-dependent manner. Treatment of DHA attenuated melanoma severity and histopathological changes in BALB/c mice. DHA also inhibited melanoma invasion, migration, and community formation in a dose-dependent manner. Flow cytometry revealed a significant increase in IFN-γ + CD8 + T cells in the DHA groups. In tumor microenvironment and spleen, DHA induced expansion of CD8 + CTL, while, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and IL-10 + CD4 + CD25 + T cells were normalized by DHA treatment. DHA diminished expression of IL-10 and IL-6, and increased the expression of IFN-γ in the tumor and spleen. Moreover, DHA administration significantly promoted the mitochondrial apoptosis of melanoma by regulating the STAT3 pathway., Conclusion: DHA induces mitochondrial apoptosis and alters cytokines expression by inhibiting the phosphorylation of STAT3. DHA improves anti-tumor immunity in mice through controlling CD8 + CTL function by counteracting IL-10-dependent Treg cells suppression, which promises to be an alternative drug for melanoma., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study, organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in needle leaves with different ages were measured in three prevalent coniferous forests including spruce, fir and pinus in southeast Tibetan Plateau (TP) to investigate accumulation behavior of persistent organic pollutants (POPs) during entire growth cycle of needles. The accumulation concentration of POPs was higher in pinus and fir needles than in spruce needles. Concentrations for most of OCPs significantly increased with needle ages, especially dichlorodiphenyltrichloroethane (DDT) and its metabolites showed more remarkable increasing trend than hexachlorocyclohexane isomers (HCHs) and hexachlorobenzene (HCB) in the three tree species. However, age dependence accumulation of PAHs was not observed in most cases, possibly due to its easier degradation property and the influence by dramatic change of ambient atmospheric concentration of PAHs. The lipid normalized concentrations in needles exhibited similar accumulation pattern with that of dry weight basis. The controlling factors for concentration variation in needles were identified using multiple linear regression. The suitability of these needle species acting as potential passive sampler for atmospheric POPs was evaluated. The different-age needles could reflect atmospheric OCP concentrations in the past long-term trend. Findings of this study provide guidance in use of needle as passive samples for the background monitoring of the atmospheric contamination at remote and poorly accessible locations such as the TP., Competing Interests: Declaration of competing interest The manuscript has not been published previously and it is not under consideration for publication elsewhere. The submission is approved by all authors, and that, if accepted, it will not be published elsewhere, in English or in any other language, including electronically without the written consent of the copyright-holder., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, we aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 was used to screen the serums of 238 admitted hospital patients between February 6 and February 14, 2020 with confirmed or suspected SARS-CoV-2. SARS-CoV-2 RNA was detected on pharyngeal swab specimens using real time RT-PCR. 194 (81.5%) of the serums were detected to be antibody (IgM and/or IgG) positive, significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibodies between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85), whose nucleic acid tests were negative. The antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped from below 50% to over 80%. However, the positive rates of viral RNA maintained above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. Overall, the suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is key for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After the 11th day post-disease onset, the diagnosis for viral infection should be majorly dependent on serological assay., Competing Interests: Declaration of Competing Interest The authors declare that no conflict of interest exists., (Copyright © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complicated interactions between genetic and environmental factors. Clinical trials, including case reports, case-control studies, and a double-blinded randomized clinical study, have suggested that high-dose vitamin D3 regimens may ameliorate the core symptoms of ASD. Vitamin D3 supplementation was effective in about three-quarters of children with ASD. To further investigate the relationship between vitamin D and ASD symptoms in vitamin D-responsive autistic children, changes in symptoms were assessed in three children with ASD who were given vitamin D3 supplementation followed by a long interruption. The core symptoms of ASD were remarkably improved during the vitamin D3 supplementation period when serum 25-hydroxyvitamin D [25(OH)]D levels reached over 40.0 ng/mL. However, symptoms reappeared after the supplementation was stopped, when serum 25(OH)D levels fell below 30.0 ng/mL but were again improved with re-administration of vitamin D3 after the interruption, when serum 25(OH)D levels exceeded 40.0 ng/mL. Overall, these results showed that the core symptoms of ASD fluctuated in severity with changes in serum 25(OH)D levels in children, indicating that maintaining a responsive 25(OH)D level is important for treating ASD. Maintaining a serum 25(OH)D level between 40.0 and 100.0 ng/ml may be optimal for producing therapeutic effects in vitamin D-responsive individuals with ASD.

We describe the design, fabrication, and use of a ceramic bulk preparation system, applied to the very high-throughput batching and molding for solid ceramic powders. Through the principle on precise volume controlling of powder materials, up to 100 ceramic block samples with maximum 6 components could be prepared in one time through 100 channels with Φ5 × 5 mm forming molds. The automatic control stage has been built to fill the target powder in a limited size and discrete small volume range. Here, we have designed a mechanical structure and software program so that rotary silo powder feeding amount could be controlled at 5-100 ml/time and the feeding precision can reach 0.005 g. Finally, the equipment is verified by preparing several infrared ceramic samples of different components.

Gliocladiosin A (1) and B (2), two dipeptides conjugated with macrolides, were identified from a verM disruption mutant of the Cordycep-colonizing fungus Clonostachys rogersoniana. The structures and absolute configurations of 1 and 2 were determined on the basis of spectroscopic data analysis, including MS, NMR, CD and X-ray diffraction. A biogenetic pathway for 1 and 2 was proposed. These two compounds showed moderate antibacterial effects.

Rationale: West syndrome (WS) is an age-dependent epileptic encephalopathy that is characterized by intractable epileptic seizures, hypsarrhythmia, and observed through electroencephalogram (EEG) and significant neurodevelopmental regression. The spontaneous remission of epileptic seizure is clinically rare and has not previously been reported in a Chinese infant. Herein, we reported a Chinese infant with WS whose seizures disappeared following a human herpesvirus 7 (HHV-7) infection., Patient Concerns: The male Chinese infant was born at the gestational age of 36 weeks with a birth weight of 1.65 kg and an Apgar score of 7 at the first minute. At the age of 6 months, the infant developed seizures that manifested as flexor spasms with trunk involvement and mental regression., Diagnosis: Brain magnetic resonance imaging revealed leukomalacia of the posterior horn and a reduction in the size of the periventricular of the bilateral ventricle and the corpus callosum. An EEG revealed hypsarrhythmia and typical spasm seizures. Therefore, the infant was diagnosed with symptomatic WS., Interventions: The infant was treated with adequate vitamin B6 intravenous drip and oral treatment with topiramate and levetiracetam., Outcomes: The observed seizures disappeared spontaneously 40 days after onset, without any changes in the anti-epileptic drug treatment, following a febrile rash due to a HHV-7 infection., Lessons: Spontaneous remission of epileptic seizures can occur following viral infection of HHV-7 in children with WS. The mechanism behind this spontaneous remission warrants further research.

Purpose: The chemotherapeutic regimen DCAG (decitabine with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor) is effective for elderly patients with acute myeloid leukemia, but recommendations for young patients remain controversial. This study investigated the tolerance and efficacy of DCAG for patients with newly diagnosed acute myeloid leukemia (aged 14-60 years). The clinical features or molecular markers that may predict response to DCAG were identified. Patients and methods: One-hundred sixty-one consecutive patients with newly diagnosed acute myelogenous leukemia received DCAG or standard (idarubicin plus cytarabine, IA) induction chemotherapy (n=64 and 97, respectively). Results: The rates of complete remission after the first cycle, overall survival (OS), and event-free survival (EFS) were comparable. After the second cycle, the complete remission rate of the DCAG group (54.7%) was significantly lower than that of the reference (78.35%, P =0.005). The following were associated with significantly worse OS, and EFS, in the DCAG group: Eastern Cooperative Oncology Group (ECOG) score ≥3 and no response after the second induction therapy; and FLT3-ITD. The multivariate analysis showed the DCAG group with significantly shorter OS associated with ECOG ≥3 and FLT3-ITD. In the DCAG group, after the first cycle of induction chemotherapy the median recovery times of neutrophils and platelets were 15.8 and 13 days. Conclusion: The DCAG and IA groups were similar with regard to complete remission rate after the first cycle, OS, and EFS. The complete remission rate after the second cycle of the DCAG was significantly lower than that of the IA. Grade 4 neutropenia and thrombocytopenia were a major adverse event associated with DCAG., Competing Interests: The authors report no conflicts of interest in this work.

There was limited information about the efficacy of myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in non-complete remission (non-CR) patients with relapsed/refractory peripheral T cell lymphomas (PTCLs). We conducted a retrospective study of 21 consecutive non-CR patients with relapsed/refractory PTCLs who received myeloablative allo-PBSCT between January 2008 and June 2016. The median follow-up of survivors was 46.5 months (range, 14-105 months). The estimated 3-year relapse rate was 24% (95% CI, 9 to 43%). The 3-year non-relapsed mortality rate was 24% (95% CI, 9 to 44%). Overall, the estimated 3-year overall survival was 47% (95% CI, 25 to 66%). And the estimated 3-year progression-free survival was 46% (95% CI, 24 to 66%). Specifically, eight patients failed to achieve a CR at the first evaluation 3 months after allo-PBSCT and received withdraw of immunosuppression. Five patients also received donor lymphocytes infusions. Five (5/8, 62.5%) patients responded subsequently to these interventions (complete = 4, partial = 1). Overall, ten patients were alive at our last follow-ups, and durable CR were achieved in nine patients without further therapy. Five (50%) of these ten alive patients experienced chronic graft-versus-host disease (GVHD). Our favorable clinical outcomes suggested myeloablative allo-PBSCT was a valid therapeutic option for non-CR patients with relapsed/refractory PTCLs. The sustained CR after immunotherapeutic intervention and high prevalence of chronic GVHD in alive patients provided evidence of graft versus T cell lymphoma effects.

To determine whether the traditional Chinese medicine Tongxinluo (TXL) is efficacious at retarding the progression of carotid atherosclerotic lesions, a total of 1,212 patients with a focal intima-media thickness (IMT) of ≥1.2 mm of the carotid arteries received TXL or placebo capsules in addition to current routine therapy. The primary outcome was between-group differences in annualized change in mean IMT of 12 sites of bilateral carotid arteries over 24 months. The secondary outcomes were between-group differences in plaque area, vascular remodeling index (RI), serum levels of lipids and high-sensitivity C-reactive protein, and a composite of first major cardiovascular events. The results showed that the annualized change in mean IMT in the TXL and placebo groups was -0.00095 (95% CI, -0.00330 to 0.00141) mm and 0.01312 (95% CI, 0.01076 to 0.01548) mm, respectively, with a difference between the two groups of -0.01407 (95% CI, -0.01740 to -0.01073) mm (P < 0.001). Compared with placebo, TXL treatment significantly reduced the change from baseline in the plaque area and RI, as well as the first major cardiovascular events. In conclusion, TXL retarded the progression of mean IMT, plaque area and vascular remodeling of the carotid artery with a good safety profile.

Suitable conditions for thermal extraction of semi-volatile organic compounds have largely been arrived at by univariate optimization or based on the recommendations provided by the manufacturers of the extraction equipment. Herein, we demonstrated the multivariate optimization of Tenax TA-thermal extraction for determining organophosphate esters in the gas phase fraction of air samples. Screening and refining experiments were performed using the eighth fraction factorial and Box-Behnken designs, respectively, and satisfactory models were obtained. Subsequently, the process was optimized by Derringer's desirability function and the global desirability was 0.7299. Following optimization, the analytes were desorbed at 290 °C for 10 minutes at a helium flow of 95 mL min -1 , with the transfer line set at 290 °C. The analytes were then cryofocused at 20 °C and then cryodesorbed into the chromatographic column at 295 °C for 6 minutes. Method validation exhibited high linearity coefficients (>0.99), good precision (CV < 14%) and low detection limits (0.1-0.5 ng m -3 ). The method was tested by pumping 0.024 m 3 of real indoor environment air through Tenax TA sorbent tubes. Furthermore, with multivariate optimization, analysis time and other resources were significantly reduced, and information about experimental factor interaction effects was investigated, as compared to the univariate optimization and other traditional methods.

Background: Autophagy is used for degradation of cellular components and nutrient recycling. Atg8 is one of the core proteins in autophagy and used as a marker for autophagic detection. However, the autophagy of filamentous fungi is poorly understood compared with that of Saccharomyces cerevisiae. Our previous study revealed that disruption of the autophagy related gene Acatg1 significantly enhanced cephalosporin C yield through reducing degradation of cephalosporin biosynthetic proteins in Acremonium chrysogenum, suggesting that modulation of autophagic process is one promising way to increase antibiotic production in A. chrysogenum., Results: In this study, a S. cerevisiae ATG8 homologue gene Acatg8 was identified from A. chrysogenum. Acatg8 could complement the ATG8 mutation in S. cerevisiae, indicating that Acatg8 is a functional homologue of ATG8. Microscope observation demonstrated the fluorescently labeled AcAtg8 was localized in the cytoplasm and autophagosome of A. chrysogenum, and the expression of Acatg8 was induced by nutrient starvation. Gene disruption and genetic complementation revealed that Acatg8 is essential for autophagosome formation. Disruption of Acatg8 significantly reduced fungal conidiation and delayed conidial germination. Localization of GFP-AcAtg8 implied that autophagy is involved in the early phase of conidial germination. Similar to Acatg1, disruption of Acatg8 remarkably enhanced cephalosporin C yield. The cephalosporin C biosynthetic enzymes (isopenicillin N synthase PcbC and isopenicillin N epimerase CefD2) and peroxisomes were accumulated in the Acatg8 disruption mutant (∆Acatg8), which might be the main reasons for the enhancement of cephalosporin C production. However, the biomass of ΔAcatg8 decreased drastically at the late stage of fermentation, suggesting that autophagy is critical for A. chrysogenum cell survival under nutrition deprived condition. Disruption of Acatg8 also resulted in accumulation of mitochondria, which might produce more reactive oxygen species (ROS) which promotes fungal death. However, the premature death is unfavorable for cephalosporin C production. To solve this problem, a plasmid containing Acatg8 under control of the xylose/xylan-inducible promoter was introduced into ∆Acatg8. Conidiation and growth of the recombinant strain restored to the wild-type level in the medium supplemented with xylose, while the cephalosporin C production maintained at a high level even prolonged fermentation., Conclusions: Our results demonstrated inducible expression of Acatg8 and disruption of Acatg8 remarkably increased cephalosporin C production. This study provides a promising approach for yield improvement of cephalosporin C in A. chrysogenum.

Acremonium chrysogenum is the industrial producer of cephalosporin C (CPC). We isolated a mutant (AC554) from a T-DNA inserted mutant library of A. chrysogenum. AC554 exhibited a reduced conidiation and lack of CPC production. In consistent with it, the transcription of cephalosporin biosynthetic genes pcbC and cefEF was significantly decreased in AC554. Thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR) was performed and sequence analysis indicated that a T-DNA was inserted upstream of an open reading frame (ORF) which was designated AcmybA. On the basis of sequence analysis, AcmybA encodes a Myb domain containing transcriptional factor. Observation of red fluorescent protein (RFP) tagged AcMybA showed that AcMybA is naturally located in the nucleus of A. chrysogenum. Transcriptional analysis demonstrated that the AcmybA transcription was increased in AC554. In contrast, the AcmybA deleted mutant (ΔAcmybA) overproduced conidia and CPC. To screen the targets of AcmybA, we sequenced and compared the transcriptome of ΔAcmybA, AC554 and the wild-type strain at different developmental stages. Twelve differentially expressed regulatory genes were identified. Taken together, our results indicate that AcMybA negatively regulates conidiation and CPC production in A. chrysogenum., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND There is currently little information on haploidentical hematopoietic cell transplantation (haplo-HCT) for T-lymphoblastic lymphoma (T-LBL). Data about peripheral blood stem cells (PBSC) as a reliable graft source for T-LBL treatment are lacking. MATERIAL AND METHODS T-LBL patients who underwent T cell-replete haploidentical peripheral blood hematopoietic cell transplantation (haplo-PBHCT) from July 2007 to January 2017 were retrospectively evaluated. RESULTS A total of 25 patients (age ≥15 years) with median age of 24 (range 15-51) years were enrolled. The median number of CD34+ cells infused was 5.0 (1.6-14.4) 106/kg. Sustained myeloid engraftment with full donor chimerism was achieved in all patients. The cumulative incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 24%. Two-year extensive chronic GVHD cumulative incidence was 20%. The 3-year overall survival rate for all patients was 70%. The median survival time of the complete remission (CR) group was better than that of the non-CR group (not reached vs. 9 m) (P<0.01). The relapse rate was 17% for patients who obtained CR and were given haplo-HCT as consolidation treatment. CONCLUSIONS This study indicates that haplo-PBHCT is a safe and effective method for the treatment of T-LBL.

Background: Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients with haematological malignancies., Aim: To evaluate the efficacy and rationality of primary antifungal prophylaxis (PAP) in a 5-year real-life setting and choose an appropriate PAP strategy., Methods: Clinical data of patients were retrospectively reviewed and IFD was diagnosed using the revised diagnostic criteria. The efficacy of PAP and the risk factors for IFD, especially the rationality of PAP, were evaluated., Results: Of the 1340 patients enrolled, 749 patients received PAP (55.9%), and IFD occurred in 157 patients: 51 (6.8%) in the PAP group and 106 (17.9%) in the non-PAP group (P = 0.000). The IFD-related mortality was 10.1 and 29.7% in the PAP group and non-PAP group (P = 0.000) respectively. PAP was an independent protective factor for IFD (odds ratio = 0.183, 95% confidence interval: 0.122-0.274, P = 0.000) and could reduce the effect of risk factors, such as allogeneic haemopoietic stem cell transplantation, prolonged neutropenia and corticosteroid. The IFD incidence was not significantly different among different PAP regimens and PAP start time subgroups, and it was lowest (4.2%) when PAP started after a short period of neutropenia (1-10 days)., Conclusion: PAP is necessary and efficient to prevent IFD in haematological patients, and the real-life PAP strategy is reasonable. Different drugs can be chosen, and it is better to start PAP as soon as neutropenia begins., (© 2017 Royal Australasian College of Physicians.)

Autism spectrum disorder (ASD) is a group of dysfunctions in social interaction, communication, and behaviors. Studies have demonstrated that vitamin D deficiency during pregnancy and in individuals increased the risk of ASD. A genetic polymorphism study has pinpointed that genotype AA/A-allele of GC rs4588 in children is associated with ASD, which encodes the vitamin D binding protein. Translating the mentioned points into clinical practice, several clinical trials have demonstrated that vitamin D supplementation can improve the core symptoms in children with ASD. One paper also showed that possible prophylactic effect for the reoccurrence of ASD by vitamin D supplement during pregnancy and early childhood. Herein, this review aims to address the recent advances in this field and to clarify the possible role of vitamin D in ASD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced in ASD and correlate with the severity of disease. Also, we hypothesized that vitamin D3 treatment may be beneficial for a considerable portion of children with ASD., Methods: In total, 215 children with ASD and 285 healthy control children were recruited in our study. Thirty seven of 215 ASD children received vitamin D3 treatment. The Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to assess autism symptoms. High-performance liquid chromatography was used to assess the serum 25-hydroxyvitamin D [25(OH) D] level. Evaluations of ABC, CARS, and serum 25(OH) D levels were performed before and after 3 months of treatment., Results: Serum levels of 25(OH) D were significantly lower in ASD children than typically developing children. Levels of serum 25(OH) D were negatively correlated with ABC total scores and language subscale scores. After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD., Conclusion: Vitamin D deficiency might contribute to the aetiology of ASD. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children (identifier ChiCTR-CCC-13004498)., Clinical Trial Registration: The trial 'Association of Polymorphisms of Vitamin D Metabolism-Related Genes With Autism and the Treatment of Autism with Vitamin D' has been registered at www.chictr.org/cn/proj/show.aspx? proj=6135 (identifier ChiCTR-CCC-13004498).

Trophic transfer of hexabromocyclododecane (HBCD) was investigated in both the terrestrial and aquatic food webs from an e-waste dismantling region in East China. The mean Σ 3 HBCD concentrations in the terrestrial species varied from 0.91 (0.16-1.85) ng g -1 lipid weight (lw) in dragonflies (Pantala flavescens) to 40.3 (22.1-51.1) ng g -1 lw in rats (Rattus norvegicus). The isomeric profile indicated that α-HBCD presented a decreasing trend along the trophic level (TL) (from 97.2% to 16.3% of Σ 3 HBCDs), while γ-HBCD showed a reverse trend (from 2.8% to 73.6% of Σ 3 HBCDs). The trophic magnification factor (TMF) derived from the slope of the regression line between TLs and ln-transferred Σ 3 HBCDs was 0.10, suggesting a trophic dilution of HBCD in the terrestrial food web. By contrast, in the aquatic species, Σ 3 HBCD concentrations varied from 5.02 (3.5-6.55) ng g -1 lw in apple snails (Ampullaria gigas spix) to 45.9 (14.9-67.8) ng g -1 lw in grass carps (Ctenopharyngodon idellus). α-HBCD was the dominant isomer, followed by γ-HBCD in the majority of species. A positive linear relationship was observed in the plots of ln Σ 3 HBCDs versus TLs (R 2 = 0.81, p = 0.06). The TMF for Σ 3 HBCDs was 6.36, indicating a trophic magnification of HBCD in the aquatic food web. Although these results demonstrated the distinct trophic transfer of Σ 3 HBCDs in different ecosystems, further research is needed to eliminate the uncertainty of the tendencies, due to the non-significant relationship and limited species.

Objective: In this study, to investigate clinical characteristics, response, outcome, and prognosis of peripheral blood stem cell transplantation (PBSCT) for patients with peripheral T-cell lymphoma (PTCL)., Methods: This study retrospectively analyzed the efficacy of PBSCT in 38 patients with PTCL. Kaplan-Meier methods were used in survival analysis, and the Cox regression model was applied in multivariate analysis. There were ten clinical parameters were analyzed., Results: The 2-year overall survival (OS) was 46%, and the 5-year OS was 34% after a median follow-up of 40 months. The patients who received allogeneic PBSCT (allo-PBSCT) had a higher nonrelapse mortality than autologous PBSCT (auto-PBSCT), but they could achieve a longer-term disease-free survival in the former, which OS could achieve 40%. Survival analysis with Kaplan-Meier method showed the pretransplant disease status, B symptoms, serum lactate dehydrogenase (LDH) in early (>275 U/L), Eastern Cooperative Oncology Group (ECOG) score (>1), prognostic index for PTCL score (>2) were all prognostic factors for posttransplant OS. Pretransplant disease status is the only prognostic factor for allo-PBSCT., Conclusion: The key was to reducing transplant-related mortality of allo-PBSCT by reduced-intensity conditioning. Factors such as level of early serum LDH, extranodal involvement, B symptoms, ECOG score, Ann Arbor stage, and pretransplant disease status were all related to the prognosis of patients treated with PBSCT. Allo-PBSCT maybe suggested as the first line therapy for late-stage PTCL patients who could reach treatment remission before transplantation.

Intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML cases, is highly heterogeneous. Although several mutations have been identified, the heterogeneity of AML is uncertain because novel mutations have yet to be discovered. Here we applied next generation sequencing (NGS) platform to screen mutational hotspots in 410 genes relevant to hematological malignancy. IR-AML samples (N=95) were sequenced by Illumina Hiseq and mutations in 101 genes were identified. Only seven genes (CEBPA, NPM1, DNMT3A, FLT3-ITD, NRAS, IDH2 and WT1) were mutated in more than 10% of patients. Genetic interaction analysis identified several cooperative and exclusive patterns of overlapping mutations. Mutational analysis indicated some correlation between genotype and phenotype. FLT3-ITD mutations were identified as independent factors of poor prognosis, while CEBPA mutations were independent favorable factors. Co-occurrence of FLT3-ITD, NPM1 and DNMT3A mutations was identified with associated with specific clinical AML features and poor outcomes. Furthermore, by integrating multiple mutations in the survival analysis, 95 IR-AML patients could be stratified into three distinct risk groups allowing reductions in IR-AML by one-third. Our study offers deep insights into the molecular pathogenesis and biology of AML and indicated that the prognosis of IR-AML could be further stratified by different mutation combinations which may direct future treatment intervention., Competing Interests: The authors declare no competing financial interests.

Aim of Study: Novel biomarkers for improving accuracy could be beneficial for disease monitoring and surveillance of Non-Hodgkin's lymphomas (NHL). So we explored the viability of analytical methods for identifying the rearranged immunoglobulin (Ig) H genes sequence., Materials and Methods: Next-generation sequencing (NGS) was used to sequence deoxyribonucleic acid (DNA) extracted directly from the tumor tissues of patients with NHL, and then specific rearranged DNA fragments from plasma was detected by polymerase chain reaction (PCR)., Results: By parallel DNA capturing and sequencing of IgH genomic regions (IgCap), the sequence of rearranged IgH loci could be detected and precisely determined in tumor tissues of 12 patients with NHL. The circulating rearranged DNA fragments had been identified in the plasma of one patient., Conclusion: IgCap may be the favorable diagnostic method for patients with NHL in clinical.

The comparative efficacy and safety of antithymocyte globulin (ATG) at fixed doses in patients undergoing allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. In this study, the records of 56 patients and 54 patients who received pre-transplant ATG-Thymoglobulin (ATG-T) at a total dose of 10 mg/kg and ATG- Fresenius (ATG-F) at a total dose of 20 mg/kg, respectively, were retrospectively analyzed. ATG-F patients had a significantly lower probability of developing chronic graft-vs-host disease (cGVHD) than those treated with ATG-T (p = 0.04). ATG-F was associated with a non-significant trend towards lower relapse rates and higher survival at 3- and 5-years of follow-up compared with ATG-T. A significantly greater proportion of ATG-T patients experienced chills and high fever than ATG-F patients (p < 0.01). The current findings suggest that ATG-F may more effectively and safely prevent cGVHD without increasing relapse rates in patients undergoing UR-PBSCT.