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In the context of global sustainable development, using natural fibers as reinforcement for composites have become increasingly attractive due to their lightweight, abundant availability, renewability, and comparable specific properties to conventional fibers. This paper investigates the tensile properties of a sycamore bark fiber-reinforced composite. The tensile tests using digital image correlation showed that, by adding 18% by volume of sycamore bark for the polyester matrix, the tensile modulus achieves 4788.4 ± 940.1 MPa. Moreover, the tensile strength of the polyester resin increased by approximately 90% when reinforced with sycamore bark fiber, achieving a tensile strength of 64.5 ± 13.4 MPa. These mechanical properties are determined by the way loads are transferred between the polyester matrix and fibers and by the strength of the bond between the fiber-matrix interfaces. Since it is difficult and time consuming to characterize the mechanical properties of natural fibers, an alternative approach was proposed in this study. The method consists of the identification of the fiber elastic modulus using a finite element analysis approach, based on tensile tests conducted on the sycamore bark fiber-reinforced composites. The model correctly describes the overall composite behavior, a good agreement is found between the experimental, and the finite element predicted stress–strain curves. The identified sycamore bark fiber elastic modulus is 17,763 ± 6051 MPa. These results show that sycamore bark fibers can be used as reinforcements to produce composite materials.

Numerous neurological disorders share a fatal pathologic process known as glutamate excitotoxicity. Among which, ischemic stroke is the major cause of mortality and disability worldwide. For a long time, the main idea of developing anti-excitotoxic neuroprotective agents was to block glutamate receptors. Despite this, there has been little successful clinical translation to date. After decades of "neuron-centered" views, a growing number of studies have recently revealed the importance of non-neuronal cells. Glial cells, cerebral microvascular endothelial cells, blood cells, and so forth are extensively engaged in glutamate synthesis, release, reuptake, and metabolism. They also express functional glutamate receptors and can listen and respond for fast synaptic transmission. This broadens the thoughts of developing excitotoxicity antagonists. In this review, the critical contribution of non-neuronal cells in glutamate excitotoxicity during ischemic stroke will be emphasized in detail, and the latest research progress as well as corresponding therapeutic strategies will be updated at length, aiming to reconceptualize glutamate excitotoxicity in a non-neuronal perspective., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis. Upon admission, gastroscopy revealed esophageal and gastric varices. Abdominal CT scan, MRI, and color Doppler ultrasound suggested cirrhosis, intrahepatic bile duct dilation, and bilateral kidney enlargement. Genetic testing identified compound heterozygous mutations in the PKHD1 gene: c.2264C>T (p.Pro755Leu) and c.1886T>C (p.Val629Ala). The c.2264C>T (p.Pro755Leu) mutation is a known pathogenic variant with previous reports, while c.1886T>C (p.Val629Ala) is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2. The child was diagnosed with autosomal recessive polycystic kidney disease. In children presenting with gastrointestinal bleeding without obvious causes, particularly those with liver or kidney disease, consideration should be given to the possibility of autosomal recessive polycystic kidney disease, and genetic testing should be conducted for definitive diagnosis when necessary.

It has been shown that prostaglandin (PG) E 2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE 2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE 2 in male rats. The core temperature (T core ) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE 2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE 2 . We demonstrated that EP3 receptor was a pivotal receptor for PGE 2 -induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE 2 , respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE 2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE 2 ; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (I A ) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE 2 ; however, the I A current density was significantly increased by PGE 2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE 2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE 2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of I A currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

RNA modifications play crucial roles in regulating gene expression and cellular homeostasis. Modulating RNA modifications, particularly by targeting the enzymes responsible for their catalysis, has emerged as a promising therapeutic strategy. However, limitations, such as the lack of identified modifying enzymes and compensatory mechanisms, hinder targeted interventions. Chemical approaches independent of enzymatic activity offer an alternative strategy for RNA modification modulation. Here, we present the identification of 2-chloro-3,5-dinitrobenzoic acid as a highly effective photochemical deprenylase of i 6 A RNA. This method demonstrates exceptional selectivity towards i 6 A, converting its substituent into a "N-doped" ozonide, which upon hydrolysis releases natural adenine. We believe that this chemical approach will pave the way for a better understanding of RNA modification biology and the development of novel therapeutic modalities., (© 2024 Wiley-VCH GmbH.)

N6-methyladenosine (m6A) is the most abundant mRNA modification within mammalian cells, holding pivotal significance in the regulation of mRNA stability, translation and splicing. Furthermore, it plays a critical role in the regulation of RNA degradation by primarily recruiting the YTHDF2 reader protein. However, the selective regulation of mRNA decay of the m6A-methylated mRNA through YTHDF2 binding is poorly understood. To improve our understanding, we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated degradation of m6A-methylated mRNAs. We meticulously assembled a high-quality training dataset by integrating multiple data sources for the HeLa cell line. To overcome the limitation of small training samples, we employed a pre-training-fine-tuning strategy by first performing a self-supervised pre-training of the model on 427 760 unlabeled m6A site sequences. The test results demonstrated the importance of this pre-training strategy in enabling m6A-BERT-Deg to outperform other benchmark models. We further conducted a comprehensive model interpretation and revealed a surprising finding that the presence of co-factors in proximity to m6A sites may disrupt YTHDF2-mediated mRNA degradation, subsequently enhancing mRNA stability. We also extended our analyses to the HEK293 cell line, shedding light on the context-dependent YTHDF2-mediated mRNA degradation., (© The Author(s) 2024. Published by Oxford University Press.)

A very mild and efficient procedure has been developed for the preparation of N -methylated uridine, pseudouridine, guanosine and inosine derivatives. This process was compatible with free hydroxyls within the ribose and did not require precautions on the protection or deprotection of other functionalities. The key to this extremely mild methylation without protection relied on the in situ generated methyl oxonium from the Wittig reagent and methanol. A putative mechanism for the selective methylation was also proposed.

Soil (n = 100) and roadside dust (n = 97) samples across a new first-tier megacity (Hangzhou, East China) were collected to systematically survey the spatial patterns and sources of 16 priority Polycyclic aromatic hydrocarbons (PAHs). The total PAH (Σ 16 PAH) concentrations in the surface soils exhibited an average of 329 ± 168 ng/g with a range of 67.7-2950 ng/g. 45 % of soils suffered from the weak - heavy PAH contaminations. By contrast, the average concentration of Σ 16 PAHs in roadside dusts was approximately three times higher than that found in the soils. Within both soil and dust samples, PAHs with a high molecular weight (HMW, 4-6 rings) were the dominant homologs. Spatial lag models revealed that industrial and traffic-related variables significantly influenced the spatial distribution of PAHs in dusts. Furthermore, a positive matrix factorization model indicated that Σ 16 PAHs in soils and dusts mainly derived from coal-related production/combustion and automobile exhaust emission (65.0 % and 77.9 %, respectively). The isotopic composition analysis conducted on heavily polluted samples further demonstrated that HMW PAHs in these soils and dusts predominantly originated from coal processing and liquid fossil fuel combustion. Overall, the findings of this study suggest that the intensive urban construction and human activities strongly stimulated PAH accumulations in soils and dusts during the rapid urbanization of Hangzhou., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Nightmare Disorder Index Questionnaire (NDI) was developed to measure the impact of nightmares. The purpose of this study was to investigate the psychometric properties of NDI among Chinese adolescents. This study investigated the validity and internal consistency of the Nightmare Disorder Index Chinese (NDI-CV) among 6014 Chinese adolescents who completed the NDI-CV, Nightmare Distress Questionnaire-Chinese Version (NDQ-CV), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Chinese Adolescent Daytime Sleepiness Scale (CADSS), Generalized Anxiety Disorder-7 Questionnaire (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). In addition, we investigated the test-retest reliability of the NDI-CV among 423 adolescents who completed a retest of the NDI-CV after a 2-week interval. Finally, NDI-CV demonstrated good psychometric properties in a sample of Chinese adolescents (Cronbach's α coefficient of 0.876), and the 95% confidence interval for the 2-week retest correlation coefficient was 0.675-0.977 (p < 0.001)., (© 2023 John Wiley & Sons Ltd.)

This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.

Objective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA)., Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness., Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h., Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Zhou et al.)

Granulosa cells (GCs) are the ovary's most critical cells since they undergo cell differentiation and hormone synthesis changes closely associated with follicle development. While micro RNA 140-3p (miRNA-140-3p) has an apparent cell signaling role, particularly in cell proliferation, its biological role in chicken ovarian follicle growth and development remains elusive. This study explored miR-140-3p's effects on chicken GC proliferation and steroid hormone synthesis. MiR-140-3p dramatically increased GC proliferation, prevented apoptosis, increased progesterone synthesis, and enhanced gene expression related to steroid hormone synthesis. In addition, the anti-Müllerian hormone (AMH) gene was identified as a direct miR-140-3p target. MiR-140-3p abundance correlated negatively with AMH mRNA and protein levels in GCs. Our findings show that miR-140-3p influences chicken GC proliferation and steroid hormone synthesis by suppressing AMH expression., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration., 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.)

Taihang chickens are a domestic breed distributed throughout Hebei province in the Taihang Mountains of China and are characterized by their high meat and egg quality. However, the relatively limited egg production by this breed constrains their more widespread commercial utilization. The follicle selection process is closely linked to oocyte development and ovulation, making it a key determinant of laying performance and fecundity in hens. To understand the biological basis for such follicle selection and to identify the associated regulatory pathways, we conducted a genome-wide analysis of long noncoding RNAs (lncRNAs) and mRNAs from the pre-hierarchical follicles and hierarchical follicles of Taihang laying hens. We identified 81 lncRNAs and 528 mRNAs that were differentially expressed during follicle selection, and integrated network analyses suggested that these RNAs were associated with the cell cycle, focal adhesion, oocyte meiosis, peroxisome proliferator-activated receptor signaling, and steroid hormone biosynthesis pathways. The identified lncRNAs were also predicted to influence a series of target genes in cis and trans, suggesting that they may be important regulators of ovarian follicular development. Overall, the present analysis of lncRNA and mRNA expression patterns associated with ovarian follicle development offers a new foundation for future studies of reproductive physiology in Taihang chickens, highlighting new opportunities to improve the laying performance of this important domestic breed., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Allergic rhinitis (AR) is an upper airways chronic inflammatory disease mediated by IgE, which affects 10%-20% of the population. The mainstay for allergic rhinitis nowadays include steroids and antihistamines, but their effects are less than ideal. Many patients therefore seek Chinese medicine for treatment and Yupingfeng Powder is one of the most common formulae prescribed. In this study, we aim to investigate the efficacy and safety of Yupingfeng Powder with variation for the treatment of allergic rhinitis. Study design: This is a double-blind, randomized, placebo-controlled trial. A 2-week screening period will be implemented, and then eligible subjects with allergic rhinitis will receive interventions of either "Yupingfeng Powder with variation" granules or placebo granules for 8 weeks, followed by post treatment visits at weeks 12 and 16. The change in the Total Nasal Symptom Score (TNSS) will be used as the primary outcome. Discussion: This trail will evaluate the efficacy and safety of Yupingfeng Powder in treating allergic rhinitis. The study may provide the solid evidence of Yupingfeng Powder with variation can produce better clinical efficacy than the placebo granules. Trial registration: ClinicalTrials.gov, identifier NCT04976023., 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 Cheong, Ho, Chan, Lo, Leung, Hon, Leung, Siu, Song, Zhang, Ching, Chow, Sum, Chia and Lin.)

Background: The central venous-to-arterial carbon dioxide difference (Pcv-aCO 2 ) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO 2 in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO 2 and procalcitonin (PCT) in the early stages of GN bacteria BSI., Methods: Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO 2 and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients., Results: A total of 132 patients with BSI were enrolled. The Pcv-aCO 2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO 2 was 0.823 (95% confidence interval (CI): 0.746-0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745-0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively., Conclusions: Pcv-aCO 2 and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria., Competing Interests: Conflicts of Interest The authors declare that they have no competing interests., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 pandemic is reported to exacerbate existing vulnerabilities of marginalized groups, and the lack of self-care can lead to the spread of the virus across society. Therefore, effective responses to the challenges imposed by the health crisis should consider the health information needs of migrant workers., Objective: We aimed to explore how migrant low-income workers seek health information and how their health-related information needs were met during a health crisis. We also investigated migrant workers' preferred information sources and types of content with the theoretical concept of health literacy to understand the development of health competencies among migrant workers., Methods: We conducted semi-structured interviews with Thai low-income migrant workers. A total of 13 Thai migrant workers participated in the study, among whom five were undocumented. The interviews were audio-taped, transcribed, and analyzed with the thematic analysis approach., Results: Our findings indicated that migrant workers' health literacy and health information behavior could be improved through technology when facing a health crisis. We found that participants sought health information proactively to reduce their perceived risks. However, there is still space for design to support the ability to process jargon information and apply local policy, such as providing easy-to-understand, accurate, and timely information. The findings of this study provide some insights for the authority and technological design to respond to migrant workers' health information needs., Conclusions: This study acknowledges and understands the needs of vulnerable migrant workers in society. The findings of this study provide insights for the authority and technological design to respond to migrant workers' health information needs. We also outline the areas worth further investigation, such as the communication between information seekers and providers, and the navigation of the healthcare system for migrants in the host country., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Deep learning has been applied in precision oncology to address a variety of gene expression-based phenotype predictions. However, gene expression data's unique characteristics challenge the computer vision-inspired design of popular Deep Learning (DL) models such as Convolutional Neural Network (CNN) and ask for the need to develop interpretable DL models tailored for transcriptomics study. To address the current challenges in developing an interpretable DL model for modeling gene expression data, we propose a novel interpretable deep learning architecture called T-GEM, or Transformer for Gene Expression Modeling. We provided the detailed T-GEM model for modeling gene-gene interactions and demonstrated its utility for gene expression-based predictions of cancer-related phenotypes, including cancer type prediction and immune cell type classification. We carefully analyzed the learning mechanism of T-GEM and showed that the first layer has broader attention while higher layers focus more on phenotype-related genes. We also showed that T-GEM's self-attention could capture important biological functions associated with the predicted phenotypes. We further devised a method to extract the regulatory network that T-GEM learns by exploiting the attributions of self-attention weights for classifications and showed that the network hub genes were likely markers for the predicted phenotypes.

Purpose: Nightmare is common and is also independently implicated in suicide risk among the adolescent population. Adolescents with major depressive disorder (MDD) are at an increased risk of suicide. Therefore, comorbid nightmares may amplify suicide risk among this clinical population. This study aimed to explore the effects of nightmares on suicide risk among adolescents with MDD., Patients and Methods: Subjects were 499 outpatients aged 12-18 in four large psychiatric hospitals clinic of China, from January 1 to October 31, 2021. Simultaneously, we matched 499 healthy controls according to gender and age. All participants underwent affective state (depressive and anxiety symptoms) and sleep variable (nightmare frequency/distress, insomnia symptoms, and daytime sleepiness) evaluation as well as MDD diagnoses and determination of suicide risk by a fully structured diagnostic clinical interview., Results: Adolescents with MDD reported a higher incidence of frequent nightmares (at least one night per week) and level of nightmare distress than healthy controls (22.0% vs 6.1%; 28.85 ± 11.92 vs 17.30 ± 5.61). Over half of the patients with suicide risk (51.6%) experienced frequent nightmares compared with approximately one-third of those at a risk for suicide (30.7%). Patients with suicide risk scored scientifically higher on sleep variables, depressive and anxiety symptoms than those without the risk. Further logistic regression analysis indicated that female gender, junior grade, recurrent depressive episode, severe nightmare distress and severe depressive symptoms were independently and significantly associated with suicide risk., Conclusion: Our study provided evidence that adolescents with MDD experienced a higher prevalence of frequent nightmares and suffered more nightmare distress. Nightmare distress is an independent risk factor for suicide risk., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Song et al.)

Quantitative assessment of livability within a city facilitates the identification of urban problems and targeted improvements to the environment. Available studies are mostly limited to static analysis of a particular phase. It is difficult to reveal the dynamic development state of cities at the micro level. Taking Sino-Singapore Tianjin Eco-city as an example, we established an evaluation index system for the livability of the eco-city from five dimensions, including environmental health, transportation convenience, urban security, facility convenience, and economic prosperity. Multi-source data from 2016 to 2020, including the remote sensing images, points of interest, and planning data, combined with the entropy method and the TOPSIS method were used to dynamically monitor the livability of the eco-city in a long-term series. The results showed that during the study period, the livability levels of different areas in the eco-city had strong spatial and temporal variations. Spatially, with the southern part of the Sino-Singapore Eco-city Cooperation Zone as the core, the overall livability was characterized by a high center and a low edge. The convenience of facilities, traffic convenience, and economic prosperity were characterized by a high center and a low edge. Urban security and environmental health showed the characteristics of low center and high edge. From 2016 to 2020, the livability improvement rate of the eco-city had gradually accelerated, with the the most obvious improvement in the southern part of the China-Singapore Cooperation Zone.

Background: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by infiltration of lipid-laden foamy macrophages within different tissues. Clinical manifestations of ECD are highly heterogeneous. Bone lesions are found in 80%-95% of patients, while extraosseous lesions usually involve the cardiovascular system, retroperitoneum, central nervous system (CNS), and skin. Pancreatic involvement in ECD has barely been reported., Case Presentation: A 29-year-old female initially presented with menoxenia, diabetes insipidus and diabetes mellitus. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) revealed hypermetabolic foci in the bilateral frontal lobe, saddle area, and pancreas. A 99mTc-MDP bone scrintigraphy scan revealed symmetrical increased uptake in distal femoral and proximal tibial metaphysis, which was confirmed to be osteosclerosis by high-resolution peripheral quantitative computed tomography. The patient underwent incomplete resection of the sellar mass. Histological examination of biopsies showed histiocytic aggregates, which were positive for S100 and negative for CD1a and CD207 on immunohistochemistry. Enhanced abdominal CT scan showed hypointense nodules within the body and tail of the pancreas. Endoscopic ultrasonography guided fine-needle aspiration (EUS-FNA) found no evidence of malignancy. She was diagnosed with ECD and treated with high-dose IFN-α. Repeated examinations at three-and eight-months post treatment revealed markedly reduction of both intracranial and pancreatic lesions., Conclusions: ECD is a rare histiocytic neoplasm that can involve almost every organ, whereas pancreatic involvement has barely been reported to date. Here, we present the rare case of pancreatic lesions in ECD that responded well to interferon-α. We further reviewed reports of pancreatic involvement in histiocytic disorders and concluded the characteristics of such lesions to help diagnosis and treatment, in which these lesions mimicked pancreatic adenocarcinoma and caused unnecessary invasive surgeries., (© 2022. The Author(s).)

Background: People may endorse suicidal behavior during a major depressive episode. Affective temperaments may play a role in this risk. We explored the relationship between affective temperaments and suicide and identified some traits that can predict suicide risk in depression., Materials and Methods: We analyzed the results of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) in 284 participants recruited from a psychiatric clinic and the community in Beijing and compared the subscale scores (temperaments of cyclothymic, dysthymic, anxious, irritable, and hyperthymic) among major depressive disorders (MDDs) vs. the general population as well as depressive patients with vs. without suicide risk, using Student's test, chi-square test, rank-sum test, and multivariable regression modeling., Results: The incidence of suicidal risk in depressive subjects was 47.62% (80/168). Being unmarried ( p < 0.001), unemployed ( p = 0.007), and temperaments of dysthymic, cyclothymic, anxious, and irritable scores (all p < 0.001) were significantly more prevalent in patients with depression than in the general population. Young age ( p < 0.001), female sex ( p = 0.037), unmarried ( p = 0.001), more severe depression ( p < 0.001), and dysthymic, anxious, and cyclothymic temperament (all p < 0.05) were significantly more prevalent in patients with depressive disorder than those without suicide risk. The logistic regression analysis showed that younger age (odds ratio [ OR ] = 0.937, 95% CI 0.905∼0.970), female sex ( OR = 2.606, 95% CI 1.142∼5.948), more severe depression ( OR = 1.145, 95% CI 1.063∼1.234), cyclothymic temperament ( OR = 1.275, 95% CI 1.102∼1.475), and dysthymic temperament ( OR = 1.265, 95% CI 1.037∼1.542) were all independently associated with high suicidal risk in patients with first-onset major depression ( p < 0.05)., Conclusion: Temperament traits differ between the general population and people suffering from MDD. Subjects with MDD who have much more severe depressive symptoms and a cyclothymic or dysthymic temperament were at a high risk of suicide., 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 Yin, Song, Wei, Zhang, Zhou, Yu, Zhang, Li and Chen.)

Red blood cell distribution width (RDW) was frequently assessed in COVID-19 infection and reported to be associated with adverse outcomes. However, there was no consensus regarding the optimal cutoff value for RDW. Records of 98 patients with COVID-19 from the First People's Hospital of Jingzhou were reviewed. They were divided into two groups according to the cutoff value for RDW on admission by receiver operator characteristic curve analysis: ≤11.5% (n = 50) and >11.5% (n = 48). The association of RDW with the severity and outcomes of COVID-19 was analyzed. The receiver operating characteristic curve indicated that the RDW was a good discrimination factor for identifying COVID-19 severity (area under the curve = 0.728, 95% CI: 0.626-0.830, p < 0.001). Patients with RDW > 11.5% more frequently suffered from critical COVID-19 than those with RDW ≤ 11.5% (62.5% vs. 26.0%, p < 0.001). Multivariate logistic regression analysis showed RDW to be an independent predictor for critical illness due to COVID-19 (OR = 2.40, 95% CI: 1.27-4.55, p = 0.007). A similar result was obtained when we included RDW > 11.5% into another model instead of RDW as a continuous variable (OR = 5.41, 95% CI: 1.53-19.10, p = 0.009). RDW, as an inexpensive and routinely measured parameter, showed promise as a predictor for critical illness in patients with COVID-19 infection. RDW > 11.5% could be the optimal cutoff to discriminate critical COVID-19 infection., (© 2022 Wiley Periodicals LLC.)

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.

DNAs' photostability is significant to the normal function of organisms. P-Z is a hydrogen bonded artificial DNA base pair, where P and Z represent 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one and 6-amino-5nitro-2(1H)-pyridone, respectively. The excited-state relaxation mechanism of P-Z pair is investigated using static TDDFT calculations combined with the non-adiabatic dynamic simulations at TDDFT level. The roles of nitro rotation, nitro out-of-plane deformation, and single proton transfer (SPT) along hydrogen bond are revealed. The results of potential energy profile calculations demonstrate that the SPT processes along the hydrogen bonds are unfavorable to occur statically, which is in great contrast to the natural base pair. The non-adiabatic dynamic simulations show that the excited-state nitro rotation and nitro out-of-plane deformation are the two important relaxation channels which lead to the fast internal conversion to S 0 state. The SPT from Z to P is also observed, followed by distortion on P, inducing the fast internal conversion to S 0 state. However, this channel (decay via SPT process) plays minor roles on the excited-state relaxation mechanism statistically. This work shows the great differences of the excited-state relaxation mechanism between the natural base pairs and artificial base pair, also sheds new light into the role of hydrogen bond and nitro group in P-Z base pair., 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 © 2021 Elsevier B.V. All rights reserved.)

Density dependence and habitat heterogeneity have been recognized as important driving mechanisms that shape the patterns of seedling survival and promote species coexistence in species-rich forests. In this study, we evaluated the relative importance of density dependence by conspecific, heterospecific, and phylogenetically related neighbors and habitat heterogeneity on seedling survival in the Lienhuachih (LHC) Forest, a subtropical, evergreen forest in central Taiwan. Age-specific effects of different variables were also studied. We monitored the fates of 1,642 newly recruited seedlings of woody plants within a 25-ha Forest Dynamics Plot for 2 years. The effects of conspecific, heterospecific, and phylogenetically related neighbors and habitat heterogeneity on seedling survival were analyzed by generalized linear mixed models. Our results indicated that conspecific negative density dependence (CNDD) had a strong impact on seedling survival, and the effects of CNDD increased with seedling age. Heterospecific positive density dependence (HPDD) and phylogenetic positive density dependence (PPDD) had a significant influence on the survival of seedlings, and stronger HPDD and PPDD effects were detected for older seedlings. Furthermore, seedling survival differed among habitats significantly. Seedling survival was significantly higher in the plateau, high-slope, and low-slope habitats than in the valley. Overall, our results suggested that the effects of CNDD, HPDD, PPDD, and habitat heterogeneity influenced seedling survival simultaneously in the LHC subtropical forest, but their relative importance varied with seedling age. Such findings from our subtropical forest were slightly different from tropical forests, and these contrasting patterns may be attributed to differences in abiotic environments. These findings highlight the importance to incorporate phylogenetic relatedness, seedling age, and habitat heterogeneity when investigating the impacts of density dependence on seedling survival that may contribute to species coexistence in seedling communities., Competing Interests: None declared., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Self-control is very important for the adaptation among adolescents. It is associated with depression and tendencies of eating disorders. This study aimed to investigate the relationship between the two and the mediating role of self-control for adolescents. In total, 1,231 adolescents (11-18 years) participated in this study. Self-control, depression, and tendencies of eating disorders were evaluated using the Dual-Mode of Self-Control Scale (DMSC-S), 11-item Kutcher Adolescent Depression Scale (KADS-11), and Eating Attitudes Test (EAT-26). The correlations among these factors were analyzed using mediating effect models. Girls had higher scores on the both subscales (impulse system and control system) of DMSC-S ( P < 0.001). Those between 15-18 years had higher scores on impulse system than those between 11-14 years ( P < 0.001). A significant mediating effect (12.8%) of the impulse system was observed between depression and tendencies of eating disorders in adolescents., 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 Li, Li, Qi, Song and Chen.)

The synthesis of evolutionary biology and community ecology aims to understand how genetic variation within one species can shape community properties and how the ecological properties of a community can drive the evolution of a species. A rarely explored aspect is whether the interaction of genetic variation and community properties depends on the species' ecological role. Here we investigated the interactions among environmental factors, species diversity, and the within-species genetic diversity of species with different ecological roles. Using high-throughput DNA sequencing, we genotyped a canopy-dominant tree species, Parashorea chinensis , and an understory-abundant species, Pittosporopsis kerrii , from fifteen plots in Xishuangbanna tropical seasonal rainforest and estimated their adaptive, neutral and total genetic diversity; we also surveyed species diversity and assayed key soil nutrients. Structural equation modelling revealed that soil nitrogen availability created an opposing effect in species diversity and adaptive genetic diversity of the canopy-dominant Pa. chinensis . The increased adaptive genetic diversity of Pa. chinensis led to greater species diversity by promoting co-existence. Increased species diversity reduced the adaptive genetic diversity of the dominant understory species, Pi. kerrii , which was promoted by the adaptive genetic diversity of the canopy-dominant Pa. chinensis . However, such relationships were absent when neutral genetic diversity or total genetic diversity were used in the model. Our results demonstrated the important ecological interaction between adaptive genetic diversity and species diversity, but the pattern of the interaction depends on the identity of the species. Our results highlight the significant ecological role of dominant species in competitive interactions and regulation of community structure., Competing Interests: The authors declare that there are no conflicts of interest., (© 2021 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Objective: To evaluate the safety and efficacy of vemurafenib in the treatment of BRAF(V600E)-mutated Erdheim-Chester disease (ECD) . Methods: We retrospectively analyzed the clinical data, response rate, adverse events and survival of 12 patients with ECD treated with vemurafenib from March 2015 to October 2020 in Peking Union Medical College Hospital. Results: Of 12 patients [7 males and 5 females, median age = 51.5 (range, 32-66) years old], the median number of organs involved was 6 (range, 4-8) , and the median treatment duration of vemurafenib was 11 (3-60) months. All patients had improvement of clinical symptoms, of which 2 cases were completely relieved, and 10 cases were partially relieved. Seven patients evaluated by (18)F-FDG-positron emission tomography/computed tomography achieved a metabolic response, including 2 patients with a complete metabolic response and 5 patients with a partial metabolic response. The common adverse events in the overall cohort were grade 1 to 2 (Common Terminology Criteria for Adverse Events 5.0) , including skin rash (58.3%) , arthralgia (25.0%) , and digestive tract reactions (16.7%) . The median follow-up time was 13.5 (3-60) months. One patient with central nervous system involvement died due to a cerebrovascular event, and one patient relapsed 10 months after drug withdrawal. The estimated 2-year overall survival rate and 2-year progression free survival rate were 88.89% and 66.67%, respectively. Conclusions: Vemurafenib is safe and effective in the treatment of BRAF(V600E)-mutated ECD.

Along with the economic and technological development and growing demand for high-quality drinking water, direct drinking water has gained general popularity in China. However, no authoritative policy has been issued, giving a clear definition of direct drinking water and existing standards and regulations concerning direct drinking water are not definitive in nature. Existing water quality parameters are not well supported and sometimes even contradict each other. We elaborated, in this paper, the history of direct drinking water in China and systematically reviewed the existing regulations and standards related to direct drinking water. We also compared and analyzed the important microbiology, toxicology, sensory perception and general chemistry parameters in the standards. This paper is the first ever attempt at an in-depth analysis of the chaotic state of the direct drinking water industry. We have also highlighted the problems in the current standards and regulations for direct drinking water. Our study provides a basis for market regulation and the supervision and management of direct drinking water. In addition, the paper provides helpful information for laying down a definition of direct drinking water, calling for and approving of project proposals concerning the establishment of national standards for direct drinking water, and actually formulating the standards. We have made a number of suggestions: A. defining direct drinking water clearly and formulating the national standards for direct drinking water as soon as possible; B. conducting research on water quality benchmarks to provide scientific support for the formulation of the national standards for direct drinking water; C. giving more attention to the formulation of standards concerning microbiology parameters and their limits and giving consideration to the inclusion of parameters concerning viruses., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Active constituents isolated from Euodia ruticarpa (ER) steam distilled essential oil (SDEO) against PC-3 prostate cancer cell growth remain unclear. To clarify the puzzle, ER SDEO was extracted and further resolved into six isolated fractions ERF1-F6 with Sephadex LH-20 gel filtration chromatography to analyze their biological activities. Active ingredients in the isolated fractions were analyzed with GC-MS. Potential isolated fractions were selected to treat PC-3 cells with direct action and indirect treatment by mouse splenocyte- (SCM) and macrophage-conditioned media (MCM). The relationship between PC-3 cell viabilities and corresponding total polyphenols, flavonoid contents as well as Th1/Th2 cytokine profiles in SCM was analyzed using the Pearson product-moment correlation coefficient (r). As a result, ERF1-F3 was abundant in total polyphenols and flavonoids contents with diverse active ingredients. Treatments with ERF1-F3 at appropriate concentrations more or less inhibit PC-3 cell growth in a direct action manner. Only SCM, respectively, cultured with ER SDEO and ERF1-F3 markedly enhanced the effects to inhibit PC-3 cell growth, suggesting that secretions by splenocytes might involve anti-PC-3 effects. There are significantly negative correlations between PC-3 cell viabilities and IL-2, IL-10 as well as IL-10/IL-2 ratios in the corresponding SCM. Total polyphenol and flavonoid contents in the media cultured with ER SDEO isolated fractions positively correlated with IL-10 (Th2) and IL-10/IL-2 (Th2/Th1) cytokine secretion ratios by splenocytes, indicating that polyphenol and flavonoid components in ER SDEO isolated fractions promote Th2-polarized and anti-inflammatory characteristics. These new findings concluded that the inhibitory effects against PC-3 prostate cancer cell growth are attributed to active anti-inflammatory ingredients in ER SDEO and its active ERF1-F3 fractions through direct action and indirect treatment by modulating splenocytes' cytokine secretion profiles.

Objective: To explore the composition of ascites lymphocytes in high-grade serous ovarian carcinoma (HGSOC) and its correlation with clinical features. Methods: A total of 59 newly-diagnosed HGSOC patients, aged (58±11) years old, who were treated at the Department of Obstetrics and Gynecology of Peking University Third Hospital from July 2019 to December 2020 were included, collecting ascites and peritoneal irrigation fluid respectively. Detect the proportion of T, B, NK cell and its subpopulations by flow cytometry, and analyze its correlation with the clinical characteristics of patients. Results: Among 59 patients, 48 patients (81.4%) had ascites, and 11 patients (18.6%) had no ascites. Compared with the peritoneal irrigation fluid, the CD3 + T (70.2%±15.6% vs 78.1%±6.7%, P =0.014), CD8 + T (38.3%±11.2% vs 47.7%±10.1%, P =0.014) and CD16 - CD56 bright NK [2.0% (0.8%, 3.6%) vs 4.2% (1.5%, 7.1%), P =0.026] cells were significantly decreased in the ascites, while the CD16 + CD56 dim NK cells was significantly increased [6.8% (2.8%, 15.7%) vs 2.6% (1.6%, 4.3%), P =0.008]. In patients with ascites volume ≥1 000 ml, CD16 - CD56 bright NK cells were significantly increased than those ascites volume<1 000 ml [3.1% (1.2%, 3.9%) vs 0.8% (0.4%, 2.3%), P =0.002]. Age was significantly positively correlated with the level of CD4 + T cells ( r =0.332, P =0.021) and the ratio of CD4 + T/CD8 + T ( r =0.379, P =0.008) in ascites. In ascites from patients with poor response to treatment, the proportion of CD4 + T cells was increased significantly than those with better response (64.7%±4.2% vs 48.3%±11.7%, P =0.002). Conclusion: The formation of ascites in newly diagnosed high-grade serous epithelial ovarian cancer patients would affect the lymphocyte composition in the abdominal cavity microenvironment, which is related to the patient's age, cancer progression and treatment response.

The photostability of DNA plays a key role in the normal function of organisms. A-5FU is a base pair derivative of the A-T dimer where the methyl group is replaced by a F atom. Here, accurate static TDDFT calculations and non-adiabatic dynamic simulations are used to systematically investigate the excited-state decay paths of the A-5FU dimer related to the proton transfer and the out-of-plane twisting deformation motion of A and 5FU in the 1ππ* and 1nπ* states. CC2 is used to check the accuracy of the current TDDFT calculations. Our results show that the deformation of the C[double bond, length as m-dash]C or C[double bond, length as m-dash]N double bond in A and 5FU provides an efficient pathway for the depopulation of the lowest excited states, which can compete with the excited-state proton transfer paths in the dimer. This finding indicates that monomer-like decay paths could be important for the photostability of weakly hydrogen-bonded DNA base pairs and provide a new insight into the excited-state decay paths in base pairs and their analogues.

Objective: To determine whether microRNAs (miRs) are elevated in the plasma of individuals with the inherited peripheral neuropathy Charcot-Marie-Tooth disease type 1A (CMT1A), miR profiling was employed to compare control and CMT1A plasma., Methods: We performed a screen of CMT1A and control plasma samples to identify miRs that are elevated in CMT1A using next-generation sequencing, followed by validation of selected miRs by quantitative PCR, and correlation with protein biomarkers and clinical data: Rasch-modified CMT Examination and Neuropathy Scores, ulnar compound muscle action potentials, and motor nerve conduction velocities., Results: After an initial pilot screen, a broader screen confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerve. Comparison to other candidate biomarkers for CMT1A (e.g., neurofilament light) measured on the same sample set shows a comparable elevation of several miRs (e.g., miR133a, -206, -223) and ability to discriminate cases from controls. Neurofilament light levels were most highly correlated with miR133a. In addition, the putative Schwann cell miRs (e.g., miR223, -199a, -328, -409, -431) correlate with the recently described transmembrane protease serine 5 (TMPRSS5) protein biomarker that is most highly expressed in Schwann cells and also elevated in CMT1A plasma., Conclusions: These studies identify a set of miRs that are candidate biomarkers for clinical trials in CMT1A. Some of the miRs may reflect Schwann cell processes that underlie the pathogenesis of the disease., Classification of Evidence: This study provides Class III evidence that a set of plasma miRs are elevated in patients with CMT1A., (© 2021 American Academy of Neurology.)

Background: Rutaecarpine (Rut) is a plant alkaloid abundant in Euodia ruticarpa which is a Chinese herbal medicine used for treating various cancers. However, the Rut administration effect on prostate cancer in vivo remains unclear., Aim: In the present study we established an allogenic TRAMP-C1 prostate cancer mouse model to evaluate the Rut administration effect and mechanism in vivo., Methods: To unravel the Rut administration effect on prostate cancer in vivo, C57BL/6J male mice (8 weeks old) were randomly grouped (n = 9), subcutaneously loaded with TRAMP-C1 prostate cancer cells and immediately given daily by gavage with Rut dissolved in soybean oil at 7 mg (low dose), 35 mg (medium dose), and 70 mg/kg b.w./day (high dose) for successive 39 days., Results: Rut administration significantly and dose-dependently reduced both tumor volume and solid prostate cancer weight in allogenic TRAMP-C1 male mice. Rut administration markedly increased (TNF-α+IFN-γ) (Th1-)/IL-10 (Th2-) cytokine secretion ratios by splenocytes and TNF-α (M1-)/IL-10 (M2-) cytokine secretion ratios by macrophages as compared to those of dietary control group, suggesting that Rut administration in vivo regulates the immune balance toward Th1- and M1-polarized characteristics. Decreased CD19 + , CD4 + and CD8 + lymphocytes in the peripheral blood of allogenic TRAMP-C1 mice were significantly elevated by Rut administration. Tumor weights positively correlated with TNF-α secretions by splenocytes, suggesting that there is a tumor cachexia in the tumor-bearing mice. Tumor weights negatively correlated with IgG (Th1-antibody) levels in the sera, suggesting that Th1-polarized immune balance may inhibit prostate cancer cell growth., Conclusions: Our results evidenced that Rut administration suppresses prostate cancer cell growth in mice subcutaneously loaded with TRAMP-C1 cells and correlated the anti-cancer effects with Th1-polarized immune balance in vivo., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Fetal growth restriction (FGR) is an important cause of perinatal death and adverse pregnancy outcomes. Asymmetric dimethylarginine (ADMA) is associated with FGR, but the mechanisms have not been thoroughly studied. Here, we determined the levels of ADMA and autophagy-related molecules in human blood samples and placental tissues. And we also used the human chorionic carcinoma cell line BeWo to investigate the mechanism of ADMA-induced FGR in vitro. Compared with the control group, ADMA levels in maternal blood and placenta were increased in patients with FGR, and the birth weight (BW) percentile was negatively correlated with maternal serum ADMA concentration in the FGR group. The expression of mammalian target of rapamycin (mTOR) in the placenta of the FGR group was lower than the control group, while the expression of Beclin-1 and microtubule-associated protein 1 light chain 3-II (LC3-II)/LC3-I was significantly increased in the FGR group. And the expression of matrix metalloproteinase 9 (MMP9) was decreased in the placenta of patients with FGR. In in vitro cell experiments, compared with the control group, the expression of mTOR and MMP9 in BeWo cells was decreased and the expression of Beclin-1 and LC3-II/LC3-I was increased in the ADMA-treated group. Moreover, ADMA had favorable effects on the formation of autophagic vacuoles, and the autophagy inhibitor 3-Methyladenine (3-MA) could reduce the autophagy-induction effect of ADMA on BeWo cells. This study found that ADMA could participate in the occurrence of FGR through inducing autophagy in trophoblasts.

Thermal ablation in combination with transarterial chemoembolization (TACE) has been reported to exert a more powerful antitumor effect than thermal ablation alone in hepatocellular carcinoma patients. However, the underlying mechanisms remain unclear. The purpose of the present study was to evaluate whether sublethal hyperthermia encountered in the periablation zone during thermal ablation enhances the anticancer activity of doxorubicin in chronically hypoxic (encountered in the tumor area after TACE) liver cancer cells and to explore the underlying mechanisms. In the present study, HepG2 cells precultured under chronic hypoxic conditions (1% oxygen) were treated in a 42°C water bath for 15 or 30 min, followed by incubation with doxorubicin. Assays were then performed to determine intracellular uptake of doxorubicin, cell viability, apoptosis, cell cycle, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and total antioxidant capacity. The results confirmed that sublethal hyperthermia enhanced the intracellular uptake of doxorubicin into hypoxic HepG2 cells. Hyperthermia combined with doxorubicin led to a greater inhibition of cell viability and increased apoptosis in hypoxic HepG2 cells as compared with hyperthermia or doxorubicin alone. In addition, the combination induced apoptosis by increasing ROS and causing disruption of MMP. Pretreatment with the ROS scavenger N-acetyl cysteine significantly inhibited the apoptotic response, suggesting that cell death is ROS-dependent. These findings suggested that sublethal hyperthermia enhances the anticancer activity of doxorubicin in hypoxic HepG2 cells via a ROS-dependent mechanism., (© 2021 The Author(s).)

Receptor interacting protein kinase 1 (RIPK1) mediates cell death and inflammatory signaling and is increased in multiple sclerosis (MS) brain samples. Here, we investigate the role of glial RIPK1 kinase activity in mediating MS pathogenesis. We demonstrate RIPK1 levels correlate with MS disease progression. We find microglia are susceptible to RIPK1-mediated cell death and identify an inflammatory gene signature that may contribute to the neuroinflammatory milieu in MS patients. We uncover a distinct role for RIPK1 in astrocytes in regulating inflammatory signaling in the absence of cell death and confirm RIPK1-kinase-dependent regulation in human glia. Using a murine MS model, we show RIPK1 inhibition attenuates disease progression and suppresses deleterious signaling in astrocytes and microglia. Our results suggest RIPK1 kinase activation in microglia and astrocytes induces a detrimental neuroinflammatory program that contributes to the neurodegenerative environment in progressive MS., Competing Interests: Declaration of interests M.Z., F.P., L.W., C.Z., A.M., Y.R., M.L., R.G., L.G., P.L., T.X., T.H., and D.O. were employees of Sanofi at the time this research was conducted. The authors declare no other conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Enhancers are non-coding DNA sequences bound by proteins called transcription factors. They function as distant regulators of gene transcription and participate in the development and maintenance of cell types and tissues. Since experimental validation of enhancers is expensive and time-consuming, many computational methods have been developed to predict enhancers and their strength. However, most of these methods still lack good performance in the prediction of enhancer strength. Here, we present a method to predict Enhancers Strength (i.e., strong and weak) by using Augmented data and Residual Convolutional Neural Network (ES-ARCNN). To train ES-ARCNN, we used two data augmentation tricks (i.e., reverse complement and shift) to previously identified enhancers for enlarging a previously identified dataset of enhancers. We further employed a residual convolutional neural network and trained it using the augmented dataset. Compared with other state-of-the-art methods in the 10-fold cross-validation (CV) test, ES-ARCNN has the best performance with the accuracy of 66.17%, and the tricks of data augmentation can effectively improve the prediction performance. We further tested ES-ARCNN on an independent dataset and obtained 65.5% accuracy, which has more than 4% improvement over the other three existing methods. The results in 10CV and independent tests show that ES-ARCNN can effectively predict the enhancer strength. The transcription factor binding sites (TFBSs) enrichment analysis shows that from the mechanistic perspective, enhancer strength is associated with a higher density of important TFBSs in a tissue. A user-friendly web-application is also provided at http://compgenomics.utsa.edu/ES-ARCNN/., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The prognostic nutritional index (PNI) has been described as a simple risk-stratified tool for several diseases. We explored the predictive role of the PNI on coronavirus disease 2019 (COVID-19) severity. Methods: A total of 101 patients with COVID-19 were included in this retrospective study from January 2020 to March 2020. They were divided into two groups according to COVID-19 severity: non-critical ( n = 56) and critical ( n = 45). The PNI was calculated upon hospital admission: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm 3 ). Critical COVID-19 was defined as having one of the following features: respiratory failure necessitating mechanical ventilation; shock; organ dysfunction necessitating admission to the intensive care unit (ICU). The correlation between the PNI with COVID-19 severity was analyzed. Results: The PNI was significantly lower in critically ill than that in non-critically ill patients ( P < 0.001). The receiver operating characteristic curve indicated that the PNI was a good discrimination factor for identifying COVID-19 severity ( P < 0.001). Multivariate logistic regression analysis showed the PNI to be an independent risk factor for critical illness due to COVID-19 ( P = 0.002). Conclusions: The PNI is a valuable biomarker that could be used to discriminate COVID-19 severity., 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 Wang, Lin, Wei, Li, Liao, Yuan, Huang, Qin, Geng and Wang.)

The objective evaluation of human settlement in cities helps find the problems exposed in urban development and make targeted adjustments to improve urban environment. Taking the downtown of Fuzhou as the research area, the residential area as the research unit, using multi-source data such as meteorological monitoring data, remote sensing imagery, map points of interest data (POI), and land planning data, we constructed monitoring system of urban human settlement from four aspects: environmental health and comfort, traffic convenience, city safety, and life conve-nience. The TOPSIS method was used to conduct a comprehensive evaluation of human settlement. The results showed that the human settlement level of downtown Fuzhou was quite different, which was high in the central area and low in the peripheral areas. The human settlement index was high in the middle of the urban area, low in the eastern and southern areas, with mixed high and low values in the western and northern areas. In each index layer, the characteristics of high-high agglomeration and low-low agglomeration of traffic convenience and life convenience were consistent with the distribution of high and low value clusters of the human settlement. Convenient transportation and complete service facilities had a greater impact on human settlement. The environmental health and comfort were characterized by interior low and edge high of the city, while city safety was characterized by interior high and edge low.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is associated with increased risk for ischemic stroke (IS). Because POEMS syndrome is rare, little is known regarding the underlying mechanism and prognosis for IS in patients in whom it occurs. The medical records of patients with POEMS syndrome were screened between January 2018 and January 2000 at Peking Union Medical College Hospital to identify those with IS. The baseline characteristics, IS features, and patient outcomes were analyzed. Forty-one (8.0%) of 510 POEMS patients were documented to have IS. Patients with IS were older, had a higher percentage of Overall Neuropathy Limitation Scale score >4, and had a higher level of fibrinogen compared with those who did not have IS. Ninety-three percent of IS events occurred before or within 3 months after a diagnosis of POEMS. Of 41 occurrences of IS, 29 (46.3%) were multifocal. Recurrent IS was observed in 13 (31.7%) of 41 patients, but not in patients with successful anti-plasma cell therapy. The 3-year overall survival rate in patients with IS was 71.0% and for those without IS, it was 88.5% (P = .002). We showed that 8.0% of POEMS patients had IS, and most IS events occurred in POEMS patients not being treated effectively. Having IS was a predictor of unfavorable prognosis. Early diagnosis, immediate initiation of treatment for POEMS, and control of POEMS syndrome is key to reducing the occurrence of IS, improving survival, and preventing recurrence of IS., (© 2020 by The American Society of Hematology.)