Search

Zi-Feng Dai, Qi-Lin Huang, Hai-Peng Liu, Wei Zhang Department of Neurosurgery, Xinqiao Hospital, The Third Military Medical University, Chongqing, People’s Republic of China Objectives: A retrospective study was undertaken to compare the efficacy of stereotactic gamma knife surgery (GKS) and microvascular decompression (MVD) in the treatment of primary trigeminal neuralgia (TN) at a single center. The study included the evaluation of clinical outcomes of pain relief and pain recurrence and complications associated with GKS and MVD.Methods: The study included 202 patients with primary TN and was conducted between January 2013 and December 2014; about 115 patients were treated with GKS and 87 patients were treated with MVD. TN pain was evaluated using the Barrow Neurological Institute and the visual analog scale scoring systems. Preoperative magnetic resonance tomographic angiography was performed for all patients. Microscope-assisted MVD used the suboccipital retrosigmoid sinus approach. GKS targeted the trigeminal nerve root entry zone with a margin radiation dose of 59.5 Gy, and brainstem dose

Objective: To investigate the protective effect of mouse astrocyte-conditioned medium (ACM) on hypoxic and mechanically injured neurons by a cell model in vitro, and to explore the possible mechanism.Methods: The model of hypoxic neuronal injury was caused by 3% O2 in three-gas incubator. Neurons were cultured with ordinary medium or 20% ACM respectively and randomly divided into hypoxic group (hypoxia for 4, 8, 24 h and marked as H4R0, H8R0, H24R0) and hypoxia reoxygenation group (H4R24, H8R24, H24R24). Mechanical injury model was developed by scratching neurons cultured in 20% ACM or ordinary medium to different degrees. Neurons in both medium were divided into normal control group, mild, moderate and severe injury groups. The 20% ACM was added 24 h before hypoxia/reoxygenation or mechanical injury. The morphology and survival of neurons were observed and counted by trypan blue staining. The concentration of NO, lactic dehydrogenase (LDH) and membrane ATPase activity were detected by corresponding kits.Results: It was showed that 20% ACM can obviously promote the survival rate of hypoxia/reoxygenated neurons and scratched neurons as well. The morphology and number of neurons exposed to hypoxia or scratch injury showed great difference between groups with or without ACM treatment. Compared with control group, the concentration of NO and LDH was much lower in hypoxic/reoxygenated neurons treated with 20% ACM, and the ATPase activity was higher. For the mechanical injury model, neurons with moderate injury also revealed a lower NO and LDH concentration than the control group. All the differences were statistically significant (P less than 0.05).Conclusion: ACM can promote the survival and functional recovery of neurons following hypoxia or scratching to a certain degree. The mechanism may be associated with reducing the synthesis and release of NO and LDH as well as increasing the activity of membrane ATPase. [ABSTRACT FROM AUTHOR]

Objective: To establish and validate reference intervals of serum vitamin K for healthy children in China. Methods: A cross-sectional study was conducted from January 2020 to May 2023, involving 807 healthy children aged 0 to 14 years, selected by stratified random sampling based on the population distribution of children in eastern, central, western, and northeastern China. Sample collection was carried out in 16 hospitals across 12 provinces, autonomous regions, and municipalities. Basic information of the children was collected using a standardized self-design questionnaire. Serum levels of vitamin K 1 and vitamin K 2 (menaquinone-4 (MK-4), menaquinone-7 (MK-7)) were measured using liquid chromatography-tandem mass spectrometry. The reference intervals was established by direct approach. The children were divided into different groups by age. Inter-group comparisons were conducted using the Kruskal-Wallis non-parametric test, and the reference intervals ( P 2.5 - P 97.5 ) were determined using non-parametric methods. Screening 40 healthy children for small sample validation based on age groups within the reference range(25 from eastern, 10 from central, and 5 from western regions). Results: The age of the 807 children was 5.00 (2.00, 9.81) years, and 495 (61.3%) were males and 312 (38.7%) females. Reference intervals were established for 795 children, of whom 303 children were aged 1 month to 3 years and 492 were aged 4 to 14 years. The reference intervals for serum vitamin K 1 were 0.09-4.54 μg/L for children aged 1 month to 3 years, and 0.10-1.73 μg/L for 4-14 years. For MK-7, the intervals were 0.07-1.42 μg/L for 1 month to 3 years and 0.19-2.03 μg/L for 4-14 years. The reference intervals for MK-4 in children aged 1 month to 14 years were 0-0.42 μg/L. The measured values of serum vitamin K 1 , MK-4, and MK-7 in the validation samples did not exceed the reference limit in more than 2 samples. Conclusion: Reference intervals for vitamin K 1 , MK-4, and MK-7 in healthy children aged 1 month to 14 years have been established and validated, and can be used to assess vitamin K nutritional status in children.

Background and Aims: The worldwide health emergency sparked by the COVID-19 pandemic has deeply shaken educational environments, posing unprecedented challenges to university students' well-being. While individual links between self-esteem, hope, and well-being are established, their combined impacts during crises remain underexplored. Our study addresses this gap by investigating the interplay among hope, self-esteem, and life satisfaction within the context of university students navigating the challenges posed by the pandemic., Methods: Conducting an online cross-sectional self-administered survey during Hong Kong's third pandemic wave, we measured hope, self-esteem, and life satisfaction using validated scales. Three hundred and fifteen university students (211 females; mean age = 22.08; SD  = 2.74) participated., Results: Through multiple regression and mediation analyses, our findings indicate that university students with elevated hope and self-esteem scored higher on life satisfaction measures. Specifically, our analysis revealed that self-esteem may serve as a partial mediator in the relationship between hope and life satisfaction, highlighting how heightened hope indirectly enhances life satisfaction by strengthening self-esteem., Conclusion: This study reveals intricate relationships among hope, self-esteem, and life satisfaction in university students, particularly during external adversities like the COVID-19 pandemic. The implications extend to mental health interventions, emphasizing the potential benefits of cultivating hope and self-esteem to enhance life satisfaction among university students confronting formidable challenges., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

This study explores the mediating role of self-regulation in the relationship between bullying victimization and depressive symptoms among adolescents, considering the moderating effects of gender and region. A cross-sectional analysis was conducted with 3984 adolescents aged 12-18 from the United Kingdom, Hong Kong, Taiwan, and the Netherlands. Data were collected via an online survey administered through Qualtrics. The survey included validated measures such as the Illinois Bullying Scale (IBS) to measure bullying victimization, the Adolescent Self-Regulatory Inventory (ASRI) to measure self-regulation, and the Patient Health Questionnaire (PHQ) to measure depression. The SPSS macro PROCESS was employed for data analysis, with model 4 used for testing the mediating effects of self-regulation and model 1 for assessing the moderating effects of gender and region. The results demonstrated significant associations between bullying victimization, self-regulation, and depressive symptoms. Self-regulation mediated the positive association between bullying victimization and depression, with notable variations across genders and regions. Specifically, male students in Hong Kong exhibited an increased susceptibility to depression when subjected to bullying. These findings underscore the protective role of self-regulation in mitigating the adverse effects of bullying victimization on adolescent mental health. Implications for interventions and prevention strategies targeting adolescent depression are discussed.

The purpose of this study was to reveal the effect of inoculating autochthonous bacterial strains (Lactobacillus and Staphylococcus simulans) on the flavor profiles, microbial community, and metabolites, and to elucidate the potential mechanism of flavor formation in dry-cured duck. The results indicated that the inoculation of bacterial strains could improve the amount of lactic acid bacteria and Staphylococcus and reduce the counts of Enterobacteria. There was a significant difference in flavor profiles between samples inoculated with different strains. Hexanal-D, acetone, 3-methyl-1-butanol-D, thiophene, hexanal-M, propanal, pentanal, (Z)-2-penten-1-ol and ethanol-D were the potential biomarkers. A total of 70 differential metabolites were screened and identified. Amino acid metabolism and lipid metabolism were the key pathways for the production of flavor and metabolites in dry-cured duck. The results of this study will improve our understanding of the mechanism of flavor formation regarding the inoculation of autochthonous starter cultures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

According to the broaden-and-build theory, positive emotions can broaden our awareness and build psychological resources, which leads to better psychological outcomes. Previous studies demonstrated that hope partially mediates the association between positive emotions and life satisfaction in college students. Yet, there has no similar model been tested among older adults. The objective of the current study was to evaluate the mediating role of hope agency and pathways in the association between positive emotions and life satisfaction. Three hundred and forty-one Chinese community-dwelling older adults (mean = 70.83, SD  = 9.16) were asked to complete a survey questionnaire comprising measures assessing positive emotions, hope, life satisfaction, and other sociodemographic variables. Results showed that hope agency, but not hope pathways, partially mediated the relationship between positive emotions and life satisfaction. We discussed the importance of these initial findings concerning positive emotions and hope as predictors of life satisfaction in the older adult population., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity., (© 2024. The Author(s).)

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: This study investigated the relationships between specific types of social participation and well-being variables (i.e., life satisfaction, positive affect, negative affect, symptoms of depression and anxiety) in Chinese older adults in Hong Kong., Methods: This study was a cross-sectional study. A convenience sample of 341 participants aged 55-95 years (mean, 70.92; SD, 9.03) was recruited to complete a survey questionnaire during the COVID-19 pandemic (between April and June 2022). Five hierarchical multiple regression analyses were conducted to examine the relationships between different types of social participation (physical, cultural, recreational, religious, and voluntary work) and outcome variables., Results: After controlling for covariates, it was revealed that only physical activities were associated with all outcome variables. Religious and cultural activities were positively related to positive affect, while an inverse relationship was found between recreational activities and anxiety., Conclusions: With the restrictions on social participation arising from the COVID-19 pandemic, these findings suggest that promoting different types of social interactions might foster various aspects of well-being in Chinese older adults. To achieve successful aging, the role of physical activities might be of paramount importance even under adverse situations. Geriatr Gerontol Int 2024; 24: 364-369., (© 2023 Japan Geriatrics Society.)

Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1β, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K + ) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Social networks play a vital role in facilitating late-life health and well-being. The current research sought to examine the psychometric properties of the abbreviated Lubben Social Network Scale (LSNS-6) among community-dwelling Hong Kong Chinese older adults and to explore the association between social network and well-being indicators such as life satisfaction, functional social support, loneliness and anxiety., Methods: We administered the LSNS-6 scale to 324 older adults (mean = 71.70, SD = 8.58, range: 58-95). We performed confirmatory factor analysis (CFA) to confirm the construct validity. Cronbach's alpha was chosen for internal consistency estimation. Correlational analysis was performed between LSNS-6 scale and other measures to ascertain the convergent validity., Results: The two-factor model of LSNS-6 indicated an adequate fit. The goodness-of-fit index values for the model were χ 2 /df = 2.61, CFI = 0.98, RSMEA = 0.07, SRMR = 0.05. The internal consistency of the scale was α = 0.75. It also demonstrated good construct validity in measuring the social network and acceptable convergent validity to other measures., Conclusions: The LSNS-6, according to current findings, can be a valid reference to the social network of Hong Kong older adults, enabling researchers and clinicians to investigate and develop further corresponding remedies for those in need., (© 2023 AJA Inc.)

The Alternative splicing (AS) of Carnitine palmitoyltransferase 1a ( CPT1a ) and their expression profiles had never been illuminated in goats until now. Herein, a novel splice transcript in the CPT1a gene that is predicted to result in the skipping of exons 6-19 (CPT1a-sv1) has been isolated in addition to the full-length transcript in goats. The result of RT-PCR showed that CPT1a-sv1 is 606 bp in length and consists of 6 exons. A novel exon 6 was consisted of partial exon 5 and partial exon 19, compared to that in CPT1a. RT-qPCR analysis showed that the expression patterns of CPT1a and CPT1a-sv1 are spatially different. In both kid and adult goats, the CPT1a transcript is strongly expressed in the liver, spleen, lung, kidney, and brain tissues. However, CPT1a-sv1 has a strong tissue-specific expression pattern, with moderate RNA levels in the liver and brain of kids, while highly expressed in the liver and minimally expressed in the brain of adults. We observed two transcripts to be involved in brain development. These findings improve our understanding of the function of the CPT1a gene in goats and provide information on the molecular mechanism of AS events.

Background: Insect pheromones are highly effective and environmentally friendly, and are widely used in the monitoring and trapping of pests. However, many researchers have found that various factors such as ultraviolet light and temperature in the field environment can accelerate the volatilization of pheromones, thus affecting the actual control effect. In recent years, electrospinning technology has demonstrated remarkable potential in the preparation of sustained carriers. Moreover, the utilization of biodegradable materials in electrospinning presents a promising avenue for the advancement of eco-friendly carriers., Results: In this study, homogeneous and defect-free pheromone carriers were obtained by electrospinning using fully biodegradable polyhydroxybutyrate materials and pheromones of Spodoptera litura. The electrospun fibers with porous structure could continuously release pheromone (the longest can be ≤80 days). They also had low light transmission, hydrophobic protection. More importantly, the pheromone-loaded electrospun fiber carriers showed stable release and good trapping effect in the field. They could trap pests for at least 7 weeks in the field environment without other light stabilizers added., Conclusion: Sustained-release carriers constructed by electrospinning and green materials could improve the efficacy of pheromones and ensure environmental friendliness, and provided a tool for the management of S. litura and other pests and sustainable development of agricultural. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

In the context of climate change and human factors, the drought problem is a particularly serious one, and environmental pollution caused by the abuse of chemical fertilizers and pesticides is increasingly serious. Endophytic fungi can be used as a protection option, which is ecologically friendly, to alleviate abiotic stresses on plants, promote plant growth, and promote the sustainable development of agriculture and forestry. Therefore, it is of great significance to screen and isolate endophytic fungi that are beneficial to crops from plants in special habitats. In this study, endophytic fungi were isolated from Cotoneaster multiflorus , and drought-tolerant endophytic fungi were screened by simulating drought stress with different concentrations of PEG-6000, and the growth-promoting effects of these drought-tolerant strains were evaluated. A total of 113 strains of endophytic fungi were isolated and purified from different tissues of C. multiflorus . After simulated drought stress, 25 endophytic fungi showed strong drought tolerance. After ITS sequence identification, they belonged to 7 genera and 12 species, including Aspergillus, Fusarium, Colletotrichum, Penicillium, Diaporthe, Geotrichum , and Metarhizium . According to the identification and drought stress results, 12 strains of endophytic fungi with better drought tolerance were selected to study their abilities of dissolving inorganic phosphorus and potassium feldspar powder and producing indole-3-acetic acid (IAA). It was found that the amount of dissolved phosphorus in 7 strains of endophytic fungi was significantly higher than that of CK, and the content of soluble phosphorus was 101.98-414.51 μg. ml -1 ; 6 endophytic fungi had significantly higher potassium solubilization than CK, and the content of water-soluble potassium ranged from 19.17 to 30.94 mg·l -1 ; 6 strains have the ability to produce IAA, and the yield of IAA ranged between 0.04 and 0.42 mg. ml -1 . This study for the first time identified the existence of endophytic fungi with drought tolerance and growth-promoting function in C. multiflorus , which could provide new direction for plant drought tolerance and growth promotion fungi strain resources. It also provides a theoretical basis for the subsequent application of endophytic fungi of C. multiflorus in agricultural and forestry production to improve plant tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lü, Liu, Wang, Chen, Huang, Zhang, Huang and Zhang.)

The global coronavirus disease 2019 (COVID-19) crisis has exerted significant psychological impacts on university students who have faced drastic changes in the learning mode and suspension of classes. Despite these challenges, many students maintained subjective well-being. In this study, we examined the role of "hope" as a potential protector to maintain their subjective well-being when facing adversity during this global crisis. Specifically, we explored the mediating role of two hope components (agency thinking and pathways thinking) on the association of positive emotions and life satisfaction among Chinese university students. We conducted an online survey at a local university and recruited a total of 315 undergraduates from the humanities, creative arts, and social sciences programs through convenience sampling. Participants confirmed their informed consent and completed a set of self-administered questionnaires measuring positive emotions, hope, life satisfaction, and demographic variables. The results of mediation testing indicated that, during a global crisis such as COVID-19, positive emotions indirectly influenced life satisfaction through agency thinking rather than pathways thinking. The findings highlight the importance of agency thinking among Chinese university students in adverse situations and provide valuable insights for psychological interventions during a crisis. The article concludes by discussing possible explanations and implications of the findings in a post-pandemic world.

Background: Obesity usually causes diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects., Aim: To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats., Methods: Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Glucose and insulin tolerance tests, analyses of biochemical parameters, histological examination, western blot, and quantitative real-time polymerase chain reaction were conducted., Results: In comparison to the sham operation group, the RYGB, SG, and GB groups had decreased body weight and food intake, reduced glucose intolerance and insulin insensitivity, downregulated biochemical parameters, alleviated morphological changes in the liver and kidneys, and decreased levels of protein kinase C β/ P66shc. The effect in the RYGB group was better than that in the SG and GB groups., Conclusion: These results suggest that RYGB, SG and GB may be helpful for the treatment of foodborne obesity-induced DM., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chronic non-healing wounds have posed a severe threat to patients mentally and physically. Behavior dysregulation of remaining cells at wound sites is recognized as the chief culprit to destroy healing process and hinders wound healing. Therefore, regulating and restoring normal cellular behavior is the core of chronic non-healing wound treatment. In recent years, the therapy with mesenchymal stem cells (MSCs) has become a promising option for chronic wound healing and the efficacy has increasingly been attributed to their exocrine functions. Small extracellular vesicles derived from MSCs (MSC-sEVs) are reported to benefit almost all stages of wound healing by regulating the cellular behavior to participate in the process of inflammatory response, angiogenesis, re-epithelization, and scarless healing. Here, we describe the characteristics of MSC-sEVs and discuss their therapeutic potential in chronic wound treatment. Additionally, we also provide an overview of the application avenues of MSC-sEVs in wound treatment. Finally, we summarize strategies for large-scale production and engineering of MSC-sEVs. This review may possibly provide meaningful guidance for chronic wound treatment with MSC-sEVs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Liu, Su, Wang, Chu, Ma, Huang, Li, Fu and Zhang.)

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t -test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P <0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

Therapeutic targeting of the nuclear enzyme poly (ADP-ribose) polymerase 1 (PARP1) with PARP inhibitors (PARPis) in patients with a homologous recombination (HR)- deficient phenotype based on the mechanism of synthetic lethality has been shown tremendous success in cancer therapy. With the clinical use of various PARPis, emerging evidence has shown that some PARPis offer hope for breakthroughs in triple-negative breast cancer (TNBC) therapy, regardless of HR status. However, similar to other conventional cytotoxic drugs, PARPis are also subject to the intractable problem of drug resistance. Notably, acquired resistance to PARPis caused by point mutations in the PARP1 protein is hard to overcome with current strategies. To explore modalities to overcome resistance and identify patients who are most likely to benefit from PARP1-targeted therapy, we developed a proteolysis-targeted chimaera (PROTAC) to degrade mutant PARP1 in TNBC. Here, we investigated a PARP1 PROTAC termed "NN3″, which triggered ubiquitination and proteasome-mediated degradation of PARP1. Moreover, NN3 degraded PARP1 with resistance-related mutations. Interestingly, compared with other reported PARP1 degraders, NN3 exhibited a unique antitumor mechanism in p53-positive breast cancer cells that effectively promoted ferroptosis by downregulating the SLC7A11 pathway. Furthermore, NN3 showed potent activity and low toxicity in vivo. In conclusion, we propose PROTAC-mediated degradation of PARP1 as a novel strategy against mutation-related PARPi resistance and a paradigm for targeting breast cancer with functional p53 via ferroptosis induction., 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 Inc. All rights reserved.)

Extracellular vesicles play crucial roles in intercellular communication in the tumor microenvironment. Here we demonstrate that in hepatic fibrosis, TGF-β stimulates the palmitoylation of hexokinase 1 (HK1) in hepatic stellate cells (HSCs), which facilitates the secretion of HK1 via large extracellular vesicles in a TSG101-dependent manner. The large extracellular vesicle HK1 is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, the nuclear receptor Nur77 transcriptionally activates the expression of depalmitoylase ABHD17B to inhibit HK1 palmitoylation, consequently attenuating HK1 release. However, TGF-β-activated Akt functionally represses Nur77 by inducing Nur77 phosphorylation and degradation. We identify the small molecule PDNPA that binds Nur77 to generate steric hindrance to block Akt targeting, thereby disrupting Akt-mediated Nur77 degradation and preserving Nur77 inhibition of HK1 release. Together, this study demonstrates an overlooked function of HK1 in HCC upon its release from HSCs and highlights PDNPA as a candidate compound for inhibiting HCC progression., (© 2022. The Author(s).)

Objective: The purpose of this study was to explore the effect of WeChat-based remote follow-up management on reducing the home care burden and anxiety of parents of premature infants., Methods: A randomized controlled study was conducted in our hospital, with 150 premature infants enrolled in this study, each with 75 cases in the intervention group and the control group. WeChat-based remote follow-up management was performed in the intervention group after discharge, while traditional outpatient follow-up management was performed in the control group. Zarit Burden Interview (ZBI) scale as the primary outcome was used to compare the parental care burden between the two groups., Results: At the 1-month follow-up, the ZBI (37.1 ± 8.3 vs. 54.2 ± 10.5 [mean ± SD], mean difference: 17.1, the 95% confidence interval for the mean difference: [14.07, 20.13], P = 0.016), Family Caregiver Task Inventory (FCTI) scale (23.1 ± 5.2 vs. 33.4 ± 6.7 [mean ± SD], mean difference: 10.3, the 95% confidence interval for the mean difference: [8.38, 12.22], P = 0.023), Self-Rating Anxiety Scale (SAS) (49.6 ± 8.5 vs. 60.2 ± 10.8 [mean ± SD], mean difference: 10.6, the 95% confidence interval for the mean difference: [7.49,13.71], P = 0.021) and Self-Rating Depression Scale (SDS) (48.2 ± 9.5 vs. 58.8 ± 11.2 [mean ± SD], mean difference: 10.6, the 95% confidence interval for the mean difference: [7.28, 13.92], P = 0.019) scores of the intervention group were lower than those of the control group, and the lower scores indicate better outcomes., Conclusion: WeChat-based remote follow-up management of premature infants after discharge can effectively improve parents' ability to care and their psychological state and reduce burden of care., (© 2022 John Wiley & Sons, Ltd.)

N4-methylcytosine (4mC) is a type of DNA modification which could regulate several biological progressions such as transcription regulation, replication and gene expressions. Precisely recognizing 4mC sites in genomic sequences can provide specific knowledge about their genetic roles. This study aimed to develop a deep learning-based model to predict 4mC sites in the Escherichia coli. In the model, DNA sequences were encoded by word embedding technique 'word2vec'. The obtained features were inputted into 1-D convolutional neural network (CNN) to discriminate 4mC sites from non-4mC sites in Escherichia coli genome. The examination on independent dataset showed that our model could yield the overall accuracy of 0.861, which was about 4.3% higher than the existing model. To provide convenience to scholars, we provided the data and source code of the model which can be freely download from https://github.com/linDing-groups/Deep-4mCW2V., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.

Diabetes is a metabolic disorder caused by insufficient insulin secretion and insulin secretion disorders. From health to diabetes, there are generally three stages: health, pre-diabetes and type 2 diabetes. Early diagnosis of diabetes is the most effective way to prevent and control diabetes and its complications. In this work, we collected the physical examination data from Beijing Physical Examination Center from January 2006 to December 2017, and divided the population into three groups according to the WHO (1999) Diabetes Diagnostic Standards: normal fasting plasma glucose (NFG) (FPG < 6.1 mmol/L), mildly impaired fasting plasma glucose (IFG) (6.1 mmol/L ≤ FPG < 7.0 mmol/L) and type 2 diabetes (T2DM) (FPG > 7.0 mmol/L). Finally, we obtained1,221,598 NFG samples, 285,965 IFG samples and 387,076 T2DM samples, with a total of 15 physical examination indexes. Furthermore, taking eXtreme Gradient Boosting (XGBoost), random forest (RF), Logistic Regression (LR), and Fully connected neural network (FCN) as classifiers, four models were constructed to distinguish NFG, IFG and T2DM. The comparison results show that XGBoost has the best performance, with AUC (macro) of 0.7874 and AUC (micro) of 0.8633. In addition, based on the XGBoost classifier, three binary classification models were also established to discriminate NFG from IFG, NFG from T2DM, IFG from T2DM. On the independent dataset, the AUCs were 0.7808, 0.8687, 0.7067, respectively. Finally, we analyzed the importance of the features and identified the risk factors associated with diabetes.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M&#95;{Pl} and that the second-order LIV scale is >10^{-3}M&#95;{Pl}. Both limits improve by at least one order of magnitude the previous results.

4mC is a type of DNA alteration that has the ability to synchronize multiple biological movements, for example, DNA replication, gene expressions, and transcriptional regulations. Accurate prediction of 4mC sites can provide exact information to their hereditary functions. The purpose of this study was to establish a robust deep learning model to recognize 4mC sites in Geobacter pickeringii. In the anticipated model, two kinds of feature descriptors, namely, binary and k -mer composition were used to encode the DNA sequences of Geobacter pickeringii . The obtained features from their fusion were optimized by using correlation and gradient-boosting decision tree (GBDT)-based algorithm with incremental feature selection (IFS) method. Then, these optimized features were inserted into 1D convolutional neural network (CNN) to classify 4mC sites from non-4mC sites in Geobacter pickeringii . The performance of the anticipated model on independent data exhibited an accuracy of 0.868, which was 4.2% higher than the existing model.

The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009-2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009-2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.

Introduction and Objectives: Pulmonary vein isolation (PVI) technique has become the cornerstone of atrial fibrillation (AF) catheter ablation. The objective of this study was to assess the efficacy and safety of extended antrum ablation based on electrophysiological substrate mapping plus PVI in AF patients who underwent cryoballoon ablation., Methods: In this observational study, a total of 121 paroxysmal AF patients and 80 persistent AF patients who did not achieve the procedure endpoint after cryoballoon ablation received extra extended antrum ablation (EAA) based on electrophysiological substrate mapping via radiofrequency ablation (EAA group). As a control group (PVI group), among paroxysmal AF and persistent AF patients, we conducted a propensity score-matched cohort, in whom only PVI was completed., Results: The average follow-up time was 15.27±7.34 months. Compared with PVI group, paroxysmal AF patients in the EAA group had a significantly higher rate of AF-free survival (90.1% vs. 80.2%, p=0.027) and AF, atrial flutter, or atrial tachycardia (AFLAT) -free rate survival (89.3% vs. 79.3%, p=0.031). Persistent AF patients in the EAA group also had a significantly higher rate of AF-free survival (90.0% vs. 75.0%, p=0.016) and AFLAT-free survival (88.8% vs. 75.0%, p=0.029) than PVI group. Complication rates did not significantly differ between both groups, in either paroxysmal AF or persistent AF patients., Conclusion: Our findings demonstrate that extra extended antrum ablation based on electrophysiological substrate mapping is effective and safe. Moreover, the strategy can improve the outcome of AF cryoablation., (Copyright © 2021 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Severe acute pancreatitis (SAP) is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options. N 6 -methyladenosine (m 6 A) modification of circRNAs plays important roles in physiological and pathological processes. However, the roles of m 6 A circRNA in the pathological process of SAP remains unknown., Aim: To identify transcriptome-wide map of m 6 A circRNAs and to determine their biological significance and potential mechanisms in SAP., Methods: The SAP in C57BL/6 mice was induced using 4% sodium taurocholate salt. The transcriptome-wide map of m 6 A circRNAs was identified by m 6 A-modified RNA immunoprecipitation sequencing. The biological significance of circRNAs with differentially expressed m 6 A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The underlying mechanism of m 6 A circRNAs in SAP was analyzed by constructing of m 6 A circRNA-microRNA networks. The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m 6 A process in SAP., Results: Fifty-seven circRNAs with differentially expressed m 6 A peaks were identified by m 6 A-modified RNA immunoprecipitation sequencing, of which 32 were upregulated and 25 downregulated. Functional analysis of these m 6 A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP, such as regulation of autophagy and protein digestion. In m 6 A circRNA-miRNA networks, several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m 6 A circRNAs, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, the total m 6 A level of circRNAs was reduced, while the demethylase alkylation repair homolog 5 was upregulated in SAP., Conclusion: m 6 A modification of circRNAs may be involved in the pathogenesis of SAP. Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

DNase I hypersensitive site (DHS) refers to the hypersensitive region of chromatin for the DNase I enzyme. It is an important part of the noncoding region and contains a variety of regulatory elements, such as promoter, enhancer, and transcription factor-binding site, etc. Moreover, the related locus of disease (or trait) are usually enriched in the DHS regions. Therefore, the detection of DHS region is of great significance. In this study, we develop a deep learning-based algorithm to identify whether an unknown sequence region would be potential DHS. The proposed method showed high prediction performance on both training datasets and independent datasets in different cell types and developmental stages, demonstrating that the method has excellent superiority in the identification of DHSs. Furthermore, for the convenience of related wet-experimental researchers, the user-friendly web-server iDHS-Deep was established at http://lin-group.cn/server/iDHS-Deep/, by which users can easily distinguish DHS and non-DHS and obtain the corresponding developmental stage ofDHS., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Epilepsy is a clinical syndrome caused by the highly synchronized abnormal discharge of brain neurons. It has the characteristics of paroxysmal, transient, repetitive, and stereotyped. Circular RNAs (circRNAs) are a recently discovered type of noncoding RNA with diverse cellular functions related to their excellent stability; additionally, some circRNAs can bind and regulate microRNAs (miRNAs). The present study was designed to screen the differentially expressed circRNA in an acute seizure model of epilepsy in mice, analyze the related miRNA and mRNA, and study their participating functions and enrichment pathways. In order to obtain the differential expression of circRNA in epilepsy and infer their function, we used next-generation sequencing and found significantly different transcripts. CIRI (circRNA identifier) software was used to predict circRNA from the hippocampus cDNA, EdgeR was applied for the differential circRNA analysis between samples, and Cytoscape 3.7.2 software was used to draw the network diagram. A total of 10,388 differentially expressed circRNAs were identified, of which 34 were upregulated and 66 were downregulated. Among them, mm9&#95;circ&#95;008777 and mm9&#95;circ&#95;004424 were the key upregulated genes, and their expression in the epilepsy group was verified using Quantitative real-time PCR (QPCR). The analysis indicated that the extracted gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were closely related to several epilepsy-associated processes. This study determined that mm9&#95;circ&#95;008777 and mm9&#95;circ&#95;004424 are potential biomarkers of epilepsy, which play important roles in epilepsy-related pathways. These results could help improve the understanding of the biological mechanisms of circRNAs and epilepsy treatments., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10 -4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 10 36 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility., Competing Interests: Authors NN, Q-LH, X-fP, J-bZ, and J-wZ were employed by the company Guangzhou Baiyunshan Zhongyi Pharmaceutical Co. Ltd. The remaining 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, Ning, Wei, Huang, Lu, Pang, Wu, Zhou, Zhou, Luo and Han.)

Cyclin proteins are capable to regulate the cell cycle by forming a complex with cyclin-dependent kinases to activate cell cycle. Correct recognition of cyclin proteins could provide key clues for studying their functions. However, their sequences share low similarity, which results in poor prediction for sequence similarity-based methods. Thus, it is urgent to construct a machine learning model to identify cyclin proteins. This study aimed to develop a computational model to discriminate cyclin proteins from non-cyclin proteins. In our model, protein sequences were encoded by seven kinds of features that are amino acid composition, composition of k-spaced amino acid pairs, tri peptide composition, pseudo amino acid composition, geary correlation, normalized moreau-broto autocorrelation and composition/transition/distribution. Afterward, these features were optimized by using analysis of variance (ANOVA) and minimum redundancy maximum relevance (mRMR) with incremental feature selection (IFS) technique. A gradient boost decision tree (GBDT) classifier was trained on the optimal features. Five-fold cross-validated results showed that our model would identify cyclins with an accuracy of 93.06% and AUC value of 0.971, which are higher than the two recent studies on the same data., 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., (© 2021 The Authors.)

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25  TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17&#95;{stat}±0.02&#95;{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160  TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 15 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays 1 . The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2 ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane 3-6 , unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.

Background: Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood., Aim: To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms., Methods: SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed., Results: APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury., Conclusion: APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The plant microbiota play a key role in plant productivity, nutrient uptake, resistance to stress and flowering. The flowering of moso bamboo has been a focus of study. The mechanism of flowering is related to nutrient uptake, temperature, hormone balance and regulation of key genes. However, the connection between microbiota of moso bamboo and its flowering is unknown. In this study, samples of rhizosphere soil, rhizomes, roots and leaves of flowering and nonflowering plants were collected, and 16S rRNA amplicon Illumina sequencing was utilized to separate the bacterial communities associated with different flowering stages of moso bamboo. We identified 5442 OTUs, and the number of rhizosphere soil OTUs was much higher than those of other samples. Principal component analysis (PCA) and hierarchical clustering (Bray Curtis dis) analysis revealed that the bacterial microorganisms related to rhizosphere soil and endophytic tissues of moso bamboo differed significantly from those in bulk soil and rhizobacterial and endosphere microbiomes. In addition, the PCA analyses of root and rhizosphere soil revealed different structures of microbial communities between bamboo that is flowering and not flowering. Through the analysis of core microorganisms, it was found that Flavobacterium, Bacillus and Stenotrophomonas played an important role in the absorption of N elements, which may affect the flowering time of moso bamboo. Our results delineate the complex host-microbe interactions of this plant. We also discuss the potential influence of bacterial microbiome in flowering, which can provide a basis for the development and utilization of moso bamboo.

Bioluminescent proteins (BLPs) are a class of proteins that widely distributed in many living organisms with various mechanisms of light emission including bioluminescence and chemiluminescence from luminous organisms. Bioluminescence has been commonly used in various analytical research methods of cellular processes, such as gene expression analysis, drug discovery, cellular imaging, and toxicity determination. However, the identification of bioluminescent proteins is challenging as they share poor sequence similarities among them. In this paper, we briefly reviewed the development of the computational identification of BLPs and subsequently proposed a novel predicting framework for identifying BLPs based on eXtreme gradient boosting algorithm (XGBoost) and using sequence-derived features. To train the models, we collected BLP data from bacteria, eukaryote, and archaea. Then, for getting more effective prediction models, we examined the performances of different feature extraction methods and their combinations as well as classification algorithms. Finally, based on the optimal model, a novel predictor named iBLP was constructed to identify BLPs. The robustness of iBLP has been proved by experiments on training and independent datasets. Comparison with other published method further demonstrated that the proposed method is powerful and could provide good performance for BLP identification. The webserver and software package for BLP identification are freely available at http://lin-group.cn/server/iBLP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Dan Zhang et al.)

Aims: Interleukin (IL)-22 activates multiple signaling pathways to exert anti-inflammatory effects, but few studies have examined whether and how IL-22 may shift macrophage polarization between M 1 (pro-inflammatory) and M 2 (anti-inflammatory) states and thereby influence the progression of hepatic fibrosis., Main Methods: Utilized CCl 4 to induce liver fibrosis in mice, detected the role of IL-22 in inhibiting liver fibrosis by regulating Kupffer cells (KCs) polarization in vivo and in vitro. U937 cells were used to confirm the mechanism of IL-22 regulating macrophage polarization via the STAT3/Erk/Akt pathways. Human liver specimens were collected to verify the correlation between the levels of IL-22 and KCs during liver fibrogenesis., Key Findings: During CCl 4 -induced liver fibrosis progression in mice, adding exogenous IL-22 significantly inhibited pro-fibrogenic and macrophage phenotype-altering factors secreted by M 1 -KCs, and it increased the number of M 2 -KCs. In co-cultures of hepatic stellate cells and KCs from mice treated with IL-22, a high M 2 /M 1 -KCs ratio inhibited collagen production and stellate cell activation. These results suggest that IL-22 can increase the ratio of M 2 -KCs to M 1 -KCs and thereby attenuate the progression of liver fibrosis. Mechanistic studies in vitro showed that IL-22 promoted polarization of lipopolysaccharide-treated U937 macrophages from M 1 to M 2 . The cytokine exerted these effects by activating the STAT3 pathway while suppressing Erk1/2 and Akt pathways. Furthermore, immunofluorescent staining in human liver specimens confirmed that IL-22 levels positively correlated with the number of M 2 -KCs during liver fibrogenesis., Significance: IL-22 regulates the STAT3/Erk/Akt to increase the M 2 /M 1 -KCs ratio and thereby slow liver fibrogenesis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Based on the latest epidemic situation and field experience, this study aims to explore the correlation of computed tomography (CT) stages and blood glucose level in patients with novel coronavirus pneumonia (COVID-19)., Patients and Methods: The clinical data of first and multiple CT imaging re-examination and blood glucose levels from 62 confirmed cases of COVID-19 were collected for a retrospective analysis to determine the correlation between glucose level and CT-based staging., Results: Of the 62 COVID-19 patients, 48 cases of early stage and 14 cases of advanced stage were found in the CT data of the first diagnosis. These 62 cases were currently under follow-up (17-32 days): 18 cases in early stage-resorption stage, 25 cases in early stage-advanced stage-resorption stage, 12 cases in advanced stage-resorption stage, 5 cases in early stage -advanced stage-severe stage-resorption stage, and 2 cases in advanced stage-severe stage-resorption stage. Among them, the CT of 14 patients with advanced stage at the first diagnosis showed multiple stage lesions (advanced stage + early stage) at the same time. Patients presented with statistically significant changes in blood glucose at early stage-resorption stage, early stage-advanced stage-resorption stage, advanced stage-resorption stage, and early stage-advanced stage-severe stage-resorption stage (p<0.05). However, no statistically significant alterations were observed in the glucose level of patients with advanced stage-severe stage-resorption stage (p>0.05)., Conclusions: Alteration of blood glucose is positively correlated with CT-based staging of COVID-19. Blood glucose is of great value in clinical diagnosis of COVID-19 and in determining the stage and prognosis of this disease.

Background: The importance of identifying osteoporotic vertebral endplate or/and cortex fracture (ECF), which primarily includes endplate fracture (EPF) and vertebral anterior cortex buckling, has been recognized. However, some old traumatic ECFs with healing process in the elderly may be mistaken as osteoporotic. This study analyzes the radiological features of traumatic EPF., Methods: This was a retrospective analysis of 194 spine trauma patients with 263 vertebral fractures (mean age: 42.11 ± 9.82 years, 118 males and 76 females). All patients had traumatic EPF identified by X-ray/CT/MRI., Results: The involved vertebra was mostly L1 (29.7%), followed by T12 and L2. Except EPFs involved both superior and inferior endplates (12.6%), only 1.9% involved inferior endplate alone, with the majority involved superior endplate. If each endplate was divided into five segments of equal lengths (from anterior to posterior: a1, a2, m, p2, p1), the most depressed point of superior EPFs was mostly at segment-a2 (approximately 45%), followed by segment-a1 (approximately 20%) or segment-m (approximately 20%), and very rarely at segment-p1. The upper 1/3 of anterior vertebral wall was more likely to fracture, followed by middle 1/3 of anterior wall. For posterior vertebral wall fracture, 68.5% broke the bony wall surrounding the basivertebral vain. 58.6%, 30.0%, and 11.4% of vertebral fractures had <1/5, 1/5-1/3, and >1/3 vertebral body height loss. As the extent of vertebral height loss increased, the chance of having both superior and inferior EPFs also increased; however, the chance of having inferior EPF alone did not increase., Conclusion: Traumatic EPF features are characterized, which may help the differentiation of traumatic and osteoporotic EPFs.

Background: To date, the literature directly comparing the translabyrinthine approach and retrosigmoid approach in the operation of patients with vestibular schwannoma was limited. We aimed to evaluate postoperative complications between translabyrinthine approach and retrosigmoid approach for treating vestibular schwannoma patients., Material and Method: Potential publications were selected from PubMed, Web of Science and Cochrane Library. Gray relevant studies were manually searched. We set the searching time spanning from the creation date of electronic engines to February 2020. STATA version 12.0 was exerted to process the pooled data., Results: A total of 9 literature included in the study, involving 2429 patients, hails from the Germany, USA, Canada, Italy, and France. Of these 2429 patients with vestibular schwannoma, there were 1628 cases from the translabyrinthine approach group versus 801 cases from the retrosigmoid approach group. The results demonstrated that the translabyrinthine approach group was associated with a lower rate of tinnitus (OR = 2.687; 95 %CI, 1.167-6.191; P = 0.02) and cranial nerve deficit (OR = 2.946; 95 %CI, 1.562-5.557; P = 0.001). And the translabyrinthine approach group was associated with a higher total resection rate (OR = 0.246; 95 %CI (0.071-0.848); P = 0.026). However, no statistic differences were found in the incidence of the near total (OR = 0.751; P = 0.351), subtotal resection (OR = 3.664; P = 0.109), postoperative facial nerve dysfunctions (OR, 0.763; P = 0.626), postoperative meningitis (OR = 2.7; P = 0.279), cerebrospinal fluid leak (OR = 1.225; P = 0.777), postoperative headache (OR = 1.412; P = 0.339), ophthalmic complications (OR = 0.87; P = 0.59), and vascular complications (OR = 2.501; P = 0.139)., Conclusion: Based on current evidence, the translabyrinthine approach was associated with a higher rate of total resection and a lower rate of the tinnitus and cranial nerve deficit. But the risk of cranial nerve deficit was clearly affected by the preoperative status. And a translabyrintine approach could imply a complete sensorineural hearing loss, which contribute to the lower rate of postoperative tinnitus. Consequently, more evidence-based researches are needed to supplement this opinion., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two new phthalideisoquinoline hemiacetal alkaloid derivatives, named corybensines A and B (1 and 2), and four known alkaloids (3-6) were isolated from the bulbs of Corydalis decumbens. Their structures were characterized by analysis of 1D/2D NMR and ECD data, quantum chemical ECD calculations, and X-ray diffraction analysis. Among them, compound 2 represents the first naturally occurring phthalideisoquinoline hemiacetal alkaloid derivative with a 2-pyrrolidinone moiety. The activity of the isolated compounds towards neuronal excitability was examined., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Eight new alkaloids, including five isoquinoline alkaloids, a benzoazepine alkaloid, two isoindole alkaloids, and three synthetic alkaloids firstly obtained from the natural sources, together with three known ones were isolated from the bulbs of Corydalis decumbens. The structures were determined by analysis of their spectroscopic data and single-crystal X-ray diffraction. This is the first report of isoindole alkaloid and benzoazepine alkaloid from the genus Corydalis. Full NMR data for 9-11 are reported here for the first time. Moreover, the ability to modulate neuronal Ca 2+ mobilization of the isolated alkaloids was tested in primary cultured neocortical neurons. Compound 7 inhibited spontaneous Ca 2+ oscillations in primary neocortical neuron cultures at low micromolar concentrations., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT., Results: Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis., Conclusions: Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

Angiopoietin-2 (Ang-2) is a proangiogenic factor that mediates inflammation and atherosclerosis. We evaluated the predictive value of circulating Ang-2 levels for periprocedural myocardial injury (PMI) in 145 patients undergoing elective percutaneous coronary intervention (PCI), and investigated whether post-PCI Ang-2 levels are influenced by PMI. PMI was defined as a post-procedural troponin elevation above the 5×99 th percentile upper reference limit. Blood samples for Ang-2 analysis were collected at admission and on postoperative days 1 and 3. PMI occurred in 40 patients (28%). At baseline, there was no difference in Ang-2 levels between PMI and non-PMI patients (P=0.554). However, a significant interaction effect between PMI occurrence and time on Ang-2 levels was observed (interaction P=0.036). Although serum Ang-2 levels in non-PMI patients gradually decreased, Ang-2 levels in PMI patients did not change between different time-points. Multiple logistic regression analysis revealed that age, total stent length, and serum levels of N-terminal pro-brain natriuretic peptide were independent PMI predictors. These findings indicate that pre-procedural Ang-2 levels do not impact PMI occurrence after elective PCI. However, changes in Ang-2 levels after the procedure are closely related to PMI.