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The effects of Lactobacillus plantarum in microencapsulation (LPM) on intestinal development in layer chicks were investigated in this study, as well as the colonization of L. plantarum in the gut. A total of 480 healthy Hy-Line Brown layer chicks at 0 d old were randomly divided into 4 groups (8 replicates each treatment), and the diets of these birds were supplemented with nothing (control), L. plantarum (0.02 g/kg feed; 109 CFU/kg feed), LPM (1.0 g/kg feed; 109 CFU/kg feed) and wall material of LPM (WM; 0.98 g/kg feed), respectively. Compared to control, LPM improved growth performance and intestinal development of layer chicks, evidenced by significantly increased body weight, average daily gain, average daily feed intake, villus height, villus height/crypt depth, as well as weight and length of the duodenum, jejunum and ileum (P < 0.05). These results could be attributed to the increased colonization of L. plantarum in the gut, which was verified by significant increases in lactic acid content, viable counts in chyme and mucosa (P < 0.05), as well as a visible rise in number of strains labeled with fluorescein isothiocyanate. Meanwhile, the relative abundances of Lactobacillus and Bifidobacterium significantly increased in response to microencapsulated L. plantarum supplementation (P < 0.05), accompanied by the significant up-regulation of colonization related genes (P < 0.05), encoding solute carrier family, monocarboxylate transporter, activin A receptor, succinate receptor and secretogranin II. To sum up, microencapsulated L. plantarum supplementation promoted intestinal development, which could be attributed to the enhancement of L. plantarum colonization in the intestine through the mutual assistance of Bifidobacterium and interactions with colonization related transmembrane proteins.

'Franch' plums were used as experimental material to elucidate the effects of short-term treatment with high concentration of carbon dioxide (CO2) on post-harvest storage quality and antioxidant metabolism. The fruits were treated with 45%, 60%, and 75% CO2 for 3 hours, and then stored at 1.0±0.5 ℃ for 49 days. The firmness, color, soluble solids content, titratable acid content, and indicators related to antioxidant metabolism of the plums were measured during cold storage. The results showed that short-term treatment with high concentration CO2 can effectively maintain the firmness, color, soluble solids, and titratable acid content of plums, among which 60% CO2 treatment showed the best effects in maintaining fruit quality. At the end of storage, the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione reductase (GR), and ascorbate peroxidase (APX) in the 60% CO2 treatment group were 5.71%, 59.95%, 27.40%, 29.18%, and 45.00% (P

Abstract BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers.

A visible-light-promoted research protocol for constructing dihydropyrido[1,2-a]indolone skeletons is herein described proceeding through a cascade cyclization mediated by trifluoromethyl radicals. This method allows the efficient synthesis of various indole derivatives without the need of photocatalysts or transition-metal catalysts. Mechanism experiments indicate that the process involves a radical chain process initiated by the homolysis of Umemoto's reagent. This straightforward method enables a rapid access to heterocycles containing a trifluoromethyl group.

Abstract Background Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non‐invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD–PH). Methods This study included 535 patients with COPD–PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD–PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan–Meier curves were used for a survival analysis. The nomograms were developed as online network software. Results Tricuspid regurgitation velocity, right ventricular diameter, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), the red blood cell count, New York Heart Association functional class and sex were non‐invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT‐proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD–PH and were used to create a predictive nomogram of overall survival rates. Conclusions The proposed nomograms based on a large sample size of patients with COPD–PH could be used as non‐invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD–PH. Additionally, the online network has the potential to provide artificial intelligence‐assisted diagnosis and treatment. Highlights A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non‐invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD–PH.

Abstract Organoboron compounds are of high significance in organic synthesis due to the unique versatility of boryl substituents to access further modifications. The high demand for the incorporation of boryl moieties into molecular structures has witnessed significant progress, particularly in the C(sp3)−H borylation of hydrocarbons. Taking advantage of special characteristics of photo/electrochemistry, we herein describe the development of an oxidative C(sp3)−H borylation reaction under metal- and oxidant-free conditions, enabled by photoelectrochemical strategy. The reaction exhibits broad substrate scope (>57 examples), and includes the use of simple alkanes, halides, silanes, ketones, esters and nitriles as viable substrates. Notably, unconventional regioselectivity of C(sp3)−H borylation is achieved, with the coupling site of C(sp3)−H borylation selectively located in the distal methyl group. Our method is operationally simple and easily scalable, and offers a feasible approach for the one-step synthesis of high-value organoboron building blocks from simple hydrocarbons, which would provide ample opportunities for drug discovery.

DNA demethylation is a very important biochemical pathway regulating a group of biological processes, such as embryo development, fruit ripening, and response to stress. Despite the essential role of DNA demethylases, their evolutionary relationship and detailed biological functions in different land plants remain unclear. In this study, 48 DNA demethylases in 12 land plants were identified and classified. A phylogenetic tree was constructed to demonstrate the evolutionary relationships among these DNA demethylases, indicating how they are related across different species. Conserved domain, protein motif, and gene structure analysis showed that these 48 DNA demethylases fell into the presently identified four classes of DNA demethylases. Amino acid alignment revealed conserved catalytic sites and a previously less-studied protein region (referred to as domain A) within the DNA demethylases. An analysis showed a conserved pattern of gene duplication for DNA demethylases throughout their evolutionary history, suggesting that these genes had been maintained due to their importance. The examination of promoter cis-elements displayed potential signaling and regulating pathways of DNA demethylases. Furthermore, the expression profile was analyzed to investigate the physiological role of rice DNA demethylase in different developmental stages, in tissues, and in response to stress and various phytohormone signals. The findings offer a deeper insight into the functional regions of DNA demethylases and their evolutionary relationships, which can guide future research directions. Understanding the role of DNA demethylases can lead to improved plant stress resistance and contribute to the development of better crop and fruit varieties.

Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.

Abstract Background Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, and has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM). Methods A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca2+ (mCa2+) levels and mitochondrial membrane potential (MMP), as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (Vat) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in the insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM). Results THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated mCa2+ uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the mCa2+ level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, mCa2+ uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red. Conclusions These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through the improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue.

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell‐derived exosomes (BMSC‐Exos) on high‐fat diet obese mice and mature 3T3‐L1 adipocyte models of IR. BMSC‐Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1‐type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC‐Exos improved IR and lipid droplet accumulation in mature 3T3‐L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC‐Exos cause increased glucose uptake and improved IR in high‐fat chow‐fed mice and PA‐acting 3T3‐L1 adipocytes by activating the phosphoinositide 3‐kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients.

Objective Endometrial cancer (EC) is one of the most prevalent cancers in women. Long non-coding RNAs (lncRNAs) are potential diagnostic biomarkers in patients with EC. Methods We obtained clinical information and transcriptome data for 552 patients with EC from The Cancer Genome Atlas database. Cuproptosis-associated lncRNAs were obtained through Pearson’s correlation analysis. Univariate and multivariate Cox regression analyses were applied and a signature predicting overall survival (OS) among patients with EC was constructed. We also analyzed the tumor immune microenvironment and drug sensitivity. The results were validated by quantitative real time-polymerase chain reaction, and 5-ethynyl-2′-deoxyuridine and wound-healing assays. Results Seven cuproptosis-associated lncRNAs related to prognosis were screened out and a signature was constructed. OS was significantly superior in the low-risk group. In addition, patients in the low-risk group had more CD8+ T cell infiltration, a stronger type II interferon response, and greater cisplatin sensitivity. Expression levels of some of the lncRNAs were significantly increased by cuproptosis. Furthermore, silencing of lncRNA AC084117.1 significantly inhibited the proliferation and migration of EC cells. Conclusion We constructed a seven cuproptosis-associated lncRNA signature to predict the prognosis of patients with EC with good predictive power.

Abstract In 2019, triggered lightning was used to directly strike phase C of a 1.5 km, 10 kV double‐circuit distribution line in Guangzhou, China, with 2 flashes (13 return strokes) recorded. This paper presents the characteristics of induced voltage at the closest pole on the parallel line. The induced voltage is bipolar, which can be divided into 3 stages: negative increase stage, fast and positive transition stage and slowly returning to zero stage. The positive peak value of phase A voltage ranges from 111.4 to 228.9 kV and that of phase C voltage is from 90.1 to 200.9 kV, corresponding to lightning current from −8.9 to −29.9 kA. The positive peak value of the induced voltage is approximately 3 to 10 times the negative peak value. The negative peak, positive peak and positive 10%–10% duration time of induced voltage show a good linear relationship with the peak value of the return stroke current. There was no flashover occurred during the whole process. The result in this paper can provide data support for numerical simulation and line protection analysis.

Lodging is a critical constraint to yield increase. There appear to be tradeoffs between yield formation and lodging resistance in maize. Hypothetically, it is feasible to reduce lodging risk as well as increase grain yield by optimizing dry-matter allocation to different organs under different environments. A three-year field experiment was conducted using four maize cultivars with differing lodging resistances and five growing environments in 2018–2020. Lodging-susceptible (LS) cultivars on average yielded more than lodging-resistant (LR) cultivars when lodging was not present. The yield components kernel number per ear (KN) and thousand-kernel weight (TKW) were both negatively correlated with lodging resistance traits (stalk bending strength, rind penetration strength, and dry matter weight per internode length). Before silking, the LR cultivar Lishou 1 (LS1) transported more assimilates to the basal stem, resulting in a thicker basal stem, which reduced dry matter allocation to the ear and in turn KN. The lower KN of LS1 was also due partly to the lower plant height (PH), which increased lodging resistance but limited plant dry matter production. In contrast, the LS cultivars Xianyu 335 (XY335) and Xundan 20 (XD20) produced and allocated more photoassimilates to ears, but limited dry matter allocation to stems. After silking, LS cultivars showed higher TKW than LR cultivars as a function of high photoassimilate productivity and high assimilate allocation to the ear. The higher lodging resistance of LS1 was due mainly to the greater assimilate allocation to stem after silking and lower PH and ear height (EH). High-yielding and high-LR traits of Fumin (FM985) were related to optimized EH and stem anatomical structure, higher leaf productivity, low assimilate demand for kernel formation, and assimilate partitioning to ear. A high pre-silking temperature accelerated stem extension but reduced stem dry matter accumulation and basal stem strength. Post-silking temperature influences lodging resistance and yield more than other environmental factors. These results will be useful in understanding the tradeoffs between KN, KW, and LR in maize and environmental influences on these tradeoffs.

Abstract The operation of disconnectors in gas insulated substation (GIS) or power plant will produce very fast transient overvoltage (VFTO), which is considered to have serious harm to transformer longitudinal insulation and other high‐voltage equipment insulation. VFTO may also lead to secondary circuit failure. In this paper, the holistic modelling of 500 kV GIS step‐up substation equipment with a double circuit and long GIS busbar in a coastal power plant is established using Electromagnetic Transient Program (EMTP). The authors calculated the VFTO waveform that may be generated in different operations of the GIS substation. The authors analyze the amplitude and frequency characteristics of the VFTO waveform at lightning arresters and the entrance of transformers and find that the amplitude of VFTO at the entrance of #1 MT is less than its impulse withstand voltage. In some cases, the VFTO waveform at the entrance of #1 MT has high‐frequency content with fast attenuation. The VFTO waveform generated when operating the disconnector close to the arrester will cause the arrester to act many times and count frequently in a short time.

Affective forecasts are people's predictions of their future feelings in response to future events. In this study, based on the self-determination theory (SDT), we examined whether satisfying basic psychological needs influence undergraduates' affective forecasting and the moderating role of subjective socioeconomic status (SES). With a total of 423 undergraduate participants (177 males, 246 females), through one pilot study and three experiments, we first manipulated participants' basic psychological need satisfaction, i.e., autonomy need satisfaction (study 1), competence need satisfaction (study 2), and relatedness need satisfaction (study 3), then we asked low-SES and high-SES participants, respectively, to predict the pleasantness of a particular new product and evaluated the actual experience with the product. Results showed that the effect of basic psychological need on affective forecasting was not significant. When the need for autonomy need and competence need was satisfied, the impact bias was greater for the high SES than the low SES. Conversely, when the relatedness need was satisfied, the impact bias was greater for the low SES than the high SES. In conclusion, subjective SES moderated the influence of basic psychological needs satisfaction on increasing the impact bias in affective forecasting.

Abstract This paper reports the observation results of three‐phase overvoltage at the lightning strike point of a 1.5 km, 10 kV power distribution line that was struck directly by rocket triggered lightning to its phase wire C. The arrester of the direct struck phase at the lightning strike point operated in all return strokes corresponding to return stroke current from −3.3 kA to −32.9 kA. The waveform of direct struck phase includes an initial spike before negative peak, operation area of metal oxide varistor, and the final attenuation with oscillation. The overvoltage waveforms of the indirect struck phase at the lightning strike point show a small initial negative peak, rapid transition to a large positive peak, and the final negative attenuation with oscillation. The negative peak value of the indirect struck phase at lightning strike point ranged from −4.1 kV to −25.2 kV and that of the direct struck phase was between −78.1 kV and −167.8 kV. The positive peak value of indirect struck phase was between 0.2 kV and 49.8 kV. The negative peak value, zero‐crossing time and the peak‐to‐peak value of voltage all have a good linear relation with the peak value of lightning return stroke current.

Abstract Background Stroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke. Methods Relevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor. Results Overall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility. Conclusions Our study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention.

Abstract A negative triggered lightning involving five types of leaders was recorded by high-speed camera using frame rate of 20,000 fps and fast antennas at different distances. Five types of leaders contained one upward positive stepped leader, one upward positive dart leader, ten downward negative dart leader, one bidirectional leader and three downward negative dart-stepped leaders were propagated successively in the same channel. The upward positive dart leader occurred after initial continuous current pulse with average 2-D speed of 1.40 × 106 m/s and started second continuous current process. The bidirectional leader was transformed from decaying unidirectional leader and showed the unique electric field changes. Faster return strokes are found to be induced by downward leaders propagating evenly and deposit more positive charge in the following residual channel. The positive charge can inhibit the potential initiation of an upward positive leader and boost the propagation of the next downward negative leader.

Today’s power system is facing various challenges brought by large-scale renewable energy (RE) integration, which brings higher demand for flexibility. With the energy network gradually showing its distributed structural characteristics, multi-energy microgrids (MEMG) become an important component to effectively utilize distributed energy sources and supplement the flexibility of power distribution system (PDS). To effectively harness the operational flexibility of distributed MEMGs, we propose in this paper an evaluation method to quantify the flexibility capability of MEMG. A virtually established MG flexibility bus (MG-FB) is endowed with MG flexibility parameters (MG-FPs), which can reflect the flexibility characteristics of MEMG. To consider the impact of operational uncertainty on MG-FPs, a two-stage adaptive robust optimization (ARO) model is proposed, which can be solved by the C&CG algorithm. The results of a typical test system show the influence of system configuration, operator’s risk preference, and other factors on the values of MG-FPs. Besides, we illustrate the effectiveness and applicability of the proposed framework in modeling and quantifying the operational flexibility of MEMG to support the operation of the upstream network.

Abstract Rubber hoses are a category of rubber products that are widely and intensively employed in construction sites for concrete conveying. There has been lack of study to investigate the life cycle environmental and economic impacts of the rubber hoses as an industrial product. In this study, we analyze four types of rubber hoses with the inner layer made of different rubber composites to resist abrasion, i.e., Baseline, S-I, S-II and S-III. Tests of the wear resistance are carried out in the laboratory and S-III shows high abrasion resisting performance with the concrete conveying volume up to 20,000 m3 during the service life. Life cycle assessment (LCA) and life cycle costing (LCC) models are established for evaluating the four types of rubber hoses. A target function is developed to integrate LCA and LCC by converting the LCA results to the environmental costs. It is found that S-III can save 13% total cost comparing to Baseline. The production stage is the largest contributor to the environmental single score, while the use stage is the largest contributor to the life cycle cost. Sensitivity analyses are conducted and the results of this study are validated with the previous studies. The integrated method of LCA and LCC developed in this study paves a way for the eco-design of industrial rubber hoses and is potentially applicable to other rubber products.

Accurately measuring systemic risk in the banking industry and identifying systemically important banks are significant parts of macro-prudential supervision. However, there is a lack of research on measuring systemic risk and identifying important banks under the same framework. And there are relatively few studies comparing different indicators of systemically important banks in the context of China's banking industry. Therefore, this paper first constructs a new Merton model to measure the dynamically evolving systemic risk of China's banking system. Then combine the Merton model with the Shapley value to construct the Merton-Shapley framework, and propose a new indicator MShv to identify systemically important banks. At last, use the data of China's banking industry from 2006 to 2019 to conduct an empirical study. The research results show that the systemic risk in China peaked in 2008 and 2015 near the stock market crash, after 2008 the risk appeared a fluctuating decline. And it is found that MShv can accurately identify important banks and simultaneously is conducive to policy implementation. By a comparison between MShv and other systemic risk contribution indicators such as ΔCoVaR, MES, and SRISK, we find that there are many differences for different indicators in the applicability of identifying systemically important banks, the information reflected, and so on. Regulators can consider using several indicators synthetically to supervise banks during different risk periods, in order to maintain the stability of the financial system.

BackgroundThe gut microbiome affects the occurrence and development of NAFLD, but its mechanism has not yet been fully elucidated. Chinese medicine is a new treatment strategy to improve NAFLD by regulating the gut microbiome. Tianhuang formula (TH) has been proved to have a lipid-lowering effect in which constituents of ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rb, ginsenoside Re, and ginsenoside R1 from Panax notoginseng and berberine, palmatine, and coptisine from Coptis chinensis have low drug permeability, which results in poor intestinal absorption into the human body, and are thus able to come into contact with the gut microflora for a longer time. Therefore, it might be able to influence the gut microbial ecosystem, but it still needs to be investigated.MethodThe characteristics of the gut microbiome were represented by 16S rRNA sequencing, and the metabolites in intestinal contents and liver were discovered by non-targeted metabolomics. Correlation analysis and fermentation experiments revealed the relationship between the gut microbiome and metabolites. Blood biochemical indicators, liver function indicators, and oxidation-related indicators were assayed. H&E staining and Oil Red O staining were used to analyze the characteristics of hepatic steatosis. RT-qPCR and western blotting were used to detect the expression of genes and proteins in liver tissues, and fecal microbial transplantation (FMT) was performed to verify the role of the gut microbiome.ResultsGut microbiome especially Lactobacillus reduced, metabolites such as 5-Methoxyindoleacetate (5-MIAA) significantly reduced in the liver and intestinal contents, the level of hepatic GSH and SOD reduced, MDA increased, and the protein expression of Nrf2 also reduced in NAFLD mice induced by high-fat diet (HFD). The normal diet mice transplanted with NAFLD mice feces showed oxidative liver injury, indicating that the NAFLD was closely related to the gut microbiome. TH and TH-treated mice feces both can reshape the gut microbiome, increase the abundance of Lactobacillus and the content of 5-MIAA in intestinal contents and liver, and improve oxidative liver injury. This indicated that the effect of TH improving NAFLD was related to the gut microbiome, especially Lactobacillus. 5-MIAA, produced by Lactobacillus, was proved with fermentation experiments in vitro. Further experiments proved that 5-MIAA activated the Nrf2 pathway to improve oxidative stress in NAFLD mice induced by HFD. TH reshaped the gut microbiome, increased the abundance of Lactobacillus and its metabolite 5-MIAA to alleviate oxidative stress, and improved NAFLD.ConclusionThe study has demonstrated a mechanism by which the gut microbiome modulated oxidative stress in NAFLD mice induced by HFD. The traditional Chinese medicine TH improved NAFLD by regulating the gut microbiome, and its mechanism was related to the “Lactobacillus-5-MIAA-Nrf2” pathway. It provided a promising way for the intervention of NAFLD.

Abstract Background Pneumocystis jirovecii and Aspergillus fumigatus, are opportunistic pathogenic fungus that has a major impact on mortality in patients with systemic lupus erythematosus. With the potential to invade multiple organs, early and accurate diagnosis is essential to the survival of SLE patients, establishing an early diagnosis of the infection, especially coinfection by Pneumocystis jirovecii and Aspergillus fumigatus, still remains a great challenge. Case presentation In this case, we reported that the application of next -generation sequencing in diagnosing Pneumocystis jirovecii and Aspergillus fumigatus coinfection in a Chinese girl with systemic lupus erythematosus (SLE). Voriconazole was used to treat pulmonary aspergillosis, besides sulfamethoxazole and trimethoprim (SMZ-TMP), and caspofungin acetate to treat Pneumocystis jirovecii infection for 6 days. On Day 10 of admission, her chest radiograph displayed obvious absorption of bilateral lung inflammation though the circumstance of repeated fever had not improved. Unfortunately, the patient discharged from the hospital since the financial burden, and during the follow-up, it was documented the patient died within one week after discharge. Conclusions This successful application of the next generation sequencing assisting the rapid diagnosis of Pneumocystis jirovecii and Aspergillus fumigatus coinfection provides a new perspective in the clinical approach against the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.

High-quality environmental governance (EG) is closely related to its governance mode. Nevertheless, few studies have examined the EG modes from the dual perspectives of quality and quantity. This article utilizes panel data of 30 Chinese provinces from 2003 to 2020 to research the influence of environmental governance efficiency (EGE) and investment (EGI) on EG through a fixed-effect mode. The outcomes show that China’s EG is driven mainly by quantitative EGI. EGE and EGI show significant geographic regions, economic development levels, resource endowments, and stage heterogeneity to EG. In light of these conclusions, this article argues that the future needs to reasonably allocate EGI based on consideration of the heterogeneity of geographical regions, economic development levels, and resource endowments to optimize EGI structure and increase EGE in each province to achieve high-quality EG.

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to heart failure and death, for which there is no effective treatment. Rhynchophylline (Rhy) is the main effective component of the Chinese herbal medicine Uncaria rhynchophylla, which mainly acts on the cardiovascular and nervous systems. However, its role in protecting against DCM remains unexplored. The present study sought to reveal the mechanism of Rhy in improving type 2 diabetes mellitus (T2DM) myocardial lesions from the perspective of regulating calcium homeostasis in cardiomyocytes. We prepared a mouse model of T2DM using a high-fat diet combined with low doses of streptozotocin. The T2DM mice were given 40 mg/kg of Rhy for 8 weeks. The results showed that Rhy can attenuate cardiac pathological changes, slow down the heart rate, decrease serum cardiac enzyme levels, reduce cardiomyocyte apoptosis, enhance cardiomyocyte contractility, and raise the calcium transient amplitude in T2DM mice. Further, Rhy downregulated the phosphorylation level of ryanodine receptor 2, upregulated the phosphorylation level of phospholamban, protected mitochondrial structure and function, and increased adenosine triphosphate levels in the cardiac tissue of T2DM mice. Our results demonstrated that Rhy may protect against myocardial damage in T2DM mice and promote cardiomyocyte contraction, and its mechanism of action seems to be related to the regulation of intracellular calcium homeostasis.

The semi-arid region of northern China is highly sensitive to environmental changes, especially the Hulunbuir Grassland, which has an essential ecological status and a fragile environment. This study focused on the NDVI characteristics of three different ecosystems and their dominant influencing factors. It proposed a method to show the immediate effects of factors influencing NDVI on a statistical level. The results showed that: (1) NDVI of floodplain wetland > NDVI of meadow > NDVI of sand ribbon. There were obvious differences among the three ecosystems, and the spatial distribution of NDVI was consistent with altitude. (2) The main explanatory factors were the phenological period, humidity, temperature, accumulated precipitation, runoff, and evaporation, which accounted for 68.8% of the total explanation. (3) Phenological period, humidity, and precipitation were positively correlated with NDVI. Temperature and evaporation had a positive effect on NDVI within a certain range. This study revealed the differences in environmental factors in different ecosystems, enriched the theory of NDVI influencing factors, and provided a scientific basis for future NDVI research and regional ecological conservation.

Parkinson’s disease (PD) is widely considered to be a disabling neurodegenerative disorder, which has been ranked second worldwide just after Alzheimer’s disease. Until present, a wide range of studies has focused on the role of circulating inflammatory cytokines in the development of PD. However, the causal relationship between circulating inflammatory cytokines and the risk and age at the onset of PD has not been elucidated. Hence, to evaluate the effects of circulating inflammatory cytokines on the risk or age at the onset of PD more accurately, we conducted this two-sample Mendelian randomization (MR) study involving summary statistics from genome-wide association studies (GWASs). Totally, we included a GWAS for inflammatory cytokines (8,293 participants), a meta-analysis of GWASs for PD risk (482,730 participants), and a GWAS dataset for age at the onset of PD (17,996 patients with PD). A total of 149 and 131 polymorphisms for exploring relationships between 19 inflammatory cytokines and the risk and age at the onset of PD were obtained as instrumental variants. Then, we used a total of five MR methods, including inverse-variance weighted (IVW), Wald ratio, MR Egger regression, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Finally, we found a causal association between circulating levels of macrophage inflammatory protein-1 beta (MIP1b) and PD risk in the IVW method (OR: 1.06; 95% CI: 1.02–1.10; P = 0.001). Meanwhile, other MR estimates by weighted median and MR-PRESSO methods yielded similar effect estimates. Besides, we identified a suggestive association of interleukin-16 (IL-16) levels with PD risk (OR: 1.08; 95% CI: 1.00–1.17; P = 0.037). For age at PD onset, there was no evidence supporting its correlation with inflammatory cytokines. Our findings implied that MIP1b and IL-16 may be novel biomarkers and promising therapeutic targets for PD development.

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disease with increasing incidence and high mortality, resulting in a considerable socio-economic burden. Till now, plenty of studies have explored the potential relationship between circulating levels of various micronutrients and ALS risk. However, the observations remain equivocal and controversial. Thus, we conducted a two-sample Mendelian randomization (MR) study to investigate the causality between circulating concentrations of 9 micronutrients, including retinol, folate acid, vitamin B12, B6 and C, calcium, copper, zinc as well as magnesium, and ALS susceptibility. In our analysis, several single nucleotide polymorphisms were collected as instrumental variables from large-scale genome-wide association studies of these 9 micronutrients. Then, inverse variance weighted (IVW) approach as well as alternative MR-Egger regression, weighted median and MR-pleiotropy residual sum and outlier (MR-PRESSO) analyses were performed to evaluate causal estimates. The results from IVW analysis showed that there was no causal relationship of 9 micronutrients with ALS risk. Meanwhile, the three complementary approaches obtained similar results. Thus, our findings indicated that supplementation of these 9 micronutrients may not play a clinically effective role in preventing the occurrence of ALS.

Abstract Objective Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. Methods Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. Results As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways “positive regulation of cytosolic calcium ion concentration” and “inositol phosphate-mediated signaling” and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. Conclusion Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

Recently, numerous studies have been performed to detect the association between H19 polymorphisms and cancer susceptibility. However, their results were inconsistent and controversial. So, we carried out a meta-analysis aiming to define the association exactly. Eligible studies were collected using PubMed and Embase databases up to March 31, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. Sensitivity analysis and publication bias were established to evaluate the robustness of our results. Totally, 60 studies involving 20763 cases and 27403 patients were analysed in our meta-analysis. Our results indicated that H19 rs217727 C > T polymorphism was significantly associated with increased cancer risk. In subgroup analysis, similarly increased risk could be found in gastrointestinal group for rs2839698 and protective effect was observed in rs2107425 polymorphism for cancer development in Caucasian population. Trial sequential analysis strengthened findings of our meta-analysis that cumulative evidence was adequate. In summary, our meta-analysis supported that H19 polymorphisms may be associated with cancer susceptibility.

Abstract Objective Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an important role in DN development. However, until now, the association between genetic polymorphisms and DN risk has remained unknown. We performed a systematic review, meta‐analysis, and trial sequential analysis (TSA) of the association between all genetic polymorphisms and DN risk. Methods Relevant published studies examining the relationship between all genetic polymorphisms and DN were obtained based on a designed search strategy up to 28 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess overall pooled effects of genetic models as well as in subgroup analyses. Sensitive analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results. Results We conducted a systematic review of a total of 1256 articles, and then 106 publications reporting on 136 polymorphisms of 76 genes were extracted. We performed 107 meta‐analyses on 36 studies involving 12,221 subjects to derive pooled effect estimates for eight polymorphisms. We identified that ACE I>D, MTHFR 1298A/C, GPx‐1 rs1050450, and CAT ‐262C/T were associated with DN, while MTHFR C677T, GSTM1, GSTT1, and IL‐10 ‐1082G/A were not. Sensitivity analysis, funnel plot, and Egger’s test displayed robust results. Furthermore, the results of TSA indicated sufficient sample size in studies of ACE, GPx‐1, GSTM1, and IL‐10 polymorphisms. Interpretation Our study assessed the association between ACE I>D, MTHFR C677T, MTHFR 1298A/C, GPx‐1 rs1050450, CAT ‐262C/T, GSTM1, GSTT1, and IL‐10 ‐1082G/A polymorphisms and DN risk. We hope that the data in our research study are used to study DN genetics.

Abstract Background Lipid accumulation product (LAP) is an index describing the overaccumulation of lipid. Baseline LAP was used for type 2 diabetes (T2D) prediction in previous studies. But the longitudinal trajectories of LAP, which reflect the efficacy of patients’ lipid-lowering treatment and lifestyle improvement, have rarely been studied. The aim of this study is to explore the association of lipid accumulation product trajectories with 5-year incidence of type 2 diabetes. Methods This cohort study included 4508 non-diabetic participants with a median age of 42 years. Using the group-based trajectory modeling (GBTM), LAP from 2011 to 2016 were determined and identified as three trajectories: low (n = 3639), moderate (n = 800), and high (n = 69). Baseline LAP was divided into groups by percentiles and tertiles respectively for the comparison of LAP trajectories. The associations between 5-year T2D incidence and LAP trajectories and baseline LAP were both assessed by generalized linear models. Results From 2011 to 2016, 169 participants developed T2D (the 5-year incidence of 3.8%). For participants with low, moderate, and high trajectories, the incidence of T2D was 2.1, 10.0, and 15.9%, respectively. A significant trend was observed in the relative risks (RRs) of 5-year incident T2D in participants with moderate (RR, 1.95; 95% CI: 1.41–2.70) and high LAP trajectory (RR, 2.20; 95% CI: 1.12–4.30) in the fully adjusted model (p for trend

Over the past decade, diverse PD-1/PD-L1 blockades have demonstrated significant clinical benefit in across a wide range of tumor and cancer types. With the increasing number of PD-1/PD-L1 blockades available in the market, differences between the clinical performance of each of them started to be reported. Here, we provide a comprehensive historical and biological perspective regarding the underlying mechanism and clinical performance of PD-1/PD-L1 blockades, with an emphasis on the comparisons of their clinical efficacy and safety. The real-world evidence indicated that PD-1 blockade may be more effective than the PD-L1, though no significant differences were found as regards to their safety profiles. Future head-to-head studies are warranted for direct comparison between them. Finally, we summarize the yet to be elucidated questions and future promise of anti-PD-1/PD-L1 immunotherapy, including a need to explore novel biomarkers, novel combinatorial strategies, and their clinical use on chronic infection.

There has been a growing awareness of the potential environmental impacts from the tire industry in the last two decades. Life cycle assessment (LCA), as an efficient technique, was applied to quantify the environmental impacts of industrial tires through the four stages of life cycle, i.e., production, transportation, use, and end-of-life. In response to the rapid development of LCA applications on tires, this article conducted a comprehensive and critical review on the related literature. The methodology, on-going trends, challenges, and future opportunities in the LCA study of tires are investigated based on a systematic review method. It is found that most studies investigated the end-of-life stage of tires, while ignoring the transportation stage. The use stage is the contributor to most environmental impacts in the entire life cycle of a tire. Notably, the carbon emissions in the use stage range from 550 kg CO2 eq to 840 kg CO2 eq per car tire. There are inconsistencies in several LCA aspects, i.e., functional units, impact assessment methods, impact categories, etc. To improve the environmental performance, the recovery of end-of-life tires (ELT), adoption of secondary materials, and new tire designs are recommended.

Objectives This study aims to investigate the relationship between daily weather and transmission rate of SARS-CoV-2, and to develop a generalised model for future prediction of the COVID-19 spreading rate for a certain area with meteorological factors.Design A retrospective, qualitative study.Methods and analysis We collected 382 596 records of weather data with four meteorological factors, namely, average temperature, relative humidity, wind speed, and air visibility, and 15 192 records of epidemic data with daily new confirmed case counts (1 587 209 confirmed cases in total) in nearly 500 areas worldwide from 20 January 2020 to 9 April 2020. Epidemic data were modelled against weather data to find a model that could best predict the future outbreak.Results Significant correlation of the daily new confirmed case count with the weather 3 to 7 days ago were found. SARS-CoV-2 is easy to spread under weather conditions of average temperature at 5 to 15°C, relative humidity at 70% to 80%, wind speed at 1.5 to 4.5 m/s and air visibility less than 10 statute miles. A short-term model with these four meteorological variables was derived to predict the daily increase in COVID-19 cases; and a long-term model using temperature to predict the pandemic in the next week to month was derived. Taken China as a discovery dataset, it was well validated with worldwide data. According to this model, there are five viral transmission patterns, ‘restricted’, ‘controlled’, ‘natural’, ‘tropical’ and ‘southern’. This model’s prediction performance correlates with actual observations best (over 0.9 correlation coefficient) under natural spread mode of SARS-CoV-2 when there is not much human interference such as epidemic control.Conclusions This model can be used for prediction of the future outbreak, and illustrating the effect of epidemic control for a certain area.

The performance of p-Anisaldehyde (PAA) for preserving pitaya fruit quality and the underpinning regulatory mechanism were investigated in this study. Results showed that PAA treatment significantly reduced fruit decay, weight loss and loss of firmness, and maintained higher content of total soluble solids, betacyanins, betaxanthins, total phenolics and flavonoids in postharvest pitaya fruits. Compared with control, the increase in hydrogen peroxide (H2O2) content and superoxide anion (O2•−) production was inhibited in fruit treated with PAA. Meanwhile, PAA significantly improved the activity of antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT). Moreover, PAA-treated pitaya fruit maintained higher ascorbic acid (AsA) and reduced-glutathione (GSH) content but lower dehydroascorbate (DHA) and oxidized glutathione (GSSG) content, thus sustaining higher ratio of AsA/DHA and GSH/GSSG. In addition, activities of ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and dehydrogenation ascorbic acid reductase (DHAR), as well as the expression of HpSOD, HpPOD, HpCAT, HpAPX, HpGR, HpDHAR and HpMDHAR, were enhanced after PAA treatment. The findings suggest that postharvest application of PAA may be a reliable method to control postharvest decay and preserve quality of harvested pitaya fruit by enhancing the antioxidant potential of the AsA-GSH cycle and activating an antioxidant defense system to alleviate reactive oxygen species (ROS) accumulation.

Abstract In recent years, spherical nanoparticles has been studied extensively on biomedical applications including bioimaging and biosensing, diagnostics and theranostics, but the effect of the shape of nanoparticles has received little attention. In the present study, we designed three different shaped fluorescent mesoporous silica nanoparticles (MSNs), long rod nanoparticles (NLR), short rod nanoparticles (NSR), and spherical nanoparticles (NS) to systematically examine their behavior in vivo after oral administration. The results of the ex vivo optical imaging study in mice indicated that rod nanoparticles had a longer residence time in the gastrointestinal compared with spherical nanoparticles. The in vivo biodistribution showed that all the orally administered MSNs were mainly taken up by the liver, and kidney. NLR had a great capacity to overcoming rapid clearance by the RES and exhibited a longer circulation in the blood than NSR and NS. During renal excretion, the spherical nanoparticles were cleared faster than rod nanoparticles. In addition, it was also found that MSNs can be degraded in vivo and NSR were degraded faster than NLR and NS probably owing to their higher specific surface area. The pharmacokinetic results demonstrated that nifedipine(NI)-loaded NLR had a higher bioavailability than NI-loaded NSR and NS.

A mild and efficient methodology for the bromination of phenols and alkenes has been developed utilizing visible light-induced photoredox catalysis. The bromine was generated in situ from the oxidation of Br− by Ru(bpy)33+, both of which resulted from the oxidative quenching process.