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Resource partitioning may allow species coexistence. Sand dunes in the typical steppe of Alxa Desert Inner Mongolia, China, consisting of desert, shrub, and grass habitats, provide an appropriate system for studies of spatial niche partitioning among small mammals. In this study, the spatial niche characteristics of four rodents, Orientallactaga sibirica, Meriones meridianus, Dipus sagitta, and Phodopus roborovskii, and their responses to environmental changes in the Alxa Desert were studied from 2017 to 2021. Using the capture-mark-recapture method, we tested if desert rodents with different biological characteristics and life history strategies under heterogeneous environmental conditions allocate resources in spatial niches to achieve sympatric coexistence. We investigated the influence of environmental factors on the spatial niche breadth of rodents using random forest and redundancy analyses. We observed that the spatial niche overlap between O. sibirica and other rodents is extremely low (overlap index ≤ 0.14). P. roborovskii had the smallest spatial niche breadth. Spatial niche overlap was observed in two distinct species pairs, M. meridianus and D. sagitta, and P. roborovskii and D. sagitta. The Pielou evenness index of rodent communities is closely related to the spatial distribution of rodents, and the concealment of habitats is a key factor affecting the spatial occupation of rodents.

Abstract Syringin is a natural chemical compound first isolated from the bark of lilac and is known to have neuroprotective effects in middle cerebral artery occlusion (MCAO). Volume regulated anion channel (VRAC) is a cell swelling‐activated anion channel, which is implicated in brain ischemia. However, the mechanism underlying the syringin protecting the neuron from damage in MCAO is still unclear. We hypothesized that syringin has an inhibitory effect on the opening of VRAC channels. To access the effect of syringin on VRAC currents and predict how syringin interacts with VRAC proteins, we performed whole‐cell patch‐clamp experiments using HEK293 cells. Initially, HEK293 cells were perfused with isotonic extracellular solution, followed by hypotonic extracellular solution to stimulate endogenous VRAC currents. Once the VRAC currents reached a steady state, the hypotonic solution containing syringin was perfused to study the effect of syringin on VRAC currents. The potential interaction between syringin and the VRAC protein was investigated using molecular docking as a predictive model. In this study, we found that syringin moderately inhibited VRAC currents in a dose‐dependent manner. The potential binding of syringin to LRRC8 protein was predicted through in silico molecular docking, which suggests an affinity of −6.6 kcal/mol and potential binding sites of arginine 103 and leucine 101. Our results herein characterize syringin as an inhibitor of the VRAC channels, which provides valuable insights for the future development of VRAC channel inhibitors.

ObjectiveUrsodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease.MethodsPatients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report.ResultsIn the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery.ConclusionUDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.

BackgroundLiposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment.Case presentationA 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1–14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months.ConclusionThis case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.

IntroductionAs a special vulnerable group, the physical and mental health of elderly cancer patients has attracted much attention. However, few studies have focused on the impact of nurses’ mental state on the mental health of elderly cancer patients during the COVID-19 pandemic. In response to this literature gap, this study aims to explore the impact of nurses’ psychological capital on the satisfaction of elderly cancer patients. The job demands-resources model (JD-R) is used to further investigate how work engagement and job resources of nurses affect this relationship.MethodsThe questionnaire survey was used to collect data, participants included 230 elderly cancer patients and their nurses from a tertiary first-class cancer hospital in China. Partial least squares structural equation modeling (PLS-SEM) was conducted with SmartPLS 3.3.9.ResultsNurses’ psychological capital has a significant positive impact on the satisfaction of elderly cancer patients during the COVID-19 pandemic. Nurses’ work engagement is an important mechanism for their psychological capital to affect the satisfaction of elderly cancer patients. In addition, nurses’ job resources positively moderate the relationship between their psychological capital and work engagement. The positive relationship between psychological capital and work engagement of nurses is stronger when they have abundant job resources.DiscussionThese findings suggest that healthcare organizations should take the psychological capital of medical staff as an important means to improve their competitive advantage. It can improve the quality of medical services to obtain good performance by effectively developing and managing the psychological capital of medical staff. In addition, healthcare organizations should recognize the importance of providing adequate job resources for medical staff.

BackgroundAs some countries announced to remove Coronavirus Disease 2019 (COVID-19) border, it indicates that the COVID-19 may have entered its terminal stage. In this COVID-19 pandemic, the mental health of frontline healthcare workers (HCWs) experienced unprecedented challenges. However, the impact of the COVID-19 pandemic on mental health among frontline HCWs lacks a high-quality and long-term systematic review and meta-analysis.MethodsWe conducted a systematic review and meta-analysis according to PRISMA guidelines. The system searches EMBASE, MEDLINE, PsycINFO, Cochrane Library, ScienceNet, and ERIC. Analyze the mental health problems of frontline HCWs in different regions and periods, including insomnia, stress, anxiety and depression. This study was registered in PROSPERO under the number CRD42021253821.ResultsA total of 19 studies on the effects of COVID-19 pandemic on mental health among frontline HCWs were included in this study. The overall prevalence of insomnia was 42.9% (95% CI, 33.9–51.9%, I2 = 99.0%) extracted from data from 14 cross-sectional studies (n = 10 127), 1 cohort study (n = 4,804), and 1 randomized controlled trial (RCT; n = 482) in 10 countries. The overall prevalence of stress was 53.0% (95% CI, 41.1–64.9%, I2 = 78.3%) extracted from data from nine cross-sectional studies (n = 5,494) and 1 RCT study (n = 482) from eight countries. The overall prevalence of anxiety and depression was 43.0% (95% CI, 33.8–52.3%, I2 = 99.0%) and 44.6% (95% CI, 36.1–53.1%, I2 = 99.0%) extracted from data from 17 cross-sectional studies (n = 11,727), one cohort study (n = 4,804), and one RCT study (n = 482) from 12 countries. The prevalence of stress and depression was higher in 2020, while the prevalence of insomnia and anxiety was higher in 2021. The prevalence of mental health problems among physicians was higher than that of other frontline HCWs. The prevalence of mental health problems among frontline HCWs is higher in South America and lower in North America.ConclusionsThis systematic review and meta-analysis showed that the COVID-19 pandemic have significant effects on mental health among frontline HCWs. The overall prevalence of insomnia, stress, anxiety and depression among frontline HCWs is high. Therefore, the health policy-makers should pay attention to and respond to the mental health problems of frontline HCWs in the context of public health emergencies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

The egg yolks of birds contain most of the maternally derived materials required for embryo development and are an important factor influencing embryo development and offspring viability. Individual variation in egg-laying date frequently occurs in passerines inhabiting highly seasonal environments. Females laying in early and late stages of the breeding season encounter different environment temperatures and food conditions, which can affect the levels of metabolities in their bodies, thereby altering the transmission of these materials to the eggs. We test a hypothesis that yolk small molecule compounds of Asian Short-toed Lark (Alaudala cheleensis) could vary between early (mid-May) and late (mid-June) broods. Using the UHPLC-MS/MS method, 683 compounds belonging to 21 compound groups are detected in the yolks. The contents of 18 compounds are significantly different between early and late broods. Ten differential compounds are significantly higher in the early laid eggs, among which γ-aminobutyric acid, creatine, prostaglandins, palmitoleic acid, linoleic acid, and trans linoleic acid are related to low environment temperature response. The eggs laid in late stage exhibit significantly higher levels of 5-L-glutamyl-L-alanine and γ-glutamate-leucine, 1,3-dimethyluric acid and mannose, which may be attributed to females in the late group consuming more insects. We suggest conducting a comprehensive investigation to reveal the yolk small molecule compounds mediated maternal effects on offspring phenotypes under varying ecological conditions.

Night lighting has been shown to affect wild animals. To date, the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear. Using model bird species Zebra Finch (Taeniopygia guttata), we investigated the effects of short-term night lighting on liver transcriptome, blood glucose, triglyceride, and thyroxine (T4 and T3) levels in birds exposed to two different night lighting duration periods (three days and six days). After three days of night lighting exposure, the expression of genes involved in fat synthesis in the liver was upregulated while the expression of genes involved in fatty acid oxidation and triglyceride decomposition was downregulated. There was also a reduction in blood triglyceride, glucose, and T3 concentrations. However, after six days of night lighting, the expression of genes associated with fatty acid decomposition and hyperglycemia in the liver was upregulated, while the expression of genes involved in fat synthesis was downregulated. Simultaneously, blood glucose levels and T3 concentration increased. These findings indicate that short-term exposure to night lighting can disrupt the lipid and glucose metabolism of small passerine birds, and longer stopovers in urban area with intense night lighting may cause birds to consume more lipid energy.

The microbial characteristics of water treated by tea polyphenols after the ultrafiltration process were studied based on the continuous disinfection performance of tea polyphenols. Metagenomics was carried out to investigate the microbial community distribution, functional characteristics, and variations after disinfection, to reveal the disinfection principle of tea polyphenols, and to provide the theoretical basis for using tea polyphenols as a disinfectant to better control the growth of microorganisms. The analysis of microbial diversity and community structure showed that the microbial diversity in water was significantly reduced after disinfection with tea polyphenols. The results of hierarchical clustering analysis showed that microbial metabolism, environmental information processing, and functional modules in genetic information processing were significantly inhibited after disinfection treatment using tea polyphenols. The tea polyphenols inhibit the growth and reproduction of microorganisms by selection on the microorganisms in the water, thus achieving the effect of bacterial inhibition. HIGHLIGHTS Tea polyphenols as disinfectants inhibit the regrowth of bacteria.; Tea polyphenols disinfection significantly reduces the diversity of microorganisms in water.; The gene function of many microorganisms in water is greatly changed after disinfection by tea polyphenols.; Tea polyphenols disinfection exerts a greater inhibitory effect on the metabolism of various nucleotides and related processes of microorganisms.;

Sublethally injured bacteria can still develop into normal bacteria under favorable growth conditions, and their pathogenicity poses a great threat to human health. In the drinking water system, some bacteria cause sublethal injury under the action of disinfectants, that is, disinfectant-injured bacteria. Hence, the detection of disinfectant-injured bacteria and the elucidation of injury mechanisms are of great significance for ensuring the microbial safety of drinking water systems. This article takes the indicator bacteria Escherichia coli as the research object, reviews and summarizes the sublethal injury conditions, damage mechanism, and detection methods of disinfectant-injured bacteria in drinking water, and puts forward a prospect for the future research directions of drinking water disinfection and disinfectant-injured bacteria. HIGHLIGHTS Sublethally injured bacteria are formed during the disinfection process.; Introduce the detection methods of disinfectant-injured bacteria.; The injury mechanisms of chlorine- and UV-injured bacteria are described.; It is recommended for an in-depth study of injury mechanisms, minimizing the potential harm of disinfectant-injured bacteria.;

Abstract There are no studies assessing the epidemiology and burden of decubitus ulcers at global, regional, and national levels. We aim to report this issue from 1990 to 2019 by extracting data from the Global Burden of Disease Study (GBD) 2019 and stratifying it by age, gender, and socio-demographic index (SDI). Globally, the number of prevalent cases of decubitus ulcers in 2019 is 0.85 (95% UI 0.78 to 0.94) million. The age-standardized rates of prevalence, incidence, and years lived with disability (YLDs) in 2019 are 11.3 (95% UI 10.2 to 12.5), 41.8 (37.8 to 46.2), and 1.7 (1.2 to 2.2) per 100,000 population, and compared with 1990, it has decreased by 10.6% (95% UI 8.7% to 12.3%), 10.2% (8.2 to 11.9%), and 10.4% (8.1 to 12.5%), respectively. In addition, the global prevalence rate of decubitus ulcers increases with age, peaking at the > 95 age group among men and women. At the regional and national levels, we observe a positive correlation between age-standardized YLDs and SDI. Malaysia, Saudi Arabia, and Thailand experienced the most significant increases in age-standardized prevalence rates at the national level. Finally, we concluded that the age-standardized prevalence, incidence, and YLDs rates of decubitus ulcer declined from 1990 to 2019, with significant regional differences. In order to monitor the dynamic changes of decubitus ulcers burden, it is recommended to improve the quality of decubitus ulcer health data in all regions and countries.

Cryptosporidium and Giardia are globally recognized protozoa that directly cause human diarrhea. Their transmission route mainly involves drinking contaminated water, thus needing proper water treatment to avoid human infection. At present, there is a lack of review on the infection status and control measures of the two protozoa. Hence, this article summarizes and compares the infection status and the role of drinking water in transmitting the Cryptosporidium and Giardia in some key countries in Asia, Africa, Europe, and the Americas. With collected data, this review offers recommendations for sanitary control and provides theoretical support for the application of drinking water treatment projects. HIGHLIGHTS Need to strengthen preventive measures of Giardia and Cryptosporidium in animals.; Improve sanitation facilities, pay attention to non-core areas, and avoid concentrated outbreaks.; Reasonable selection of testing methods according to the needs and conditions of each country.; The water treatment process parameters need to be reasonably selected according to the natural water quality conditions.;

In this study, Qin et al. present a murine-adapted SARS-CoV-2 strain, MASCp36, as a model for studying the pathogenicity, evolution and adaptation of the virus to human and animal hosts.

Degradation activity of plasma catalysis between dielectric barrier discharge (DBD) and carbon nanotubes-graphene-nickel foam (CNTs-G-Nif) has been studied in treatment of dye wastewater. CNTs-G-Nif was prepared through a two-step chemical vapor deposition (CVD) approach. The composite has been characterized by different techniques such as X-ray diffraction (XRD), scanning electron microscope (SEM) and Raman spectroscopy. SEM results showed that the Nif as the growth substrate was evenly wrapped by G and then CNTs were successfully grown on G as the support. The growth mechanism of composite was proposed. The possible coupled catalytic mechanism between DBD and CNTs-G-Nif were addressed. In addition, the modification on G-Nif was found by SEM during the discharge process in liquid phase. And the modification mechanism of DBD plasma (DBDP) acting on composites was discussed. Finally, by means of analyses of ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), the general degradation pathway and stepwise degradation pathways of alizarin green (AG) were proposed in detail. HIGHLIGHTS A novel degradation system DBD plasma/CNTs-G-Nif is proposed.; The new model of coupling factor is put forward to evaluate the degradation effect.; DBD plasma has modification on G-Nif in degradation of dye wastewater.; Comprehensive mechanisms of preparing,coupling,modifying and degrading are explored.;

Abstract Background Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants.

With the service-dominant logic gradually replacing the traditional commodity-dominant reason, co-creating value with consumers has become an essential marketing practice for enterprises. As a critical information carrier in enterprise marketing communication, the co-creation signal impacts co-creation observers. Enterprises are now exploring how to effectively release co-creation signals to attract most observers to participate in value creation activities actively. Based on self-determination theory, this study investigates the influence mechanism of co-creation signals on observers’ willingness to co-create and the moderating role of mental simulation through the experimental method. The conclusions are as follows: (a) The co-creation signal has a significant positive effect on the co-creation intention of observers. Self-designed co-creation signals generate more important co-creation willingness than self-produced co-creation signals; (b) Self-determination and its dimensions mediate the relationship between co-creation signals and the observer’s co-creation willingness; and (c) Mental simulation moderates the relationship between co-creation signal and self-determination. This study has important theoretical significance in enriching co-creation signals and mental simulation research. It also provides management implications for enterprises to release co-creation signals and optimize co-creation marketing practices effectively.

Aging-related muscle loss is a hallmark of aging and is the cause of some negative outcomes. An optimized diet and supplements have a positive effect in slowing down the process of muscle loss. D-galactose(d-gal) has been used widely to develop aging model. This study explored the beneficial effects of whey protein peptides (WPPs) on sarcopenia in d-gal-induced aging mice. A total of 72 SPF male C57BL/6N mice were used in this study. Sixty mice were modeled by injected intraperitoneally with d-gal (100 mg/kg body weight for 6 weeks), and the other 12 mice were used as control, and injected with the same amount of normal saline. After 6 weeks, the modeled mice were randomly divided into the model control group, whey protein group (1.5 g/kg*bw), and three WPPs intervention groups (0.3 g/kg*bw, 1.5 g/kg*bw, 3.0 g/kg*bw), according to serum malondialdehyde (MDA) level. The test samples were orally given to mice by daily garaged. During the 30 days intervention period, the model control group, whey protein group, and WPPs group continued receiving intraperitoneal injections of d-gal, whereas the control group continued receiving intraperitoneal injections of normal saline. The results showed that WPPs could significantly improve the grip strength of aged mice. WPPs could significantly increase lean mass of aged mice and increase muscle weight of gastrocnemius and extensor digitorum longus. WPPs could significantly increase the level of insulin-like growth factor-1 (IGF-1) and reduce level of interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-α) in serum. WPPs could affect the muscle fiber size in d-gal-induced aging mice. Its specific mechanism may be related to the activation of IGF-1/Akt/mTOR protein synthesis signaling pathway and reduction of the level of inflammation. These results indicate that WPPs can improve aging-related sarcopenia. Compared with whey protein, WPPs supplement seems a better form for sarcopenia.

The uterus is the core place for breeding new life. The balance and imbalance of uterine microecology can directly affect or even dominate the female reproductive health. Emerging data demonstrate that endometrial microbiota, endometrium and immunity play an irreplaceable role in regulating uterine microecology, forming a dynamic iron triangle relationship. Up to nowadays, it remains unclear how the three factors affect and interact with each other, which is also a frontier topic in the emerging field of reproductive tract microecology. From this new perspective, we aim to clarify the relationship and mechanism of the interaction of these three factors, especially their pairwise interactions. Finally, the limitations and future perspectives of the current studies are summarized. In general, these three factors have a dynamic relationship of mutual dependence, promotion and restriction under the physiological or pathological conditions of uterus, among which the regulatory mechanism of microbiota and immunity plays a role of bridge. These findings can provide new insights and measures for the regulation of uterine microecology, the prevention and treatment of endometrial diseases, and the further multi-disciplinary integration between microbiology, immunology and reproductive medicine.

Abstract Metabolic syndrome (MetS) is associated with depression, but its role in major depressive disorder comorbid with anxiety (AMD) is unclear. This study aimed to investigate the prevalence and clinical correlates of MetS in first-episode drug-naive (FEDN) patients with AMD in a Chinese Han population. In total, 1380 FEDN outpatients with AMD were recruited in this cross-sectional study. The sociodemographic features, clinical characteristics, history of suicide attempts, thyroid-stimulating hormone (TSH) levels, and MetS parameters of each subject were evaluated. All subjects were rated on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and the Positive and Negative Syndrome Scale positive symptom subscale. The prevalence of MetS among AMD patients was 8.04%. Compared to the non-MetS group, age, age of onset, TSH level, HAM-A and HAM-D scores, history of attempted suicide, and comorbid psychiatric symptoms were higher in the MetS group. Those in this group were also more likely to be married, and they had a lower educational level. Furthermore, age, psychiatric symptoms, suicide attempts, and higher TSH levels were independently associated with MetS in AMD patients. This study suggests a lower prevalence of MetS in FEDN patients with AMD in a Chinese Han population. Older age, comorbid psychiatric symptoms, history of attempted suicide, and higher TSH levels are related factors for MetS in AMD patients.

Abstract Bipolar disorder (BD) and major depressive disorder (MDD) have both common and distinct clinical features, that pose both conceptual challenges in terms of their diagnostic boundaries and practical difficulties in optimizing treatment. Multivariate machine learning techniques offer new avenues for exploring these boundaries based on clinical neuroanatomical features. Brain structural data were obtained at 3 T from a sample of 90 patients with BD, 189 patients with MDD, and 162 healthy individuals. We applied sparse partial least squares discriminant analysis (s-PLS-DA) to identify clinical and brain structural features that may discriminate between the two clinical groups, and heterogeneity through discriminative analysis (HYDRA) to detect patient subgroups with reference to healthy individuals. Two clinical dimensions differentiated BD from MDD (area under the curve: 0.76, P

Here, the authors characterize replication of SARS-CoV-2 in human airway epithelial (HAE) cultures and show that it can infect ciliated and secretory cells, affects transepithelial electrical resistance and causes plaque-like cytopathic effects associated with apoptosis.

Abstract Background Predicting the possibility of severe effects of global warming on animals is important for understanding the ecological consequences of climate change on ecosystem. Spring is the season during which birds have to physiologically prepare for the subsequent breeding period, and unusual spring temperature rising probably becomes a heat stress to the birds which have adapted to the low spring temperature. Therefore, it is necessary to understand the physiological effect of spring warming on the temperate birds. Methods Using the activities of blood anti-oxidative enzymes (SOD, CAT, GPx) and the concentrations of serum immunogloblins (IgA, IgY, IgM) as indicators, we compared the anti-oxidative and immune functions of Asian Short-toed Larks (Calandrella cheleensis) captured between 10 and 15 March, 2015 and housed under conditions of 21 °C and 16 °C. Results The SOD activities of birds in 21 °C group were significantly lower than those in 16 °C group on all the treatment days. The CAT activities of the birds in 21 °C group were significantly lower than those in 16 °C group on the 1st, 5th, 13th, 17 treatment days. The GPx activities of the birds in 21 °C group were signifthicantly lower than those in 16 °C group on the 1st, 13th and 17th, but significantly higher on the 21st treatment day. The IgA, IgY and IgM concentrations of birds in 21 °C group were significantly lower than those in 16 °C group on all the treatment days. Conclusions This study shows that spring temperature rising negatively influences antioxibative and humoral immune functions, which indicates that spring climate warming might reduce the fitness of the temperate passerine birds which have adapted to the low spring temperature.

Previous studies suggest that patients with nephrolithiasis exhibit dysbiosis in their gut microbiota, but those studies were conducted in calcium oxalate stone patients. We aimed to explore the association of gut microbiota and biochemical features of renal uric acid stone (UAS) patients in a Chinese population and identify the related bacteria that may affect the pathopoiesis of UAS. A case-control study of 117 patients with UAS, 123 patients with gout, and 135 healthy controls were included from January 2014 to October 2020. For each subject, data on demographics, biochemical parameters of blood and urine were analyzed. Fifteen patients with gout, 16 patients with UAS, 17 UAS patients with gout, and 17 healthy subjects were enrolled and provided fecal samples. The characteristics of gut microbiota were explored by using 16S ribosomal RNA (rRNA) gene sequencing and analyzed by using a combination of software mother and R. Hyperuricemia was the main risk factor for the development of gout and UAS. Obesity, dyslipidemia, and aciduria were unique risk factors for UAS patients. The richness, diversity, and relative abundance of dominant bacteria at the phylum and genus levels of gut microbiota in UAS patients were significantly distinct from other subjects. Abundance of Bacteroides and Fusobacterium was significantly positively correlated with the serum uric acid (UA) level of UAS patients. Fusobacteria was involved in the metabolism and degradation of certain short-chain fatty acids, amino acids, and sugars in pathopoiesis of UAS, and inhibited their synthesis pathways. Fusobacteria may be related to the pathogenesis of UAS, and this finding contributes to the personalized treatment of UAS from the perspective of maintaining micro-ecological equilibrium in gut.

This study examined the relationship between adherence to 24 h movement guidelines (24 h MGs) and internalising and externalising behavioural problems in Chinese children aged 3–6 years, with a specific focus on the differences between weekdays and weekends. The guidelines include recommendations for physical activity (PA), screen time (ST), and sleep duration (SD). The results indicated a stronger association between adherence to these guidelines and behavioural problems on weekends compared to weekdays. Specifically, the odds of experiencing internalising problems were 1.33 higher (95% CI: 1.05–1.69) when not satisfying all three behaviours compared to not satisfying one or two. Moreover, on weekends, when ST was not fulfilled, there was a higher likelihood of externalising behaviour problems compared to when it was fulfilled (OR, 1.18, 95% CI, 1.01–1.38), and when all three behaviours were not met, the likelihood was even higher (OR, 1.50, 95% CI, 1.04–2.18). Children who met all three guidelines had fewer internalising and externalising behavioural problems, suggesting a potential beneficial effect on mental health. The study revealed that a higher adherence to these recommendations corresponded to a lower risk of mental health problems. Additionally, higher screen time was linked to an increase in externalising behavioural issues. These findings underscore the importance of adherence to 24 h MGs for optimal mental health in children. Future interventions should consider these behavioural factors and incorporate strategies to promote adherence to these guidelines, particularly on weekends.

Current knowledge regarding the long-term humoral response of people infected with human immunodeficiency virus to the third dose of inactivated coronavirus disease (COVID-19) vaccine is incomplete. As a result, concerns remain about the safety and efficacy of the vaccination. To improve our understanding of the safety and immunogenicity of the COVID-19 inactivated vaccine booster in people living with HIV (PLWH), a prospective study was conducted on participants who had not yet received a third dose of the COVID-19 inactivated vaccine, had no history of SARS-CoV-2 infection, and had received a second dose of the vaccine more than six months prior. The primary safety outcomes included the incidence of adverse reactions, changes in CD4+ T-cell count, viral load, blood routine examination, liver and kidney function examination, blood sugar, and blood lipid examination. The pseudovirus-neutralizing antibody responses to the D614G variant, Delta variant, and Omicron variants BA.5 and BF.7 were evaluated before vaccination, 14 days, 28 days, 3 months, and 6 months after vaccination to evaluate the immune response of PLWH to the injection of inactivated vaccine booster and the safety of the vaccine. In conclusion, COVID-19 vaccine booster shots were effective in PLWH, resulting in an increase in the number of CD4+ T-cells, neutralizing antibodies that lasted up to six months, and higher levels of neutralizing antibodies lasting approximately 3 months. However, the vaccine protection against the two variants of BA.5 and BF.7 was significantly lower than that of D614G and Delta.

The rechargeable aluminum batteries (RAB) have shown great potential for energy storage applications due to their low-cost and superior volumetric capacity. However, the battery performances are far from satisfactory owing to the poor kinetics of electrode reactions, including the solid-state ionic diffusion and interfacial charge transfer. The charge transfer reaction, typically the cation desolvation at the interface (Helmholtz plane), is crucial for determining the interfacial charge transfer, which induces the solvent effect in batteries but has not been explored in RABs. Herein, we provide a comprehensive understanding of solvent effects on interface kinetics and electrochemical performance of RAB by analyzing the desolvation process and charge transfer energy barrier. The pivotal role of solvent effects is confirmed by the successful application of Al(OTF)3-H2O electrolyte, which displays easy desolvation, low charge transfer resistance, and thus superior Al-ion storage performance over other electrolytes in our studies. In addition, based on the strong correlation between the calculated desolvation energy and charge transfer energy barrier, the calculation of dissociation energy of ion-solvent complex is demonstrated as an efficient index for designing electrolytes. The in-depth understanding of solvent effects provides rational guidance for new electrolyte and RAB design.

Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of MCs and As exposures on CKD remains unclear. In Hunan province, China, 135 controls and 135 CKD cases were enrolled in a case-control study. Serum MCs, plasma As and Cd concentrations were measured for all participants. We investigated the association between MCs/As and CKD risk using conditional logistic regression. The additive model explored the interaction effect, and the Bayesian kernel machine regression (BKMR) models investigated the combined effects of MCs, As, and Cd on CKD. The results showed that MCs and As were significantly associated with CKD risk. Participants in the highest MCs concentration had a 4,81-fold increased risk of CKD compared to those in the lowest quartile (95% confidence interval [CI]: 1,96 to 11,81). The highest quartile of As concentrations corresponded to an adjusted odds ratio of 3.40 (95% CI: 1.51, 7.65) relative to the lowest quartile. MCs/As and CKD risk exhibited significant dose–response correlations (all p for trend < 0.01). In addition, a positive interaction effect of MCs and As on CKD was also reported. The CKD risk due to interaction was 2.34 times (95% CI: 0.14, 4.54) relative to the CKD risk without interaction, and the attributable proportion of CKD due to interaction among individuals with both exposures was 56% (95% CI: 0.22, 0.91). In the BKMR, the combined effect of MCs, As, and Cd was positively associated with CKD. In conclusion, both MCs and As are independent risk factors for CKD, exerting a synergistic effect between them. Combined exposure to MCs, As, and Cd can increase the risk of CKD.

Exogenous nucleotides (NTs) are considered conditionally essential nutrients, and the brain cannot synthesize NTs de novo. Therefore, the external supplementation of exogenous NTs is of great significance for maintaining normal neuronal metabolism and function under certain conditions, such as brain aging. This study, therefore, sets out to assess the neuroprotective effect of four kinds of single exogenous NTs and a mixture of the NTs, and to elucidate the potential mechanism. A rat pheochromocytoma cell line PC-12 was treated with different concentrations of exogenous NTs after 4 h of exposure to 200 µM H2O2. We found that the exogenous NTs exerted significant neuroprotection through decreasing neuron apoptosis and DNA damage, ameliorating inflammation and mitochondrial dysfunction, promoting cell viability, and augmenting antioxidant activity, and that they tended to up-regulate the NAD+/SIRTI/PGC-1α pathway involved in mitochondrial biogenesis. Among the different NTs, the neuroprotective effect of AMP seemed to be more prominent, followed by the NT mixture, NMN, and CMP. AMP also exhibited the strongest antioxidant activity in H2O2-treated PC-12 cells. UMP was excellent at inhibiting neuronal inflammation and improving mitochondrial function, while GMP offered major advantages in stabilizing mitochondrial membrane potential. The mixture of NTs had a slightly better performance than NMN, especially in up-modulating the NAD+/SIRTI/PGC-1α pathway, which regulates mitochondrial biogenesis. These results suggest that antioxidant activity, anti-inflammatory activity, and protection of mitochondrial function are possible mechanisms of the neuroprotective actions of exogenous NTs, and that the optimization of the mixture ratio and the concentration of NTs may achieve a better outcome.

BackgroundDrug resistance remains a serious challenge to rituximab therapy in B-NHL (B cell non-Hodgkin’s lymphoma). CDC (complement-dependent cytotoxicity) has been proposed as a major antitumor mechanism of rituximab, and direct abrogation of CD59 function partially restores rituximab sensitivity with high efficacy. However, universal blockade of CD59 may have deleterious effects on normal cells. Sp1 regulates constitutive CD59 expression, whereas NF-κB and CREB regulate inducible CD59 expression.MethodsImmunohistochemistry (IHC) assay was used to detect the expression levels of CD59 and other related molecules. Quantitative Real-time PCR (RT-PCR) analysis was used to explore the levels of transcripts in the original and resistant cells. We chose LY8 cells to test the effects of NF-κB and CBP/p300 inhibition on CD59 expression using flow cytometry (FACS). Immunoblotting analysis was employed to detect the effects of curcumin and POH. The in vitro and in vivo experiments were used to evaluate the toxicity and combined inhibitory effect on tumor cells of curcumin and POH.ResultsWe demonstrated that herbal (curcumin and perillyl alcohol) blockade of NF-κB specifically suppresses the expression of inducible CD59 but not CD20, thus sensitizing resistant cells to rituximab-mediated CDC. Moreover, activation of NF-κB and CREB is highly correlated with CD59 expression in B-NHL tissues.ConclusionsOur findings suggest the potential of CD59 expression as a predictor of therapeutic efficacy of NF-κB inhibitors in clinical application as well as the rationality of a NF-κB inhibitor-rituximab regimen in B-NHL therapy.

Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats’ model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.

The topic of one article reflects its main semantic content, which is also the main guidance for researchers to choose reference literature. In order to explore whether the topic of an article will affect its citation trend in future, this paper establishes a machine learning framework to study the role of topic characteristics in the prediction of future high influential articles. Articles from four different disciplines are collected as experimental samples to verify whether the framework proposed in this paper can be applied to the prediction task in different disciplines. The Latent Dirichlet Allocation (LDA) is used to determine the topic characteristics of sample articles. LDA can map sample articles to current hot topics and generate the mapping probability of sample articles under different hot topics. The maximum mapping probability of the sample article under the hot topics is extracted as the topic feature of the article. Then the feature space for the prediction task is constructed by combining the topic feature and some bibliometrics indices of articles. Three feature selection algorithms, Fisher Score, Relief-F and Spectral Feature Selection (SPEC), are taken to select the important features in the feature space. The prediction performance of these features is finally tested by three classifiers, SVM, KNN and Bagging. The experimental results show that the topic characteristics of article, the early citation characteristics of article, and the reputation of the author are the key factors that determine whether an article can grow into a highly influential one. The important value of topic characteristics in articles' citation activities shows that the content of the article is an important factor in attracting more citations.

Abstract Background Group 1 pulmonary arterial hypertension (PAH) is a rare disease with high mortality despite recent therapeutic advances. Pathogenic remodeling of pulmonary arterioles leads to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. Mutations in bone morphogenetic protein receptor type 2 and other risk genes predispose to disease, but the vast majority of non-familial cases remain genetically undefined. Methods To identify new risk genes, we performed exome sequencing in a large cohort from the National Biological Sample and Data Repository for PAH (PAH Biobank, n = 2572). We then carried out rare deleterious variant identification followed by case-control gene-based association analyses. To control for population structure, only unrelated European cases (n = 1832) and controls (n = 12,771) were used in association tests. Empirical p values were determined by permutation analyses, and the threshold for significance defined by Bonferroni’s correction for multiple testing. Results Tissue kallikrein 1 (KLK1) and gamma glutamyl carboxylase (GGCX) were identified as new candidate risk genes for idiopathic PAH (IPAH) with genome-wide significance. We note that variant carriers had later mean age of onset and relatively moderate disease phenotypes compared to bone morphogenetic receptor type 2 variant carriers. We also confirmed the genome-wide association of recently reported growth differentiation factor (GDF2) with IPAH and further implicate T-box 4 (TBX4) with child-onset PAH. Conclusions We report robust association of novel genes KLK1 and GGCX with IPAH, accounting for ~ 0.4% and 0.9% of PAH Biobank cases, respectively. Both genes play important roles in vascular hemodynamics and inflammation but have not been implicated in PAH previously. These data suggest new genes, pathogenic mechanisms, and therapeutic targets for this lethal vasculopathy.

The chemical vapor deposition technique was used to prepare the Ag doped ZnO microrods, which were located on Si substrates at two different positions. The scanning electron microscopy revealed that the samples have a clear hexagonal shape. X-ray diffraction provided information about the preferential orientation along the c-axis. The Raman analysis revealed that a new Raman mode appears at 492 cm-1 due to Ag doping. As this mode has not been reported early, it could be used as a characteristic mode of Ag doping in Raman spectrum. The red shift of the E2 (high) mode proves the existence of tensile stress in the samples. DOI: http://dx.doi.org/10.5755/j01.ms.25.3.19130

In this paper, fast high-order finite difference algorithms for solving the electromagnetic scattering from the finite array of two-dimensional rectangular cavities are proposed in TE polarization. The scattering problem from the cavity array is described as coupled Helmholtz equations with transparent boundary conditions on open apertures. Second-order and fourth-order schemes for solving the coupled systems are developed in TE polarization respectively. A special technique is applied to construct a fourth-order scheme for transparent boundary conditions. Further, we propose fast algorithms which can simplify the larger global system to a small linear interface system on the apertures of cavities. Numerical experiments show the validity and efficiency of the proposed fast algorithms for solving the scattering problem with high wave numbers.

Epidemiological studies of human and animal experiments indicated that gestational exposure to atmospheric pollutants could be followed by the abnormal placental development. However, the effects of this exposure on the placental transportation for nutrients have not been systematically investigated. In this study, fine particulate matters (PM2.5) samples were collected in Taiyuan and pregnant rodent models were administered with 3 mg/kg b.w. PM2.5 by oropharyngeal aspiration every other day starting on embryonic day 0.5 (E0.5). Then the pregnant mice were sacrificed and their placentas were collected at different time points. The results showed that maternal PM2.5 exposure (MPE) disrupted the expression of proliferating cell nuclear antigen (PCNA) at all time points and inhibited the cell proliferation in placenta. Following that, the capacity for placental nutrient transport was impaired. The changes at E18.5 were observed most significantly, showing the altered mRNA expression of amino acid, long-chain polyunsaturated fatty acid (LCPUFA), glucose and folate transporters. In addition, the glycogen content was elevated at E18.5, and the triglyceride content was increased at E13.5 and E15.5 and decreased at E18.5 in the placenta after MPE. In a word, the adverse effect induced by MPE revealed that MPE led tothe disruption on the nutrient supply to the developing fetus via modulating the abundance of placental nutrient transporters (PNT).

Developing post-lithium-ion battery technology featured with high raw material abundance and low cost is extremely important for the large-scale energy storage applications, especially for the metal-based battery systems such as aluminum, sodium, and magnesium ion batteries. However, their developments are still in early stages, and one of the major challenges is to explore a safe and reliable electrolyte. An ionic liquid-based electrolyte is attractive and promising for developing safe and nonflammable devices with wide temperature ranges owing to their several unique properties such as ultralow volatility, high ionic conductivity, good thermal stability, low flammability, a wide electrochemical window, and tunable polarity and basicity/acidity. In this review, the recent emerging limitations and strategies of ionic liquid-based electrolytes in the above battery systems are summarized. In particular, for aluminum-ion batteries, the interfacial reaction between ionic liquid-based electrolytes and the electrode, the mechanism of aluminum storage, and the optimization of electrolyte composition are fully discussed. Moreover, the strategies to solve the problems of electrolyte corrosion and battery system side reactions are also highlighted. Finally, a general conclusion and a perspective focusing on the current development limitations and directions of ionic liquid-based electrolytes are proposed along with an outlook. In order to develop novel high-performance ionic liquid electrolytes, we need in-depth understanding and research on their fundamentals, paving the way for designing next-generation products.

Objectives This study was aimed to assess the relationship between serum uric acid (SUA) level and the clinical, pathological phenotype of IgA nephropathy (IgAN), and to determine the role of SUA level in the progression and prognosis of IgAN. Methods A total of 208 patients with IgAN were included in this study, and were classified into the normo-uricemia group and hyperuricemia group according to the SUA level. The clinical data at baseline, IgAN Oxford classification scores (MEST-C scoring system), and other pathological features were collected and further analyzed. All patients were followed up and the prognosis was assessed using Kaplan-Meier survival curves. GraphPad Prism 7.0 and SPSS 23.0 were used for statistical analyses. Results In clinical indicators, patients with hyperuricemia had the significantly higher proportion of males to females, mean arterial pressure, the levels of total cholesterol, triglyceride, Scr, BUN, 24 hour-urine protein, C3, and C4, the lower levels of high-density lipoprotein cholesterol and eGFR than those without (p 0.05). As for the depositions of immune complexes deposition in IgAN, the hyperuricemia group had less deposition of immunoglobulin G and FRA than the normo-uricemia group (p

This study aimed to investigate the immunomodulatory effects of walnut (Juglans regia L.) oligopeptides (WOPs). Female BALB/c mice were randomly assigned to control, whey protein control and three WOPs groups, given deionized water, 220 mg/kg BW whey protein, 110, 220 and 440 mg/kg BW WOPs daily through drinking water for 30 days, respectively. The immonomodulatory activity determination of WOPs involved innate and adaptive immunity, spleen T lymphocyte subpopulations, serum cytokine and immunoglobulin levels. Our results showed that WOPs could significantly improve humoral and cell-mediated immune responses, macrophage phagocytosis and natural killer cell activity. Moreover, increased T and Th cells percentages, cytokines secretion of interleukin (IL)-2, IL-10, IL-12 and granulocyte–macrophage colony stimulating factor, and production of immunoglobulin (Ig)A, IgG, IgM and intestinally secreted IgA also contributed to these improvements. All these above indicated that WOPs could be a promising immunomodulatory dietary supplement at dosages ranging from 110 to 440 mg/kg BW.

Acute kidney injury (AKI) is a common and serious complication of sepsis accompanied by kidney dysfunction resulting from various etiologies and pathophysiological processes. Unfortunately, there is currently no ideal therapeutic strategy for AKI. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) play important regulatory roles in the pathogenesis of sepsis-associated AKI. In this study, lncRNA TCONS_00016406 (termed lncRNA 6406), a novel lncRNA identified by using TargetScan, was significantly downregulated in the kidney tissues of mice with sepsis-associated AKI. This study aimed to explore the role of lncRNA 6406 in lipopolysaccharide (LPS)-induced AKI and its potential molecular mechanism. The models of sepsis-induced AKI (called LPS-induced AKI models) in mice and cell lines were established with male C57BL/6 mice and renal tubular epithelial (PTEC) cells, respectively. Twenty-four hours after LPS administration, kidneys and cell samples were collected after various treatments to examine the alterations in the lncRNA 6406 levels and to evaluate the effects on LPS-induced inflammation, oxidative stress, and apoptosis through real-time PCR (RT-PCR) analysis, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The results revealed that lncRNA 6406 could significantly attenuate LPS-induced AKI, as shown by the alleviation of inflammation, the suppression of oxidative stress and the inhibition of apoptosis. Mechanistically, a luciferase reporter assay and additional research showed that lncRNA 6406 functioned as a ceRNA to sponge miRNA-687, thereby modulating LPS-stimulated AKI by targeting the miR-687/PTEN axis; thus, this study presents a novel therapeutic strategy or sepsis-associated AKI.

The instability of the host structure of cathode materials and sluggish aluminium ion diffusion are the major challenges facing the Al-ion battery. Here the authors show Al x MnO2·nH2O as a cathode that allows for reversible Al3+ (de)intercalation in an aqueous electrolyte and impressive electrochemical performance for a battery device.

Abstract Background Pulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive pulmonary arterial pressures, right-sided heart failure, and a high mortality rate. Up to 30% of adult and 75% of pediatric PAH cases are associated with congenital heart disease (PAH-CHD), and the underlying etiology is largely unknown. There are no known major risk genes for PAH-CHD. Methods To identify novel genetic causes of PAH-CHD, we performed whole exome sequencing in 256 PAH-CHD patients. We performed a case-control gene-based association test of rare deleterious variants using 7509 gnomAD whole genome sequencing population controls. We then screened a separate cohort of 413 idiopathic and familial PAH patients without CHD for rare deleterious variants in the top association gene. Results We identified SOX17 as a novel candidate risk gene (p = 5.5e−7). SOX17 is highly constrained and encodes a transcription factor involved in Wnt/β-catenin and Notch signaling during development. We estimate that rare deleterious variants contribute to approximately 3.2% of PAH-CHD cases. The coding variants identified include likely gene-disrupting (LGD) and deleterious missense, with most of the missense variants occurring in a highly conserved HMG-box protein domain. We further observed an enrichment of rare deleterious variants in putative targets of SOX17, many of which are highly expressed in developing heart and pulmonary vasculature. In the cohort of PAH without CHD, rare deleterious variants of SOX17 were observed in 0.7% of cases. Conclusions These data strongly implicate SOX17 as a new risk gene contributing to PAH-CHD as well as idiopathic/familial PAH. Replication in other PAH cohorts and further characterization of the clinical phenotype will be important to confirm the precise role of SOX17 and better estimate the contribution of genes regulated by SOX17.

The authors would like to correct spelling mistakes (undenatured type II collagen) in the title, as well as in the main manuscript including the tables and figures in the title paper [...]

Apple Valsa canker is one of the most serious diseases, having caused significant apple yield and economic loss in China. However, there is still no effective biological methods for controlling this disease. Our present study focused on the inhibitory activity and mechanisms of Trichoderma longibrachiatum (T6) fermentation on Valsa mali that causes apple Valsa canker (AVC). Our results showed that the T6 fermentation exhibited effective antifungal activity on the mycelial growth and conidia germination of V. mali, causing mycelium malformation and the hyphal disintegrating in comparison to the control. The activity of pathogenically related enzymes that are secreted from V. mali and the expression level of gene of V. mali were significantly inhibited and downregulated by treatment with T6 fermentation. In addition, the lesion area and number of pycnidia of V. mali formed on the branches were significantly reduced after treatment with the T6 fermentation through the pathogenicity test on the detached branches. Our results indicate that the possible mechanism of T6 fermentation against V. mali occurs through inhibiting its growth and reproduction, the pathogenic enzyme activity, and its related gene expression.

Aluminum (Al) metal has been regarded as a promising anode for rechargeable batteries because of its natural abundance and high theoretical specific capacity. However, rechargeable aluminum batteries (RABs) using Al metal as anode display poor cycling performances owing to interface problems between anode and electrolyte. The solid-electrolyte interphase (SEI) layer on the anode has been confirmed to be essential for improving cycling performances of rechargeable batteries. Therefore, we immerse the Al metal in ionic liquid electrolyte for some time before it is used as anode to remove the passive film and expose fresh Al to the electrolyte. Then the reactions of exposed Al, acid, oxygen and water in electrolyte are occurred to form an SEI layer in the cycle. Al/electrolyte/V2O5 full batteries with the thin, uniform and stable SEI layer on Al metal anode perform high discharge capacity and coulombic efficiency (CE). This work illustrates that an SEI layer is formed on Al metal anode in the cycle using a simple and effective pretreatment process and results in superior cycling performances for RABs.

Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (ΔΨm) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1α to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1α/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.

Integrating patterned, low-loss magnetic materials into microwave devices and circuits presents many challenges due to the specific conditions that are required to grow ferrite materials, driving the need for flip-chip and other indirect fabrication techniques. The low-loss (α = (3.98 ± 0.22) × 10−5), room-temperature ferrimagnetic coordination compound vanadium tetracyanoethylene (V[TCNE]x) is a promising new material for these applications that is potentially compatible with semiconductor processing. Here, we present the deposition, patterning, and characterization of V[TCNE]x thin films with lateral dimensions ranging from 1 μm to several millimeters. We employ electron-beam lithography and liftoff using an aluminum encapsulated poly(methyl methacrylate), poly(methyl methacrylate-methacrylic acid) copolymer bilayer [PMMA/P(MMA-MAA)] on sapphire and silicon. This process can be trivially extended to other common semiconductor substrates. Films patterned via this method maintain low-loss characteristics down to 25 μm with only a factor of 2 increase down to 5 μm. A rich structure of thickness and radially confined spin-wave modes reveals the quality of the patterned films. Further fitting, simulation, and analytic analysis provide an exchange stiffness, Aex = (2.2 ± 0.5) × 10−10erg/cm, as well as insights into the mode character and surface-spin pinning. Below a micron, the deposition is nonconformal, which leads to interesting and potentially useful changes in morphology. This work establishes the versatility of V[TCNE]x for applications requiring highly coherent magnetic excitations ranging from microwave communication to quantum information.

Vanadium tetracyanoethylene (V[TCNE]x) is an organic-based ferrimagnet that exhibits robust magnetic ordering (TC of over 600 K), high quality-factor (high-Q) microwave resonance (Q up to 3500), and compatibility with a wide variety of substrates and encapsulation technologies. Here, we substantially expand the potential scope and impact of this emerging material by demonstrating the ability to produce engineered nanostructures with tailored magnetic anisotropy that serve as a platform for the exploration of cavity magnonics, revealing strongly coupled quantum confined standing wave modes that can be tuned into and out of resonance with an applied magnetic field. Specifically, time-domain micromagnetic simulations of these nanostructures faithfully reproduce the experimentally measured spectra, including the quasiuniform mode and higher-order spin-wave (magnon) modes. Finally, when the two dominant magnon modes present in the spectra are brought into resonance by varying the orientation of the in-plane magnetic field, we observe anticrossing behavior, indicating strong coherent coupling between these two magnon modes at room temperature. These results position V[TCNE]x as a leading candidate for the development of coherent magnonics, with potential applications ranging from microwave electronics to quantum information.

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of undenatured type II collagen (UC II) on bone impairment in ageing db/db mice, and the ageing model was established by normal feeding for 48-week-old. Then, the ageing db/db mice were randomly assigned to UC II intervention, the ageing model, and the chondroitin sulfate + glucosamine hydrochloride control groups. After 12 weeks of treatment, femoral microarchitecture and biomechanical parameters were observed, biomarkers including bone metabolism, inflammatory cytokines, and oxidative stress were measured, and the gastrocnemius function and expressions of interleukin (IL) 1β, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were analyzed. The results showed that the mice in the UC II intervention group showed significantly superior bone and gastrocnemius properties than those in the ageing model group, including bone mineral density (287.65 ± 72.77 vs. 186.97 ± 32.2 mg/cm3), gastrocnemius index (0.46 ± 0.07 vs. 0.18 ± 0.01%), muscle fiber diameter (0.0415 ± 0.005 vs. 0.0330 ± 0.002 mm), and cross-sectional area (0.0011 ± 0.00007 vs. 0.00038 ± 0.00004 mm2). The UC II intervention elevated bone mineralization and formation and decreased bone resorption, inflammatory cytokines, and the oxidative stress. In addition, lower protein expression of IL-1β, RANKL, and TRAP in the UC II intervention group was observed. These findings suggested that UC II improved bones impaired by T2DM during ageing, and the likely mechanism was partly due to inhibition of inflammation and oxidative stress.