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Widely used isotope ratio mass spectrometers have limited capabilities to measure metabolites, drugs, or small polyatomic ions without the loss of structural isotopic information. A new approach has recently been introduced that uses electrospray ionization Orbitrap to measure multidimensional isotope signatures of intact polar compounds. Using nitrate as a model compound, this study aims to establish performance metrics for comparisons with conventional IRMS at the natural abundance level. We present a framework on how to convert isotopolog intensities to δ values that are commonly used in the isotope geochemistry community. The quantification of seven nitrate isotopologs provides multiple pathways for obtaining the primary N and O δ values including non-mass-dependent O isotope variations, as well as opportunities to explore nonrandom isotopic distributions (i.e., clumping effects) within molecular nitrate. Using automation and the adaptation of measurement principles that are specific to isotope ratio analysis, nitrate δ 15 N AIR , δ 18 O VSMOW , and δ 17 O VSMOW were measured with a long-term precision of 0.4‰ or better for isotopic reference materials and purified nitrate from environmental samples. In addition, we demonstrate promising results for unpurified environmental samples in liquid form. With these new developments, this study connects the two largely disparate mass spectrometry fields of bioanalytical MS and isotope ratio MS, thus providing a route to measure new isotopic signatures in diverse organic and inorganic solutes.

Background: Growth in insect pest populations poses a significant threat to ecosystem functions and services, societal development, and food security in alpine regions under climate change. Risk assessments are important prioritization tools for pest management, which must be used to study insect pest expansion in alpine ecosystems under global warming. We used species distribution modeling to simulate the current and future distribution probabilities of 58 insect pest species in the Qinghai Province, China, based on a comprehensive field investigation. Subsequently, general linear modeling was used to explore the relationship between the distribution probability of these species and the damage caused by them. Finally, we assessed the ecological risk of insect pest expansion across different alpine ecosystems under climate change., Results: Climate change could increase the distribution probabilities of insect pest species across different alpine ecosystems. However, the presence of insect pest species may not correspond to the damage occurrence in alpine ecosystems based on percent leaf loss, amount of stunting, and seedling death of their host species. Significant positive relationships between distribution probability and damage occurrence were found for several of the examined insect pest species. Insect pest expansion is likely to increase extensively in alpine ecosystems under increasing carbon dioxide (CO 2 ) emission scenarios., Conclusion: The relationships between distribution probability and damage occurrence should be considered in species distribution modeling for risk assessment of insect pest expansion under climate change. Our study could improve the effectiveness of risk assessment of insect pest expansion under changing climate conditions. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Mono Lake is a closed-basin, hypersaline, alkaline lake located in Eastern Sierra Nevada, California, that is dominated by microbial life. This unique ecosystem offers a natural laboratory for probing microbial community responses to environmental change. In 2017, a heavy snowpack and subsequent runoff led Mono Lake to transition from annually mixed (monomictic) to indefinitely stratified (meromictic). We followed microbial succession during this limnological shift, establishing a two-year (2017-2018) water-column time series of geochemical and microbiological data. Following meromictic conditions, anoxia persisted below the chemocline and reduced compounds such as sulfide and ammonium increased in concentration from near 0 to ~400 and ~150 µM, respectively, throughout 2018. We observed significant microbial succession, with trends varying by water depth. In the epilimnion (above the chemocline), aerobic heterotrophs were displaced by phototrophic genera when a large bloom of cyanobacteria appeared in fall 2018. Bacteria in the hypolimnion (below the chemocline) had a delayed, but systematic, response reflecting colonization by sediment "seed bank" communities. Phototrophic sulfide-oxidizing bacteria appeared first in summer 2017, followed by microbes associated with anaerobic fermentation in spring 2018, and eventually sulfate-reducing taxa by fall 2018. This slow shift indicated that multi-year meromixis was required to establish a sulfate-reducing community in Mono Lake, although sulfide oxidizers thrive throughout mixing regimes. The abundant green alga Picocystis remained the dominant primary producer during the meromixis event, abundant throughout the water column including in the hypolimnion despite the absence of light and prevalence of sulfide. Our study adds to the growing literature describing microbial resistance and resilience during lake mixing events related to climatic events and environmental change., (© 2021 The Authors. Geobiology published by John Wiley & Sons Ltd.)

The hormones oxytocin, vasopressin, and testosterone have been implicated in cooperative behaviours and have attracted increasing research interest for their potential to regulate human cooperation in both healthy and clinical populations. However, the behavioural effects of the administration of these hormones remain to be verified. The current analysis included 41 studies involving 3,269 participants with a narrow age range. We examined the administration effects of these hormones on cooperative behaviour and the regulatory effects of individual characteristics, hormone interventions, and task structure and context. Results revealed a moderate positive effect size of oxytocin intranasal administration, a large negative effect size of vasopressin intranasal administration, and nonsignificant effects of testosterone administration on cooperative behaviours. Participants with mental dysfunctions were less sensitive to oxytocin and vasopressin administration. Oxytocin administration was effective in an in-group situation and for initial choices, corroborating a Tit-for-Tat strategy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: During the COVID-19 pandemic, the Chinese government had transferred many medical rescuers to Wuhan, which provided effective support in disease control. The high-intensity working and mental stress during rescue could induce distress and negatively impact the performance of rescuer afterward. Materials and Methods: To identify the characteristics of stress load and its possible effects on performance, the study surveyed 90 medical rescuers in Wuhan using a mobile phone-based self-rated questionnaire. Results: The results showed an existence of universal but mostly mild distress in rescuers. About 95.6% of the participants reported that they had at least one symptom of distress, whereas, the median scores were <30 (100 as max). Compared with civilian rescuers, a higher proportion of working with immediate virus contact was found in military medical rescuers ( P = 0.008); however, no statistical differences of stress load were found between civilians and militaries. The rescuers with positive cognition or good psychological preparation were found having lower stress loads than other rescuers. An inverse correlation between the stress load and performance (R = -0.24, P = 0.023) and a positive correlation between social support and working performance (R = 0.349, P = 0.001) were found in our survey, suggesting the possible negative effects of stress and the beneficial effects of social support on performance. Conclusion: Our study indicated that more attention should be paid to the distress of medical rescuers against COVID-19. Positive cognitions, good psychological preparations, and sufficient social support would be necessary to reduce the distress and improve the performance in COVID-19 rescue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xie, Wang, Zhao, Wang, Xue, Wang, Chen and Qian.)

Coral-like Ag-Mo 2 C/C-I and blocky Ag-Mo 2 C/C-II composites were obtained from one-step in situ calcination of [Ag(HL) 3 (Mo 8 O 26 )] n ·nH 2 O [L: N-(pyridin-3-ylmethyl) pyridine-2-amine] under N 2 /H 2 and N 2 atmospheres, respectively. The coral-like morphology of Ag-Mo 2 C/C-I is composed of interwoven nanorods embedded with small particles, and the nano-aggregate of Ag-Mo 2 C/C-II is formed by cross-linkage of irregular nanoparticles. The above composites are decorated on glassy carbon electrode (GCE) drop by drop to generate two enzyme-free electrochemical sensors (Ag-Mo 2 C/C/GCE) for amperometric detection of H 2 O 2 . In particular, the coral-like Ag-Mo 2 C/C-I/GCE sensor possesses rapid response (1.2 s), high sensitivity (466.2 μA·mM -1 ·cm -2 ), and low detection limit (25 nM) towards trace H 2 O 2 and has wide linear range (0.08 μM~4.67 mM) and good stability. All these sensing performances are superior to Ag-Mo 2 C/C-II/GCE, indicating that the calcining atmosphere has an important influence on microstructure and electrochemical properties. The excellent electrochemical H 2 O 2 sensing performance of Ag-Mo 2 C/C-I/GCE sensor is mainly attributed to the synergism of unique microstructure, platinum-like electron structure of Mo 2 C, strong interaction between Mo and Ag, as well as the increased active sites and conductivity caused by co-doped Ag and carbon. Furthermore, this sensor has been successfully applied to the detection of H 2 O 2 in human serum sample, contact lens solution, and commercial disinfector, demonstrating the potential in related fields of environment and biology. Graphical abstract.

Objective: To explore the possible way of proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) influencing diabetes mellitus-osteoarthritis (DM-OA) progression., Methods: In vivo, eight-week-old male Sprague Dawley rats were induced with DM-OA by intraperitoneal injection of streptozotocin with high-fat diet feeding and intra-articular injection of monoiodoacetate. PSTPIP2 overexpression was achieved by intra-articular injection of lentivirus vectors. PSTPIP2 expression was verified by real-time polymerase chain reaction and Western blotting. Histological changes were examined by hematoxylin/eosin and safranin-O/fast-green staining. In vitro, rat synovial fibroblasts were induced DM-OA by stimulation of high glucose (HG) and interleukin (IL)-1β. PSTPIP2 overexpression was achieved by lentivirus infection. U0126 was added as an ERK inhibitor. Levels of tumor necrosis factor (TNF)-α, IL-6, and IL-1β were detected using enzyme-linked immunosorbent assay. Expression of matrix metalloproteinase (MMP)-3, MMP-13, aggrecanase-2 (ADAMTS-5), intercellular cell adhesion molecule (ICAM)-1, extracellular regulated protein kinase (ERK) and phospho-ERK (p-ERK) was detected by Western blotting., Results: In DM-OA rats, PSTPIP2 relative messenger RNA (mRNA) level was significantly decreased compared to control rats. The protein expression was also decreased obviously. Inflammation score in synovium was dramatically increased, accompanying with increased TNF-α, IL-6, and IL-1β levels. Osteoarthritis research society international (OARSI) score in cartilage was markedly increased, along with increased MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK expression. In PSTPIP2-overexpressed DM-OA rats, PSTPIP2 mRNA level and protein expression was increased compared to DM-OA rats received negative-control lentivirus vectors. The inflammation score, as well as TNF-α, IL-6, and IL-1β levels were dramatically decreased. Also, the OARSI score and protein expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were decreased. In HG+IL-1β-treated rat synovial fibroblasts, PSTPIP2 protein expression was decreased compared to normal glucose (NG)-treated cells. Levels of TNF-α, IL-6, and IL-1β, as well as expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were increased. After cells were infected with PSTPIP2-overexpressed lentivirus, levels of TNF-α, IL-6, and IL-1β, and expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were obviously decreased compared to cells infected with NC lentivirus. In addition, ERK inhibitor U0126 treatment also decreased the TNF-α, IL-6, and IL-1βlevels and MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK expression in HG + IL-1β treated rat synovial fibroblasts., Conclusion: Overexpression of PSTPIP2 alleviates synovial inflammation and cartilage injury during DM-OA progression via inhibiting ERK phosphorylation., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Cerebrospinal fluid (CSF) progranulin (PGRN) is related to various neurodegeneration diseases. And sleep problems can cause abnormality in protein metabolism in vivo. We aim to explore the potential associations between the self-reported sleep characteristics and CSF PGRN in cognitively intact older adults. Our study recruited 747 participants (mean (standard deviation (SD)) age, 61.99 (10.52) years, 329 (42.89%) females) who had normal cognition from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study with CSF PGRN and sleep characteristics measured. The multiple linear regression and nonlinear regression adjusted for age, gender, education, and apolipoprotein E-epsilon 4 gene (APOE4) status were used to assess the associations between sleep characteristics and PGRN. Interaction effects were explored between APOE4 status and sleep characteristics on CSF PGRN level. Sleep disturbances indicated lower CSF PGRN (β = - 0.0186, p = 0.0160). For detailed items in sleep disturbances, lower CSF PGRN was found in males who woke up during sleep (β = - 0.0121, p = 0.0062) and in females who had breathing difficulties (β = - 0.0258, p = 0.0271). Meanwhile, sleep efficiency was associated with CSF PGRN (β = - 0.0512, p = 0.0497). No significant interaction effects between sleep characteristics and APOE4 status were found. Meanwhile, we did not find a nonlinear relationship between nocturnal sleep duration and CSF PGRN. Sleep problems may influence the metabolism of PGRN, thus attenuating the protective effects of PGRN on neurodegeneration diseases.

Background: Previous studies have demonstrated that Luteolin has a positive effect on epithelial barrier integrity by promoting the function of tight protein, however, little is known about the underline mechanism of Luteolin. In this study, we constructed Caco-2 cell monolayer to explore the effects and the regulation mechanism of Luteolin in intestinal epithelial barrier integrity., Methods: Caco-2 cells were co-treated with TNF-α, Interferon-γ (IFN-γ) and Luteolin for 24 h. Overexpression or knockdown of SHP-1 was applied to study the effects of protein phosphoserine phosphatase-1 (SHP-1) on epithelial barrier integrity. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Barrier function was detected by trans-epithelial electrical resistance (TEER) and FITC-dextran assay. The expression levels of SHP-1, phosphorylation signal transducer and activator of transcription 3 (p-STAT3), STAT3 and tight junction proteins were measured by qRT-PCR or western blot. In vivo model of ulcerative colitis was established to detect the function of Luteolin in ulcerative colitis., Results: We clarified that Luteolin protected intestinal epithelial barrier function of Caco-2 monolayers by increasing the resistance values and tight junction (TJ) protein expression. The expression of OCLN, CLDN1, and ZO1 was increased by Luteolin, while the expression of CLDN2 was decreased. Furthermore, Luteolin significantly alleviated the symptom of ulcerative colitis in DSS-induced mice. The in vitro cell model proved that overexpression of SHP-1 promotes the epithelial barrier function and knockdown of SHP-1 or STAT3 activation destroyed the protective effects of Luteolin on the expression of TJ proteins., Conclusion: We found that the treatment of Luteolin promoted epithelial barrier function and Luteolin might preserve intestinal epithelial barrier function through suppression of STAT3 signaling pathway by SHP-1.

Background/aims: Maxillofacial soft tissue injuries (STIs) may differ in epidemiological characteristics from other maxillofacial injuries. The aim of this study was to investigate the epidemiology of maxillofacial STIs in a public oral emergency department in Beijing, China, from 2017 to 2018., Material and Methods: In this retrospective study, 5949 patients with maxillofacial STIs and complete medical records were evaluated. Gender, age, etiology, visit date and time, interval between accident and treatment, anatomic injury site, treatment modality, and the number of associated maxillofacial bone fractures or tooth injuries were analyzed., Result: There were 3831 males and 2118 females (ratio 1.81:1). Patients younger than 10 years were the most frequently seen group (44.2%). Among adults, 20- to 29-years-old (16.2%) was the most prominent age group. The month of May (11.8%) had the highest incidence of maxillofacial STIs, and February (4.5%) had the lowest incidence. The average number of daily visits was significantly higher on holidays than on workdays. Of the 5949 patients, 45.9% attended at night, 2021 patients had dental trauma, and 31 had jaw fractures. The lips were the most common site of STIs, followed by the chin and gingiva. Lip and gingival STIs were more common in the 0- to 10-years-old group. Chin STIs were more common in the 20- to 39-years-old group. A fall was the leading cause of injury, especially in patients younger than 10 years and older than 70 years. Approximately 56.7% of the falls resulted in injuries to the lower one-third of the face. Sports injuries were more common among 10- to 29-years-old individuals., Conclusion: STIs of the maxillofacial region were most likely to occur at night, in May and during holidays. Males, children younger than 10 years and 20- to 29-years-old adults were high-risk populations. Most maxillofacial STIs involved the lips, and one-third of the patients had dental trauma., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Adipogenesis of bone marrow mesenchymal stem cells (MSCs) promotes chemoresistance of acute myeloid leukaemia (AML) cells. MSCs from AML patients (AML-MSCs) display enhanced adipogenesis compared with bone marrow MSCs from healthy donors. However, the precise molecular mechanism by which adipogenesis of MSCs from AML marrow differs from normal counterparts remains obscure. We found that METTL3 significantly inhibits MSC adipogenesis. Here, we aimed to identify the molecular mechanism linking METTL3 and MSC adipogenesis. Analysis of m 6 A epigenetic changes in MSCs determined via RIP-qPCR and MeRIP-qPCR indicated that METTL3 affects AKT protein expression in MSCs by mediating m 6 A modification of AKT1-mRNA. Downregulated METTL3 expression in AML-MSCs induced an increase in AKT protein, resulting in enhanced MSC adipogenesis, thereby contributing to chemoresistance in AML cells. Therefore, targeting AKT regulation by mRNA modification in MSC adipogenesis might provide a novel therapeutic strategy to overcome AML chemoresistance., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Fly ash-the residuum of coal burning-contains a considerable amount of fossilized particulate organic carbon (FOC ash ) that remains after high-temperature combustion. Fly ash leaks into natural environments and participates in the contemporary carbon cycle, but its reactivity and flux remained poorly understood. We characterized FOC ash in the Chang Jiang (Yangtze River) basin, China, and quantified the riverine FOC ash fluxes. Using Raman spectral analysis, ramped pyrolysis oxidation, and chemical oxidation, we found that FOC ash is highly recalcitrant and unreactive, whereas shale-derived FOC (FOC rock ) was much more labile and easily oxidized. By combining mass balance calculations and other estimates of fly ash input to rivers, we estimated that the flux of FOC ash carried by the Chang Jiang was 0.21 to 0.42 Mt C⋅y -1 in 2007 to 2008-an amount equivalent to 37 to 72% of the total riverine FOC export. We attributed such high flux to the combination of increasing coal combustion that enhances FOC ash production and the massive construction of dams in the basin that reduces the flux of FOC rock eroded from upstream mountainous areas. Using global ash data, a first-order estimate suggests that FOC ash makes up to 16% of the present-day global riverine FOC flux to the oceans. This reflects a substantial impact of anthropogenic activities on the fluxes and burial of fossil organic carbon that has been made less reactive than the rocks from which it was derived., Competing Interests: The authors declare no competing interest.

Surface-enhanced Raman spectroscopy (SERS) is a promising ultrasensitive analysis technology due to outstanding molecular fingerprint identification. However, the measured molecules generally need to be adsorbed on a SERS substrate, which makes it difficult to detect weakly adsorbed molecules, for example, the volatile organic compound (VOC) molecules. Herein, we developed a kind of a SERS detection method for weak adsorption molecules with Au@ZIF-8 core-shell nanoparticles (NPs). The well-uniformed single- and multicore-shell NPs can be synthesized controllably, and the shell thickness of the ZIF-8 was able to be precisely controlled (from 3 to 50 nm) to adjust the distance and electromagnetic fields between metal nanoparticles. After analyzing the chemical and physical characterization, Au@ZIF-8 core-shell NPs were employed to detect VOC gas by SERS. In contrast with multicore or thicker-shell nanoparticles, Au@ZIF-8 with a shell thickness of 3 nm could efficiently probe various VOC gas molecules, such as toluene, ethylbenzene, and chlorobenzene. Besides, we were capable of observing the process of toluene gas adsorption and desorption using real-time SERS technology. As observed from the experimental results, this core-shell nanostructure has a promising prospect in diverse gas detection and is expected to be applied to the specific identification of intermediates in catalytic reactions.

We determined the complete mitochondrial genome of Oplophorus spinosus with a typical circular structure. The complete mitogenomes of O. spinosus was 17,346 bp in length, with 37 genes containing 13 protein-coding genes, 22 tRNAs, two rRNAs, and a confirmed D-loop zone. The GC content of O. spinosus was 34.39%. The phylogenetic results showed that O. spinosus was most closed to O. typus , providing useful mitochondrial information for its further evolutionary and taxonomy study., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The cerebellum has long been conceptualized to control motor learning and motor coordination. However, increasing evidence suggests its roles in cognition and emotion behaviors. In particular, the cerebellum has been recognized as one of key brain regions affected in autism spectrum disorder (ASD). To better understand the contribution of the cerebellum in ASD pathogenesis, we here discuss recent behavioral, genetic, and molecular studies from the human and mouse models. In addition, we raise several questions that need to be investigated in future studies from the point view of cerebellar dysfunction, cerebro-cerebellar connectivity and ASD., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Cryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals. However, the molecular mechanisms underlying host and Cryptosporidium interactions are still not clear., Methods: To study the roles of circRNAs in host cells during Cryptosporidium infection, the expression profiles of circRNAs in HCT-8 cells infected with C. parvum were investigated using a microarray assay, and the regulatory role of a significantly upregulated circRNA, ciRS-7, was investigated during C. parvum infection., Results: C. parvum infection caused notable alterations in the expression profiles of circRNAs in HCT-8 cells, and a total of 178 (including 128 up- and 50 downregulated) circRNAs were significantly differentially expressed following C. parvum infection. Among them, ciRS-7 was significantly upregulated and regulated the NF-κB signaling pathway by sponging miR-1270 during C. parvum infection. Furthermore, the ciRS-7/miR-1270/relA axis markedly affected the propagation of C. parvum in HCT-8 cells., Conclusions: Our results revealed that ciRS-7 would promote C. parvum propagation by regulating the miR-1270/relA axis and affecting the NF-κB pathway. To the best of our knowledge, this is the first study to investigate the role of circRNA during Cryptosporidium infection, and the findings provide a novel view for implementing control strategies against Cryptosporidium infection.

Cytoskeletal protein β-actin is abundant both in the cytoplasm and the nucleus, its mRNA is commonly utilized an internal control for gene expression analysis. Recent reports demostrated that hypoxia influences the levels of β-actin in a variety of cells. The mechanism underlying this change are not yet elucidated. In this work, we show that the changes in the levels of hypoxia-induced Nuclear respiratory factor-1 (NRF-1) lead to the change in expression of β-actin. We compared the protein levels of NRF-1 and β-actin in gastric cancer and adjacent tissues and found their significantly upregulation in cancer (33% patitents). When gastric cancer cells and normal gastric cells were treated with 1% O2 for 48 h, the trends in expression levels of NRF-1 and β-actin were similar. When NRF-1 expression was modified by its overexpressing or silencing, the levels of β-actin changed accordingly. In β-actin gene (ACTB), three binding sites for NRF-1 were found. These sites are conserved in human, mouse and rat genomes. In ChIP experiments, we showed that NRF-1 directly binds to human ACTB and mouse Actb coding regions. Its seems that the transcription of β-actin encoding gene is NRF-1 dependent.

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo . RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors have no conflicts of interest to declare., (Copyright © 2021 Wang, Peng, An, Shang, Xiao, He, Chen, Zhang, Wang, Wang, Zhang, Gao, Zhu and Feng.)

In order to clarify the characteristics of anaerobic ammonia oxidizing (ANAMMOX) sludge and the succession rule of bacteria based on particle size differentiation, the performance change and microbial community structure of ANAMMOX floc sludge during the formation of particles in the reaction system of a high ammonia-nitrogen biofilter were studied. The results indicated that the specific activity (SAA) and tolerance of the ANAMMOX granular sludge (AnGS) were significantly improved by increasing the particle size, and the SAA of R4(>4.75 mm) was up to 426.8 mg·(g·d) -1 , but it also had adverse effects on mass transfer. The results of the high-throughput sequencing showed that dynamic changes between bacterial genera were common. When the particle size was less than 4.75 mm, the increase in particle size strengthened the stability of the bacterial flora, the ammonia oxidizing bacteria (AOB) with more flocs were eliminated, and the nitrogen removal ratio gradually stabilized. R3 (2.8-4.75 mm) exhibited the most specific flora composition, and the functional bacteria Candidatus Kuenenia accounted for 52.7%, while the R4 community complexity increased. Furthermore, the proportion of functional bacteria decreased, and the abundance of heterotrophic bacteria increased, which negatively affected the particle structure. In addition, the R3 microorganism has the best gene function expression level, which is significantly better than small particles in gene replication repair and energy conversion. Finally, the evolution of AnGS was analyzed through the OTU matrix between the samples. These results have some guiding significance for the optimization of the AnGS system and will be helpful for the application of the ANAMMOX process.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca 2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca 2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases., Competing Interests: The authors declare no competing interest.

The high charge-discharge voltage gap is one of the main bottlenecks of zinc-air batteries (ZABs) because of the kinetically sluggish oxygen reduction/evolution reactions (ORR/OER) on the oxygen electrode side. Thus, an efficient bifunctional catalyst for ORR and OER is highly desired. Herein, honeycomb-like MnCo 2 O 4.5 spheres were used as an efficient bifunctional electrocatalyst. It was demonstrated that both ORR and OER catalytic activity are promoted by Mn IV -induced oxygen vacancy defects and multiple active sites. Importantly, the multivalent ions present in the material and its defect structure endow stable pseudocapacitance within the inactive region of ORR and OER; as a result, a low charge-discharge voltage gap (0.43 V at 10 mA cm -2 ) was achieved when it was employed in a flexible hybrid Zn-based battery. This mechanism provides unprecedented and valuable insights for the development of next-generation metal-air batteries., (© 2021 Wiley-VCH GmbH.)

Objective: To explore the effect of failure mode and effect analysis (FMEA) in the management of nosocomial infection, and provide reference for the effective prevention and control of nosocomial infection. Methods: Using FMEA to identify, analyze, evaluate and screen out the high-risk events of nosocomial infection in January 2020, from which two hospital level priority improvement projects of hand hygiene compliance and blood-borne occupational exposure were determined. After risk control and intervention measures, the effects before and after improvement were compared. Results: Except for the lack of incentive mechanism and insufficient communication between medical and nursing teams, the differences in hand hygiene compliance and blood-borne occupational exposure risk priority coefficients before and after the implementation of FMEA were statistically significant ( P <0.05) . After the implementation of FMEA, the hand hygiene compliance was 74.92% (79375/105953) , which was significantly higher than 68.40% (58361/85328) before the implementation of FMEA, and the difference was statistically significant (χ(2)=996.55, P <0.01) . The incidence of blood-borne occupational exposure after the implementation of FMEA was 3.85% (80/2080) , which was lower than the 6.16% (123/1998) before the implementation of FMEA, and the difference was statistically significant (χ(2)=11.49, P <0.01) . Conclusion: FMEA has a good effect in nosocomial infection management. It can identify and evaluate the risk of nosocomial infection prospectively, so as to control the risk effectively.

Objective: To observe the functional changes of skeletal muscle in severely burned rats, and to investigate the effects and possible mechanisms of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway inhibitor in skeletal muscle function. Methods: The experiment research method was applied. One hundred and twenty male Wistar rats of 8-week-old were divided into sham injury group, simple burn group, and burn+JAK/STAT3 inhibitor group according to the random number table, with 40 rats in each group. Rats in simple burn group and burn+JAK/STAT3 inhibitor group were inflicted with 50% total body surface area full-thickness scald on the back and abdomen, and rats in sham injury group were sham injured. Rats in burn+JAK/STAT3 inhibitor group were intraperitoneally injected with JAK/STAT3 inhibitor ruxolitinib. On post injury day (PID) 0 (immediately), 1, 4, 7, and 14, 8 rats in each group were used to measure the specific force generated by extensor digitorum longus in optimal length stimulated with pulse frequency of 20, 40, 60, 80, 100, 120, 140, and 160 Hz using a multichannel electrophysiological instrument, and specific force in fatigue period of extensor digitorum longus in optimal length stimulated with pulse frequency of 50 Hz for 0, 10, 20, 30, 60, 120, 180, 240, and 300 s. On PID 0, 1, 4, 7, and 14, carbonyl compound content of extensor digitorum longus was determined by ultraviolet spectrophotometry, and ATP content of extensor digitorum longus was determined by micrometry. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, Bonferroni method, and t test. Results: Compared with those of sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased after being stimulated with all the pulse frequency on PID 0, 1, 7, and all the pulse frequency except for 20 Hz on PID 4, and pulse frequency of 20 and 40 Hz on PID 14 ( P <0.05 or P <0.01). Compared with those of simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were significantly increased after being stimulated with all the pulse frequency except for 20 Hz on PID 1 and all the pulse frequency on PID 4, 7, and 14 ( P <0.05 or P <0.01). Compared with those of sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased in fatigue period at all the time points post injury and stimulation time points except for 240 s on PID 7 ( P <0.05 or P <0.01). Compared with those of simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were obviously increased in fatigue period at all the stimulation time points except for 60 and 300 s on PID 1 and 240 s on PID 4, and all the stimulation time points on PID 7 and 14 ( P <0.05 or P <0.01). The carbonyl compound content of extensor digitorum longus of rats in simple burn group on PID 0, 1, 4, 7, and 14 was (0.651±0.155), (0.739±0.194), (0.618±0.086), (0.813±0.162), (0.615±0.115) nmol/mg, which were obviously higher than (0.196±0.019), (0.156±0.004), (0.169±0.023) (0.156±0.027), (0.175±0.008) nmol/mg in sham injury group ( t =7.219, 6.491, 10.938, 9.182, 11.589, P <0.01) and (0.538±0.069), (0.369±0.059), (0.273±0.061), (0.334±0.109), (0.318±0.101) nmol/mg in burn+JAK/STAT3 inhibitor group ( t =2.446, 4.689, 8.355, 5.754, 6.097, P <0.05 or P <0.01). The ATP content in extensor digitorum longus of rats in simple burn group on PID 1, 4, 7, and 14 was obviously lower than that in sham injury group ( t =7.159, 7.591, 7.473, 4.026, P <0.01) and burn+JAK/STAT3 inhibitor group ( t =2.295, 2.575, 2.453, 2.997, P <0.05). Conclusions: After severe burn, the specific force of extensor digitorum longus in rats decreased significantly after being stimulated with different pulse frequencies, and the extensor digitorum longus in rats was prone to fatigue. Blocking the JAK/STAT3 signaling pathway can reduce the oxidative stress of muscle protein and increase ATP content, thereby reducing the muscle strength decline caused by burn injury and improving the muscle strength decline during fatigue period.

Elucidating hydrogen oxidation reaction (HOR) mechanisms in alkaline conditions is vital for understanding and improving the efficiency of anion-exchange-membrane fuel cells. However, uncertainty remains around the alkaline HOR mechanism owing to a lack of direct in situ evidence of intermediates. In this study, in situ electrochemical surface-enhanced Raman spectroscopy (SERS) and DFT were used to study HOR processes on PtNi alloy and Pt surfaces, respectively. Spectroscopic evidence indicates that adsorbed hydroxy species (OH ad ) were directly involved in HOR processes in alkaline conditions on the PtNi alloy surface. However, OH ad species were not observed on the Pt surface during the HOR. We show that Ni doping promoted hydroxy adsorption on the platinum-alloy catalytic surface, improving the HOR activity. DFT calculations also suggest that the free energy was decreased by hydroxy adsorption. Consequently, tuning OH adsorption by designing bifunctional catalysts is an efficient method for promoting HOR activity., (© 2020 Wiley-VCH GmbH.)

Muqubilin, negombatoperoxide B, and negombatoperoxide C/D were synthesized through enantioselective routes, with the quaternary center derived from a peroxy chiral building block of known absolute configuration. The C-2/C-3 stereogenic centers were introduced by asymmetric aldol condensation, and the 1,2-dioxane ring was constructed via an intramolecular alkylation of a hydroperoxide with a mesylate. The synthetic samples showed physical and spectroscopic data consistent with those reported in the literature and thus verified the configurations of the natural products. A potentially more expeditious enantioselective entry to the 1,2-dioxane-aldol moiety (C-1 to C-6) of such cyclic peroxides was also briefly explored, where the C-2/C-3 stereogenic centers were installed through a [2+2] cycloaddition and the 1,2-dioxane ring was closed via an intramolecular alkylation coupled with an alkyl-oxygen cleavage of a β-lactone.

Objective: To compare the value of new gastric cancer screening scoring system and serum pepsinogen (PG) combined with gastrin-17 (G-17) (new ABC method) in screening gastric cancer and precancerous lesions. Methods: A total of 576 patients were enrolled after the examination of endoscopy at Endoscopy Center,Department of Gastroenterology,from December 2017 to December 2019. There were 275 males and 301 females with an age of 40-72 (52±10) years. According to the new ABC method and the new gastric cancer screening scoring system, the population was divided into three groups according to age,gender,serum helicobacter pylori antibody test, PG Ⅰ/PG Ⅱ(PGR) and G-17 before endoscopy. The detection rates of gastric cancer and atrophic gastritis by two different methods were analyzed and the value in screening gastric cancer and precancerous lesions were evaluated. Statistical analysis was accomplished by Chi-square test and Gamma coefficient analysis. Results: A total of 576 patients were enrolled. According to the new ABC method, 382 patients were classified into low-risk group, 170 patients into middle-risk group and 24 patients into high-risk group, respectively. In the new ABC method, 1 case of gastric cancer (0.3%) was detected in low-risk group, 8 cases (4.7%) in middle-risk group and 3 cases (12.5%) in high-risk group. As for atrophic gastritis, 89 cases (23.3%) was detected in low-risk group, 94 cases (55.3%) in middle-risk group and 18 cases (75.0%) in high-risk group. According to the new gastric cancer screening scoring system, 336 patients were classified into low-risk group, 205 patients into middle-risk group and 35 patients into high-risk group, respectively. One case of gastric cancer (0.3%) was detected in low-risk group, 6 cases (2.9%) in middle-risk group and 5 cases (14.3%) in high-risk group. As for atrophic gastritis, 41 cases (12.2%) were detected in low-risk group, 134 cases (65.4%) in middle-risk group and 26 cases (74.3%) in high-risk group. In this two methods, the prevalence of gastric cancer increased according to the disease stage ( χ ² = 22.509, P <0.01; χ ²=24.156, P <0.01); in terms of atrophic gastritis, the detection rate of the new screening scoring system in the low-risk group was significantly lower than that in the new ABC method ( χ ²=14.844, P <0.01), but higher in the middle-risk group ( χ 2 =3.955, P =0.047). Gamma coefficient test showed that there were strong correlations between gastroscopy pathology and classification grade of both methods ( P <0.01). Conclusions: Both methods are suitable for screening gastric cancer and precancerous lesions, and the new scoring system may be more valuable in screening gastric cancer and precancerous lesions.

The cerebellum is conceptualized as a processor of complex movements. Many diseases with gene-targeted mutations, including Fahr's disease associated with the loss-of-function mutation of meningioma expressed antigen 6 ( Mea6 ), exhibit cerebellar malformations, and abnormal motor behaviors. We previously reported that the defects in cerebellar development and motor performance of Nestin-Cre; Mea6 F/F mice are severer than those of Purkinje cell-targeted pCP2-Cre; Mea6 F/F mice, suggesting that Mea6 acts on other types of cerebellar cells. Hence, we investigated the function of Mea6 in cerebellar granule cells. We found that mutant mice with the specific deletion of Mea6 in granule cells displayed abnormal posture, balance, and motor learning, as indicated in footprint, head inclination, balanced beam, and rotarod tests. We further showed that Math1-Cre; Mea6 F/F mice exhibited disrupted migration of granule cell progenitors and damaged parallel fiber-Purkinje cell synapses, which may be related to impaired intracellular transport of vesicular glutamate transporter 1 and brain-derived neurotrophic factor. The present findings extend our previous work and may help to better understand the pathogenesis of Fahr's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zhou, Cai, Xu, Xu, Li and Shen.)

Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients., Methods: We enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined., Results: Plasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38-6.64) vs 4.13 (3.20-5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608-8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647-6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection., Conclusions: Increased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.

Background: Mitochondrial dysfunction plays an important role in the development of septic cardiomyopathy. This study aimed to reveal the protective role of uncoupling protein 2 (UCP2) in mitochondria through AMP-activated protein kinase (AMPK) on autophagy during septic cardiomyopathy., Methods: UCP2 knockout mice via a cecal ligation and puncture (CLP) model and the H9C2 cardiomyocyte cell line in response to lipopolysaccharide (LPS) in vitro were used to study the effect. The myocardial morphological alterations, indicators of mitochondrial injury and levels of autophagy-associated proteins (pAMPK, pmTOR, pULK1, pTSC2, Beclin-1, and LC3-I/II) were assessed. In addition, the mechanism of the interaction between UCP2 and AMPK was further studied through gain- and loss-of-function studies., Results: Compared with the wild-type mice, the UCP2 knockout mice exhibited more severe cardiomyocyte injury after CLP, and the AMPK agonist AICAR protected against such injury. Consistent with this result, silencing UCP2 augmented the LPS-induced pathological damage and mitochondrial injury in the H9C2 cells, limited the upregulation of autophagy proteins and reduced AMPK phosphorylation. AICAR protected the cells from morphological changes and mitochondrial membrane potential loss and promoted autophagy. The silencing and overexpression of UCP2 led to correlated changes in the AMPK upstream kinases pLKB1 and CAMKK2., Conclusions: UCP2 exerts cardioprotective effects on mitochondrial dysfunction during sepsis via the action of AMPK on autophagy., Competing Interests: Conflicts of Interest: All authors completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4819). JYM received support for the present research from the Beijing Municipal Natural Science Foundation of China. The other authors have no potential conflicts of interest to disclose., (2021 Annals of Translational Medicine. All rights reserved.)

PtNi alloy catalysts have excellent catalytic activity and are considered some of the most promising electrocatalysts capable of replacing pure Pt for the oxygen reduction reaction (ORR). For PtNi alloys, Ni-doping can improve performance by changing the electronic and structural properties of the catalyst surface and its interaction with reaction intermediates. However, to date there is no direct spectral evidence detecting or identifying the effect of Ni on the ORR in PtNi alloy catalysts. Herein, we introduce a surface-enhanced Raman spectroscopic (SERS) "borrowing" strategy for investigating ORR processes catalyzed by Au@PtNi nanoparticles (NPs). The bond vibration of adsorbed peroxide intermediate species (*OOH) was obtained, and the effect of Ni on the interaction between surface Pt and *OOH was studied by varying the Ni content in the alloy. The frequency of the *OOH spectral band has an obvious red-shift with increasing Ni content. Combined with density functional theory (DFT) calculations, we show that Ni-doping can optimize *OOH surface binding on the Pt surface, achieving more efficient electron transfer, thus improving the ORR rate. Notably, these results evidence the SERS borrowing strategy as an effective technique for in situ observations of catalytic processes.

Background: Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology., Methods: Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I-T) and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC., Results: Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway., Conclusions: S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

Background: Subjective cognitive decline (SCD) as an early pathological manifestation of brain aging has become more prevalent among older adults., Objectives: We aimed to investigate the associations of subjective cognitive decline (SCD) with the combined risk of cognitive impairment and dementia., Design: We performed a systematic review and meta-analysis via searching Embase, PubMed and Cochrane electronic databases from January 1 st 1970 to June 4th, 2020., Setting: Prospective cohort studies Participants: Healthy individuals were recruited from community, clinics and population., Measurements: Healthy individuals with SCD were classified into exposure groups, while those without were considered as the reference group. Adjusted relative risks (RR) were estimated in a random-effects model. Both primary and subgroup analyses were conducted., Results: Of 28,895 identified studies, 21 studies containing 22 cohorts were eligible for inclusion in the meta-analysis. SCD increased the risk of subsequent cognitive disorders (RR=2.12, 95% confidence intervals [CI] =1.75-2.58, I2=87%, P<0.01). To be specific, SCD conferred a 2.29-fold excess risk for cognitive impairment (RR=2.29, 95% CI=1.66-3.17, I2=83%, P<0.01) and a 2.16-fold excess risk for dementia (RR=2.16, 95% CI=1.63-2.86, I2=81%, P<0.01). In subgroup analyses, participants with SCD in the subgroup of 65-75 years old, long-education (>15 years) subgroup and subgroup of clinics showed a higher risk of developing objective cognitive disorders., Conclusions: SCD is associated with an increased combined risk of cognitive impairment and incident dementia and should be considered a risk factor for objective cognitive disorders., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting-state functional magnetic resonance imaging (rs-fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment., Method: Thirty PI patients were recruited to accept 5-week electroacupuncture treatment on HT-7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs-fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low-frequency fluctuations (fALFF)., Result: The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p < .05). The gender-related difference in the cerebral response to electroacupuncture was mainly in posterior cingulate and supramarginal gyrus., Conclusion: There is a gender-related difference in the clinical treatment efficacy of electroacupuncture for PI patients, and female patients may benefit more from electroacupuncture. Gender-related differences in the cerebral response to electroacupuncture may be one of the factors affecting clinical treatment efficacy., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: The associations between sleep characteristics and cognition are complicated. Alzheimer's disease (AD) pathologies have been proven to be associated with sleep characteristics., Objective: We aimed to investigate the associations between sleep characteristics and cognitive function and examine the roles of AD pathologies in modulating the association of sleep duration with cognition., Methods: A total of 974 participants who had measurements of cerebrospinal fluid (CSF) amyloid-β (Aβ), phosphorylated tau (P-tau), total tau proteins (T-tau), cognitive function, and sleep characteristics were included from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Linear regression analyses were utilized to explore the associations of sleep characteristics with cognition. Non-linear regression analyses were utilized to explore the associations of sleep habits with cognition. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition., Results: The Pittsburgh Sleep Quality Index (PSQI) total score was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score (p = 0.0176). Long latency (p = 0.0054) and low efficiency (p = 0.0273) were associated with cognitive impairment. Habitual nap behavior was associated with lower MoCA scores (p = 0.0045). U-shaped associations were observed between sleep habits (bedtime and nocturnal sleep duration) and cognition. A causal mediation analysis indicated that P-tau/Aβ42 mediated the association of sleep duration with cognition., Conclusion: These findings showed sleep characteristics were associated with cognitive functions. Sleep habits (duration, bedtime) had U-shaped associations with cognition. AD core pathologies might partially mediate the influence of sleep duration on cognitive impairments.

Objective This study aimed to determine which parameters in transthoracic echocardiography (TTE) are more likely to be affected when applied in a critical care setting with mechanical ventilation.Methods Ninety mechanically ventilated ICU patients were enrolled into the study group. The control group consisted of 90 patients who underwent interventional therapy. All patients had bedside TTE for parametric measurements including the right ventricular size, septal kinetics and left ventricular ejection fraction (LVEF) by eyeballing (visual assessment), the tricuspid annular plane systolic excursion (TAPSE), mitral annular plane systolic excursion (MAPSE) by M-mode sonography, the right ventricular outflow tract velocity-time integral (RVOT VTI) and left ventricular outflow tract velocity-time integral (LVOT VTI) by pulse-Doppler, the right ventricular fraction of area change (FAC) and left ventricular ejection fraction (LVEF Simpson) by endocardium tracing. We compared the differences in the frequency of optimal image acquisition in assessments of these parameters between the two groups, as well as the differences in acquisition rates of parameter measurements in ventilated ICU patients.Results There were significantly fewer patients in the study group than in the control group who had optimal images acquisitions for parameter assessments with M-mode method, pulse Doppler method and endocardium-tracing method ( P <0.05); no significant difference was obsered in the number of patients with optimal images for RV eyeballing and LVEF eyeballing between the two groups. In the study group, significantly fewer optimal images were acquired for FAC than for TAPSE (22.2% vs . 72.2%, χ 2 =45.139, P <0.001) and RVOT VTI (22.2% vs . 71.1%, χ 2 =43.214, P <0.001); there were also fewer optimal images acquired for LVEF Simpson than for MAPSE (37.8% vs . 84.4%, χ 2 =41.236, P <0.001) and LVOT VTI (37.8% vs . 85.6%, χ 2 =43.455, P <0.001).Conclusions Images acquisition of optimal TTE images tend to be difficult in mechanically ventilated ICU patients, but eyeballing method for functional evaluation could be an alternative method. For quantitative parameters measurements, M-mode based longitudinal function evaluation and pulse Doppler-based VTI were superior to the endocardium-tracing based parameter assessments.

Objective: We aimed to compare the characteristics of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China, Italy, and South Korea., Materials and Methods: Detailed national epidemiological information of COVID-19 was retracted from the latest statistics reports from China, Italy, and South Korea. Population-based analysis of the age distribution among confirmed cases was conducted and their crude case fatality ratio in each c RESULTS: The age distributions among COVID-19 cases were relatively similar between China and Italy with primarily elderly populations infected, which were considerably different from that in South Korea with primarily younger individuals infected. Most deaths occurred among elderly individuals who were older than 60 years in both Italy (98.0%) and South Korea (87.9%), consistent with the previous data from China (81.0%)., Conclusions: Most deaths occurred among elderly individuals who were over 60 in China, Italy, and South Korea. South Korea's data suggest that younger individuals might be more susceptible to SARS-CoV-2 infection, which might be fully under detected in China and Italy.

Objective: This study aimed to explore the significance of renal Doppler ultrasound in evaluating systemic and renal perfusion in sepsis patients before and after fluid resuscitation., Patients and Methods: Forty sepsis patients admitted to the Department of Intensive Medicine and intensive care unit (ICU) of the Fourth Hospital of Hebei Medical University from June 2014 to December 2014 were enrolled in this study, and 35 patients were included in the final analysis. These patients were divided into positive and negative fluid responsiveness groups. They were also divided into an acute kidney injury (AKI) group and a non-AKI group according to changes in creatinine and urine volume. The correlations of the changes in hemodynamics before and after fluid resuscitation in each group with the changes in renal resistance index (RRI) and renal blood flow (RBF) grades were evaluated., Results: Before and after fluid resuscitation, the heart rate (HR), blood creatinine (Cre), and lactate (Lac) levels of all patients, including the patients in the positive fluid responsiveness group decreased, and the stroke volume (SV) and central venous pressure (CVP) increased. Only HR decreased in the negative fluid responsiveness group. In the AKI group, HR, Cre, and Lac decreased, while in the non-AKI group, HR decreased, but CVP and SV increased. There were differences between HR, Lac, and change rate of Lac (Lac%) after fluid resuscitation for the positive and negative fluid responsiveness groups. There was no statistical difference between the RRI values of each group before and after fluid resuscitation. The RRI values of the AKI group were higher than those of the non-AKI group, while the AKI group's RBF grades were lower than those of the non-AKI group. The change rate of RRI (RRI%) was higher in the AKI group than in the non-AKI group. Except for the negative fluid responsiveness group, the RBF grade of each group increased., Conclusions: The approach of RBF classification based on Doppler ultrasound can be used to evaluate the systemic and renal perfusion of patients with severe sepsis before and after fluid resuscitation, while the RRI value cannot be used for evaluation. However, the RRI value can be used as a dynamic index for the evaluation of renal perfusion in patients with AKI.

SIVA-1 plays a critical role in the induction of apoptosis in a number of different cell lines and participates in the mechanism of cisplatin (DDP)-mediated antitumor effects. However, the involvement of SIVA-1 in cisplatin resistance in gastric carcinoma has not been revealed. To explore the effect of SIVA-1 on DDP resistance, a recombinant pGV358-GFP-SIVA-1 lentiviral vector was constructed and transfected into human cisplatin-resistant MKN45/DDP gastric cancer cells. Subsequently, stable SIVA-1 overexpression was established in MKN45/DDP cells, which resulted in increased DDP sensitivity in MKN45/DDP cells in vitro. Flow cytometry demonstrated that SIVA-1 overexpression increased the percentage of apoptotic cells compared to that in the control. The colony formation assay clearly revealed that cell growth and proliferation were significantly suppressed following SIVA-1 overexpression. In addition, overexpression of SIVA-1 inhibited the migratory and invasive potential of MKN45/DDP cells in vitro. Western blot analysis indicated that SIVA-1 increased the expression levels of p53, p73, and p14ARF, whereas it reduced Bcl-2, MDM2, and Bcl-xL expression. In short, SIVA-1 upregulated the protein expression of p53, p73, and p14ARF and decreased that of Bcl-2, MDM2, and Bcl-xL in vitro and subsequently reversed cisplatin resistance in gastric cancer cells, suggesting that SIVA-1 serves as a valuable potential target for attenuating chemotherapy resistance.

We examined soil physical and chemical properties and plant community characteristics of four Kobresia alpine meadows at different degradation stages in Damxung County, Lhasa City, Tibet Autonomous Region, China, with the method of spatial sequence instead of time succession. The results showed that soil organic carbon, total nitrogen, available phosphorus, available potassium, ammonium, nitrate, and water content showed a decreasing trend as the degree of soil degradation increased, while pH showed an increasing trend. Plant community height, richness, diversity index and evenness index of the moderately degraded meadow were the highest. Community coverage and total biomass were the largest in undegraded meadow and the smallest in the severely degraded meadow. As the degree of meadow degradation intensifies, the biomass and proportion of Cyperaceae decreased, the biomass and proportion of legumes and weeds increased, and the biomass and proportion of Gramineae first increased and then decreased. The aboveground biomass of meadow was significantly positively correlated with soil organic carbon content, total nitrogen content, total phosphorus content, and soil water content, and significantly negatively correlated with soil pH. With the vegetation degradation in meadow, soil degradation had worsened, which ultimately manifested as a significant decline in grassland productivity.

Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a retrospective study of the Department of Critical Care Medicine of Peking Union Medical College Hospital and a secondary analysis of the MIMIC-III clinical database. The relationship between the ranges of driving pressure and central venous pressure during the first 72 h and their associations with prognosis were investigated. Data from 2790 patients were analyzed. Wide range of driving airway pressure (odds ratio, 1.0681; 95% CI, 1.0415-1.0953; p  < 0.0001) were independently associated with mortality, ventilator-free time, intensive care unit and hospital length of stay. Furthermore, wide range of driving pressure and elevated central venous pressure exhibited a close correlation. The area under receiver operating characteristic demonstrated that range of driving pressure and central venous pressure were measured at 0.689 (95% CI, 0.670-0.707) and 0.681 (95% CI, 0.662-0.699), respectively. Patients with high ranges of driving pressure and elevated central venous pressure had worse outcomes. Post hoc tests showed significant differences in 28-day survival rates (log-rank (Mantel-Cox), 184.7; p  < 0.001). In conclusion, during the first 72 h of mechanical ventilation, patients with hypoxia with fluctuating driving airway pressure have elevated central venous pressure and worse outcomes., (© The Author(s) 2020.)

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of the MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion-exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor-binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.

One of the most effective ways to cope with the problems of global warming and the energy shortage crisis is to develop renewable and clean energy sources. To achieve a carbon-neutral energy cycle, advanced carbon sequestration technologies are urgently needed, but because CO 2 is a thermodynamically stable molecule with the highest carbon valence state of +4, this process faces many challenges. In recent years, electrochemical CO 2 reduction has become a promising approach to fix and convert CO 2 into high-value-added fuels and chemical feedstock. However, the large-scale commercial use of electrochemical CO 2 reduction systems is hindered by poor electrocatalyst activity, large overpotential, low energy conversion efficiency, and product selectivity in reducing CO 2 . Therefore, there is an urgent need to rationally design highly efficient, stable, and scalable electrocatalysts to alleviate these problems. This minireview also aims to classify heterogeneous nanostructured electrocatalysts for the CO 2 reduction reaction (CDRR)., (© 2020 Wiley-VCH GmbH.)

Despite huge promises, bioanalysis of protein biomarkers in formalin-fixed paraffin-embedded (FFPE) tissues by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for clinical applications is still very challenging. Here, we describe a sensitive and robust LC-MS/MS assay to quantify clinical protein biomarkers in FFPE tumor sections using automated antipeptide antibody immunocapture followed by in-sample calibration curve (ISCC) strategy with multiple isotopologue reaction monitoring (MIRM) technique. ISCC approach with MIRM of stable isotopically labeled (SIL) peptides eliminated the need for authentic matrices for external calibration curves, overcame the matrix effects, and validated the quantification range in each individual sample. Specifically, after deparaffinization, rehydration, antigen retrieval, and homogenization, the protein analytes in FFPE tumor tissues were spiked with a known concentration of one SIL peptide for each analyte, followed by trypsin digestion and antipeptide immunocapture enrichment prior to MIRM-ISCC-based LC-MS/MS analysis. This approach has been successfully used for sensitive quantification of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) in 15 representative FFPE tumor samples from lung, colorectal, and head and neck cancer patients. Except for one sample, PD-L1 and PD-1 in all samples were quantifiable using this assay with concentrations of 27.85-798.43 (amol/μg protein) for PD-L1 and 16.96-129.89 (amol/μg protein) for PD-1. These results were generally in agreement with the immunohistochemistry (IHC) data but with some exceptions. This approach demonstrated the feasibility to quantify low abundant protein biomarkers in FFPE tissues with improved sensitivity, specificity, and robustness and showed great potential as an orthogonal analytical approach to IHC for clinical applications.

Objective: The study aims to analyze the pregnancy outcomes of multiple gestations with preterm premature rupture of membranes (PPROM) that occurred within 24 h after fetal reduction with potassium chloride (KCL)., Materials and Methods: We identified and evaluated the outcomes of 16 retrospectively recorded multigestational pregnancies that met the inclusion criteria between 2006 and 2016, from the Obstetrics Department of Shandong Provincial Hospital. A total of 16 patients carrying twins or higher order multiple gestations experienced PPROM within 24 h after fetal reduction, and all of them received expectant management after understanding the relevant risks. The maternal and neonatal records were retrospectively collected and reviewed. Every surviving child was followed up to at least 2 years old., Result: Of the 16 cases, 12 cases (75%) ended in successful pregnancy, resulting in the delivery of at least 1 child surviving from a multiple gestational pregnancy. All cases of successful pregnancies were either term (≥37 weeks) or near-term (36 +5 weeks) at delivery. And of those 20 infants delivered, only 3 were low birth weight infants (<2500g) (15%), None of the 16 women had fever, or other clinical symptoms and signs of chorioamnionitis during hospital stay. Postnatal follow-up of the surviving babies showed no obvious sequelae thus far. No newborn baby had neonatal complications, or needed to be transferred to neonatal intensive care unit., Conclusion: Overall, our data demonstrate that dichorionic diamniotic (DCDA) twins or higher-order gestations who experienced PPROM of the reduced fetus within 24 h after selective reduction with KCL had relatively good outcomes with expectant management alone., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)