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The irrational application of chemical fertilizers in wheat cultivation not only threatens the agricultural ecosystem but also significantly contributes to carbon emissions, impeding the achievement of “carbon peaking” and “carbon neutrality” goals. The objective of this research is to assess the efficiency of chemical fertilizer use in wheat production across ten major wheat-producing provinces in China from 2004 to 2020. We employed a stochastic frontier production function to evaluate the technical efficiency of fertilizer use, determining feasible reduction levels. The Gini coefficient, kernel density estimation, and Markov chain analysis were further utilized to dissect the spatio-temporal dynamics of carbon emission reduction potential. Our findings provide a detailed analysis of the carbon emission reduction potential in wheat chemical fertilizer use across China’s ten major wheat-producing provinces from 2004 to 2020. The average carbon emission reduction potential is significant, at 251.1 kg CE/hm2, with considerable variation observed among regions. The western region, in particular, stands out with the highest potential, reaching up to 336.51 kg CE/hm2, which is notably higher compared to the eastern (230.05 kg CE/hm2) and central regions (158.28 kg CE/hm2). The spatial distribution of this potential is uneven, and the disparities are progressively increasing, primarily due to inter-regional differences. Despite a general decline in carbon reduction potential, the spatial distribution remains relatively consistent. To foster sustainable wheat production, it is imperative to prioritize the western region for targeted chemical fertilizer carbon reduction initiatives. Attention must also be given to the issue of regional disparities in low-carbon wheat production. Enhancing the role of soil testing and fertilizer recommendations is essential to increase the effectiveness of carbon reduction efforts. Additionally, a multi-faceted approach that incorporates various alternative measures is necessary to drive further reductions in chemical fertilizer-related carbon emissions.

IntroductionYeast culture (YC) enhances ruminant performance, but its functional mechanism remains unclear because of the complex composition of YC and the uncertain substances affecting rumen fermentation. The objective of this study was to determine the composition of effective metabolites in YC by exploring its effects on rumen fermentation in vitro, growth and slaughter performance, serum index, rumen fermentation parameters, rumen microorganisms, and metabolites in lambs.MethodsIn Trial 1, various YCs were successfully produced, providing raw materials for identifying effective metabolites. The experiment was divided into 5 treatment groups with 5 replicates in each group: the control group (basal diet without additives) and YC groups were supplemented with 0.625‰ of four different yeast cultures, respectively (groups A, B, C, and D). Rumen fermentation parameters were determined at 3, 6, 12, and 24 h in vitro. A univariate regression model multiple factor associative effects index (MFAEI; y) was established to correlate the most influential factors on in vitro rumen fermentation with YC metabolites (x). This identified the metabolites promoting rumen fermentation and optimal YC substance levels. In Trial 2, metabolites in YC not positively correlated with MFAEI were excluded, and effective substances were combined with pure chemicals (M group). This experiment validated the effectiveness of YC metabolites in lamb production based on their impact on growth, slaughter performance, serum indices, rumen parameters, microorganisms, and metabolites. Thirty cross-generation rams (Small tail Han-yang ♀ × Australian white sheep ♂) with good body condition and similar body weight were divided into three treatment groups with 10 replicates in each group: control group, YC group, pure chemicals combination group (M group).ResultsGrowth performance and serum index were measured on days 30 and 60, and slaughter performance, rumen fermentation parameters, microorganisms, and metabolites were measured on day 60. The M group significantly increased the dressing percentage, and significantly decreased the GR values of lambs (p < 0.05). The concentration of growth hormone (GH), Cortisol, insulin (INS), and rumen VFA in the M group significantly increased (p

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.

The Corona Virus Disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has quickly spread worldwide and resulted in significant morbidity and mortality. Although most infections are mild, some patients can also develop severe and fatal myocarditis. In eukaryotic RNAs, 5-methylcytosine (m5C) is a common kind of post-transcriptional modification, which is involved in regulating various biological processes (such as RNA export, translation, and stability maintenance). With the rapid development of m5C modification detection technology, studies related to viral m5C modification are ever-increasing. These studies have revealed that m5C modification plays an important role in various stages of viral replication, including transcription and translation. According to recent studies, m5C methylation modification can regulate SARS-CoV-2 infection by modulating innate immune signaling pathways. However, the specific role of m5C modification in SARS-CoV-2-induced myocarditis remains unclear. Therefore, this review aims to provide insights into the molecular mechanisms of m5C methylation in SARS-CoV-2 infection. Moreover, the regulatory role of NSUN2 in viral infection and host innate immune response was also highlighted. This review may provide new directions for developing therapeutic strategies for SARS-CoV-2-associated myocarditis.

BackgroundGenome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported.Case presentationIn this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.ConclusionThis case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.

BackgroundImmune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention.MethodsWe searched the Chinese People’s Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients.Results110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49–79 years). 6 were males. The most common was lung cancer (n = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2–15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, p = 0.016). Overlap of myositis with MG (OR = 3.148, p = 0.009) and anti-AChR antibody positivity (OR = 3.364, p = 0.005) were both significantly associated with poor outcomes.ConclusionOur study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.

As a geographical dimension of justice, spatial justice is characterized by the interplay of social justice and heterogeneous spaces, including the ocean. Despite the generous contribution of ocean to humankind, concerns over aquatic spatial justice are disproportionately lacking. Among the core disruptors of ocean justice, illegal, unreported and unregulated (IUU) fishing imposes a major threat to global fisheries governance. The synthesis of spatial analysis and justice perspective can generate new insights to help understand and potentially address IUU fishing. To examine the spatial (in)justices concerning IUU fishing, we first propose a novel tripartite framework that envisions space as a form of opportunity, society and rights to externalize its socio-environmental implications. Then we integrate productive, distributive and consumptive justices to examine the spatial variations of IUU stakeholders along the fish value chain, and use stakeholder analysis to investigate spatial powers and conflicts regarding both a micro scale of fish communities, and a macro scale of states (coastal state, flag state, port state and market state) and supernational players (regional fisheries management organizations and marine protected areas). It is discovered that certain regions provide greater spatial benefits that stimulate IUU behaviors; IUU misconducts cause spatial differentiation and spatial deprivation that disrupt social orders in fish communities; space can empower stakeholders’ inclusive and proper engagement into the place-based management process against IUU fishing. Since the spatialized vision has been increasingly highlighted in marine fisheries management, it is suggested to intervene in the world ocean by leveraging spatial knowledge, managing spatial conflicts and facilitating spatial action, in order to promote spatial justice and better combat IUU fishing globally.

Background and aims: The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective anti-thrombotic agents. Leech, as a traditional Chinese medicine, has the effect of promoting blood circulation and removing blood stasis, but its real material basis and mechanism of action for the treatment of diseases such as blood stasis and thrombosis have not been reported.Methods: In this study, Whitmania Pigra Whitman (WPW), Hirudo nipponica Whitman (HNW) and Whitmania acranutata Whitman (WAW) were hydrolyzed by biomimetic enzymatic hydrolysis to obtain the active peptides of WPW (APP), the active peptides of HNW (APH) and the active peptides of WAW (APA), respectively. Then their structures were characterized by sykam amino acid analyzer, fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectrometer and LC-MS. Next, the anti-thrombotic activities of APP, APH and APA were determined by carrageenan-induced tail vein thrombosis model in mice, and the anti-thrombotic mechanisms of high-dose APP group (HAPP), high-dose APH group (HAPH) and high-dose APA group (HAPA) were explored based on UHPLC-Q-Exactive Orbitrap mass spectrometry.Results: The results showed that the amino acid composition of APP, APH and APA was consistent, and the proportion of each amino acid was few different. The results of FT-IR and CD showed that there were no significant differences in the proportion of secondary structures (such as β-sheet and random coil) and infrared absorption peaks between APP, APH and APA. Mass spectrometry data showed that there were 43 common peptides in APP, APH and APA, indicating that the three have common material basis. APP, APH and APA could significantly inhibit platelet aggregation, reduce black-tail length, whole blood viscosity (WBV), plasma viscosity (PV), and Fibrinogen (FIB), and prolong coagulation time, including activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT). In addition, 24 metabolites were identified as potential biomarkers associated with thrombosis development. Among these, 19, 23, and 20 metabolites were significantly normalized after administration of HAPP, HAPH, and HAPA in the mice, respectively. Furthermore, the intervention mechanism of HAPP, HAPH and HAPA on tail vein thrombosis mainly involved in linoleic acid metabolism, primary bile acid biosynthesis and ether lipid metabolism.Conclusion: Our findings suggest that APP, APH and APA can exert their anti-blood stasis and anti-thrombotic activities by interfering with disordered metabolic pathways in vivo, and there is no significant difference in their efficacies.

Casing connection is a common connection method in oil and gas reservoir production, and the tripping of casing will seriously hinder the production process. To study the casing tripping process and the minimum tensile load required for casing tripping under different loosening buckle states, three kinds of casing tripping tensile tests were carried out. The thread morphology of the casing head and casing coupling was analyzed by local cutting at the end of the experiment, and the thread failure area was analyzed by scanning electron microscope, and then other loosening states were studied and analyzed using numerical simulation. The research results show that as the number of loosening buckles increases, the minimum tensile load required for the casing head and casing coupling to trip decreases. The observation of the thread shape shows that the thread part of the casing head was seriously damaged. Scanning electron microscopy results show that the fracture mode at the thread of the casing head is ductile fracture. Numerical simulation results show that the maximum stress area during the tripping process is at the contact position between the thread heads. Based on the experimental and numerical simulation results, the relationship between the number of casing loosening and the minimum tensile load required for casing tripping is obtained. The research results can be used as the experimental and theoretical basis for the investigation of casing tripping accidents and can also provide experimental reference for the design of the next-generation of casing.

IntroductionThe deep-sea environment is always characterized by high hydrostatic pressure, fluctuating temperatures, heavy metals, darkness, and others. The Vesicomyidae inhabit cold seep zones, hydrothermal vents, and other chemically reduced environments.MethodsTo enhance the understanding of the adaptation mechanisms of clams in extreme environments, a comprehensive proteomic study was conducted on the cold seep clam Archivesica marissinica and shallow water clam Ruditapes philippinarum.ResultsA total of 4,557 proteins were identified from the comparative groups. The Gene Ontology results indicated that the differentially expressed proteins (DEP) for the comparative group Rpgill vs. Amgill were enriched in the nitrogen compound metabolic process, and others. The comparative analysis for Amfoot vs. Amgill and Ammantle vs. Amgill revealed significant enrichment of the differential proteins that were involved in metal ion transport, divalent inorganic cation transport, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the comparative group Rpgill vs. Amgill was significantly enriched in the regulation of actin cytoskeleton, lysosome, and others. The proteins that exhibited differential expression in the cold seep clam’ different tissues were also enriched in important pathways, such as lysosome, fatty acid degradation, nitrogen metabolism.DiscussionThe further analysis identified crucial response proteins involved in various biological pathways. For example, the pattern recognition receptors, such as galectin and peptidoglycan recognition protein, participated in recognition of symbiotic microorganisms. The lysosome pathway members, such as cathepsin and saposins, were engaged in the degradation process of symbiont proteins during symbiont digestion. Profilin and gelsolin from actin cytoskeleton pathway might be pressure-related proteins. Furthermore, carbonic anhydrases from nitrogen metabolism KEGG pathway provide inorganic carbon for symbiotic bacteria. Additionally, Mn superoxide dismutase plays a role in the scavenging of superoxide anion radicals and antioxidant activity. Then, arginine kinases facilitate the low temperature adaptation of deep-sea shellfish with its cold adaptation characters. These findings offer novel perspectives on the proteins that are implicated in A. marisica’s response to cold seep environments, thereby contributing to the understanding of deep-sea biological adaptation and the preservation of deep-sea ecosystems.

BackgroundPrior epidemiological studies have established a correlation between inflammatory cytokines and inflammatory bowel disease (IBD). However, the nature of this relationship remains uncertain. Mendelian randomization (MR) study has the advantages of avoiding confounding and reverse causality compared with traditional observational research.ObjectiveWe aimed to evaluate whether genetically determined circulating levels of cytokines are associated with the risk of IBD by using the MR approach.Materials and methodsWe selected genetic variants associated with circulating levels of 28 cytokines at the genome-wide significance level from a genome-wide association study (GWAS) including 8,293 individuals. Summary-level data for IBD (including Crohn’s disease and ulcerative colitis) were obtained from the International Inflammatory Bowel Disease Genetics Consortium and UK Biobank. We performed the primary analysis using the inverse-variance weighted method, as well as sensitivity analyses to test the stability of our results. We subsequently replicated the results of IBD in the UK Biobank dataset. A reverse MR analysis was also conducted to evaluate the possibility of reverse causation.ResultsGenetically predicted elevated levels of interleukin-17 (IL-17) and monokine induced by interferon-gamma (MIG) were associated with an increased risk of IBD[odds ratio (OR): 1.52, 95% confidence interval (CI):1.10-2.08, P =0.010 for IL-17 and OR: 1.58, 95% CI: 1.24-2.00, P = 1.60×10-4 for MIG]. Moreover, we observed suggestive associations between β-NGF and MIP-1β with the risk of Crohn’s disease (OR: 0.71, 95% CI: 0.52-0.98, P = 0.039) and ulcerative colitis (OR: 1.08, 95% CI: 1.01-1.15, P= 0.019). In the reverse MR study, there was no evidence of causal effects of IBD and these cytokines.ConclusionOur study suggests the potential causal associations of IL-17 and MIG with IBD. Further studies are needed to determine whether IL-17 and MIG or their downstream effectors could be useful in the management of IBD.

Alcohol-associated liver disease (ALD) is a condition that develops due to prolonged and excessive alcohol consumption. It encompasses various stages of liver damage, including fatty liver, alcoholic hepatitis, and cirrhosis. Immune cells, particularly macrophages, of various types play a significant role in the onset and progression of the disease. Macrophages observed in the liver exhibit diverse differentiation forms, and perform a range of functions. Beyond M1 and M2 macrophages, human macrophages can polarize into distinct phenotypes in response to various stimuli. Recent advancements have improved our understanding of macrophage diversity and their role in the progression of ALD. This mini-review provides a concise overview of the latest findings on the role and differentiation of macrophages in ALD. Additionally, it discusses potential therapeutic targets associated with macrophages and explores potential therapeutic strategies.

IntroductionThe intestinal microbiota participates in host physiology and pathology through metabolites, in which short-chain fatty acids (SCFAs) are considered principal products and have extensive influence on intestine homeostasis. It has been reported that skin ulceration syndrome (SUS), the disease of Apostichopus japonicus caused by Vibrio splendidus, is associated with the alteration of the intestinal microbiota composition.MethodTo investigate whether the intestinal microbiota affects A. japonicus health via SCFAs, in this study, we focus on the SCFA profiling and intestinal barrier function in A. japonicus treated with V. splendidus.Results and discussionWe found that V. splendidus could destroy the mid-intestine integrity and downregulate the expression of tight junction proteins ZO-1 and occludin in A. japonicus, which further dramatically decreased microorganism abundance and altered SCFAs contents. Specifically, acetic acid is associated with the largest number of microorganisms and has a significant correlation with occludin and ZO-1 among the seven SCFAs. Furthermore, our findings showed that acetic acid could maintain the intestinal barrier function by increasing the expression of tight junction proteins and rearranging the tight junction structure by regulating F-actin in mid-intestine epithelial cells. Thus, our results provide insights into the effects of the gut microbiome and SCFAs on intestine barrier homeostasis and provide essential knowledge for intervening in SUS by targeting metabolites or the gut microbiota.

The taxonomic composition and abundance of phytoplankton have a direct impact on marine ecosystem dynamics and global environment change. Phytoplankton classification is crucial for phytoplankton analysis, but it is challenging due to their large quantity and small size. Machine learning is the primary method for automatically performing phytoplankton image classification. As large-scale research on marine phytoplankton generates overwhelming amounts of data, more powerful computational resources are required for the success of machine learning methods. Recently, quantum machine learning has emerged as a potential solution for large-scale data processing by harnessing the exponentially computational power of quantum computers. Here, for the first time, we demonstrate the feasibility of using quantum deep neural networks for phytoplankton classification. Hybrid quantum-classical convolutional and residual neural networks are developed based on the classical architectures. These models strike a balance between the limited function of current quantum devices and the large size of phytoplankton images, making it possible to perform phytoplankton classification on near-term quantum computers. Our quantum models demonstrate superior performance compared to their classical counterparts, exhibiting faster convergence, higher classification accuracy and lower accuracy fluctuation. The present quantum models are versatile and can be applied to various tasks of image classification in the field of marine science.

ImportanceEarly neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions.ObjectiveThis study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT.Design, setting, and participantsThe Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022).OutcomesEND defined as NIHSS score increase >4 points or death within 24 h of stroke onset.Results1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796–0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814–0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0–3 and 4–9, respectively.ConclusionCNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT.

Among various sunscreen materials, zinc oxide and titanium dioxide are excellent physical sunscreen components; however, these two materials tend to aggregate and form micrometer-sized particles that may impact their performance. This study utilizes fine grinding techniques to break up the aggregated oxide particles into small nanoparticles with a narrow size distribution averaging around 200 nm in diameter. The ground zinc oxide and titanium dioxide particles exhibit enhanced ability in absorbing and scattering ultraviolet radiation compared to their original state before grinding. Consequently, this research offers innovative concepts as well as approaches towards developing highly efficient yet low-toxic physical sunscreen components while significantly contributing to the preparation process optimization for mixed material performance.

Background: Cold exposure (CE) can effectively modulate adipose tissue metabolism and improve metabolic health. Although previous metabolomics studies have primarily focused on analyzing one or two samples from serum, brown adipose tissue (BAT), white adipose tissue (WAT), and liver samples, there is a significant lack of simultaneous analysis of multiple tissues regarding the metabolic changes induced by CE in mice. Therefore, our study aims to investigate the metabolic profiles of the major tissues involved.Methods: A total of 14 male C57BL/6J mice were randomly assigned to two groups: the control group (n = 7) and the CE group (n = 7). Metabolite determination was carried out using gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to identify metabolites exhibiting differential expression between the two groups.Results: In our study, we identified 32 discriminant metabolites in BAT, 17 in WAT, 21 in serum, 7 in the liver, 16 in the spleen, and 26 in the kidney, respectively. Among these metabolites, amino acids, fatty acids, and nucleotides emerged as the most significantly altered compounds. These metabolites were found to be associated with 12 differential metabolic pathways closely related to amino acids, fatty acids, and energy metabolism.Conclusion: Our study may provide valuable insights into the metabolic effects induced by CE, and they have the potential to inspire novel approaches for treating metabolic diseases.

ObjectivePostural control plays a key role in skill-oriented sports. Athletes of skill-oriented sports (hereinafter referred to as “skilled athletes”) usually showed better control ability compared with non-athletes. However, research focused on the single postural task, rarely considering the actual situation in skill-oriented sports in which other processes, such as cognitive control, frequently accompany postural control. This study aims to explore how skilled athletes control their posture under the dual-task situation and use limited attentional resources.MethodA total of 26 skilled athletes and 26 non-athletes were required to perform the postural control and N-back tasks simultaneously. Center of pressure (COP) trajectory, reaction times (RTs), and discriminability (d′) of N-back tasks were recorded and evaluated, along with event-related potentials, including N1 (Oz, PO7, and PO8), P2 (Fz, FCz, Cz, and Pz) components, and the spectral power of alpha band.ResultsSkilled athletes demonstrated more postural control stability and a higher d′ than non-athletes in all dual tasks. Besides, they showed enhanced N1, P2 amplitudes and reduced alpha band power during dual-tasking. Notably, in skilled athletes, a significant negative correlation between N1 amplitude and d′ was observed, while significant positive correlations between alpha band power and postural control performance were also identified.ConclusionThis study investigates the potential advantages of skilled athletes in postural control from the view of neuroscience. Compared to non-athletes, skilled athletes could decrease the consumption of attentional resources in postural control and recruit more attentional resources in stimulus discrimination and evaluation in cognitive tasks. Since the allocation of attentional resources plays a crucial part in postural control in skilled athletes, optimizing the postural control training program and the selection of skilled athletes from a dual-task perspective is important.

BackgroundNeutrophilic asthma is poorly responsive to corticosteroids, and the mechanism underlying its pathogenesis remains unclear. Non-typeable Haemophilus influenzae (NTHi) is the most common bacterium found in induced sputum from patients with neutrophilic asthma. NTHi can release outer membrane vesicles (OMVs), which transfer biomolecules to host cells and the external environment. However, the role and mechanisms of NTHi OMVs in the pathogenesis of neutrophilic asthma remain unclear.MethodsWe conducted assays to investigate whether NTHi OMVs can induce neutrophilic asthma when inhaled. We isolated and purified NTHi OMVs and administered them via a nebulizer to ovalbumin (OVA)-sensitized mice. We collected and sequenced serum, blood, bronchoalveolar lavage fluid, and lung tissue from each group and gathered lung function data.ResultsInhaled NTHi OMVs-induced neutrophilic asthma in OVA-sensitized mice. High-throughput sequencing revealed that NTHi OMV inhalation in OVA-sensitized mice significantly enriched inflammatory and immune-related signaling pathways. We found increased transcription and secretion of interleukin (IL)-1β and IL-17, which may contribute to neutrophilic asthma. Furthermore, we discovered that airway epithelium is the first receptor cell of NTHi OMVs and releases IL-1β. These findings suggest that NTHi OMVs could be a potential target for neutrophilic asthma therapy.

IntroductionCurrently, hyperuricemia has shown a surprisingly rising trend, which attracts widespread attention due to potentially major health risks. Considering the inevitable side effects of long-term medicine, probiotics are emerging as potential therapeutics due to their ability to improve uric acid metabolism and superior safety.MethodsIn our study, two strains of probiotics, Lactobacillus gasseri LG08 (LG08) and Leuconostoc mesenteroides LM58 (LM58) isolated from kimchi were evaluated for the prebiotic properties in vitro and uric-lowering effects in vivo. Here, hyperuricemia animal model and 16S rRNA gene amplicons analysis were further studied to investigate whether these probiotics exert different effects in prevention and treatment.ResultsIn vivo indicators and intestinal flora immunity revealed that both LG08 and LM58 significantly prevent the development and progression of hyperuricemia, repair the antioxidant system and maintain intestinal flora balance in healthy rats, especially LM58. After hyperuricemia was formed, although the effect of LG08 and LM58 could decrease the level of uric acid, the effect to reverse and repair antioxidant levels in the body was limited.DiscussionIn our study, these findings have important implications for hyperuricemia prevention and therapy, and provided more mechanistic insights into the effect of probiotics in hyperuricemia.

Long-term fertilization can result in the changes in carbon (C) cycle in the maize rhizosphere soil. However, there have been few reports on the impacts of microbial regulatory mechanisms on the C cycle in soil. In the study, we analyzed the response of functional genes that regulate the C fixation, decomposition and methane (CH4) metabolism in maize rhizosphere soil to different fertilization treatments using metagenomics analysis. As the dominant C fixation pathway in maize rhizosphere soil, the abundance of the functional genes regulating the reductive citrate cycle (rTCA cycle) including korA, korB, and IHD1 was higher under the chemical nitrogen (N) fertilizer treatments [nitrogen fertilizer (N), compound chemical fertilization (NPK), the combination of compound chemical fertilizer with maize straw (NPKS)] than maize straw return treatments [maize straw return (S), the combination of phosphorus and potassium fertilizer with maize straw (PKS)]. The NPK treatment decreased the abundance of functional genes involved in 3-hydroxypropionate bicycle (3-HP cycle; porA, porB, and porD), which was one of the major C fixation pathways in soil aside from dicarboxylate-hydroxybutyrate (DC/4-HB cycle) and Calvin cycle. The abundance of functional genes related to C degradation was higher in S, PKS and NPKS treatments than N and NPK treatments, and chemical N fertilizer application had a significant effect on C degradation. The dominant Methanaogenesis pathway in maize rhizosphere soil, used acetate as a substrate, and was significantly promoted under chemical N fertilizer application. The functional genes that were related to CH4 oxidation (i.e., pmoA and pmoB) were reduced under N and NPK treatments. Moreover, soil chemical properties had a significant impact on the functional genes related to C fixation and degradation, with SOC (r2 = 0.79) and NO3−-N (r2 = 0.63) being the main regulators. These results implied that N fertilization rather than maize straw return had a greater influence on the C cycle in maize rhizosphere soil.

ObjectiveHypertension is a public health challenge worldwide due to its high prevalence and multiple complications. Hypertension-induced damage to the hippocampus leads to behavioral changes and various brain diseases. Despite the multifaceted effects of hypertension on the hippocampus, the mechanisms underlying hippocampal lesions are still unclear.MethodsThe 32-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were selected as the study subjects. Behavioral experiments such as an open field test (OFT), an elevated plus maze (EPM) test, and the Morris water maze (MWM) test were performed to show the behavioral characteristics of the rats. A comprehensive transcriptomic and metabolomic analysis was performed to understand the changes in the hippocampus at the metabolic and genetic levels.ResultsBehavioral tests showed that, compared to WKY rats, SHR showed not only reduced memory capacity but more hyperactive and impulsive behavior. In addition, transcriptomic analysis screened for 103 differentially expressed genes. Metabolomic analysis screened 56 metabolites with significant differences, including various amino acids and their related metabolites.ConclusionComprehensive analysis showed that hypertension-induced hippocampal lesions are closely associated with differential metabolites and differential genes detected in this study. The results provide a basis for analyzing the mechanisms of hypertension-induced hippocampal damage.

Introduction: Photodynamic therapy (PDT) and photothermal therapy (PTT) are widely used in the treatment of tumors. However, their application in the treatment of clinical tumors is limited by the complexity and irreversible hypoxia environment generated by tumor tissues. To overcome this limitation, a nanoparticle composed of indocyanine green (ICG) and Fe-MOF-5 was developed.Methods: We prepared F-I@FM5 and measured its morphology, particle size, and stability. Its enzyme like ability and optical effect was verified. Then we used MTT, staining and flow cytometry to evaluated the anti-tumor effect on EMT-6 cells in vitro. Finally, the anti-tumor effect in vivo has been studied on EMT-6 tumor bearing mice.Results: For the composite nanoparticle, we confirmed that Fe-MOF-5 has the best nanozyme activity. In addition, it has excellent photothermal conversion efficiency and generates reactive oxygen species (ROS) under near-infrared light irradiation (808 nm). The composite nanoparticle showed good tumor inhibition effect in vitro and in vivo, which was superior to the free ICG or Fe-MOF-5 alone. Besides, there was no obvious cytotoxicity in major organs within the effective therapeutic concentration.Discussion: Fe-MOF-5 has the function of simulating catalase, which can promote the decomposition of excessive H2O2 in the tumor microenvironment and produce oxygen to improve the hypoxic environment. The improvement of tumor hypoxia can enhance the efficacy of PDT and PTT. This research not only provides an efficient and stable anti-tumor nano platform, but also has broad application prospects in the field of tumor therapy, and provides a new idea for the application of MOF as an important carrier material in the field of photodynamic therapy.

Archaeal viruses are one of the most mysterious parts of the virosphere because of their diverse morphologies and unique genome contents. The crenarchaeal viruses are commonly found in high temperature and acidic hot springs, and the number of identified crenarchaeal viruses is being rapidly increased in recent two decades. Over fifty viruses infecting the members of the order Sulfolobales have been identified, most of which are from hot springs distributed in the United States, Russia, Iceland, Japan, and Italy. To further expand the reservoir of viruses infecting strains of Sulfolobaceae, we investigated virus diversity through cultivation-dependent approaches in hot springs in Tengchong, Yunnan, China. Eight different virus-like particles were detected in enrichment cultures, among which five new archaeal viruses were isolated and characterized. We showed that these viruses can infect acidophilic hyperthermophiles belonging to three different genera of the family Sulfolobaceae, namely, Saccharolobus, Sulfolobus, and Metallosphaera. We also compared the lipid compositions of the viral and cellular membranes and found that the lipid composition of some viral envelopes was very different from that of the host membrane. Collectively, our results showed that the Tengchong hot springs harbor highly diverse viruses, providing excellent models for archaeal virus-host studies.

ObjectivePrevious observational studies have suggested that antioxidant imbalance is correlated with neurodegenerative diseases, while its cause–effect remains unclear. Thus, the goal of the present study is to explore the causal relationship between 11 antioxidant biomarkers and 3 most common neurodegenerative diseases [Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease (PD)].MethodsA bidirectional Mendelian randomization (MR) study was performed to investigate the causal effects by using 3 main methods (Variance Weighted (IVW), Weighted Median (WM), and MR-Egger regression) in the European population. The data of 11 antioxidant biomarkers were obtained from the open database by the most up-to-date Genome-Wide Association Studies (GWAS), the summary statistics of PD and ALS were obtained from the International Parkinson’s Disease Genomics Consortium (IPDGC) (33,674 cases, and 449,056 controls), and the International Amyotrophic Lateral Sclerosis Genomics Consortium (IALSC) (20,806 cases and 59,804 controls), respectively. For AD, we specifically used two recently published GWAS data, one from the International Genomics of Alzheimer’s Project (IGAP) (21,982 cases and 41,944 controls), and the other from a large meta-analysis (71,880 cases and 383,378 controls) as validation data.ResultsBased on the Bonferroni correction p

A small subpopulation of Vibrio splendidus AJ01 that was exposed to tetracycline at 10 times the minimal inhibitory concentration (MIC) still survived, named tetracycline-induced persister cells in our previous work. However, the formation mechanisms of persister is largely unknown. Here, we investigated tetracycline-induced AJ01 persister cells by transcriptome analysis and found that the purine metabolism pathway was significantly downregulated, which was consistent with lower levels of ATP, purine, and purine derivatives in our metabolome analysis. Inhibition of the purine metabolism pathway by 6-mercaptopurine (6-MP, inhibits ATP production), increased persister cell formation and accompanied with the decreasing intracellular ATP levels and increasing cells with protein aggresome. On the other hand, the persister cells had reduced intracellular tetracycline concentrations and higher membrane potential after 6-MP treatment. Inhibition of the membrane potential by carbonyl cyanide m-chlorophenyl hydrazone reversed 6-MP-induced persistence and resulted in higher levels of intracellular tetracycline accumulation. Meanwhile, cells with 6-MP treatment increased the membrane potential by dissipating the transmembrane proton pH gradient, which activated efflux to decrease the intracellular tetracycline concentration. Together, our findings show that reduction of purine metabolism regulates AJ01 persistence and is associated with protein aggresome formation and intracellular tetracycline efflux.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear.Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed.Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups.Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

This study investigated glass ceramics produced using coal gasification slag (CGS) and petrochemical incineration fly ash (PIFA) to immobilize hazardous heavy metals such as Cr and As. However, the crystallization kinetics and stabilization behavior mechanism of different heavy metals in the petrochemical incineration fly ash-derived glass-ceramics remains unclear. And X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and inductively coupled plasma mass spectrometry were used to characterize glass and crystalline products. In this paper, we reported the crystallization kinetics and chemical leaching characteristics of the glass ceramic. A low crystallization activation energy of 121.49 kJ/mol was achieved from crystallization peak of several different heating rates around 850°C, implying that it is easier to produce the glass ceramics at that temperature. The Avrami parameter of the former crystallization was determined to be 1.23 ± .12, which indicated two-dimensional crystal growth with heterogeneous nucleation. The toxicity characteristic leaching procedure results indicated that the heavy metals were well solidified, and that the leaching concentration was significantly lower than the limit specified by governmental agencies. The potentially toxic element index of the parent glass and the two glass ceramics were 11.7, 5.8, and 3.6, respectively. Therefore, the conversion of hazardous petrochemical incineration fly ash and other solid waste into environmentally friendly glass ceramics shows considerable potential and reliability.

IntroductionOral microbial homeostasis is a key factor affecting oral health, and saliva plays a significant role in maintaining oral microbial homeostasis. The submandibular gland (SMG) and sublingual gland (SLG) together produce the most saliva at rest. Organic ingredients, including antimicrobial proteins, are rich and distinctive and depend on the type of acinar cells in the SMG and SLG. However, the functions of the SMG and SLG in maintaining oral microbial homeostasis have been difficult to identify and distinguish, given their unique anatomical structuresMethodsIn this study, we independently removed either the SMG or SLG from mouse models. SMGs were aseptically removed in three mice in the SMG-removal group, and SLGs were aseptically removed in three mice in the SLG-removal group. Three mice from the sham-operated group were only anesthetized and incised the skin. After one month, we analyzed their oral microbiome through 16S rRNA sequencing. And then, we analyzed each gland using proteomics and single-cell RNA sequencing.ResultsOur study revealed that the microbiome balance was significantly disturbed, with decreased bacterial richness, diversity, and uniformity in the groups with the SMG or SLG removed compared with the sham-operated group. We identified eight secreted proteins in the SMG and two in the SLG that could be involved in maintaining oral microbial homeostasis. Finally, we identified multiple types of cells in the SMG and SLG (including serous acinar, mucinous acinar, ductal epithelial, mesenchymal, and immune cells) that express potential microbiota homeostasis regulatory proteins. Our results suggest that both the SMG and SLG play crucial roles in maintaining oral microbial homeostasis via excretion. Furthermore, the contribution of the SMG in maintaining oral microbial homeostasis appears to be superior to that of the SLG. These findings also revealed the possible antimicrobial function of gland secreta.DiscussionOur results suggest that control of oral microbial dysbiosis is necessary when the secretory function of the SMG or SLG is impaired. Our study could be the basis for further research on the prevention of oral diseases caused by microbial dysbiosis.

BackgroundGlioma is one of the most typical tumors in the central nervous system with a poor prognosis, and the optimal management strategy remains controversial. Lactate in the tumor microenvironment is known to promote cancer progression, but its impact on clinical outcomes of glioma is largely unknown.MethodsGlioma RNA-seq data were obtained from TCGA and GCGA databases. Lactate metabolism genes (LMGs) were then evaluated to construct an LMG model in glioma using Cox and LASSO regression. Immune cell infiltration, immune checkpoint gene expression, enriched pathways, genetic alteration, and drug sensitivity were compared within the risk subgroups. Based on the risk score and clinicopathological features, a nomogram was developed to predict prognosis in patients with glioma.ResultsFive genes (LDHA, LDHB, MRS2, SL16A1, and SL25A12) showed a good prognostic value and were used to construct an LMG-based risk score. This risk score was shown as an independent prognostic factor with good predictive power in both training and validation cohorts (p < 0.001). The LMG signature was found to be correlated with the expression of immune checkpoint genes and immune infiltration and could shape the tumor microenvironment. Genetic alteration, dysregulated metabolism, and tumorigenesis pathways could be the underlying contributing factors that affect LMG risk stratification. The patients with glioma in the LMG high-risk group showed high sensitivity to EGFR inhibitors. In addition, our nomogram model could effectively predict overall survival with an area under the curve value of 0.894.ConclusionWe explored the characteristics of LMGs in glioma and proposed an LMG-based signature. This prognostic model could predict the survival of patients with glioma and help clinical oncologists plan more individualized and effective therapeutic regimens.

BackgroundStress hyperglycemia has served as a reliable biomarker to predict poor outcomes after ischemic stroke. However, recent studies have reported some contrary conclusions. Different stroke subtypes may respond inconsistently to stress hyperglycemia. The progression of intracranial atherosclerotic stenosis (ICAS) is tightly related to hyperglycemia. Thus, this study aims to determine the relationship between stress hyperglycemia and recurrent stroke in ischemic stroke patients with or without intracranial atherosclerotic stenosis.MethodsThis is a multicenter retrospective observational cohort study. Patients with acute minor ischemic stroke and eligible computed tomography and magnetic resonance imaging data were enrolled. The severity of stress hyperglycemia is measured by the stress hyperglycemia ratio (SHR). SHR was calculated based on fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels. The primary outcome was stroke recurrence during hospitalization. The interaction of SHR levels with the presence of ICAS on the primary outcome was investigated using univariable and multivariable Cox proportional hazards models. Restricted cubic splines were applied to determine the nonlinear relationship between SHR and primary outcome. A two-piecewise linear regression model was used to identify the threshold of SHR.ResultsA total of 610 participants were included in the study. The average age of the patients was 61.4 ± 12.9 years old, and approximately 70% of participants were males. A total of 189 (30.98%) patients had ICAS. The patients were categorized into 3 groups based on the tertiles of SHR. Compared with the group with a lower SHR, a higher SHR was significantly associated with the risk of stroke recurrence in the ICAS group (hazard ratio [HR], 8.52, 95% confidence interval [CI], 3.16-22.96, P

Arctigenin is a phenylpropanoid dibenzylbutyro lactone lignan compound with multiple biological functions. Previous studies have shown that arctigenin have neuroprotective effects in Alzheimer’s disease (AD) models both in vivo and in vitro; however, its metabolism in vivo has not been studied. Most traditional analytical methods only partially characterize drug metabolite prototypes, so there is an urgent need for a research strategy that can fully characterize drug metabolites. In the present study, ions fishing with a serial five-membered lactone ring as a fishhook strategy based on ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilised to characterise the metabolism of arctigenin, and the establishment of this strategy also solved the challenge of creating a comprehensive metabolic profile of neolignan. Based on the proposed strategy, a total of 105 metabolites were detected and characterised, 76 metabolites of which were found in rats and 49 metabolites in liver microsomes. These metabolites were postulated to be produced through oxidation, reduction, hydrolysis, and complex reactions. Subsequently, network pharmacology was utilized to elucidate the mechanism of arctigenin and its main metabolites against Alzheimer’s disease, screening 381 potential targets and 20 major signaling pathways. The study on the comprehensive metabolism of arctigenin provides a holistic metabolic profile, which will help to better understand the mechanism of arctigenin in the treatment of Alzheimer’s disease (AD) and also provide a basis for the safe administration of arctigenin.

Acorus calamus var. angustatus Besser (ATT) is a traditional herb with a long medicinal history. The volatile oil of ATT (VOA) does possess many pharmacological activities. It can restore the vitality of the brain, nervous system and myocardial cells. It is used to treat various central system, cardiovascular and cerebrovascular diseases. It also showed antibacterial and antioxidant activity. Many studies have explored the benefits of VOA scientifically. This paper reviews the extraction methods, chemical components, pharmacological activities and toxicology of VOA. The molecular mechanism of VOA was elucidated. This paper will serve as a comprehensive resource for further carrying the VOA on improving its medicinal value and clinical use.

The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the ‘third party synapse’ hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice.

The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both in vivo and in vitro experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test. We identified 232 differentially expressed genes induced by sevoflurane exposure, including 126 upregulated genes and 106 downregulated genes. Sevoflurane exposure caused cognitive impairment and neuronal injury, and increased p-IP3R levels and ER stress. An IP3R inhibitor, 2-APB, suppressed these changes, while an IP3R agonist, FK-506, aggravated these changes. Together, these findings suggest that sevoflurane exposure causes marked cognitive dysfunction in aged rats and neuronal injury in isolated hippocampal neurons by activating the IP3R and inducing cytoplasmic calcium overload, thereby resulting in ER stress and hippocampal neuronal apoptosis.GRAPHICAL ABSTRACT

It is widely documented that social capital can benefit individual and social development. However, research on the roles of internet technologies in cultivating social capital has not arrived at a consensus. This article aims to understand the effects of online social interactions (OSIs) on generalized trust and prosocial civic engagement, two essential forms of social capital, with a longitudinal study and structural equation model. Fixed-effect model estimations consistently show that OSIs can effectively increase levels of generalized trust in China. Also, trust in parents is used as an alternative dependent variable to provide a comparative analysis. The mechanisms of these two sources of trust are different, and insignificant effects of OSIs on trust in parents are found to implicitly support the causal link between OSIs and trust in strangers. In this study, we implemented a series of robustness checks, for example, examinations using only the netizens as a sample and cross-sectional methods. Furthermore, we explored the relationship between OSIs and prosocial civic engagement (charitable donation), a behavior form of social capital. The SEM results suggested that charitable behaviors were positively affected by OSIs and generalized trust played a positive mediating role. Additionally, significant positive direct and indirect effects through the generalized trust in OSIs were found on prosocial behaviors.

Essentially, wound healing is a complicated physiological process in which there exists an interaction between the organism’s immune regulation and antimicrobial therapy. However, multiple drug-resistant bacteria implicated in chronic non-healing wound are not merely impeding the cure process, but more than a burden on economic and social development. Due to the inefficiency of conventional antibiotics, nanomedicine in the biomedical field is emerging as a prospective anti-infective therapy method. Herein, a novel nano-drug with antibacterial and anti-inflammatory characteristics was synthesized by loading Rutin into zeolitic imidazolate framework-8 (ZIF-8), abided by the principle of electrostatic adsorption. The synthetic ZIF-8 loaded Rutin (ZIF-8@Rutin) was affirmed by testing the changes in the diameter and chemical functional group. Interestingly, the ladened Rutin afforded nanocomposite with anti-inflammatory activity by its antioxidant capacity for the polarization of macrophages. Further, the prepared ZIF-8@Rutin exhibited highly effective antibacterial activity against Escherichia coli and Staphylococcus aureus in vitro. More importantly, it could shorten the infected wound healing process and alleviate the inflammation around the wound in vivo. Also, ZIF-8@Rutin had acceptable cytocompatibility. Thus, ZIF-8@Rutin may become a multifunctional nanomedicine with anti-inflammatory and bactericidal properties to promote infected wound healing.

The dysbiosis of gut flora and its metabolites plays important roles in the progression of hyperlipidemia (HL), and some bioactive peptides are available for HL treatment. In this study, we aimed to isolate an active peptide (AR-9) from active peptides of E. sinensis (APE) and determine whether AR-9 could improve many symptoms of a HL rat induced by a high-fat diet (HFD) by modulating gut flora and its metabolites. Above all, AR-9 was derived from APE using ion-exchange chromatography, and its structure was deconstructed by Fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectroscopy, and UHPLC-Q-Exactive-Orbitrap MS. Then, an HFD-induced HL model in SD rats was established and used to clarify the regulatory effects of AR-9 (dose of 3 mg/kg) on HL. Normal diet–fed rats were taken as the control. The plasma samples and liver were harvested for biochemical and histopathological examinations. 16S rRNA gene sequencing and untargeted metabolomics were sequenced to assess changes in gut flora and its metabolites from rat fecal samples. Finally, Spearman’s correlation analysis was used to assess the relationship between lipid-related factors, gut flora, and its metabolites so as to evaluate the mechanism of AR-9 against HL. The results of the separation experiments showed that the amino acid sequence of AR-9 was AVFPSIVGR, which was a fragment of the actin protein from Blattaria insects. Moreover, HFD rats developed exaltation of index factors, liver lipid accumulation, and simple fibrosis for 8 weeks, and the profiles of gut flora and its metabolites were significantly altered. After treatment, AR-9 decreased the levels of lipid factors in plasma and the extent of liver damage. 16S rRNA gene sequencing results indicated that AR-9 significantly increased the relative abundance of beneficial bacteria Bacteroidetes and reduced the relative abundance of the obesity-associated bacteria Firmicutes. Furthermore, AR-9 changed gut microbiota composition and increased the relative abundance of beneficial bacteria: Lactobacillus, Clostridium, Dehalobacterium, and Candidatus arthromitus. Fecal metabolomics showed that the pathway regulated by AR-9 was “arginine biosynthesis”, in which the contents were citrulline and ornithine. Spearman’s correlation analysis revealed that two metabolites (ornithine and citrulline) showed significantly negative correlations with obesity-related parameters and positive correlations with the gut genera (Clostridium) enriched by AR-9. Overall, our results suggested interactions between gut microbial shifts and fecal amino acid/lipid metabolism and revealed the mechanisms underlying the anti-HL effect of AR-9. The abovementioned results not only reveal the initial anti-HL mechanism of AR-9 but also provide a theoretical basis for the continued development of AR-9.

PurposeTo identify the most important factors affecting physician decision-making regarding antiplatelet therapy.MethodsWe retrospectively gathered data from minor ischemic stroke patients with NIHSS scores ≤ 5 within 72 h of onset from 2010 to 2018. The population was divided into four groups by initial antiplatelet therapy: aspirin monotherapy (AM), dual antiplatelet therapy with aspirin and a loading dose of clopidogrel (clopidogrel loading dose of 300 mg on the first day; DAPT-ALC), dual antiplatelet therapy with aspirin and no loading dose of clopidogrel (clopidogrel 75 mg daily, no loading dose; DAPT-AUC), and clopidogrel monotherapy (CM).ResultsIn total, 1,377 patients were included in the analysis (excluding patients who accepted thrombolytic drugs, participated in other clinical trials, or had not used antiplatelet drugs). The mean ± S.D. age was 62.0 ± 12.7 years; 973 (70.7%) patients were male. The four groups were AM (n = 541, 39.3%), DAPT-ALC (n = 474, 34.4%), DAPT- AUC (n = 301, 21.9%), and CM (n = 61, 4.4%). Patients receiving antiplatelet monotherapy were older than those receiving dual antiplatelet therapy (63.7–65.7 vs. 59.6–61.4 years), and the median initial systolic blood pressure level was higher in the DAPT-ALC group than in the other groups (all P < 0.05). Patients under 75 years old with an admission SBP lower than 180 mmHg, a history of AM, coronary heart disease, no history of intracerebral hemorrhage, stroke onset occurring after guideline recommendations were updated (the year of 2015), onset-to-arrival time within 24 h, and initial NIHSS score ≤ 3 were more likely to take DAPT-ALC than AM. Compared with DAPT-ALC, DAPT-AUC was associated with an initial SBP level lower than 180 mmHg, a history of smoking, hypertension, no history of ICH, previous treatment with antihypertensives, and onset year after the recommendations were updated.ConclusionsMany factors affect doctors' decisions regarding antiplatelet therapy, especially guidelines, age, admission SBP level, and hypertensive disease.

Pyroptosis is a relatively newly discovered programmed cell death accompanied by an inflammatory response. In the classical view, pyroptosis is mediated by caspases-1,-4,-5,-11 and executed by GSDMD, however, recently it was demonstrated that caspase-3 and-8 also participate in the process of pyroptosis, by cleaving GSDMD/E and GSDMD respectively. Different from autophagy and apoptosis, many pores are formed on the cell membrane during pyroptosis, which makes the cell membrane lose its integrity, eventually leading to the release of cytokines interleukin(IL)-1β and IL-18. When the body is infected with pathogens or exposed to some stimulations, pyroptosis could play an immune defense role. It is found that pyroptosis exists widely in infectious and inflammatory respiratory diseases such as acute lung injury, bronchial dysplasia, chronic obstructive pulmonary disease, and asthma. Excessive pyroptosis may accompany airway inflammation, tissue injury, and airway damage, and induce an inflammatory reaction, leading to more serious damage and poor prognosis of respiratory diseases. This review summarizes the relationship between pyroptosis and related respiratory diseases.

We investigated the protective effect of young plasma on anesthesia- and surgery-induced cognitive impairment and the potential underlying mechanism using bioinformatics, functional enrichment analysis, gene set enrichment analysis, Golgi-Cox staining, dendritic spine analysis, immunofluorescence assay, western blot analysis, and transmission electron microscopy. Furthermore, we performed behavioral assessments using the open field test, the novel object recognition test, and the Morris water maze test. We identified 1969 differentially expressed genes induced by young plasma treatment, including 800 upregulated genes and 1169 downregulated genes, highlighting several enriched biological processes (signal release from synapse, postsynaptic density and neuron to neuron synapse). Anesthesia- and surgery-induced cognitive impairment in aged rats was comparatively less severe following young plasma preinfusion. In addition, the decreased levels of synapse-related and tyrosine kinase B/extracellular signal-regulated protein kinase/cyclic adenosine monophosphate response element-binding protein (TrkB/ERK/CREB) signaling pathway-related proteins, dendritic and spine deficits, and ultrastructural changes were ameliorated in aged mice following young plasma preinfusion. Together, these findings suggest that young plasma reverses anesthesia- and surgery-induced cognitive impairment in aged rats and that the mechanism is associated with the activation of the TrkB/ERK/CREB signaling pathway and improvement in hippocampal synaptic plasticity.

BackgroundPrevious prediction models of osteosarcoma have not focused on survival in patients undergoing surgery, nor have they distinguished and compared prognostic differences among amputation, radical and local resection. This study aimed to establish and validate the first reliable prognostic nomogram to accurately predict overall survival (OS) after surgical resection in patients with osteosarcoma. On this basis, we constructed a risk stratification system and a web-based nomogram.MethodsWe enrolled all patients with primary osteosarcoma who underwent surgery between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. In patients with primary osteosarcoma after surgical resection, univariate and multivariate cox proportional hazards regression analyses were utilized to identify independent prognostic factors and construct a novel nomogram for the 1-, 3-, and 5-year OS. Then the nomogram's predictive performance and clinical utility were evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultThis study recruited 1,396 patients in all, with 837 serving as the training set (60%) and 559 as the validation set (40%). After COX regression analysis, we identified seven independent prognostic factors to develop the nomogram, including age, primary site, histological type, disease stage, AJCC stage, tumor size, and surgical method. The C-index indicated that this nomogram is considerably more accurate than the AJCC stage in predicting OS [Training set (HR: 0.741, 95% CI: 0.726–0.755) vs. (HR: 0.632, 95% CI: 0.619–0.645); Validation set (HR: 0.735, 95% CI: 0.718–0.753) vs. (HR: 0.635, 95% CI: 0.619–0.652)]. Moreover, the area under ROC curves, the calibration curves, and DCA demonstrated that this nomogram was significantly superior to the AJCC stage, with better predictive performance and more net clinical benefits.ConclusionThis study highlighted that radical surgery was the first choice for patients with primary osteosarcoma since it provided the best survival prognosis. We have established and validated a novel nomogram that could objectively predict the overall survival of patients with primary osteosarcoma after surgical resection. Furthermore, a risk stratification system and a web-based nomogram could be applied in clinical practice to assist in therapeutic decision-making.

Cotton is an important source of fiber. The precise and intelligent management of cotton fields is the top priority of cotton production. Many intelligent management methods of cotton fields are inseparable from cotton boll localization, such as automated cotton picking, sustainable boll pest control, boll maturity analysis, and yield estimation. At present, object detection methods are widely used for crop localization. However, object detection methods require relatively expensive bounding box annotations for supervised learning, and some non-object regions are inevitably included in the annotated bounding boxes. The features of these non-object regions may cause misjudgment by the network model. Unlike bounding box annotations, point annotations are less expensive to label and the annotated points are only likely to belong to the object. Considering these advantages of point annotation, a point annotation-based multi-scale cotton boll localization method is proposed, called MCBLNet. It is mainly composed of scene encoding for feature extraction, location decoding for localization prediction and localization map fusion for multi-scale information association. To evaluate the robustness and accuracy of MCBLNet, we conduct experiments on our constructed cotton boll localization (CBL) dataset (300 in-field cotton boll images). Experimental results demonstrate that MCBLNet method improves by 49.4% average precision on CBL dataset compared with typically point-based localization state-of-the-arts. Additionally, MCBLNet method outperforms or at least comparable with common object detection methods.

Bifacial dye-sensitized solar cells (DSCs), harvesting light from both front and rear sides, are potential high-efficiency photovoltaic devices with broad application environments. The electrocatalytic counter electrodes (CEs) of bifacial DSCs could determine the light-harvesting from the rear side and the charge collection of solar cells through electrocatalytic processes. As a result, high-activity and high-transparency CEs are essential for bifacial DSCs. Recently, novel CEs based on strong metal-support interaction (SMSI) have been proven to improve the catalysis and stability of the metal catalytic sites and induce great efficiency increase of bifacial DSCs. However, the contradiction between the transparency and conductivity of support is still a major challenge for the application of SMSI-based CEs on bifacial DSCs. Herein, we utilized a solution plasma (SP) method to introduce oxygen vacancies into a transparent MoOx support film. These SP-induced oxygen vacancies improved the conductivity of MoOx and the interaction between the metal Pt catalytic sites and support, thereby enhancing the catalytic activity and transparency of MoOx/Pt CEs. Consequently, the bifacial DSCs with MoOx/Pt CEs yielded a high efficiency of 7.56% and 6.41% with the front- and rear-side illumination, respectively. This impressive front-to-rear efficiency ratio of 85% indicates that the SP method has a positive effect in constructing high-performance CEs and other electrocatalytic materials based on the SMSI.

ObjectiveThe study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years.MethodsThe top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field.ResultsThe average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). “Chemotherapy” (n=36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (=4.01), followed by “nivolumab” (=3.85), “blockade” (=2.86), and “efficacy” (=2.85).ConclusionsThe United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.

Gut microbiota play a vital role in fish health homeostasis. Antibiotics are known to alter microbial community composition and diversity; however, the substantial effects of antibiotics upon the gut microbiome with respect to immune-related pathways in healthy fish remain unclear. Accordingly, here we explored the impact of two antibiotics on the intestinal health, immune response, microbiome dynamics, and transcriptome profiles of grass carp. A two-week feeding trial was carried out in which the basal diet was complemented with enrofloxacin (10 mg/kg) or florfenicol (10 mg/kg). The results showed that: (1) Enrofloxacin and florfenicol both induced intestinal oxidative stress and reduced the digestive enzyme activity of grass carp. (2) High-throughput sequencing of 16S rDNA revealed that enrofloxacin but not the florfenicol treatment influenced gut microbiota diversity in grass carp by shifting α/β-diversity with more abundant pathogens detected. (3) Transcriptome profiling demonstrated that florfenicol down-regulated the immune-related pathways of grass carp, and the network analysis revealed that IgA was negatively correlated with certain pathogens, such as Shewanella and Aeromonas. (4) Antibiotic-induced alternations of gut core microbes were revealed via immune-related transcripts, as were lower mRNA expression levels of mucosal-related genes. (5) Apoptosis and histopathological changes were detected in the enrofloxacin- and florfenicol-treated groups compared with the control group. Overall, administering antibiotics will promote oxidative stress, cause intestinal flora dysbiosis, inhibit the mucosal immune system, and induce apoptosis in grass carp.

Both moist heatwaves (HWs) and heavy precipitation events (HP) have increased in both frequency and magnitude over China in recent decades. However, the relationship between HW and HP and changes in the lagged coincidence of events (i.e., the occurrence of an HP event several days after an HW event, noted HWHP) remain unknown. We show here that HWHP events account for nearly one-third of HP events over China in summer, with high values in North China, Northeast China, and the East arid zone. HWHP events assessed using the heat index and the wet-bulb temperature methods increased by 45.25 and 23.97% from 1961 to 2019, respectively. These concurrent HWHP events tend to be spatially clustered, and the areas affected simultaneously have grown significantly. The increase in HW is the major driver of these changes in HWHP events, except in the western arid zone and North China. Our findings provide an understanding of the spatiotemporal changes in HWHP events over China and their implications for disaster mitigation.

BackgroundThe capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI).MethodsConventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH.ResultsCompared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%.ConclusionNMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.