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Abstract Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by a variety of cellular stress. Biologically, STC2 induction and secretion promote cell survival but attenuate cell proliferation during nutrient insufficiency, thus switching the priority of cancer cells from proliferation to survival. Loss of STC2 impairs tumour growth by inducing both apoptosis and necrosis in mouse xenografts. Mechanistically, under nutrient insufficient conditions, cells have increased levels of reactive oxygen species (ROS), and lack of STC2 further elevates ROS levels that lead to increased apoptosis. RNA-Seq analyses reveal STC2 induction suppresses the expression of monoamine oxidase B (MAOB), a mitochondrial membrane enzyme that produces ROS. Moreover, a negative correlation between STC2 and MAOB levels is also identified in human tumour samples. Importantly, the administration of recombinant STC2 to the culture media effectively suppresses MAOB expression as well as apoptosis, suggesting STC2 functions in an autocrine/paracrine manner. Taken together, our findings indicate that nutrient insufficiency induces STC2 expression, which in turn governs the adaptation of cancer cells to nutrient insufficiency through the maintenance of redox homoeostasis, highlighting the potential of STC2 as a therapeutic target for cancer treatment.

IntroductionAnaerobic–anoxic–oxic (A2/O) and deoxidation ditch (DOD) processes are being increasingly preferred owing to their effectiveness in treating various wastes in wastewater treatment plants (WWTPs). Considering seasonal variations is crucial in optimizing treatment processes, ensuring compliance with regulations, and maintaining the overall efficiency and effectiveness of WWTPs. This study aimed to determine the influence of seasonality on nitrogen removing microbes and functional genes within A2/O and DOD processes in the humid Wuhan and semi-arid Xi’an cities, China.MethodsThe physicochemical parameters of water quality were determined, and molecular and bioinformatic analyses of the bacterial community and nitrogen metabolism functional genes in the two different treatment processes of two WWTPs were performed over four seasons.Results and discussionOur analyses revealed a significant difference in all physicochemical parameters across all experimental groups (p

ABSTRACT Dental caries is associated with microbial dysbiosis caused by the excessive proliferation of Streptococcus mutans in dental biofilms, where oxidative stress serves as the major stressor to microbial communities. The adaptability of S. mutans to oxidative stress is a prerequisite for its proliferation and even for exerting its virulence. Protein acetylation is a reversible and conserved regulatory mechanism enabling bacteria to rapidly respond to external environmental stressors. However, the functions of protein acetylation in regulating oxidative stress adaptability of S. mutans are still unknown. Here, we unveil the impact of acetyltransferase ActA-mediated acetylation on regulating the oxidative stress response of S. mutans. actA overexpression increased the sensitivity of S. mutans to hydrogen peroxide and diminished its competitive ability against Streptococcus sanguinis. In contrast, actA deletion enhanced oxidative stress tolerance and competitiveness of S. mutans. The mass spectrometric analysis identified pyruvate kinase (PykF) as a substrate of ActA, with its acetylation impairing its enzymatic activity and reducing pyruvate production. Supplementation with exogenous pyruvate mitigated oxidative stress sensitivity and restored competitiveness in multi-species biofilms. In vitro acetylation analysis further confirmed that ActA directly acetylates PykF, negatively affecting its enzymatic activity. Moreover, 18 potential lysine-acetylated sites on PykF were identified in vitro, which account for 75% of lysine-acetylated sites detected in vivo. Taken together, our study elucidates a novel regulatory mechanism of ActA-mediated acetylation of PykF in modulating oxidative stress adaptability of S. mutans by influencing pyruvate production, providing insights into the importance of protein acetylation in microbial environmental adaptability and interspecies interactions within dental biofilms.IMPORTANCEDental caries poses a significant challenge to global oral health, driven by microbial dysbiosis within dental biofilms. The pathogenicity of Streptococcus mutans, a major cariogenic bacterium, is closely linked to its ability to adapt to changing environments and cellular stresses. Our investigation into the protein acetylation mechanisms, particularly through the acetyltransferase ActA, reveals a critical pathway by which S. mutans modulates its adaptability to oxidative stress, the dominant stressor within dental biofilms. By elucidating how ActA affects the oxidative stress adaptability and competitiveness of S. mutans through the regulatory axis of ActA-PykF-pyruvate, our findings provide insights into the dynamic interplay between cariogenic and commensal bacteria within dental biofilms. This work emphasizes the significance of protein acetylation in bacterial stress response and competitiveness, opening avenues for the development of novel strategies to maintain oral microbial balance within dental biofilms.

The complexity of depression presents a significant challenge to traditional treatment methods, such as medication and psychotherapy. Recent studies have shown that exercise can effectively reduce depressive symptoms, offering a new alternative for treating depression. However, some depressed patients are unable to engage in regular physical activity due to age, physical limitations, and other factors. Therefore, pharmacological agents that mimic the effects of exercise become a potential treatment option. A newly discovered myokine, irisin, which is produced during exercise via cleavage of its precursor protein fibronectin type III domain-containing protein 5 (FNDC5), plays a key role in regulating energy metabolism, promoting adipose tissue browning, and improving insulin resistance. Importantly, FNDC5 can promote neural stem cell differentiation, enhance neuroplasticity, and improve mood and cognitive function. This review systematically reviews the mechanisms of action of exercise in the treatment of depression, outlines the physiology of exercise-related irisin, explores possible mechanisms of irisin’s antidepressant effects. The aim of this review is to encourage future research and clinical applications of irisin in the prevention and treatment of depression.

Background Several previous cross‐sectional studies suggested that body roundness index (BRI) may be associated with cardiovascular disease (CVD). However, the association should be further validated. Our study aimed to assess the association of the BRI trajectories with CVD among middle‐aged and older Chinese people in a longitudinal cohort. Methods and Results A total of 9935 participants from the CHARLS (China Health and Retirement Longitudinal Study) with repeated BRI measurements from 2011 to 2016 were included. The BRI trajectories were identified by group‐based trajectory modeling. The primary outcome was incident CVD (stroke or cardiac events), which occurred in 2017 to 2020. Cox proportional hazards regression models were used to examine the association of BRI trajectories with CVD risk. Participants were divided into 3 BRI trajectories, named the low‐stable BRI trajectory, moderate‐stable BRI trajectory and high‐stable BRI trajectory, accounting for 49.81%, 42.35%, and 7.84% of the study population, respectively. Compared with participants in the low‐stable BRI trajectory group, those in the moderate‐stable and high‐stable BRI trajectory groups had an increased risk of CVD, with multivariable adjusted hazard ratios of 1.22 (95% CI, 1.09–1.37) and 1.55 (95% CI, 1.26–1.90), respectively. Furthermore, simultaneously adding the BRI trajectory to the conventional risk model improved CVD risk reclassification (all P

Study region: The Ailaoshan National Nature Reserve forest is a mountainous water catchment area for the Lancang River basin and a subtropical ecological conservation area in southwest China. Study focus: The study aimed to understand how water fluxes in a subtropical forest responds to extreme weather disturbances and their recoveries in the post-damage years. We used eddy covariance data (2010–2019) to investigate the evapotranspiration (ET), transpiration (T), evaporation (E), and canopy conductance (Gc) before and after an extreme snow event in 2015. New Hydrological Insights: In the snow damage year, the leaf area index (LAI) decreased by 49 % compared to the pre-damage levels. The severe vegetation damage caused a significant decrease in ET, T, E, and Gc by 35 %, 36 %, 23 %, and 33 %, respectively, compared to the pre-damage levels. T returned to its pre-damage level in 2016, one year after the snow damage. In contrast, LAI, ET, E and Gc recovered to their pre-damage levels in 2018, four years after the initial damage. Reduced ET caused a strong positive RFET, which diminished forest evaporative cooling and resilience. Our results suggest that the delayed E recovery enables water reserves in the ecosystems to be used through T to support rapid understory vegetation growth. This mechanism plays critical in bolstering ecosystem resilience as it facilitates swift recovery following disturbances in subtropical forests.

Abstract Neuroinflammation is considered to be a significant mechanism contributing to depression. Several studies have reported that A1 astrocytes were highly prevalent in human neuroinflammatory and neurodegenerative diseases. However, the precise mechanism by which A1 astrocytes contribute to depression remains unclear. Clinical studies have suggested a correlation between TNF-α, an activator of A1 astrocytes, and the severity of depression. Based on these findings, we hypothesized that TNF-α might worsen depression by activating A1 astrocytes. Our previous studies indicated that Rhodomyrtone (Rho) has the potential to improve depression-like behavior in mice. However, the exact mechanism for this effect has not been fully elucidated. Importantly, it was reported that Rho alleviated skin inflammation in a mouse model of psoriasis by inhibiting the expression of TNF-α. Based on this finding, we hypothesized that rhodomyrtone may exert antidepressant effects by modulating the TNF-α pathway. However, further research is required to investigate and validate these hypotheses, shedding light on the relationships between neuroinflammation, A1 astrocytes, TNF-α, and depression. By obtaining a deeper understanding of the underlying mechanisms, these findings could lead to the development of novel antidepressant strategies that target the TNF-α pathway in the context of neuroinflammation. In vivo, based on the established chronic unpredictable mild stress (CUMS) mouse depression model, we characterized the mechanism of TNF-α and Rho during depression by using several behavioral assays, adeno-associated virus(AAV) transfection, western blotting, immunofluorescence, and other experimental methods. In vitro, we characterized the effect of Rho on inflammation in TNF-α-treated primary astrocytes. TNFR1 expression was significantly increased in the hippocampus of depression-like mice, with increased astrocytes activation and neuronal apoptosis. These processes were further enhanced with increasing levels of TNF-α in the cerebrospinal fluid of mice. However, this process was attenuated by knockdown of TNFR1 and infliximab (Inf; a TNF-α antagonist). Injection of rhodomyrtone decreased the expressions of TNFR1 and TNF-α, resulting in significant improvements in mouse depression-like behaviors and reduction of astrocyte activation. TNF-α could be involved in the pathophysiological process of depression, through mediating astrocytes activation by binding to TNFR1. By blocking this pathway, Rho may be a novel antidepressant.

Abstract Invasive plants disrupt the structure and function of ecosystems, causing a decline in their diversity. The coexistence of Solidago canadensis and Erigeron canadensis within shared habitats is a common phenomenon, and the frequent occurrence of co‐invasion has substantial implications for ecosystems. However, the effects of the co‐invasion of two plants on the soil ecosystem across varying degrees of invasion remain uninvestigated. Therefore, we investigated how the co‐invasion of S. canadensis and E. canadensis affects soil physiochemical properties and microorganisms across various degrees of invasion. The invaded regions exhibited significantly lower soil moisture content and pH values than those in the uninvaded areas (p

Addressing nitrate contamination in water bodies is a critical environmental challenge, and Intimately Coupling Photocatalysis and Biodegradation (ICPB) presents a promising solution. However, there is still debate about the effectiveness of ICPB in reducing nitrate under hypotrophic conditions. Further research is needed to understand its microbial metabolic mechanism and the functional changes in bacterial structure. Here we explored microbial metabolic mechanisms and changes in bacterial structure in ICPB reactors integrating a meticulously screened TiO2/g-C3N4 photocatalyst with biofilm. We achieved a 26.3% increase in nitrate reduction using 12.2% less organic carbon compared to traditional biodegradation methods. Metagenomic analysis of the microbial communities in ICPB reactors revealed evolving metabolic pathways conducive to nitrate reduction. This research not only elucidates the photocatalytic mechanism behind nitrate reduction in hypotrophic conditions but also provides genomic insights that pave the way for alternative approaches in water remediation technologies.

IntroductionThe presence of excessive heavy metal content in food poses potential risks to human health.MethodsThis paper presents the fabrication of a novel type of Carbon Dots (CDs) using green tea residue as a carbon source, which can be applied for simultaneous detection of Hg2+, Pb2+, Fe3+, and Cu22+ through particle swarm optimization (PSO) based optimized variable-weighted least-squares support vector machine (VWLS-SVM) model and the partial least squares discriminant analysis (PLSDA) method.Results and DiscussionThe utilization of PSO-VWLS-SVM model discovered and verified two fluorescence enhancement markers of CDs, namely isoquercitrin and 5-methyl furfural in green tea residues. By employing PLSDA, simultaneous qualitative and quantitative determination of these four metal ions was achieved. These CDs are capable of detecting four types of metal ions at low concentrations even when there are high concentrations of other metal ions and amino acids. More importantly, the CDs were successfully applied for the detection of Hg2+, Pb2+, Fe3+, and Cu2+ in real food samples. The recovery rates of four metal ions spiked into five different matrices were found to be the range of 99.1–101.3%, while both intra-day and inter-day relative standard deviations remained below 0.5% for all samples. This study on chemometrics-assisted exploration into formation mechanisms of endogenous CDs provides theoretical guidance for enhancing their fluorescence properties and expanding their application in heavy metal detection in food.

ObjectiveTo explore the association between the quantity of hibernating myocardium (HM) and collateral circulation in patients with coronary chronic total occlusion (CTO).Materials and methods88 CTO patients were retrospectively analyzed who underwent evaluation for HM using both 99mTc-sestamibi Single photon emission computed tomography (99mTc-MIBI SPECT) myocardial perfusion imaging (MPI) combined with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) myocardial metabolism imaging (MMI). They were divided into two groups according Rentrop grading: the poorly/well-developed collateral circulation group (PD/WD group, Rentrop grades 0–1/2–3). After adjusting for the potential confounding factors and conducting a stratified analysis, we explored the association between the HM index within CTO region and the grading of collateral circulation.ResultsIn the WD group, the HM index was notably higher than PD group (46.2 ± 15.7% vs. 20.9 ± 16.7%, P

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10−5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Post-transcriptional regulation by small RNAs and post-translational modifications (PTM) such as lysine acetylation play fundamental roles in physiological circuits, offering rapid responses to environmental signals with low energy consumption. Yet, the interplay between these regulatory systems remains underexplored. Here, we unveil the cross-talk between sRNAs and lysine acetylation in Streptococcus mutans, a primary cariogenic pathogen known for its potent acidogenic virulence. Through systematic overexpression of sRNAs in S. mutans, we identified sRNA SmsR1 as a critical player in modulating acidogenicity, a key cariogenic virulence feature in S. mutans. Furthermore, combined with the analysis of predicted target mRNA and transcriptome results, potential target genes were identified and experimentally verified. A direct interaction between SmsR1 and 5'-UTR region of pdhC gene was determined by in vitro binding assays. Importantly, we found that overexpression of SmsR1 reduced the expression of pdhC mRNA and increased the intracellular concentration of acetyl-CoA, resulting in global changes in protein acetylation levels. This was verified by acetyl-proteomics in S. mutans, along with an increase in acetylation level and decreased activity of LDH. Our study unravels a novel regulatory paradigm where sRNA bridges post-transcriptional regulation with post-translational modification, underscoring bacterial adeptness in fine-tuning responses to environmental stress.

Abstract Background 18F-FDG PET/CT provides precise information about dissemination of lymphoma lesions. Dmax, defined as distance between the two lesions that were farthest apart by PET/CT, was found to be a promising predictor of Diffuse large B-cell lymphoma (DLBCL) outcome in a small size of clinical trial data. We analyzed the impact of Dmax on the outcome of a large real-world DLBCL cohort. Methods Data of newly diagnosed DLBCL at the Third Affiliated Hospital of Soochow University were retrospectively collected. Baseline Dmax, clinical data and survival information were recorded. A metabolic parameter, metabolic bulk volume (MBV), was also measured to verify the independent impact of Dmax. Results Optimal cut-off values for Dmax and MBV were 45.34 cm and 21.65 cm3. With a median follow-up of 32 months, Dmax significantly impacted progression-free survival (PFS) and overall survival (OS) in 253 DLBCL patients. For Dmaxlow and Dmaxhigh groups, estimated 3-year OS were 87.0% and 53.8% (p

Abstract Background The recently developed Hybrid Hernia Repair technique (HHR), an adaptation of the laparoscopic method, has been proposed as a potential alternative for the treatment of complex Incisional Ventral Hernias (IVH). While single-arm studies have reported promising outcomes, a comprehensive meta-analysis affirming these benefits is lacking. This meta-analysis aims to compare the clinical outcomes of HHR and Laparoscopic Hernia Repair (LHR) in the management of IVH. Methods An exhaustive search of the literature was conducted, targeting publications in both English and Chinese that compare HHR and LHR up to March 31, 2023. The primary outcomes examined were operation time, blood loss, and intestinal injury. Secondary outcomes included rates of seroma, wound infection, post-operative acute/chronic pain, recurrence, and mesh bulging. The RevMan 5.0 software facilitated the statistical meta-analysis. Results The final analysis incorporated data from 14 studies, encompassing a total of 1158 patients, with 555 undergoing HHR and 603 treated with LHR. Follow-up data, ranging from 12 to 88 months, were available in 12 out of the 14 identified studies. The HHR method was associated with a significantly lower risk of seroma (OR = 0.29, P = 0.0004), but a higher risk of wound infection (OR = 2.10, P = 0.04). No significant differences were observed between the two techniques regarding operation time, blood loss, intestinal injury, intestinal obstruction, post-operative pain, mesh bulging, and recurrence. Conclusions The HHR technique did not demonstrate a clear advantage over LHR in reducing surgical complications, apart from a lower incidence of postoperative seroma. Surgeons with substantial expertise may choose to avoid incidental conversion or intentional hybrid procedures. Further research is needed to clarify the optimal surgical approach for IVH.

Baijiu is an ancient, distilled spirit with a complicated brewing process, unique taste, and rich trace components. These trace components play a decisive role in the aroma, taste, and especially the quality of baijiu. In this paper, the redox reaction between the Fenton reagent and four reducing agents, including o-phenylenediamine (OPD), p-phenylenediamine (PPD), 4-aminophenol (PAP), and 2-aminophenol (OAP), was adopted to construct a four-channel visual sensor array for the rapid detection of nine kinds of common organic acids in baijiu and the identification of baijiu and its adulteration. By exploiting the color-changing fingerprint response brought by organic acids, each organic acid could be analyzed accurately when combined with an optimized variable-weighted least-squares support vector machine based on a particle swarm optimization (PSO-VWLS-SVM) model. What is more, this novel sensor also could achieve accurate semi-quantitative analysis of the mixed organic acid samples via partial least squares discriminant analysis (PLSDA). Most importantly, the sensor array could be further used for the identification of baijiu with different species through the PLSDA model and the adulteration assessment with the one-class partial least squares (OCPLS) model simultaneously.

Objective: Solid tumor cells utilize amino acid transporters (AATs) to increase amino acid uptake in response tonutrient-insufficiency. The upregulation of AATs is therefore critical for tumor development and progression. This studyidentifies the upregulated AATs under amino acid deprived conditions, and further determines the clinicopathologicalimportance of these AATs in evaluating the prognosis of patients with cancers.Materials and Methods: In this experimental study, the Gene Expression Omnibus (GEO) datasets (GSE62673,GSE26370, GSE125782 and GSE150874) were downloaded from the NCBI website and utilized for integrateddifferential expression and pathway analysis v0.96, Gene Set Enrichment Analysis (GSEA), and REACTOME analysesto identify the AATs upregulated in response to amino acid deprivation. In addition, The Cancer Genome Atlas (TCGA)datasets with prognostic information were assessed and employed to evaluate the association of identified AATs withpatients’ prognoses using SurvExpress analysis.Results: Using analysis of NCBI GEO data, this study shows that amino acid deprivation leads to the upregulationof six AAT genes; SLC3A2, SLC7A5, SLC7A1, SLC1A4, SLC7A11 and SLC1A5. GSEA and REACTOME analysesidentified altered signaling in cells exposed to amino acid deprivation, such as pathways related to stress responses,the cell cycle and apoptosis. In addition, Principal Component Analysis showed these six AAT genes to be well dividedinto two distinct clusters in relation to TCGA tumor tissues versus normal counterparts. Finally, Log-Rank analysisconfirmed the upregulation of this panel of six AAT genes is correlated with poor prognosis in patients with colorectal,esophageal, kidney and lung cancers.Conclusion: The upregulation of a panel of six AATs is common in several human cancers and may provide a valuablediagnostic tool to evaluate the prognosis of patients with colorectal, esophageal, kidney and lung cancers.

Abstract Purpose To use 18 F-FDG microPET dynamic imaging to preliminarily identify the changes of myocardial glucose metabolism corresponding to different functional phenotypes of diabetic cardiomyopathy (DCM) in mice and elucidate their relationships. Methods Left ventricular function was measured by echocardiography in C57BL/KsJ-db/db (db/db) mice and their controls at 8, 12, 16, and 20 weeks of age to divide DCM stages and functional phenotypes. Myocardial histopathology was used to verify the staging accuracy and list-mode microPET dynamic imaging was conducted. The myocardial metabolic rate of glucose (MRglu) and the glucose uptake rate constant (Ki) were derived via Patlak graphical analysis, and the differences in myocardial glucose metabolism levels in different DCM stages were compared. The key proteins involved in myocardial glucose metabolism signaling pathway were analyzed by Western blotting to elucidate the underlying mechanism of abnormal glucose metabolism in DCM. Results Compared with the controls, the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (E/e’) of db/db mice was significantly increased from the age of 12 weeks, while the left ventricular ejection fraction (LVEF) was significantly decreased from the age of 16 weeks (all P 0.05). MRglu and SUV were moderately negatively correlated with the E/e’ ratio (r=-0.539 and − 0.512, P = 0.007 and 0.011), which were not significantly correlated with LVEF (P > 0.05). Meanwhile, Ki was not significantly correlated with LVEF or E/e’ ratio. The decreased expression of glucose transporter (GLUT) -4 in db/db mice preceded GLUT-1 and was accompanied by decreased phosphorylated AMP-activated protein kinase (p-AMPK) expression. Myocardial MRglu, Ki and SUV were significantly positively correlated with the expression of GLUT-4 (MRglu: r = 0.537; Ki: r = 0.818; SUV: r = 0.491; P = 0.000 ~ 0.046), but there was no significant correlation with GLUT-1 expression (P = 0.238 ~ 0.780). Conclusions During the progression of DCM, with the changes of left ventricular functional phenotype, abnormal and dynamic changes of myocardial glucose metabolism can occur in the early stage.

Inhibition of pancreatic lipase can be effective in controlling or treating obesity. Phenolic acids have good pancreatic lipase inhibitory effects and are widely found in plants. The identification of phenolic acids and their derivatives that can efficiently inhibit pancreatic lipase has attracted widespread attention. Therefore, it is crucial to screen natural pancreatic lipase inhibitors efficiently by establishing quantitative structure-activity relationships (QSAR) models. In this study, machine learning was used to perform multiple computational analyses of 28 phenolic acids and their derivatives with pancreatic lipase inhibitory activity, and multiple QSAR models were established. Molecular parameters were analyzed, IC50 was predicted, and molecular docking and molecular dynamics simulations analysis were done for the screened natural compounds. The results showed that the model with the highest level of accuracy is the 2D-3D mix model with a numerator parameter value of 8 (R2fitting of 0.9537 and MAE of 0.2230), and MATS6c is a key descriptor. Further screened 5 compounds that have not yet been reported and have the potential to inhibit lipase activity (IC50pre ≤ 16.69 μM), these all bound to key residues (Tyr114 and Ser152) of pancreatic lipase, of which 3–4,1,5-carboxylic acid bound the most tightly (affinity of −9.8 kJ/mol). And the compounds-pancreatic lipase complexes (2-3-2-enoate) had good stability. The three compounds with high bioavailability have the potential to become novel pancreatic lipase inhibitors. This study provides a novel approach for the prediction of phenolic acids and their derivatives capable of inhibiting pancreatic lipase.

Most current JPEG steganalytic methods can only extract features from a series of linear residuals.Non-linear filters are not considered in these JPEG steganalytic methods, resulting in single types of residuals.Hence, a JPEG steganalytic method using non-linear residuals was proposed.Firstly, non-linear residuals were generated without a high computational cost by using element-wise minimum and maximum operations across a couple of linear residuals which had been obtained in the current JPEG steganalytic method.Secondly, according to the JPEG phase, the non-linear residual was divided into sub-residuals in which the histogram features were extracted.Thirdly, considering the minimum and maximum operators, the symmetrization method was accordingly designed.Finally, all the symmetrized histogram features were concatenated to form the final feature set.Experimental results indicate that the performance for JPEG steganalysis can be improved effectively by using both the linear and the non-linear residuals.

Abstract Background Acute appendicitis is the most common cause of acute abdomen. During the pandemic, to contain the spread of COVID-19, there were some integral changes in the medical processes based on the pandemic prevention policy, especially regarding emergency surgery. This study was conducted to investigate whether this pandemic also impacted the decision-making for both patients and medical personnel along with the treatment outcomes. Methods Patients of age 18 years or older who were diagnosed clinically and radiologically with acute appendicitis between Jan 1, 2017, and Dec 31, 202,0 were reviewed. The data of 1991 cases were collected and used for this study. Two groups were formed, one group before and the other group after the outbreak. The gathered data included gender, age, appendiceal fecalith, outcomes of treatment, and long-term outcomes of non-operation (8 months follow-up). We also collected details of surgical cases from the above two groups. This data also included age, gender, appendiceal fecalith, fever, jaundice, length of onset before presenting to an emergency department (ED), anesthesia, surgery, white cell count, pathology, complications, and length of stay. We compared the above data respectively and analyzed the differences. Results Compared to the period before the outbreak, patient visits for acute appendicitis remarkably dropped (19.8%), but surgical cases showed no change (dropped by roughly 5%). There were significant differences (P 0.05) concerning age, gender, fever, jaundice, appendiceal fecalith, white cell count, and length of onset before presenting to the ED. Conclusion The current pandemic prevention policy is very effective, but some decision-making processes of doctor-patient have changed in the context of COVID-19 pandemic, that further influenced some treatment outcomes and might lead to a potential economic burden. It is essential to address the undue concern of everyone and optimize the treatment process.

It is important to improve the production of bioactive secondary products for drug development. The Escherichia coli—Streptomyces shuttle vector pSET152 and its derived vector pIB139 containing a strong constitutive promoter ermEp* are commonly used as integrative vectors in actinomycetes. Four new integrative vectors carrying the strong constitutive promoter kasOp*, hrdBp, SCO5768p, and SP44, respectively, were constructed and proven to be functional in different mangrove-derived Streptomyces host strains by using kanamycin resistance gene neo as a reporter. Some biosynthetic genes of elaiophylins, azalomycin Fs, and armeniaspirols were selected and inserted into these vectors to overexpress in their producers including Streptomyces sp. 219807, Streptomyces sp. 211726, and S. armeniacus DSM 43125, resulting in an approximately 1.1–1.4-fold enhancement of the antibiotic yields.

The volatile compounds produced by plants play an important role in plant growth, plant communication, and resistance to biological and abiotic stresses. Astragalus membranaceus var. mongholicus (AM) is a perennial herbaceous plant (Leguminosae) that is widely cultivated in northwest China. The bioactive compounds in its root have shown various pharmacological activities. Root rot disease caused by Fusarium spp. often occurs in AM planting with increasing severity in continuous monoculture. It is currently still unclear what are the effects of the volatile compounds produced by fresh AM on itself, other crops cultivated on the same field after AM, pathogen, and rhizobia. In this study, we found that seed germination and seedling growth of AM, lettuce (Lactuca sativa L.), and wheat (Triticum aestivum L.) could be affected if they were in an enclosed space with fresh AM tissue. Additionally, 90 volatile compounds were identified by SPME-GC-MS from whole AM plant during the vegetative growth, 36 of which were specific to aerial parts of AM (stems and leaves, AMA), 17 to roots (AMR), and 37 were found in both AMA and AMR. To further identify the allelopathic effects of these volatile compounds, five compounds (1-hexanol, (E)-2-hexenal, (E,E)-2,4-decadienal, hexanal, and eugenol) with relatively high content in AM were tested on three receptor plants and two microorganisms. We found that (E,E)-2,4-decadienal and (E)-2-hexenal showed significant inhibitory effects on the growth of AM and lettuce. One-hexanol and hexanal suppressed the growth of wheat, while eugenol showed a similar effect on all three plant species. Moreover, the activities of these compounds were dose dependent. Notably, we discovered that (E)-2-hexenal and eugenol also inhibited the growth of the pathogen Fusarium solani by as high as 100%. Meanwhile, all five compounds tested suppressed the rhizobia Sinorhizobium fredii. In summary, this study furthered our understanding of the comprehensive allelopathic effects of the main volatile components of AM.

Abstract Background The aim of this study was to compare one-month acquisition and half-a-year quality retention of cardiopulmonary resuscitation (CPR) skills after initial training of medical students between peer videorecording feedback training (PVF) and traditional peer verbal feedback training (TVF). Methods Participants were randomly assigned to the PVF group (n = 62) and the TVF group (n = 65). All participants received a 45-min CPR training program performed by an American Heart Association basic life support-certified instructor, and then they began two hours of practice in groups. During interactive peer learning, students cooperated in couples of a doer and a helper to realize maximization of each other’s learning. In the PVF group, training performance feedback came from peers based on practice videorecording. In the TVF group, feedback came from peers verbally without videorecording. CPR quality was tested at 1 and 6 months after training. Results After 1 month of initial training, the PVF group had a better presentation of CPR skills acquisition than the TVF group. Compared to the TVF group, the PVF group had significantly higher total scores, compression depth, appropriate compression depth, and complete chest recoil (p 0.05). Conclusions Compared to TVF, PVF is more effective in enhancing CPR skill acquisition at 1 month. After half a year, CPR skill quality was obviously reduced in both groups, and no difference in CPR quality was found between the two groups.

Abstract Background Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase–stimulator of interferon gene (cGAS–STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS–STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear. Methods A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2′3′-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry. Results cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS–STING axis. RU.521 decreased the levels of 2′3′-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1β, and cleaved IL-1β/pro-IL-1β. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2′3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA. Conclusions Our data demonstrate that repression of the cGAS–STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.

Abstract Background Bacterial floc formation plays a central role in the activated sludge (AS) process. The formation of AS flocs has long been known to require exopolysaccharide biosynthesis. We had demonstrated that both expolysaccharides and PEP-CTERM (a short C-terminal domain includes a near-invariant motif Pro-Glu-Pro (PEP)) proteins were required for floc-forming in Zoogloea resiniphila MMB, a dominant AS bacterium. However, the PEP-CTERM proteins are not encoded in the genome of AS bacterium Shinella zoogloeoides ATCC 19623 (formerly known as Zoogloea ramigera I-16-M) and other sequenced AS bacteria strains. The mechanism underlying floc formation of Shinella and related AS bacteria remained largely unclear. Results In this study, we have sequenced and annotated the complete genome of S. zoogloeoides ATCC 19623 (aka I-16-M), previously isolated in USA and treated as the neotype for the AS floc-forming bacterium Zoogloea ramigera I-16-M, and another AS strain XJ20 isolated in China. Mariner transposon mutagenesis had been conducted to isolate floc-forming-deficient mutants in the strain ATCC 19623 as previously performed by using Tn5 transposon three decades ago. The transposon insertional sites of multiple mutants were mapped to the gene cluster for bacterial cellulose synthesis (bcs) and secretion, and the role played by these genes in floc-formation had been further confirmed by genetic complementation. Interestingly, the restriction map of this bcs locus-flanking region was highly similar to that of the previously identified DNA fragment required for floc-formation in 1980s. Cellulase treatment abolished the floc-forming phenotype of S. zoogloeoides ATCC 19623 but not that of Z. resiniphila MMB strain. The FTIR spectral analyses revealed that the samples extracted from S. zoogloeoides ATCC 19623 were cellulose polymer. Conclusion Our results indicated that we have largely reproduced and completed the unfinished pioneering work on AS floc-formation mechanism, demonstrating that the floc-formation and flocculating capability of Shinella were mediated by extracellular cellulose polymers.

This paper presents a Piezoelectric micromechanical ultrasonic transducer (PMUT) based on a Pt/ScAlN/Mo/SiO2/Si/SiO2/Si multilayer structure with a circular suspension film of scandium doped aluminum nitride (ScAlN). Multiphysics modeling using the finite element method and analysis of the effect of different Sc doping concentrations on the resonant frequency, the effective electromechanical coupling coefficient (keff2) and the station sensitivity of the PMUT cell are performed. The calculation results show that the resonant frequency of the ScAlN-based PMUT can be above 20 MHz and its keff2 monotonically rise with the increasing doping concentrations in ScAlN. In comparison to the pure AlN thin film-based PMUT, the static receiving sensitivity of the PMUT based on ScAlN thin film with 35% Sc doping concentration is up to 1.61 mV/kPa. Meanwhile, the static transmitting sensitivity of the PMUT is improved by 152.95 pm/V. Furthermore, the relative pulse-echo sensitivity level of the 2 × 2 PMUT array based on the Sc doping concentration of 35% AlN film is improved by 16 dB compared with that of the cell with the same Sc concentration. The investigation results demonstrate that the performance of PMUT on the proposed structure can be tunable and enhanced by a reasonable choice of the Sc doping concentration in ScAlN films and structure optimization, which provides important guidelines for the design of PMUT for practical applications.

Aiming at the problems of Uyghur oblique deformation, character adhesion and character similarity in scene images, this paper proposes a scene Uyghur recognition model with enhanced visual prediction. First, the content-aware correction network TPS++ is used to perform feature-level correction for skewed text. Then, ABINet is used as the basic recognition network, and the U-Net structure in the vision model is improved to aggregate horizontal features, suppress multiple activation phenomena, better describe the spatial characteristics of character positions, and alleviate the problem of character adhesion. Finally, a visual masking semantic awareness (VMSA) module is added to guide the vision model to consider the language information in the visual space by masking the corresponding visual features on the attention map to obtain more accurate visual prediction. This module can not only alleviate the correction load of the language model, but also distinguish similar characters using the language information. The effectiveness of the improved method is verified by ablation experiments, and the model is compared with common scene text recognition methods and scene Uyghur recognition methods on the self-built scene Uyghur dataset.

Summary Antibiotic resistance in Helicobacter pylori has been growing worldwide with current treatment regimens. Development of new compounds for treatment of H. pylori infections is urgently required to achieve a successful eradication therapy in the future. Armeniaspirols, a novel class of natural products isolated from Streptomyces armeniacus, have been previously identified as antibacterial agents against Gram‐positive pathogens. In this study, we found that armeniaspirol A (ARM1) exhibited potent antibacterial activity against H. pylori, including multidrug‐resistant strains, with MIC range values of 4–16 μg ml‐1. The underlying mechanism of action of ARM1 against H. pylori involved the disruption of bacterial cell membranes. Also, ARM1 inhibited biofilm formation, eliminated preformed biofilms and killed biofilm‐encased H. pylori in a dose‐dependent manner. In a mouse model of multidrug‐resistant H. pylori infection, dual therapy with ARM1 and omeprazole showed efficient in vivo killing efficacy comparable to the standard triple therapy, and induced negligible toxicity against normal tissues. Moreover, at acidic pH 2.5, ARM1 exhibited a much more potent anti‐H. pylori activity than metronidazole. Thus, these findings demonstrated that ARM1 is a novel potent anti‐H. pylori agent, which can be developed as a promising drug lead for treatment of H. pylori infections.

BackgroundPrevious studies have explored the correlation between short-term exposure to air pollution and urinary system diseases, but lack of evidence on the correlation between air pollution and urolithiasis.MethodsDaily data of emergency department visits (EDVs), concentrations of six air pollutants (SO2, NO2, PM2.5, PM10, CO, and O3) and meteorological variables were collected in Wuhan, China, from 2016 to 2018. And a time-series study was conducted to investigate short-term effects of air pollutants on urolithiasis EDVs. In addition, stratified analyses by season, age and gender were also conducted.ResultsA total of 7,483 urolithiasis EDVs were included during the study period. A 10-μg/m3 increase of SO2, NO2, PM2.5, CO, PM10, and O3 corresponded to 15.02% (95% confidence interval [CI]: 1.69%, 30.11%), 1.96% (95% CI: 0.19%, 3.76%), 1.09% (95% CI:−0.24%, 2.43%), 0.14% (95% CI: 0.02%, 0.26%), 0.72% (95% CI: 0.02%, 1.43%), and 1.17% (95% CI: 0.40%, 1.94%) increases in daily urolithiasis EDVs. Significant positive correlations were observed between SO2, NO2, CO, and O3 and urolithiasis EDVs. The correlations were mainly among females (especially PM2.5 and CO) and younger people (especially SO2, NO2, and PM10) but the effect of CO was more obvious in elders. Furthermore, the effects of SO2 and CO were stronger in warm seasons, while the effects of NO2 were stronger in cool seasons.ConclusionOur time-series study indicates that short-term exposure to air pollution (especially SO2, NO2, CO, and O3) was positively correlated with EDVs for urolithiasis in Wuhan, China, and the effects varied by season, age and gender.

Advancements in nanotechnology have promoted the rapid development of diverse nanosystems for biomedical applications. Manganese dioxide (MnO2) nanomaterials have attracted numerous attentions in the field of biosensing and cancer treatment due to their unique properties, such as simple fabrication procedures, broad optical absorption, and high oxidation and catalytic ability. Especially, the intelligent stimuli‐responsiveness of MnO2 nanomaterials to tumor microenvironment (TME) greatly improves their performance in tumor imaging and cancer therapy. In this review, the synthetic methods of different MnO2 nanostructures (nanoparticles, nanosheets, and nanoflowers) are first introduced, followed by the introduction of MnO2 nanomaterials for various biosensing applications based on their unique characteristics. Then, the recent achievements and progress of MnO2 nanomaterials for cancer treatment are comprehensively summarized with a focus on various therapeutic enhancements profiting from their disassembled ingredients under TME guidance. Finally, the current challenges and future perspectives of this promising research are discussed in the fields of biomedicine.

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

ABSTRACT Lysine acetylation, a ubiquitous and dynamic regulatory posttranslational modification (PTM), affects hundreds of proteins across all domains of life. In bacteria, lysine acetylation can be found in many essential pathways, and it is also crucial for bacterial virulence. However, the biological significance of lysine acetylation events to bacterial virulence factors remains poorly characterized. In Streptococcus mutans, the acetylome profiles help identify several lysine acetylation sites of lactate dehydrogenase (LDH), which catalyzes the conversion of pyruvate to lactic acid, causing the deterioration of teeth. We investigated the regulatory mechanism of LDH acetylation and characterized the effect of LDH acetylation on its function. We overexpressed the 15 Gcn5 N-acetyltransferases (GNAT) family members in S. mutans and showed that the acetyltransferase ActA impaired its acidogenicity by acetylating LDH. Additionally, enzymatic acetyltransferase reactions demonstrated that purified ActA could acetylate LDH in vitro, and 10 potential lysine acetylation sites of LDH were identified by mass spectrometry, 70% of which were also detected in vivo. We further demonstrated that the lysine acetylation of LDH inhibited its enzymatic activity, and a subsequent rat caries model showed that ActA impaired the cariogenicity of S. mutans. Collectively, we demonstrated that ActA, the first identified and characterized acetyltransferase in S. mutans, acetylated the LDH enzymatically and inhibited its enzymatic activity, thereby providing a starting point for the further analysis of the biological significance of lysine acetylation in the virulence of S. mutans. IMPORTANCE Lysine acetylation, a dynamic regulatory posttranslational modification, remains poorly characterized in bacteria. Hundreds of proteins have been identified to be acetylated in bacteria, with advances made in acetylome analyses. However, the regulatory mechanisms and functional significance of the majority of these acetylated proteins remain unclear. We analyzed the acetylome profiles of Streptococcus mutans and found that lactate dehydrogenase (LDH) contains several lysine acetylation sites. We also demonstrated that the acetyltransferase ActA, a member of the Gcn5 N-acetyltransferases (GNAT) family in S. mutans, acetylated LDH, inhibited its enzymatic ability to catalyze the conversion of pyruvate to lactic acid, and impaired its cariogenicity in a rat caries model. Therefore, LDH acetylation might be a potential target that can be exploited in the design of novel therapeutics to prevent dental caries.

Piezoelectric micromachined ultrasonic transducers (PMUTs) have attracted widespread attention due to their high performance, miniaturization, and easy integration with semiconductor processes. In this paper, a PMUT device based on high-performance and lead-free Na0.5Bi0.5TiO3-BaTiO3 (NBBT) piezoelectric single-crystal thin films was designed for the application of medical high-frequency ultrasonics. Three-dimensional modeling and analysis of PMUT elements on the proposed structure were performed via the finite element method. The relationship between structure configuration in terms of the top electrode and the cavity shape of the bottom was studied. The PMUT properties and its device performance, including resonant frequency, effective electromechanical coupling factor (keff2), and the static sensitivity of different device structures, were analyzed. In addition, by rotating the Euler Angle γ of the NBBT piezoelectric single-crystal film, the static sensitivity and keff2 of the model are improved to 1.34 when γ is rotated to 45 ± 5°. It was shown that the PMUT using rotated NBBT demonstrated an enhanced relative pulse-echo sensitivity of −46 dB and a bandwidth of 35% when the reflective surface was 200 μm. We conclude that the PMUT in accordance with an NBBT piezoelectric single-crystal film designed by simulation offers a high frequency, larger keff2, and high sensitivity, which provides application prospects in high-resolution and high-frequency medical ultrasonic imaging.

Anthocyanins are water-soluble natural pigments with good antioxidant and antibacterial properties, and their colors are pH sensitive to the environment. At present, the use of plant anthocyanins to prepare active and smart packaging film has attracted increasing attention in the field of food engineering. The use of anthocyanin-based pH-sensitive smart packaging films can not only effectively prolong the shelf life, but also monitor the freshness of food. This review mainly summarizes the mostly used packaging materials, preparation, structural and physicochemical properties, and the applications of anthocyanin-based films as pH-sensitive smart packaging for monitoring food freshness.

Abstract Background The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays. Results X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The “silent mutation” of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes’ expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB 2043 T>C, similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type. Conclusion The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency.

Abstract Patients with atopic dermatitis experience increased nocturnal pruritus which leads to scratching and sleep disturbances that significantly contribute to poor quality of life. Objective measurements of nighttime scratching and sleep quantity can help assess the efficacy of an intervention. Wearable sensors can provide novel, objective measures of nighttime scratching and sleep; however, many current approaches were not designed for passive, unsupervised monitoring during daily life. In this work, we present the development and analytical validation of a method that sequentially processes epochs of sample-level accelerometer data from a wrist-worn device to provide continuous digital measures of nighttime scratching and sleep quantity. This approach uses heuristic and machine learning algorithms in a hierarchical paradigm by first determining when the patient intends to sleep, then detecting sleep–wake states along with scratching episodes, and lastly deriving objective measures of both sleep and scratch. Leveraging reference data collected in a sleep laboratory (NCT ID: NCT03490877), results show that sensor-derived measures of total sleep opportunity (TSO; time when patient intends to sleep) and total sleep time (TST) correlate well with reference polysomnography data (TSO: r = 0.72, p

Abstract Background The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. Objective To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. Methods Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. Results At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. Conclusions Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

Purpose – This study aims to analyze the differences of electrocardiograph (ECG) characteristics for female drivers in calm and anxious states during driving. Design/methodology/approach – The authors used various materials (e.g. visual materials, auditory materials and olfactory materials) to induce drivers’ mood states (calm and anxious), and then conducted the real driving experiments and driving simulations to collect driver’s ECG signal dynamic data. Physiological changes in ECG during the stimulus process were recorded using PSYLAB software. The paired T-test analysis was conducted to determine if there is a significant difference in driver’s ECG characteristics between calm and anxious states during driving. Findings – The results show significant differences in the characteristic parameters of female driver’s ECG signals, including (average heart rate), (atrioventricular interval), (percentage of NN intervals > 50ms), (R wave average peak), (Root mean square of successive), (Q wave average peak) and ( S wave average peak), in time domain, frequency domain and waveform in emotional states of calmness and anxiety. Practical implications – Findings of this work show that ECG can be used to identify driver’s anxious and calm states during driving. It can be used for the development of personalized driver assistance system and driver warning system. Originality/value – Only a few attempts have been made on the influence of human emotions on physiological signals in the transportation field. Hence, there is a need for transport scholars to begin to identify driver’s ECG characteristics under different emotional states. This study will analyze the differences of ECG characteristics for female drivers in calm and anxious states during driving to provide a theoretical basis for developing the intelligent and connected vehicles.

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. As a result, 38 metabolites related to the arginine–creatinine metabolic pathway, the urea cycle, the serine synthesis pathway, metabolism of lipids, choline, histamine, lysine, and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I. These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions. This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.

Constrained image splicing detection and localization (CISDL) is a newly formulated image forensics task and plays an important role in verifying the generating process of a forged image. CISDL conducts dense matching between two investigated images and detects whether one image has forged regions pasted from the other. In this work, we introduce a novel attention-aware encoder-decoder deep matching network named as AttentionDM for CISDL. An encoder-decoder with atrous convolution is newly designed for hierarchical features dense matching and fine-grained masks generation. A novel attention-aware correlation computation module is built on normalization operations and informative features recalibration with channel attention blocks. Last but not least, VGG and ResNets are respectively formulated as feature extractors for comprehensive comparisons in CISDL. Extensive experiments demonstrate the superior performance of AttentionDM over the state-of-the-art methods.

A new method of dispersive liquid-liquid microextraction (DLLME) combined with graphite furnace atomic absorption spectrometry (GFAAS) was proposed for the determination of ultra-trace copper. It was based on the reaction of Cu(II) with the laboratory-prepared chelating agent 2-(5-bromo-2-pyridylazo)-5-dimethylaminoaniline (5-Br-PADMA) in a HAc-NaAc buffer solution at pH 5.0 to form stable hydrophobic chelates, which were separated and enriched by DLLME with chlorobenzene (C6H5Cl) and acetonitrile (CH3CN) as extraction and disperser solvents, respectively. The sedimented phase containing the chelates was then determined with GFAAS. Various operating variables that may be affected by the extraction process such as the pH of the solution, the concentration of the chelating agent 5-Br-PADMA, the types and volumes of extraction and disperser solvents, the extraction time, and the centrifugation time were investigated. Under optimum conditions, the calibration curve was linear in the range from 0.02 ng/mL to 0.16 ng/mL of copper with a correlation coefficient of r = 0.9961, and the detection limit was 0.01 ng/mL based on 3Sb. The relative standard deviation for six replicate measurements of 0.05 ng /mL of copper was 3.9%. An enrichment factor (EF) of 110 was obtained. The method has the advantages of low detection limit, high sensitivity, simple operation, less consumption of organic solvents, higher enrichment factor, and environmental friendliness and was applied to the determination of trace copper in environmental water samples with satisfactory results.

Oral bacteria colonize the oral cavity, surrounding complex and variable environments. Post-translational modifications (PTMs) are an efficient biochemical mechanism across all domains of life. Oral bacteria could depend on PTMs to quickly regulate their metabolic processes in the face of external stimuli. In recent years, thanks to advances in enrichment strategies, the number and variety of PTMs that have been identified and characterized in oral bacteria have increased. PTMs, covalently modified by diverse enzymes, occur in amino acid residues of the target substrate, altering the functions of proteins involved in different biological processes. For example, Ptk1 reciprocally phosphorylates Php1 on tyrosine residues 159 and 161, required for Porphyromonas gingivalis EPS production and community development with the antecedent oral biofilm constituent Streptococcus gordonii, and in turn Php1 dephosphorylates Ptk1 and rapidly causes the conversion of Ptk1 to a state of low tyrosine phosphorylation. Protein acetylation is also widespread in oral bacteria. In the acetylome of Streptococcus mutans, 973 acetylation sites were identified in 445 proteins, accounting for 22.7% of overall proteins involving virulence factors and pathogenic processes. Other PTMs in oral bacteria include serine or threonine glycosylation in Cnm involving intracerebral hemorrhage, arginine citrullination in peptidylarginine deiminases (PADs), leading to inflammation, lysine succinylation in P. gingivalis virulence factors (gingipains, fimbriae, RagB, and PorR), and cysteine glutathionylation in thioredoxin-like protein (Tlp) in response to oxidative stress in S. mutans. Here we review oral bacterial PTMs, focusing on acetylation, phosphorylation, glycosylation, citrullination, succinylation, and glutathionylation, and corresponding modifying enzymes. We describe different PTMs in association with some examples, discussing their potential role and function in oral bacteria physiological processes and regulatory networks. Identification and characterization of PTMs not only contribute to understanding their role in oral bacterial virulence, adaption, and resistance but will open new avenues to treat oral infectious diseases.

Lysine acetylation is a frequently occurring post-translational modification (PTM), emerging as an important metabolic regulatory mechanism in prokaryotes. This process is achieved enzymatically by the protein acetyltransferase (KAT) to specifically transfer the acetyl group, or non-enzymatically by direct intermediates (acetyl phosphate or acetyl-CoA). Although lysine acetylation modification of glucosyltransferases (Gtfs), the important virulence factor in Streptococcus mutans, was reported in our previous study, the KAT has not been identified. Here, we believe that the KAT ActG can acetylate Gtfs in the enzymatic mechanism. By overexpressing 15 KATs in S. mutans, the synthesized water-insoluble extracellular polysaccharides (EPS) and biofilm biomass were measured, and KAT (actG) was identified. The in-frame deletion mutant of actG was constructed to validate the function of actG. The results showed that actG could negatively regulate the water-insoluble EPS synthesis and biofilm formation. We used mass spectrometry (MS) to identify GtfB and GtfC as the possible substrates of ActG. This was also demonstrated by in vitro acetylation assays, indicating that ActG could increase the acetylation levels of GtfB and GtfC enzymatically and decrease their activities. We further found that the expression level of actG in part explained the virulence differences in clinically isolated strains. Moreover, overexpression of actG in S. mutans attenuated its cariogenicity in the rat caries model. Taken together, our study demonstrated that the KAT ActG could induce the acetylation of GtfB and GtfC enzymatically in S. mutans, providing insights into the function of lysine acetylation in bacterial virulence and pathogenicity.

Abstract Background Most species of Shewanella harbor two ferrochelatase paralogues for the biosynthesis of c-type cytochromes, which are crucial for their respiratory versatility. In our previous study of the Shewanella loihica PV-4 strain, we found that the disruption of hemH1 but not hemH2 resulted in a significant accumulation of extracellular protoporphyrin IX (PPIX), but it is different in Shewanella oneidensis MR-1. Hence, the function and transcriptional regulation of two ferrochelatase genes, hemH1 and hemH2, are investigated in S. oneidensis MR-1. Result In the present study, deletion of either hemH1 or hemH2 in S. oneidensis MR-1 did not lead to overproduction of extracellular protoporphyrin IX (PPIX) as previously described in the hemH1 mutants of S. loihica PV-4. Moreover, supplement of exogenous hemins made it possible to generate the hemH1 and hemH2 double mutant in MR-1, but not in PV-4. Under aerobic condition, exogenous hemins were required for the growth of MR-1ΔhemH1ΔhemH2, which also overproduced extracellular PPIX. These results suggest that heme is essential for aerobic growth of Shewanella species and MR-1 could also uptake hemin for biosynthesis of essential cytochrome(s) and respiration. Besides, the exogenous hemin mediated CymA cytochrome maturation and the cellular KatB catalase activity. Both hemH paralogues were transcribed in wild-type MR-1, and the hemH2 transcription was remarkably up-regulated in MR-1ΔhemH1 mutant to compensate for the loss of hemH1. The periplasmic glutathione peroxidase gene pgpD, located in the same operon with hemH2, and a large gene cluster coding for iron, heme (hemin) uptake systems are absent in the PV-4 genome. Conclusion Our results indicate that the genetic divergence in gene content and gene expression between these Shewanella species, accounting for the phenotypic difference described here, might be due to their speciation and adaptation to the specific habitats (iron-rich deep-sea vent versus iron-poor freshwater) in which they evolved and the generated mutants could potentially be utilized for commercial production of PPIX.

With the rapid development of Internet technologies and business models, the new Internet financial model represented by crowdfunding has become more and more popular among entrepreneurs and small and medium investors, serving as an important financing source for entrepreneurship and innovation. Accordingly, all major Internet entrepreneurial financing platforms have launched a standardized reputation evaluation system to facilitate investors to evaluate the quality of entrepreneurship program and service. Potential investors can also make investment choices based on the above-mentioned evaluation, which, together with the response to the evaluation, forms a reputation mechanism specific to Internet finance. Different from the traditional customer evaluation and evaluation feedback model, the aforesaid rating and entrepreneurs' responses are open and can transform the word of mouth into the entrepreneurs' reputation which will influence potential investors. Therefore, they have great significance and special research value. In spite of fairly complete research on evaluation of Internet financial investors, the research on entrepreneurs' response to the above-mentioned evaluation, especially that from the perspective of social network theory, is still in its infancy, lacking empirical verification and theoretical analysis. This paper, based on the data of 5893 science and technology programs collected from crowdfunding websites, specifies the empirical verification on effects and boundaries of different response behaviors and proposes corresponding management suggestions by effective combination and development of empirical research and social network theory.

As applied sciences grow by leaps and bounds, semiparametric regression analyses have broad applications in various fields, such as engineering, finance, medicine, and public health. Single-index varying-coefficient model is a common class of semiparametric models due to its flexibility and ease of interpretation. The standard single-index varying-coefficient regression models consist mainly of parametric regression and semiparametric regression, which assume that all covariates can be observed. The assumptions are relaxed by taking the models with missing covariates into consideration. To eliminate the possibility of bias due to missing data, we propose a probability weighted objective function. In this paper, we investigate the robust variable selection for a single-index varying-coefficient model with missing covariates. Using parametric and nonparametric estimates of the likelihood of observations with fully observed covariates, we examine the estimators for estimating the likelihood of observations. For variable selection, we use a weighted objective function penalized by a non-convex SCAD. Theoretical challenges include the treatment of missing data and a single-index varying-coefficient model that uses both the non-smooth loss function and the non-convex penalty function. We provide Monte Carlo simulations to evaluate the performance of our approach.