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Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complication of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Abstract Background Metabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear. Aim of the study This study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism. Methods High-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment. Results ZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver. Conclusion Our study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY.

Objective To investigate and analyze the effect of body mass index (BMI) on early changes of blood pressure and cardiac structure and function in the elderly. Methods The clinical data of 108 elderly patients who underwent health examination in the Provincial Hospital Affiliated to Shandong First Medical University from May 2020 to September 2022 were retrospectively analyzed. All patients received height and body mass measurement, and their blood pressure and cardiac ultrasound were monitored. They were divided into emaciation group (33 cases), normal group (31 cases), overweight group (25 cases) and obese group (19 cases) according to different BMI. The blood pressure levels and cardiac function structural indicators of patients with different BMI were compared for analysis of variance; multiple linear regression analysis was used to investigate the correlation between BMI and early blood pressure and cardiac structure and function indicators in the elderly. Results There were significant differences in systolic blood pressure, diastolic blood pressure, left ventricular mass index (LVMI), left ventricular posterior wall thickness of end-diastolic (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWs), left ventricular end-systolic diameter (LVESd), left ventricular end-diastolic diameter (LVEDd), interventricular septum thickness (IVSs), and left ventricular ejection fraction (LVEF) among the lean, normal, overweight, and obese groups (P

Abstract Background Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice. Methods The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα −/−) mice were used to confirm the CP-mediated pathway. Results CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn’t affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect. Conclusion This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.

Emerging evidence shows that disrupted gut microbiota-bile acid (BA) axis is critically involved in the development of neurodegenerative diseases. However, the alterations in spatial distribution of BAs among different brain regions that command important functions during aging and their exact roles in aging-related neurodegenerative diseases are poorly understood. Here, we analyzed the BA profiles in cerebral cortex, hippocampus, and hypothalamus of young and natural aging mice of both sexes. The results showed that aging altered brain BA profiles sex- and region- dependently, in which TβMCA was consistently elevated in aging mice of both sexes, particularly in the hippocampus and hypothalamus. Furthermore, we found that aging accumulated-TβMCA stimulated microglia inflammation in vitro and shortened the lifespan of C. elegans, as well as behavioral impairment and neuroinflammation in mice. In addition, metagenomic analysis suggested that the accumulation of brain TβMCA during aging was partially attributed to reduction in BSH-carrying bacteria. Finally, rejuvenation of gut microbiota by co-housing aged mice with young mice restored brain BA homeostasis and improved neurological dysfunctions in natural aging mice. In conclusion, our current study highlighted the potential of improving aging-related neuro-impairment by targeting gut microbiota-brain BA axis.

Remote sensing, particularly satellite-based, can play a valuable role in monitoring areas prone to geohazards. The high spatial and temporal coverage provided by satellite data can be used to reconstruct past events and continuously monitor sensitive areas for potential hazards. This paper presents a range of techniques and methods that were applied for in-depth analysis and utilization of Earth observation data, with a particular emphasis on: (1) detecting mining subsidence, where a novel approach is proposed by combining an improved U-Net model and Interferometry Synthetic Aperture Radar (InSAR) technology. The results showed that the Efficient Channel Attention (ECA) U-Net model performed better than the U-Net (baseline) model in terms of Mean Intersection over Union (MIoU) and Intersection over Union (IoU) indicators; (2) monitoring water conservancy and hydropower engineering. The Xiaolangdi multipurpose dam complex was monitored using Small BAsline Subsets (SBAS) InSAR method on Sentinel-1 time series data and four small regions with high deformation rates were identified on the slope of the reservoir bank on the north side. The dam body also showed obvious deformation with a velocity exceeding 60 mm/a; (3) the evaluation of the potential of InSAR results to integrate monitoring and warning systems for valuable heritage and architectural preservation. The overall outcome of these methods showed that the use of Artificial Intelligence (AI) techniques in combination with InSAR data leads to more efficient analysis and interpretation, resulting in improved accuracy and prompt identification of potential hazards; and (4) finally, this study also presents a method for detecting landslides in mountainous regions, using optical imagery. The new temporal landslide detection method is evaluated over a 7-year analysis period and unlike conventional bi-temporal change detection methods, this approach does not depend on any prior-knowledge and can potentially detect landslides over extended periods of time such as decades.

ABSTRACT The 2019 Infectious Diseases Society of America guideline for the management of community-acquired pneumonia (CAP) emphasizes the need for clinician to understand local epidemiological data to guide selection of appropriate treatment. Currently, the local distribution of causative pathogens and their associated resistance patterns in CAP is unknown. A retrospective observational study was performed of patients admitted to an 870-bed safety net hospital between March 2016 and March 2021 who received a diagnosis of CAP or healthcare-associated pneumonia within the first 48 hours of admission. The primary outcome was the incidence of CAP caused by methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PsA) as determined by comparing the number of satisfactory sputum cultures or blood cultures with these drug-resistant organisms to the total number of reviewed patients. Secondary outcomes studied included risk factors associated with CAP caused by drug-resistant organisms, utilization of broad-spectrum antibiotics, appropriate antibiotic de-escalation within 72 hours, and treatment duration. In this 220-patient cohort, MRSA or PsA was isolated from three sputum cultures and no blood cultures. The local incidence of drug-resistant pathogens among the analyzed sample of CAP patients was 1.4% (n = 3/220). The overall incidence of CAP caused by MRSA or PsA among admitted patients is low at our safety-net county hospital. Future research is needed to identify local risk factors associated with the development of CAP caused by drug-resistant pathogens.IMPORTANCEThis study investigates the incidence of drug-resistant pathogens including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa among community-acquired pneumonia (CAP) patients at a safety net hospital. Understanding local bacteria resistance patterns when treating CAP is essential and supported by evidence-based guidelines. Our findings empower other clinicians to investigate resistance patterns at their own institutions and identify methods to improve antibiotic use. This has the potential to reduce the unnecessary use of broad-spectrum antibiotic agents and combat the development of antibiotic resistance.

PurposeThe study was designed to describe the level of family resilience and identify the protective factors and vulnerability factors of family resilience in families of children with epilepsy. So as to provide theoretical guidance for implementing intervention programs to promote family resilience.MethodsFrom November 2020 to July 2021, 258 parents of children with epilepsy were investigated using a convenience sampling method. The questionnaire included demographic data, Chinese-Family Resilience Assessment Scale, Social Support Rating Scale, and the Beck Depression Inventory. SPSS25.0 was used for descriptive statistical analysis, univariate analysis, and multivariate linear regression analysis.ResultsIn this study, two hundred and fifty-eight primary caregivers completed the paper questionnaires. The total score of family resilience was (134.97 ± 16.57), which was above the medium level. Multiple linear regression analysis revealed that subjective support (β=0.327, P

Due to the therapeutic resistance of endocrine therapy and the limited efficacy of immune checkpoint inhibitors in estrogen receptor (ER)-positive breast cancer (BRCA), there is an urgent need to develop novel prognostic markers and understand the regulation of the tumor immune microenvironment (TIME). As a matricellular protein, CYR61 has been shown to either promote or suppress cancer progression depending on cancer types. However, how CYR61 functions in ER-positive BRCA remains elusive. In this study, we comprehensively analyzed the expression of CYR61 in BRCA based on the TCGA and METABRIC databases. Our findings showed that the expression of CYR61 is downregulated in different subtypes of BRCA, which is associated with elevated promoter methylation levels and predicts bad clinical outcomes. By comparing the high or low CYR61 expression groups of ER-positive BRCA patients, we found that CYR61 is intimately linked to the expression of genes involved in tumor-suppressive pathways, such as the TGF-β and TNF signaling pathways, and genes related to cytokine-receptor interaction that may regulate cancer immunity. Moreover, reduced CYR61 expression is associated with an altered TIME that favors cancer progression. Finally, experimental analyses ascertained that CYR61 is downregulated in clinical BRCA tissues compared to matched normal breast tissues. Furthermore, CYR61 is able to impede the proliferation and colony formation of ER-positive BRCA cells. In summary, our study reveals that CYR61 could serve as a novel prognostic marker for ER-positive BRCA, and function as an inhibitor of cancer progression by both acting on cancer cells and remodeling the TIME.

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear. Here, we identified the MCR-1 M6 variant carrying two-point mutations that conferred co-resistance to β-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe disturbance in lipid A, resulting in up-regulation of L, D-transpeptidases (LDTs) pathway, which explains co-resistance to β-lactams. Moreover, we show that a lipid A loading pocket is localized at the linker domain of MCR-1 where these 2 mutations are located. This pocket governs colistin resistance and bacterial membrane permeability, and the mutated pocket in M6 enhances the binding affinity towards lipid A. Based on this new information, we also designed synthetic peptides derived from M6 that exhibit broad-spectrum antimicrobial activity, exposing a potential vulnerability that could be exploited for future antimicrobial drug design.

Given that meat is easily contaminated by microorganisms during processing and storage, a short shelf-life has become the main factor restricting the distribution of meat. Electron beam irradiation (EBI) can effectively inactivate microorganisms in meat and prolong its shelf-life, but it affects the sensory quality and nutritional values of meat simultaneously. This paper briefly introduces the antibacterial mechanism of EBI, and focuses on discussing the influence of different doses of EBI and their actions on meat quality (e.g., color, flavor, quality, and texture), nutritional value, and microorganisms. This review aims to extend the shelf-life and maintain the original quality of meat significantly by using EBI, which would provide a theory and technology guidance for the technology application of EBI.

Abstract Background Radiotherapy is widely applied in breast cancer treatment, while radiotherapy resistance is inevitable. TGF-β1 has been considered to be an endogenous factor for the development of radiotherapy resistance. As a large portion of TGF-β1 is secreted in an extracellular vesicles-associated form (TGF-β1EV), particularly in radiated tumors. Thus, the understanding of the regulation mechanisms and the immunosuppressive functions of TGF-β1EV will pave a way for overcoming the radiotherapy resistance in cancer treatment. Methods The superoxide-Zinc-PKC-ζ-TGF-β1EV pathway in breast cancer cells was identified through sequence alignments of different PKC isoforms, speculation and experimental confirmation. A series of functional and molecular studies were performed by quantitative real-time PCR, western blot and flow cytometry analysis. Mice survival and tumor growth were recorded. Student’s t test or two-way ANOVA with correction was used for comparisons of groups. Results The radiotherapy resulted in an increased expression of the intratumoral TGF-β1 and an enhanced infiltration of the Tregs in the breast cancer tissues. The intratumoral TGF-β1 was found mainly in the extracellular vesicles associated form both in the murine breast cancer model and in the human lung cancer tissues. Furthermore, radiation induced more TGF-β1EV secretion and higher percentage of Tregs by promoting the expression and phosphorylation of protein kinase C zeta (PKC-ζ). Importantly, we found that naringenin rather than 1D11 significantly improved radiotherapy efficacy with less side effects. Distinct from TGF-β1 neutralizing antibody 1D11, the mechanism of naringenin was to downregulate the radiation-activated superoxide-Zinc-PKC-ζ-TGF-β1EV pathway. Conclusions The superoxide-zinc-PKC-ζ-TGF-β1EV release pathway was elucidated to induce the accumulation of Tregs, resulting in radiotherapy resistance in the TME. Therefore, targeting PKC-ζ to counteract TGF-β1EV function could represent a novel strategy to overcome radiotherapy resistance in the treatment of breast cancer or other cancers. Trial registration: The using of patient tissues with malignant Non-Small Cell Lung Cancer (NSCLC) was approved by the ethics committees at Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (NCC2022C-702, from June 8th, 2022).

Copy number variations (CNVs) critically influence individual genetic diversity and phenotypic traits. In this study, we employed whole-genome resequencing technology to conduct an in-depth analysis of 50 pigs from five local swine populations [Rongchang pig (RC), Wuzhishan pig (WZS), Tibetan pig (T), Yorkshire (YL) and Landrace (LR)], aiming to assess their genetic potential and explore their prospects in the field of animal model applications. We identified a total of 96,466 CNVs, which were subsequently integrated into 7112 non-redundant CNVRs, encompassing 1.3% of the swine genome. Functional enrichment analysis of the genes within these CNVRs revealed significant associations with sensory perception, energy metabolism, and neural-related pathways. Further selective scan analyses of the local pig breeds RC, T, WZS, along with YL and LR, uncovered that for the RC variety, the genes PLA2G10 and ABCA8 were found to be closely related to fat metabolism and cardiovascular health. In the T breed, the genes NCF2 and CSGALNACT1 were associated with immune response and connective tissue characteristics. As for the WZS breed, the genes PLIN4 and CPB2 were primarily linked to fat storage and anti-inflammatory responses. In summary, this research underscores the pivotal role of CNVs in fostering the diversity and adaptive evolution of pig breeds while also offering valuable insights for further exploration of the advantageous genetic traits inherent to China’s local pig breeds. This facilitates the creation of experimental animal models tailored to the specific characteristics of these breeds, contributing to the advancement of livestock and biomedical research.

Doxorubicin (DOX) is a potent chemotherapeutic agent known for its multi-organ toxicity, especially in the heart, which limits its clinical application. The toxic side effects of DOX, including DNA damage, oxidative stress, mitochondrial dysfunction and cell apoptosis, are intricately linked to the involvement of nicotinamide adenine dinucleotide (NAD+). To assess the effectiveness of the NAD+ precursor nicotinamide mononucleotide (NMN) in counteracting the multi-organ toxicity of DOX, a mouse model was established through DOX administration, which led to significant reductions in NAD+ in tissues with evident injury, including the heart, liver and lungs. NMN treatment alleviated both multi-organ fibrosis and mortality in mice. Mechanistically, tissue fibrosis, macrophage infiltration and DOX-related cellular damage, which are potentially implicated in the development of multi-organ fibrosis, could be attenuated by NAD+ restoration. Our findings provide compelling evidence for the benefits of NMN supplementation in mitigating the adverse effects of chemotherapeutic drugs on multiple organs.

Outer membrane vesicles (OMVs) are attractive for biomedical applications based on their intrinsic properties in relation to bacteria and vesicles. However, their widespread use is hampered by low yields and purities. In this study, EVscore47 multifunctional chromatography microspheres were synthesized and used to efficiently isolate functional OMVs from Escherichia coli. Through this technology, OMV loss can be kept to a minimum, and OMVs can be harvested using EVscore47 at 11-fold higher yields and ~13-fold higher purity than those achieved by means of ultracentrifugation. Based on the results presented here, we propose a novel EVscore47-based isolation of OMVs that is fast and scalable.

Introduction:Mycobacterium tuberculosis (MTB) has a type III-A clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) system consisting of a Csm1-5 and CRISPR RNA (crRNA) complex involved in the defense against invading nucleic acids. However, CRISPR/Cas system in the MTB still is clearly unknown and needs to be further explored.Methods: In our work, two non-Cas system proteins EspB and HtpG protein were found and identified by LC-MS/MS. The effect of EspB and HtpG on Type III-A CRISPR/Cas System of M. tuberculosis was examined by using Plasmid interference assay and Co-immunoprecipitation analyses. We explored that EspB could interact with the crRNA RNP complex, but HtpG could inhibit the accumulation of the MTB Csm proteins and defense the mechanism of CRISPR/Cas system.Results: The proteins ESAT-6 secretion system-1(Esx-1) secreted protein B (EspB) and high-temperature protein G (HtpG), which were not previously associated with CRISPR/Cas systems, are involved in mycobacterial CRISPR/Cas systems with distinct functions.Conclusion: EspB is a novel crRNA-binding protein that interacts directly with the MTB crRNP complex. Meanwhile, HtpG influences the accumulation of MTB Csm proteins and EspB and interferes with the defense mechanism of the crRNP complex against foreign DNA in vivo. Thereby, our study not only leads to developing more precise clinical diagnostic tool to quickly detect for MTB infection, but also knows these proteins merits for TB biomarkers/vaccine candidates.

The rapid development of the aerospace and nuclear industries is accompanied by increased exposure to high-energy ionising radiation. Thus, the performance of radiation shielding materials needs to be improved to extend the service life of detectors and ensure the safety of personnel. The development of novel lightweight materials with high electron density has therefore become urgent to alleviate radiation risks. In this work, new MAPbI3/epoxy (CH3NH3PbI3/epoxy) composites were prepared via a crystal plane engineering strategy. These composites delivered excellent radiation shielding performance against 59.5 keV gamma rays. A high linear attenuation coefficient (1.887 cm−1) and mass attenuation coefficient (1.352 cm2 g−1) were achieved for a representative MAPbI3/epoxy composite, which was 10 times higher than that of the epoxy. Theoretical calculations indicate that the electron density of MAPbI3/epoxy composites significantly increases when the content ratio of the (110) plane in MAPbI3 increases. As a result, the chances of collision between the incident gamma rays and electrons in the MAPbI3/epoxy composites were enhanced. The present work provides a novel strategy for designing and developing high-efficiency radiation shielding materials.

IntroductionDespite the potential of smart home technology to promote sustainable lifestyles, the adoption rate among older adults remains relatively low. This study aims to investigate the influence of intergenerational relationships on the acceptance of smart home services among seniors.MethodsA survey was conducted among 298 older adults in China, and data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). Ten predictor variables were examined to assess their impact on the willingness to use smart home services.ResultsIntergenerational relationships significantly influenced the utilization of smart home services among older adults. Specifically, intergenerational instrumental support had a direct positive effect on the behavioral intention to use smart homes. Additionally, intergenerational emotional and financial support affected life satisfaction, which subsequently influenced the behavioral intention to use smart homes.DiscussionThe assistance and guidance provided by younger generations play a crucial role in shaping the willingness of older adults to adopt smart home technology. Intergenerational support can contribute positively to enabling aging individuals to age in place through the utilization of technology.

In recent years, the levels of cadmium (Cd) in agricultural soils have been increasing. Cd is highly toxic and can enter the human body through the food chain, threatening human health, therefore, reducing the Cd content in vegetables and producing green and non-polluting food has become a common concern in society. However, the physiological properties of exogenous selenium in alleviating Cd stress in cabbage seedlings have not been thoroughly investigated. In this study, exogenous Se (10 μMol/L) was applied under Cd (25 μMol/L) stress and the physiological characteristics such as biomass, photosynthetic fluorescence parameters, Se and Cd contents, chloroplast ultrastructure, leaf membrane esterification, and antioxidant enzyme activities were determined. The results showed that the exogenous application of Se could effectively alleviate the decrease in growth, photosynthetic pigment, and the gas exchange characteristics of the cabbage seedlings under Cd stress, improve cabbage root vitality, reduce root leaf Cd content, and alleviate the Cd stress-induced damage. Ultrastructural observation showed that the Cd stress caused the disruption to the chloroplasts’ internal structure in the cabbage leaves, while an exogenous Se treatment alleviated the chloroplast damage to some extent, improved the stability of the inner capsule membrane, and alleviated the Cd stress-induced damage to the photosynthetic organs. Cd stress also caused oxidative damage and the excessive accumulation of reactive oxygen species (ROS) in the leaves of cabbage seedlings, as evidenced by the significant accumulation of superoxide anion (O2−), hydrogen peroxide (H2O2), malondialdehyde (MDA), and electrolyte leakage. On the other hand, after the exogenous Se treatment, the Cd stress-induced oxidative damage could be reduced by up-regulating the activities of the antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX). At the same time, Cd stress significantly increased glutathione (GSH) levels, and the exogenous Se treatment further increased the GSH levels, thereby increasing the tolerance of the cabbage to Cd stress. In conclusion, exogenous Se can further improve the Cd tolerance of the cabbage seedlings by protecting the photosynthetic system, eliminating excessive accumulation of reactive oxygen species under Cd stress, alleviating oxidative stress, and reducing Cd levels in plants, among other physiological properties.

ABSTRACT Dalbavancin is a second-generation lipoglycopeptide antibiotic with activity against Gram-positive organisms. Dalbavancin is Food and Drug Administration (FDA)-approved for acute bacterial skin and soft tissue infections (ABSSTIs). There is a lack of substantial data on dalbavancin in more invasive infections, particularly in high-risk populations (patients with intravenous drug use and unstable living conditions). In this retrospective observational study, we reviewed all patients that received at least one dose of dalbavancin in an inpatient or outpatient setting at Parkland Hospital from February of 2019 to August of 2021. The demographics, type of infection, and rationale for dalbavancin were collected at the baseline. Clinical failure was measured by an avoidance of emergency department (ED) visits or hospital readmission at 30, 60, and 90 days. A separate analysis was conducted to estimate hospital, rehabilitation, or nursing facility days saved based on the projected length of treatment. 40 patients were included, and the majority were uninsured (85%), experiencing homelessness (60%), or had intravenous drug use (IDU) (57.5%). Indications for use included ABSSTIs (45%), bloodstream infection (67.5%), osteomyelitis (40%), infective endocarditis (10%), and septic arthritis (10%). Clinical failure was observed in 5 of the 40 patients (12.5%). Nonadherence to medical recommendations, a lack of source control, and ongoing IDU increased the risk of failure. Dalbavancin saved a total of 566 days of inpatient, rehabilitation, and nursing facility stays. Dalbavancin is a reasonable alternative to the standard of care in an at-risk population, offering decreased lengths of stays and cost savings. The uses of second-generation lipoglycopeptides are desirable alternatives to traditional outpatient parenteral antibiotic therapies for patients who otherwise would not qualify or for patients who desire less hospital contact in light of the COVID-19 pandemic. IMPORTANCE This study contributes additional experience to the literature of dalbavancin use in off-label indications, particularly for patients who do not qualify for outpatient parenteral antimicrobial therapy. The majority of the patient population were people who inject drugs and the uninsured. There is difficulty in tracking outcomes in this patient population, given their outpatient follow-up rates; however, we were able to track emergency room visits and readmissions throughout the majority of the local metroplex. The clinical use of dalbavancin at our institution also increased in the midst of the COVID-19 pandemic in an effort to preserve hospital resources and limit health care exposure. In addition, we are able to provide institution-specific cost-saving data with the use of dalbavancin.

IntroductionDisseminating health science information via the internet has become an essential means for improving Chinese residents' health literacy, which has received constant attention from the Chinese government. Therefore, it is important to explore Chinese residents' perceived value and emotional response to mobile health science information for determining Chinese residents' satisfaction and use intention.MethodsThis study applied the cognition–affect–conation model to evaluate the perceived value, arousal, pleasure, trust, satisfaction, and continuous use intention. A mobile device was used to obtain health science information from 236 Chinese residents via an online survey and the data were analyzed using partial least squares (PLS)-structural equation modeling.ResultsThe results showed that Chinese residents' perceived value of health science information obtained using the mobile device directly affect the degree of arousal (β = 0.412, P < 0.001), pleasure (β = 0.215, P < 0.01), and trust (β = 0.339, P < 0.001). The degree of arousal (β = 0.121, P < 0.01), pleasure (β = 0.188, P < 0.01), and trust (β = 0.619, P < 0.001) directly affected Chinese residents' satisfaction, which further affected their continuous use intention (β = 0.513, P < 0.001). Similarly, trust directly affected Chinese residents' continuous use intention (β = 0.323, P < 0.001). The degree of arousal directly affected their degree of pleasure (β = 0.304, P < 0.001), and pleasure also imposed a direct effect on trust (β = 0.293, P < 0.001).DiscussionThe result of this study provided an academic and practical reference to improve mobile health science popularization information. Affective changes have imposed an important effect on Chinese residents' continuous use intention. High-quality, diversified and frequent use of health science information can significantly increase residents' continuous use intention, improving their health literacy as a consequence.

The role of prokaryotic CRISPR/Cas system proteins as a defensive shield against invasive nucleic acids has been studied extensively. Non-canonical roles in pathogenesis involving intracellular targeting of certain virulence-associated endogenous mRNA have also been reported for some Type I and Type II CRISPR/Cas proteins, but no such roles have yet been established for Type III system proteins. Here, we demonstrate that M. tuberculosis (Type III-A system) CRISPR/Cas proteins Csm1, Csm3, Csm5, Csm6, and Cas6 are secreted and induce host immune responses. Using cell and animal experiments, we show that Cas6, in particular, provokes IFN-γ release from PBMCs from active tuberculosis (TB) patients, and its deletion markedly attenuates virulence in a murine M. tuberculosis challenge model. Recombinant MTBCas6 induces apoptosis of macrophages and lung fibroblasts, and interacts with the surface of cells in a caspase and TLR-2 independent manner. Transcriptomic and signal pathway studies using THP-1 macrophages stimulated with MTBCas6 indicated that MTBCas6 upregulates expression of genes associated with the NF-κB pathway leading to higher levels of IL-6, IL-1β, and TNF-α release, cytokines known to activate immune system cells in response to M. tuberculosis infection. Our findings suggest that, in addition to their intracellular shielding role, M. tuberculosis CRISPR/Cas proteins have non-canonical extracellular roles, functioning like a virulent sword, and activating host immune responses.

Currently, there are no particularly effective biomarkers to distinguish between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB) and evaluate the outcome of TB treatment. In this study, we have characterized the changes in the serum metabolic profiles caused by Mycobacterium tuberculosis (Mtb) infection and standard anti-TB treatment with isoniazid–rifampin–pyrazinamide–ethambutol (HRZE) using GC-MS and LC-MS/MS. Seven metabolites, including 3-oxopalmitic acid, akeboside ste, sulfolithocholic acid, 2-decylfuran (4,8,8-trimethyldecahydro-1,4-methanoazulen-9-yl)methanol, d-(+)-camphor, and 2-methylaminoadenosine, were identified to have significantly higher levels in LTBI and untreated PTB patients (T0) than those in uninfected healthy controls (Un). Among them, akeboside Ste and sulfolithocholic acid were significantly decreased in PTB patients with 2-month HRZE (T2) and cured PTB patients with 2-month HRZE followed by 4-month isoniazid-rifampin (HR) (T6). Receiver operator characteristic curve analysis revealed that the combined diagnostic model showed excellent performance for distinguishing LT from T0 and Un. By analyzing the biochemical and disease-related pathways, we observed that the differential metabolites in the serum of LTBI or TB patients, compared to healthy controls, were mainly involved in glutathione metabolism, ascorbate and aldarate metabolism, and porphyrin and chlorophyll metabolism. The metabolites with significant differences between the T0 group and the T6 group were mainly enriched in niacin and nicotinamide metabolism. Our study provided more detailed experimental data for developing laboratory standards for evaluating LTBI and cured PTB.

Under the hit of the epidemic, an increasing number of young people exchange and purchase goods by watching and resorting to mobile short video advertisements. Therefore, it is of great significance to explore the influence mechanism of mobile short video advertising on the consumption behavior of young people. This study develops a theoretical framework including fashion, socialization, entertainment, personalization, brand, psychological needs, satisfaction, and consumption behavior using a stimulus–organism–response (SOR) theory. The data from 332 young people using mobile short video advertising revealed that psychological needs exerted significant impacts on satisfaction, mediating the advertisements, and consumer satisfaction. The attributes of advertising, including fashion, socialization, entertainment, personalization, and branding, significantly promote young people’s psychological needs and satisfaction. In addition, satisfaction affects consumer behavior, and in the same manner, fashion and brand attribute directly impact consumer satisfaction.

Ethambutol (EMB) is a first-line antituberculosis drug currently being used clinically to treat tuberculosis. Mutations in the embCAB operon are responsible for EMB resistance. However, the discrepancies between genotypic and phenotypic EMB resistance have attracted much attention. We induced EMB resistance in Mycobacterium tuberculosis in vitro and used an integrated genome–methylome–transcriptome–proteome approach to study the microevolutionary mechanism of EMB resistance. We identified 509 aberrantly methylated genes (313 hypermethylated genes and 196 hypomethylated genes). Moreover, some hypermethylated and hypomethylated genes were identified using RNA-seq profiling. Correlation analysis revealed that the differential methylation of genes was negatively correlated with transcription levels in EMB-resistant strains. Additionally, two hypermethylated candidate genes (mbtD and celA1) were screened by iTRAQ-based quantitative proteomics analysis, verified by qPCR, and corresponded with DNA methylation differences. This is the first report that identifies EMB resistance-related genes in laboratory-induced mono-EMB-resistant M. tuberculosis using multi-omics profiling. Understanding the epigenetic features associated with EMB resistance may provide new insights into the underlying molecular mechanisms.

Abstract Background The occurrence of non-alcoholic fatty liver disease (NAFLD) is found to be higher in patients with obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia. Activation of hypoxia-inducible factors has been shown in the development and progression of NAFLD, implying a cause and effects relationship between NAFLD and hypoxia. The present study was designed to investigate the interaction of lipotoxicity and hypoxia in the pathogenesis of NAFLD using mice model with high-fat diet (HFD) feeding or hypoxic treatment. Methods NAFLD model was induced in mice by HFD feeding, and in cultured primary hepatocytes by administration of palmitate acid. Mouse hypoxic model was produced by placing the mice in a Animal incubator with oxygen concentration at 75% followed by a 21% oxygen supplement. Hypoxic condition was mimicked by treating the hepatocytes with cobalt chloride (CoCl2) or 1% oxygen supply. Pimonidazole assay was conducted to evaluate hypoxia. Lipid metabolic genes were measured by real-time polymerase-chain reaction. HIF-1α and HIF-2α genes were silenced by siRNA. Results HFD feeding and palmitate acid treatment provoked severe hepatic hypoxia along with TG accumulation in mice and in cultured primary hepatocytes respectively. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured primary hepatocytes. Hypoxic treatment inhibited the expression of lipolytic genes, while increased the expression of lipogenicgenes in mice. Although both lipotoxicity and hypoxia could activate hepatic hypoxia-induced factor 1α and 2α, while neither lipotoxicity- nor hypoxia- induced hepatic steatosis was affected when HIF was knocked down. Conclusions HFD resulted in hepatic TG accumulation and concomitant hypoxia. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured heptocytes. Thus lipotoxicity and hypoxia might work as reciprocal causation and orchestrate to promote the development of NAFLD.

Background: Air pollution is one of the greatest public health concerns worldwide. In order to understand its mechanism of harm, we investigated the effects of diesel exhaust particles (DEPs), one of the major constituents of ambient air pollutants, on reactive cell viability, oxygen stress, autophagy, and apoptosis. Materials and Methods: In in vitro human umbilical vein endothelial cell (HUVEC) model, cells were exposed to freshly dispersed DEP preparations at 0, 12.5, 25, 50, 100, or 200 µg/mL for 24 h or at 50 µg/mL DEP for 1, 3, 6, 12, or 24 h. Cell survival and oxidative stress were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), and generation of reactive oxygen species (ROS). Protein expressions of autophagy (Beclin-1, p62, and light chain 3 [LC3]-II) and apoptosis (Bcl2 and Bax) were assayed by Western blotting. Results: DEP induced a significant dose-dependent and temporal decrease in cell viability and increase in ROS generation and NOX activity, in association with decreased or increased protein levels of p62 or Beclin-1, as well as conversion of the LC3 in a dose-dependent manner. DEP increased pro-apoptotic protein Bax and decreased anti-apoptotic protein Bcl2. Conclusions: These results demonstrated that DEP exposure induced cytotoxicity, oxidative stress, autophagy, and apoptosis in HUVECs. Novel insight into the mechanisms of cardiovascular diseases caused by air pollution may be provided through these findings.

Abstract Background Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. Methods We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. Results Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. Conclusions Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.

PurposeThis study was designed to assess the effects of epilepsy severity, family resilience, and social support on depression in primary caregivers of children with epilepsy (CWE), and to test the mediating roles of family resilience and social support in this relationship.MethodTwo hundred fifty-two caregivers of children with epilepsy were recruited from October 2020 to May 2021. The questionnaire contained sociodemographic characteristics, Epilepsy Severity, Chinese-Family Resilience Assessment Scale (C-FRAS), Social Support Rating Scale (SSRS), Beck Depression Inventory (BDI). Structural equation models were used to evaluate whether family resilience and social support as mediators between epilepsy severity and depression.ResultsIn this study, the prevalence of depressive symptoms among primary caregivers of CWE in China was 69.84%. Epilepsy severity was positively associated with depression. Family resilience and social support were negatively correlated with depressive symptoms (both p < 0.01). Furthermore, the fitness indices of structural models were satisfactory. The direct effect of epilepsy severity on depression was 0.266 (95% CI 0.064–0.458), this pathway explained 62.88% variance of depression. The indirect effect of family resilience and then social support was 0.069 (95% CI 0.025–0.176), indicating that the serial multiple mediation was significant. The serial mediation pathway explained 16.31% variance of depression.ConclusionsThe high incidence of depression among primary carers of CWE deserves more attention. They should be screened routinely, especially those parents of children with severe epilepsy. Family resilience and social support could be protective factors for caregivers' mental adjustment. Therefore, future psychosocial interventions for enhancing family resilience and social support should be implemented, in order to reduce their depression.

BackgroundThe current Infectious Diseases Society of America guidelines for the treatment of acute uncomplicated pyelonephritis (AUP) advise caution when using oral beta-lactams due to concern for potentially inferior efficacy compared to fluoroquinolones (FQs) and trimethoprim-sulfamethoxazole; however, studies specifically evaluating the efficacy of oral cephalosporins (CPs) in AUP are limited.ObjectiveTo assess the safety and efficacy of oral CPs versus FQs for the treatment of AUP.Design, setting and participantsThis is a retrospective, chart review study conducted at a single-center, tertiary care hospital.MeasurementsThe primary endpoint was treatment failure within 30 days, defined as a change in antibiotic or return to ED or clinic due to persistent symptoms. Secondary endpoints included adverse drug reactions (ADRs) and C. difficile infection (CDI) within 30 days.ResultsOf the 343 patients included in the study, treatment failure occurred in 54/338 (16.0%) patients and was similar between oral CPs and FQs (35/229 [15.3%] vs. 19/109 [17.4%]). A higher percentage of treatment failures were observed for third generation (3GC) and first generation (1GC) CPs compared to second generation CPs (2GC) (3GC: 15/65 [23.4%]; 1GC: 11/49 [22.4%]; 2GC: 9/115 [7.8%]). Documented ADRs were low (6/343 [1.7%]) and no cases of CDI were documented.ConclusionsOral CPs appear to be as safe and effective as FQs for the treatment of AUP. Fewer treatment failures were noted with 2GCs as compared to 3GCs and 1GCs.

Background: Late-onset Alzheimer’s disease (LOAD) and early-onset Alzheimer’s disease (EOAD) are different subtypes of AD. This study aimed to build and validate radiomics models of the hippocampus for EOAD and young controls (YCs), LOAD and old controls (OCs), as well as EOAD and LOAD.Methods: Thirty-six EOAD patients, 36 LOAD patients, 36 YCs, and 36 OCs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were enrolled and allocated to training and test sets of the EOAD-YC groups, LOAD-OC groups, and EOAD-LOAD groups. Independent external validation sets including 15 EOAD patients, 15 LOAD patients, 15 YCs, and 15 OCs from Shanghai Mental Health Center were constructed, respectively. Bilateral hippocampal segmentation and feature extraction were performed for each subject, and the least absolute shrinkage and selection operator (LASSO) method was used to select radiomic features. Support vector machine (SVM) models were constructed based on the identified features to distinguish EOAD from YC subjects, LOAD from OC subjects, and EOAD from LOAD subjects. The areas under the receiver operating characteristic curves (AUCs) were used to evaluate the performance of the models.Results: Three, three, and four features were selected for EOAD and YC subjects, LOAD and OC subjects, and EOAD and LOAD subjects, respectively. The AUC and accuracy of the SVM model were 0.90 and 0.77 in the test set and 0.91 and 0.87 in the validation set for EOAD and YC subjects, respectively; for LOAD and OC subjects, the AUC and accuracy were 0.94 and 0.86 in the test set and 0.92 and 0.78 in the validation set, respectively. For the SVM model of EOAD and LOAD subjects, the AUC was 0.87 and the accuracy was 0.79 in the test set; additionally, the AUC was 0.86 and the accuracy was 0.77 in the validation set.Conclusion: The findings of this study provide insights into the potential of hippocampal radiomic features as biomarkers to diagnose EOAD and LOAD. This study is the first to show that SVM classification analysis based on hippocampal radiomic features is a valuable method for clinical applications in EOAD.

The study aims to improve the enterprise’s ability to respond to financial crises and find some countermeasures to prevent potential financial risks. The enterprise financial risk is assessed, and the automatic summary function of mobile payment platforms based on long short-term memory (LSTM) is performed to extract the structured data and unstructured texts from its annual report. On this basis, the early warning system model of financial risks is implemented and its accuracy is improved. The structured data and unstructured text in the company’s annual report are extracted. The enterprise financial risk early warning system model is constructed. The accuracy of the enterprise financial risk early warning system has been improved. Firstly, we use the convolutional neural network (CNN) to establish a financial risk prediction system using financial data and test various indicators of the system. Secondly, the financial annual report of the listed company is obtained from the Internet. The required financial statements are obtained in two ways. The first is to set high special treatment (ST) sample weights and delete some non-ST samples. The second is to delete punctuation marks, interjections, numbers, and so on and process the collected text data. The financial risk prediction model is established using the financial text, and the LSTM + attention mechanism is used to optimize the model. Finally, combining structured financial data and unstructured financial text to establish a forecasting model, the model uses LSTM. Combined with a single-layer neural network or CNN model, the comparison experiment is carried out in two ways. Experiments show that the CNN or LSTM attention mechanism cannot significantly improve the performance of the system only using financial data or texts. Using the financial data and financial text using the LSTM + CNN model, the F1 value reached 85.29%. Financial data and other indicators in the text have also been greatly improved, and the overall performance is the best. In summary, LSTM using financial data and financial texts combined with CNN to establish a risk prediction system can help investors and companies themselves find possible financial crises in listed companies as soon as possible and help companies deal with their financial risks in a timely manner.

ABSTRACTp-Aminosalicylic acid (PAS) is an important second-line antibiotic for treating multidrug-resistant tuberculosis (MDR-TB). Due to gastrointestinal disturbance and intolerance, its potent and efficacy in the treatment of extensively drug-resistant (XDR)-TB commonly are poor. Thus, it is important to reveal the mechanism of susceptibility and resistance of Mycobacterium tuberculosis (Mtb) to this drug. Herein, we screened and established PAS-resistant (PASr) folC mutated and un-mutated Mtb strains, then utilized a multi-omics (genome, proteome, and metabolome) analysis to better characterize the mechanisms of PAS resistance in Mtb. Interestingly, we found that promotion of SAM-dependent methyltransferases and suppression of PAS uptake via inhibiting some drug transport associated membrane proteins were two key pathways for the folC mutated strain evolving into the PASr Mtb strain. However, the folC un-mutated strain was resistant to PAS via uptake of exogenous methionine, mitigating the role of inhibitors, and promoting DfrA, ThyA and FolC expression. Beyond these findings, we also found PAS resistance in Mtb might be associated with the increasing phenylalanine metabolism pathway. Collectively, our findings uncovered the differences of resistant mechanism between folC mutated and un-mutated Mtb strains resistant to PAS using multi-omics analysis and targeting modulators to these pathways may be effective for treatment of PASr Mtb strains.

Tuberculosis caused by the pathogen Mycobacterium tuberculosis (MTB), remains a significant threat to global health. Elucidating the mechanisms of essential MTB genes provides an important theoretical basis for drug exploitation. Gene mtsp17 is essential and is conserved in the Mycobacterium genus. Although Mtsp17 has a structure closely resembling typical steroidogenic acute regulatory protein-related lipid transfer (START) family proteins, its biological function is different. This study characterizes the transcriptomes of Mycobacterium smegmatis to explore the consequences of mtsp17 downregulation on gene expression. Suppression of the mtsp17 gene resulted in significant down-regulation of 3% and upregulation of 1% of all protein-coding genes. Expression of desA1, an essential gene involved in mycolic acid synthesis, and the anti-SigF antagonist MSMEG_0586 were down-regulated in the conditional Mtsp17 knockout mutant and up-regulated in the Mtsp17 over-expression strain. Trends in the changes of 70 of the 79 differentially expressed genes (Log2 fold change > 1.5) in the conditional Mtsp17 knockout strain were the same as in the SigF knockout strain. Our data suggest that Mtsp17 is likely an activator of desA1 and Mtsp17 regulates the SigF regulon by SigF regulatory pathways through the anti-SigF antagonist MSMEG_0586. Our findings indicate the role of Mtsp17 may be in transcriptional regulation, provide new insights into the molecular mechanisms of START family proteins, and uncover a new node in the regulatory network of mycobacteria.

The increasing usage of zinc oxide nanoparticles (ZnONPs) inevitably leads to their release into the environment. To understand their fate and toxicity in water systems, a reliable method for the quantitative analysis of ZnONPs in environmental waters is urgently needed to be established. In this study, a quantitative analytical method of ZnONPs in environmental waters was developed by cloud point extraction (CPE) combined inductively coupled plasma mass spectrometry (ICP-MS). To obtain high recoveries of ZnONPs, the CPE parameters including pH, surfactant concentration, salt concentration, bath temperature, and time were optimized. The results demonstrated that the addition of β-mercaptoethylamine could significantly reduce the interference of Zn2+ on the extraction of ZnONPs, while the CPE approach was not affected significantly by the typical environmental inorganic ion and ENMs (such as Au, TiO2, and Al2O3). The extraction method of ZnONPs with different diameters was also assessed, and satisfactory extraction efficiency was obtained. The results of ZnONP concentration in collected environmental water were in the range of 0.2±0.009-8.2±1.8 μg/L. And the recoveries of ZnONPs in different environmental waters were 62.2±2.0-88.1±9.6% at low concentration spiked levels (12.57-54.68 μg/L), demonstrating that it is efficient to extract trace ZnONPs from real environmental waters. This established method offered a reliable method for the quantitative determination of ZnONPs in environmental waters, which could further promote the study of the environmental behavior, fate, and toxicity of ZnONPs in an aqueous environment.

In recent years, the treatment of tuberculosis is once again facing a severe situation because the existing antituberculosis drugs have become weaker and weaker with the emergence of drug-resistant Mycobacterium tuberculosis (Mtb). The studies of cell division and cell cycle-related factors in Mtb are particularly important for the development of new drugs with broad-spectrum effects. Mycobacterium smegmatis (Msm) has been used as a model organism to study the molecular, physiological, and drug-resistant mechanisms of Mtb. Bioinformatics analysis has predicted that MSMEG_6171 is a MinD-like protein of the septum site-determining protein family associated with cell division in Mycobacterium smegmatis. In our study, we use ultrastructural analysis, proteomics, metabolomics, and molecular biology techniques to comprehensively investigate the function of MSMEG_6171. Overexpression of MSMEG_6171 in Msm resulted in elongated cells, suggesting an important role of MSMEG_6171 in regulating cell wall morphology. The MSMEG_6171 overexpression could enhance the bacterial resistance to vancomycin, ethionamide, meropenem, and cefamandole. The MSMEG_6171 overexpression could alter the lipid metabolism of Msm to cause the changes on cellular biofilm property and function, which enhances bacterial resistance to antibiotics targeting cell wall synthesis. MSMEG_6171 could also induce the glyceride and phospholipid alteration in vivo to exhibit the pleiotropic phenotypes and various cellular responses. The results showed that amino acid R249 in MSMEG_6171 was a key site that can affect the level of bacterial drug resistance, suggesting that ATPase activity is required for function.

Background: Anti-staphylococcal penicillins have long been the first-line treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Recent retrospective data comparing nafcillin and cefazolin report similar clinical efficacy despite concerns about high inoculum MSSA infections. Methods: This was a retrospective, non-inferiority, cohort study comparing treatment failure rates between nafcillin and cefazolin in patients with MSSA bacteremia from any source, other than meningitis. Multiple logistic regression was used to adjust for confounding variables. Results: A total of 142 patients were included in the study. The overall treatment failure rate among patients receiving cefazolin was non-inferior to nafcillin (11.3% versus 8.5%; 90% confidence interval −5.2% to 10.8%). Rates of adverse drug events were significantly higher in the nafcillin arm (19.7% versus 7%; p = 0.046). After adjustment for confounding variables, no difference between treatment groups was found in treatment failure (adjusted odds ratio (OR) = 1.2; 95% CI, 0.3–4.5), but nafcillin was associated with significantly higher nephrotoxicity (adjusted odds ratio (OR) = 5.4; 95% CI, 1.1–26.8). Conclusion: Cefazolin was associated with lower nephrotoxicity and similar treatment failure rates compared to nafcillin suggesting that cefazolin is an appealing first line agent for most MSSA bloodstream infections. Keywords: Nafcillin, Cefazolin, Methicillin-susceptible Staphylococcus aureus, MSSA, Bacteremia

The primary energy consumption and greenhouse gas emissions from nickel smelting products have been assessed through case studies using a process model based on mass and energy balance. The required primary energy for producing nickel metal, nickel oxide, ferronickel, and nickel pig iron is 174 GJ/t alloy (174 GJ/t contained Ni), 369 GJ/t alloy (485 GJ/t contained Ni), 110 GJ/t alloy (309 GJ/t contained Ni), and 60 GJ/t alloy (598 GJ/t contained Ni), respectively. Furthermore, the associated GHG emissions are 14 tCO2-eq/t alloy (14 tCO2-eq/t contained Ni), 30 t CO2-eq/t alloy (40 t CO2-eq/t contained Ni), 6 t CO2-eq/t alloy (18 t CO2-eq/t contained Ni), and 7 t CO2-eq/t alloy (69 t CO2-eq/t contained Ni). A possible carbon emission reduction can be observed by comparing ore type, ore grade, and electricity source, as well as allocation strategy. The suggested process model overcomes the limitation of a conventional life cycle assessment study which considers the process as a ‘black box’ and allows for an identification of further possibilities to implement sustainable nickel production.

Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold) and 6 microRNAs that are down-regulated (0.003-0.11 fold) (P

Transforming growth factor-β (TGF-β) and Hippo signaling are two critical pathways engaged in cancer progression by regulating both oncogenes and tumor suppressors, yet how the two pathways coordinately exert their functions in the development of hepatocellular carcinoma (HCC) remains elusive. In this study, we firstly conducted an integrated analysis of public liver cancer databases and our experimental TGF-β target genes, identifying CYR61 as a pivotal candidate gene relating to HCC development. The expression of CYR61 is downregulated in clinical HCC tissues and cell lines than that in the normal counterparts. Evidence revealed that CYR61 is a direct target gene of TGF-β in liver cancer cells. In addition, TGF-β-stimulated Smad2/3 and the Hippo pathway downstream effectors YAP and TEAD4 can form a protein complex on the promoter of CYR61, thereby activating the promoter activity and stimulating CYR61 gene transcription in a collaborative manner. Functionally, depletion of CYR61 enhanced TGF-β- or YAP-mediated growth and migration of liver cancer cells. Consistently, ectopic expression of CYR61 was capable of impeding TGF-β- or YAP-induced malignant transformation of HCC cells in vitro and attenuating HCC xenograft growth in nude mice. Finally, transcriptomic analysis indicates that CYR61 can elicit an antitumor programin liver cancer cells. Together, these results add new evidence for the crosstalk between TGF-β and Hippo signaling and unveil an important tumor suppressor function of CYR61 in liver cancer. [ABSTRACT FROM AUTHOR]