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Abstract Fluorinated or fluoroalkylated alcohols are common structural motifs in biologically active molecules, natural products, and pharmaceuticals. However, pentafluorosulfanyl (SF5) alcohols, a unique class of SF5 compounds that serve as synthetically valuable building blocks, are difficult to prepare with current methodologies. In this article, we present a single-step, metal-free, and photo-induced hydroxypentafluorosulfanylation of styrenes or α,β-unsaturated esters/amide, producing a series of structurally diverse pentafluorosulfanyl alcohols with up to 89% yields. This reaction is mild and operationally simple, using molecular oxygen as the hydroxy source. The protocol is suitable for a wide range of alkenes, including natural products and drug molecule derivatives. The formed SF5 alcohol units can be readily converted into diverse functionalized SF5 compounds, such as α-SF5 ketones, SF5 diols, and SF5 cyclic carbonates. The potential applications of these SF5 compounds in pharmaceutical and material sciences are vast, making this research a step forward in the field.

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P

Recently, with the increasing worldwide demand for low-temperature freezers, applying natural working medium hydrocarbon refrigerants has been widely concerned. For obtaining a −70 °C freezer, the Joule-Thomson refrigeration cycle of two kinds of binary hydrocarbon mixtures, R1150/R600 and R170/R600, were analyzed and experimentally verified. The theoretical analyses results indicated that the thermodynamic performance of R1150/R600 mixed refrigerant was better than that of R170/R600 when it was used in Joule-Thomson refrigeration system of −70 °C freezer. The coefficient of performance (COP) and the volume cooling capacity of using R1150/R600 was improved by 37.9 % and 50.7 %, respectively, compared with that of R170/R600. For further verify the results of theoretical analysis, two kinds of mixed refrigerants were tested with a low-temperature freezer prototype. The experimental results demonstrate that the lowest cabinet temperature that R170/R600 could reach was −66.9 °C at an ambient temperature of 32 °C with a refrigerant charge of 150g. On the other hand, when the concentration of R1150 is 27.5 %, the average temperature in the cabinet could reach −72 °C, indicating that the application of R1150/R600 in a low-temperature freezer at −70 °C has great potential. In summary, under the existing system configuration, the R1150/R600 was more suitable for −70 °C freezer than the R170/R600. This study could provide theoretical and experimental guidance for the selection of refrigerants for low-temperature freezers based on the Joule-Thomson refrigeration system.

Because the deformation parameters (temperature, strain rate) in the actual manufacturing process are non-constant. We investigate meta-dynamic recrystallization behavior under the transient mutation state. First, based on a single-pass thermal deformation experiment and electron backscatter diffraction (EBSD) technique, this study establishes a quantitative calculation method for the volume fraction of meta-dynamic recrystallization under different deformation conditions, and find the GOS threshold basis for judging the occurrence of meta-dynamic recrystallization. Comparing the experimental results with the numerical simulation results, it is found that the MDRX behavior of the material could be accurately described. The meta-dynamic recrystallization evolution law of the material in the thermal deformation insulation stage under the variable strain rate state is investigated by continuous variable rate thermal deformation experiment and numerical simulation. It is observed that an increase of the average strain rate in the continuous variable strain rate state would promote the meta-dynamic recrystallization softening behavior of the material in comparison with the steady state deformation stage, and vice versa.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a key factor for hepatocellular carcinoma (HCC) development. As a metabolic hepatic damage, there is still a lack of efficient therapy for NAFLD-HCC. Kurarinol (KUR) is a flavanone extracted from the root of Sophora flavescens, and exerts excellent hepatoprotective and lipid-lowering activities. But its potential on NAFLD-HCC still remains unclear, and thus was explored in our present study. Firstly, in vitro experiments revealed that KUR treatments markedly reduced lipid deposition and inflammatory response in hepatocytes under palmitate and oleic acid stimulation (PO) with decreased expression levels of fatty acid synthesis markers including fatty acid synthase (FASN), stearoyl-CoA desaturase-1 (SCD1) and sterol receptor element binding protein-1 (SREBP-1). Importantly, the proliferation of HCC cell lines was strongly limited by KUR in a dose-dependent manner. Of note, PO stimulation accelerated the proliferative capacity of HCC cells, whereas being significantly suppressed by KUR. Mechanistically, we found that epidermal growth factor receptor (EGFR) and its phosphorylation protein expression levels were highly down-regulated in hepatocytes and HCC cell lines under PO stimuli. More importantly, the functions of KUR to restrain lipid accumulation and HCC cell proliferation were diminished upon EGFR overexpression, confirming that EGFR suppression was necessary for KUR to treat NAFLD-HCC. Murine mouse models were finally established by the use of diethylnitrosamine (DEN) with high-fat/high-cholesterol diet (HFHC) feeding to determine the role of KUR in NAFLD-HCC. Oral gavage of KUR efficiently suppressed NAFLD-HCC formation in mice, as evidenced by the decreased tumor number and loading. KUR also ameliorated lipid accumulation, liver dysfunction, fibrosis and HCC cell proliferation in DEN/HFHC-challenged mice, along with decreased EGFR expression. Collectively, KUR may be an effective strategy for NAFLD-HCC prevention via EGFR signaling suppression.

Molecular marker-assisted selection (MAS) can significantly accelerate and improve the efficiency of the breeding process in seedless grape cultivars. In this study, we developed the KASP_VviAGL11 and VviAGL11_410 markers based on a single nucleotide polymorphism (SNP) site (Chr18: 26889437 (A/C)) of the VviAGL11 gene, and compared them with previously reported SSR markers p3_VvAGL11 and 5U_VviAGL11 by testing 101 cultivars and 81 F1 hybrid progenies. The results showed that both of the proposed markers obtained 100% accuracy rates in detecting allele A, which was closely associated with the seedless trait in grapes, while p3_VvAGL11 and 5U_VviAGL11 had lower accuracy rates due to their tendency to produce false positives. After careful evaluation of the technical advantages and disadvantages associated with these markers, we concluded that KASP_VviAGL11 was superior in terms of simplicity, cost-effectiveness, efficiency, and accuracy. Thus, we optimized the process of molecular MAS for seedless grapes, focusing on the KASP_VviAGL11 marker as a central component, to provide key technical support for the development of new seedless grape cultivars.

Background: Sepsis, a severe infectious disease, carries a high mortality rate. Early detection and prompt treatment are crucial for reducing mortality and improving prognosis. The aim of this research is to develop a clinical prediction model using machine learning algorithms, leveraging complete blood cell (CBC) parameters, to detect sepsis at an early stage. Methods: The study involved 572 patients admitted to West China Hospital of Sichuan University between July 2020 and September 2021. Among them, 215 were diagnosed with sepsis, while 357 had local infections. Demographic information was collected, and 57 CBC parameters were analyzed to identify potential predictors using techniques such as the Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), Support Vector Machine (SVM), and eXtreme Gradient Boosting (XGBoost). The prediction model was built using Logistic Regression and evaluated for diagnostic specificity, discrimination, and clinical applicability including metrics such as the area under the curve (AUC), calibration curve, clinical impact curve, and clinical decision curve. Additionally, the model's diagnostic performance was assessed on a separate validation cohort. Shapley's additive explanations (SHAP), and breakdown (BD) profiles were used to explain the contribution of each variable in predicting the outcome. Results: Among all the machine learning methods' prediction models, the LASSO-based model (λ = min) demonstrated the highest diagnostic performance in both the discovery cohort (AUC = 0.9446, P

Abstract Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.

Flexible rolling is important for increasing rolling production capacity. Since the wear rolls withdrawn and new rolls launched into the rolling process causing thermal deformation parameters variation, such as deformation temperature, strain rate, and strain. This paper studies the coupling behavior of static recrystallization (SRX), metadynamic recrystallization (MDRX), and thermal deformation parameters based on the double-pass thermal simulation experiments, analyzes the flow stress curves and reveals the variation law of recrystallization with thermal deformation parameters. The result shows that the second-pass flow stress of SRX is significantly dependent on the inter-pass time, deformation temperature and strain rate, Compared to MDRX, SRX requires time to nucleus of conception and is more influenced by initial strain. Considering the recovery effect and the multi-pass static softening solution algorithm of materials, the kinetic models of SRX and MDRX are established, and the predicted values of the models are in good agreement with the experimental values. The EBSD microstructure characterization technique is used to characterize the morphology of SRX and MDRX. The result shows that increasing inter-pass time, deformation temperature and strain rate can promote the SRX and MDRX process and improve static softening effect. Under the condition of constant deformation temperature and strain rate, increasing the initial strain can increase the SRX volume fraction. However, deformation temperature and strain rate have a more significant effect on the static softening than the initial strain. This paper provides a theoretical basis for designing and optimizing recrystallization behavior of flexible rolling gaps.

As a type of non-pneumatic wheel, mechanical elastic wheel (MEW) can is resistant to deformation and continue to be used when rubber is damaged by the bullet. In order to prove the deformation resistance ability of MEW, the model of rubber damaged by bullet based on the non-ordinary state-based peridynamic is proposed for the first time. By considering the two conditions with bullet penetrating and staying in rubber respectively, the model is simulated and predicted. The results show that the simulations about the model of rubber damaged by bullet is consistent with experiments, the validity of the model is verified. It explains the physical process of penetrating bullet hole being smaller than the bullet diameter, and explains the reasons for the rubber forming bulge after bullet staying in rubber. The MEW damaged by bullet still has the running ability, the damage wheel does not have obvious secondary damage after running, and MEW has the deformation resistance ability after bullet damage. It has reference significance for the research of rubber tearing problem.

Abstract Background There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. Methods This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. Results The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors

The dissolution-derived release of bioactive ions from ceramic coatings on metallic implants, despite improving osseointegration, renders a concern on the interfacial breakdown of the metal/coating/bone system during long-term service. Consequently, persistent efforts to seek alternative strategies instead of dissolution-derived activation are pressingly carrying out. Inspired by bone mineral containing ions as Ca2+, Mg2+, Sr2+ and Zn2+, here we hydrothermally grew the quadruple ions co-doped Na2TiO3 nanorod-like coatings. The co-doped ions partially substitute Na+ in Na2TiO3, and can be efficiently released from cubic lattice via exchange with Na+ in fluid rather than dissolution, endowing the coatings superior long-term stability of structure and bond strength. Regulated by the coatings-conditioned extracellular ions, TLR4-NFκB signalling is enhanced to act primarily in macrophages (MΦs) at 6 h while CaSR-PI3K-Akt1 signalling is potentiated to act predominately since 24 h, triggering MΦs in a M1 response early and then in a M2 response to sequentially secrete diverse cytokines. Acting on endothelial and mesenchymal stem cells with the released ions and cytokines, the immunomodulatory coatings greatly promote Type-H (CD31hiEmcnhi) angiogenesis and osteogenesis in vitro and in vivo, providing new insights into orchestrating insoluble ceramics-coated implants for early vascularized osseointegration in combination with long-term fixation to bone.

Lycii Radicis Cortex (LRC) is a traditional medicine in East Asia with various beneficial effects, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and anti-depressant properties. However, its potential effects on skeletal muscle atrophy have not been studied. In this study, the protective effects of LRC extract (LRCE) on dexamethasone (DEX)-induced muscle atrophy were investigated in C2C12 myotubes and mice. We evaluated the effect of LRCE on improving muscle atrophy using a variety of methods, including immunofluorescence staining, quantitative polymerase chain reaction (qPCR), Western blot, measurements of oxidative stress, apoptosis, ATP levels, and muscle tissue analysis. The results showed that LRCE improved myotube diameter, fusion index, superoxide dismutase (SOD) activity, mitochondrial content, ATP levels, expression of myogenin and myosin heavy chain (MHC), and reduced reactive oxygen species (ROS) production in dexamethasone-induced C2C12 myotubes. LRCE also enhanced protein synthesis and reduced protein degradation in the myotubes. In mice treated with DEX, LRCE restored calf thickness, decreased mRNA levels of muscle-specific RING finger protein 1 (MuRF1) and atrogin-1, and increased insulin-like growth factor 1 (IGF-1) mRNA level. Moreover, LRCE also repaired gastrocnemius muscle atrophy caused by DEX. Although human studies are not available, various preclinical studies have identified potential protective effects of LRCE against muscle atrophy, suggesting that it could be utilized in the prevention and treatment of muscle atrophy.

DRX (dynamic recrystallization) behavior, which can improve the product's microstructure and enhance its performance, is vital in the high-temperature plastic deformation of metal materials. In this paper, single-pass hot compression tests were carried out on a Gleeble-3800 thermo-mechanical simulator to investigate the DRX behavior of a low carbon steel at a deformation temperature of 900°C–1100 °C and a strain rate of 0.01s−1-0.1s−1. The effect of temperature and strain rate on DRX was investigated based on the direct connection between DRX and dynamic softening behavior. The Zener–Hollomon model revealed the relationship between temperature, strain rate, and stress was established. A DRX kinetic model was established for the hot-rolled condition based on the relationship between the characteristic parameters of DRX and temperature and strain rate. The results showed that the predicted and tested values were in good agreement. The established DRX kinetic model was embedded into DEFORM-3D software to simulate the DRX behavior of the hot rolling process of a round bar. The results showed that the fraction of DRX of the whole section of the bar after hot rolling showed noticeable non-uniformity. The DRX ability of the surface area in direct contact with the roller is significantly lower than in other areas. This phenomenon is related to the high-temperature deformation behavior during the rolling process. Reducing the roller speed has almost no effect on this phenomenon; increasing the rolling temperature can significantly improve this phenomenon.

Seed vigor is an important aspect of seed quality. It is critical to predict seed vigor and plant seedling emergence under diverse environmental conditions using the laboratory vigor test. Accordingly, laboratory experiments were conducted to determine the standard germination (SG), early individual counts of radicle emergence (RE), mean germination time (MGT), and vigor index (VI) for 16 commercially available seed lots of Siberian wildrye (Elymus sibiricus), an economically and ecological important grass species. The field emergence (FE) for seed lots was explored using a three-year field trial from 2021 to 2023. Meanwhile, pot experiments were carried out to determine the seedling emergence performance under different environmental conditions, including control, drought, and salinity stress. The correlation and regression analysis were done to investigate the links between laboratory vigor test with emergence performance under both field and pot conditions. The results showed that the SG of 16 seed lots were high, similar, and did not differ significantly between seed lots. However, the seedling emergence performance (emergence percentage, seedling dry weight, and simplified vigor index) differed significantly between seed lots under both field and pot conditions. The SG was not significantly correlated with seedling emergence performance under either the field or pot conditions. The counts of RE at selected timing, MGT, and VI showed a significant relationship with seed vigor as reflected by seedling emergence performance under diverse environmental conditions, and we found that RE at 108 h was highly predictive of seed vigor and seedling emergence. The RE at 108 h and VI were positively related to seed vigor, while MGT was negatively related. The seed lots with low vigor had lower RE at 108 h and VI but longer MGT. Overall, both RE at 108 h, MGT, and VI can be used to estimate seed vigor and predict seedling emergence under different environmental conditions, and we highly recommend RE at 108 h as a quick, precise, and convenient vigor test and early warning sign for seed storage of E. sibiricus. These results will enable seed researchers, plant breeders, farmers, and government program directors to target higher seed vigor more effectively for E. sibiricus and similar grass species.

To improve the tribological characteristics of materials employed in spatial mechanisms, there is a significant requirement to develop solid lubricating composites with superior performance. This study investigates the tribological characteristics of composites consisting of a nickel matrix combined with silver molybdate and barium molybdate. The experimental analysis focuses on evaluating the tribological behaviors of these composites from 25 °C to 800 °C. The findings indicate that the combined application of silver molybdate and barium molybdate resulted in enhanced self-lubricating properties of the composites, particularly at temperatures over 400 °C. The inclusion of both silver molybdate and barium molybdate in the composite resulted in the achievement of a low friction coefficient (0.34–0.5), as well as a wear rate ranging from 0.47 to 1.25 × 10−4 mm3 N−1m−1, within the temperature range of 400 to 800 °C. Furthermore, an analysis was conducted to examine the wear processes of the composites at various sliding temperatures. This analysis was based on the evaluation of the chemical composition and morphologies of the sliding surfaces, which were verified by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy.

To endow Ti-based orthopedic implants immunomodulatory capability and thus enhanced osseointegration, different amounts of Sr are doped in Na2TiO3 nanorods in the arrays with identical nanotopographic parameters (rod diameter, length and inter-rod spacing) by substitution of Na+ using hydrothermal treatment. The obtained arrays are denoted as STSr2, STSr4, and STSr7, where the arabic numbers indicate the incorporating amounts of Sr in Na2TiO3. The modulation effects of the Sr-doped nanorods arrays on macrophage polarization and osteogenetic functions of osteoblasts are investigated, together with the array without Sr (ST). Moreover, osseointegration of these arrays are also assayed in rat femoral condyles. Sr-doped nanorods arrays accelerate M1 (pro-inflammatory phenotype)-to-M2 (anti-inflammatory phenotype) transformation of the adhered macrophages, enhancing secretion of pro-osteogenetic cytokines and growth factors (TGF-β1 and BMP2), moreover, the Sr doped arrays directly enhance osteogenetic functions of osteoblasts. The enhancement of paracrine of M2 macrophages and osteogenetic function of osteoblasts is promoted with the increase of Sr incorporating amounts. Consequently, Sr doped arrays show significantly enhanced osseointegration in vivo compared to ST, and STSr7 exhibits the best performance. Our work sheds a new light on the design of surface chemical components and structures for orthopedic implants to enhance their osseointegration.

ObjectivesTo summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells in the pathogenic mechanism.MethodsThe PubMed, Cochrane Library, Embase, and Web of Science databases were searched for various articles that assessed the concentrations of cytokines/chemokines in the unstimulated cerebrospinal fluid (CSF) or serum of patients with NMDAR-E in this systematic review and meta-analysis. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by Stata17.0.ResultsA total of 19 articles were included in the systematic review from 260 candidate papers, and cytokine/chemokine levels reported in the CSF/serum were examined in each article. This meta-analysis included 17 eligible studies comprising 579 patients with NMDAR-E, 367 patients with noninflammatory neurological disorders, and 42 healthy controls from China, Spain, South Korea, Australia, Czechia, and Sweden. The results indicated that the levels of different cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, IL-13, IL-1β, IL-12, and IL-17 and chemokine C-X-C motif ligand (CXCL)10 in the CSF were significantly higher in NMDAR-E patients with a large effect size. In addition, B cell activating factor (BAFF), CXCL13, and interferon (IFN)-γ levels in the CSF were higher in NMDAR-E patients with a middle effect size. In contrast, levels of IL-2 and IL-4 in the CSF and CXCL13 and BAFF in the serum did not show a significant difference between cases and controls.ConclusionsThese analyses showed that the central immune response in NMDAR-E is a process that involves multiple immune cell interactions mediated by cytokines/chemokines, and T cells play an important role in the pathogenesis of immunity.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022342485).

IntroductionInfectious meningitis and encephalitis (ME) are life-threatening conditions are caused by various pathogens. Conventional laboratory tests with low sensitivity and specificity cannot help with early diagnosis.MethodsA prospective study using the novel multiplex PCR detection for 18 pathogens of ME (MME-18) was conducted to investigate the clinical utilization and the epidemiology characteristics of ME in southwestern China. Patients with suspected intracranial infection were recruited between May and October 2019 at West China Hospital of Sichuan University. The MME-18 was used to detect cerebrospinal fluid, and conventional experiments including cryptococcal capsular antigen detection, GeneXpert, real-time PCR, and clinical feedback were used to verify the result of MME-18.ResultsAmong 581 tested patients, 139 eligible individuals were enrolled in the study. Among them, Mycobacterium tuberculosis was the most common pathogen in mono-infection. Viruses and Cryptococcus neoformans were also frequently detected. Of 139 infected patients, 12 cases were diagnosed by MME-18 only, 57 patients by conventional testing only, and 70 cases by both comparator tests and MME-18. There were 96.3% (79/82) diagnoses made by MME-18 had a favorable outcome, and two of twelve diagnoses, made solely by MME-18, had a likely unclear clinical significance.DiscussionThe MME-18 showed satisfactory consistency with expert clinical consensus for patients presenting with ME. Combined with conventional testing and clinical suspicion, MME-18 may help clinicians with the early identification of pathogens.

Skeletal muscle atrophy is associated with many diseases including cancer, inflammatory diseases, neuromuscular diseases, and acute critical illness. Justicia procumbens L. has been used as a herbal remedy, but the pharmacological effect of J. procumbens on muscle atrophy has not yet been reported. Herein, we investigate the anti-atrophic effect of the n-butanol fraction of J. procumbens (JPBuFr) on dexamethasone (DEX)-induced muscle atrophy in C2C12 myotubes. The myotubes diameter, MHC positive area, ROS production, and mitochondria contents were observed under a fluorescence microscope, and various proteins related to degradation or synthesis were analyzed by western blots. JPBuFr significantly attenuated a reduction of myotube diameter, mitochondrial content, ATP level, myosin heavy chain, and myogenin expression induced by DEX. Furthermore, co-treatment of DEX and JPBuFr not only increased phosphorylation of Akt, mTOR, and p70S6K proteins but also decreased reactive oxygen species production and expression of protein degradation factors (MuRF1, Atrogin-1, FoxO3a) compared to DEX treatment. These results suggest that JPBuFr may provide potential protective effects against muscle atrophy, giving it potential for the development of anti-atrophic health functional foods.

Bioactivity-guided isolation was conducted using centrifugal partition chromatography (CPC) from an extract of Sinomenium acutum rhizome, which has shown promising preventive effects in a dexamethasone-induced C2C12 myotube atrophy model. CPC was operated with a solvent system of n-butanol–acetonitrile–water (10:2:8, v/v/v, containing 0.5% triethylamine) in dual mode (ascending to descending), which provided a high recovery rate (>99%) with a high resolution. Then, the preventive effects of the obtained CPC fractions were examined against dexamethasone-induced atrophy in C2C12 myotubes according to the weight ratios of the obtained fractions. The active fractions were further purified by semi-preparative HPLC that led to obtaining five alkaloids, one lignan glycoside, and one phenylpropanoid glycoside. Among these, at a concentration of 1 nM, sinomenine, magnoflorine, and acutumine could ameliorate dexamethasone-induced myotube atrophy in C2C12 myotubes by 9.3%, 13.8%, and 11.3%, respectively.

Abstract The worldwide pandemic of coronavirus disease 2019 (COVID-19) presents us with a serious public health crisis. To combat the virus and slow its spread, wider testing is essential. There is a need for more sensitive, specific, and convenient detection methods of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Advanced detection can greatly improve the ability and accuracy of the clinical diagnosis of COVID-19, which is conducive to the early suitable treatment and supports precise prophylaxis. In this article, we combine and present the latest laboratory diagnostic technologies and methods for SARS-CoV-2 to identify the technical characteristics, considerations, biosafety requirements, common problems with testing and interpretation of results, and coping strategies of commonly used testing methods. We highlight the gaps in current diagnostic capacity and propose potential solutions to provide cutting-edge technical support to achieve a more precise diagnosis, treatment, and prevention of COVID-19 and to overcome the difficulties with the normalization of epidemic prevention and control.

Xylanases are the preferred enzymes for the extracting of oligosaccharides from wheat bran. However, free xylanases have poor stability and are difficult to reuse, which limit their industrial application. In the present study, we covalently immobilized free maleic anhydride-modified xylanase (FMA-XY) to improve its reusability and stability. The immobilized maleic anhydride-modified xylanase (IMA-XY) exhibited better stability compared with the free enzyme. After six repeated uses, 52.24% of the activity of the immobilized enzyme remained. The wheat bran oligosaccharides extracted using IMA-XY were mainly xylopentoses, xylohexoses, and xyloheptoses, which were the β-configurational units and α-configurational units of xylose. The oligosaccharides also exhibited good antioxidant properties. The results indicated that FMA-XY can easily be recycled and can remain stable after immobilization; therefore, it has good prospects for future industrial applications.

Exercise fatigue can exert deleterious effects on the body. This study evaluated the effects and mechanisms by which Lonicera caerulea berry polyphenols extract (LCBP) improved the treadmill endurance of mice. Comparison was performed between the effects at 25°C and low temperatures (-5°C). Energy storage, product metabolism, and other biochemical indices were determined using vitamin C (VC) as a positive control. Co-immunoprecipitation was performed to detect the interaction between different proteins. Dietary supplementation with LCBP significantly prolonged the exhaustion time during treadmill exercise by 20.4% (25 °C) and 27.4% (-5 °C). LCBP significantly regulated the expression of antioxidant and inflammatory proteins, Bcl-2 /Bax apoptosis proteins, and the PKCα -NOx2 / Nox4 pathway proteins, and activated the expression of AMPK-PGC1α -NRF1-TFAM proteins in skeletal muscle mitochondria. The gene and protein expression of miRNA-133a/IGF-1/PI3K/Akt/mTOR in skeletal muscle cells was also activated. Molecular docking confirmed that the main components of LCBP such as cyanidin-3-glucoside, catechin, and chlorogenic acid, have strong binding affinity toward AMPKα. LCBP alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, and apoptosis of skeletal muscle cells, enhances mitochondrial biosynthesis and cell proliferation, reduces fatigue, and enhances performance. These effects are also significant in a low-temperature environment (Graphical Abstract). Consequently, these results provide novel insights into the anti- fatigue roles of LCBP in exercise fatigue.

BackgroundTimely diagnosis of ischemic stroke (IS) in the acute phase is extremely vital to achieve proper treatment and good prognosis. In this study, we developed a novel prediction model based on the easily obtained information at initial inspection to assist in the early identification of IS.MethodsA total of 627 patients with IS and other intracranial hemorrhagic diseases from March 2017 to June 2018 were retrospectively enrolled in the derivation cohort. Based on their demographic information and initial laboratory examination results, the prediction model was constructed. The least absolute shrinkage and selection operator algorithm was used to select the important variables to form a laboratory panel. Combined with the demographic variables, multivariate logistic regression was performed for modeling, and the model was encapsulated within a visual and operable smartphone application. The performance of the model was evaluated on an independent validation cohort, formed by 304 prospectively enrolled patients from June 2018 to May 2019, by means of the area under the curve (AUC) and calibration.ResultsThe prediction model showed good discrimination (AUC = 0.916, cut-off = 0.577), calibration, and clinical availability. The performance was reconfirmed in the more complex emergency department. It was encapsulated as the Stroke Diagnosis Aid app for smartphones. The user can obtain the identification result by entering the values of the variables in the graphical user interface of the application.ConclusionThe prediction model based on laboratory and demographic variables could serve as a favorable supplementary tool to facilitate complex, time-critical acute stroke identification.

IntroductionThe insufficient understanding and misdiagnosis of clinically diagnosed pulmonary tuberculosis (PTB) without an aetiological evidence is a major problem in the diagnosis of tuberculosis (TB). This study aims to confirm the value of Long non-coding RNA (lncRNA) n344917 in the diagnosis of PTB and construct a rapid, accurate, and universal prediction model.MethodsA total of 536 patients were prospectively and consecutively recruited, including clinically diagnosed PTB, PTB with an aetiological evidence and non-TB disease controls, who were admitted to West China hospital from Dec 2014 to Dec 2017. The expression levels of lncRNA n344917 of all patients were analyzed using reverse transcriptase quantitative real-time PCR. Then, the laboratory findings, electronic health record (EHR) information and expression levels of n344917 were used to construct a prediction model through the Least Absolute Shrinkage and Selection Operator algorithm and multivariate logistic regression.ResultsThe factors of n344917, age, CT calcification, cough, TBIGRA, low-grade fever and weight loss were included in the prediction model. It had good discrimination (area under the curve = 0.88, cutoff = 0.657, sensitivity = 88.98%, specificity = 86.43%, positive predictive value = 85.61%, and negative predictive value = 89.63%), consistency and clinical availability. It also showed a good replicability in the validation cohort. Finally, it was encapsulated as an open-source and free web-based application for clinical use and is available online at https://ziruinptb.shinyapps.io/shiny/.ConclusionCombining the novel potential molecular biomarker n344917, laboratory and EHR variables, this web-based prediction model could serve as a user-friendly, accurate platform to improve the clinical diagnosis of PTB.

Background: Predicting the risk of progression to severe coronavirus disease 2019 (COVID-19) could facilitate personalized diagnosis and treatment options, thus optimizing the use of medical resources.Methods: In this prospective study, 206 patients with COVID-19 were enrolled from regional medical institutions between December 20, 2019, and April 10, 2020. We collated a range of data to derive and validate a predictive model for COVID-19 progression, including demographics, clinical characteristics, laboratory findings, and cytokine levels. Variation analysis, along with the least absolute shrinkage and selection operator (LASSO) and Boruta algorithms, was used for modeling. The performance of the derived models was evaluated by specificity, sensitivity, area under the receiver operating characteristic (ROC) curve (AUC), Akaike information criterion (AIC), calibration plots, decision curve analysis (DCA), and Hosmer–Lemeshow test.Results: We used the LASSO algorithm and logistic regression to develop a model that can accurately predict the risk of progression to severe COVID-19. The model incorporated alanine aminotransferase (ALT), interleukin (IL)-6, expectoration, fatigue, lymphocyte ratio (LYMR), aspartate transaminase (AST), and creatinine (CREA). The model yielded a satisfactory predictive performance with an AUC of 0.9104 and 0.8792 in the derivation and validation cohorts, respectively. The final model was then used to create a nomogram that was packaged into an open-source and predictive calculator for clinical use. The model is freely available online at https://severeconid-19predction.shinyapps.io/SHINY/.Conclusion: In this study, we developed an open-source and free predictive calculator for COVID-19 progression based on ALT, IL-6, expectoration, fatigue, LYMR, AST, and CREA. The validated model can effectively predict progression to severe COVID-19, thus providing an efficient option for early and personalized management and the allocation of appropriate medical resources.

ObjectiveThis study screened potential fluid biomarkers and developed a prediction model based on the easily obtained information at initial inspection to identify ataxia patients more likely to have multiple system atrophy-cerebellar type (MSA-C).MethodsWe established a retrospective cohort with 125 ataxia patients from southwest China between April 2018 and June 2020. Demographic and laboratory variables obtained at the time of hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to construct a diagnosis score. The receiver operating characteristic (ROC) and decision curve analyses were performed to assess the accuracy and net benefit of the model. Also, independent validation using 25 additional ataxia patients was carried out to verify the model efficiency. Then the model was translated into a visual and operable web application using the R studio and Shiny package.ResultsFrom 47 indicators, five variables were selected and integrated into the prediction model, including the age of onset (AO), direct bilirubin (DBIL), aspartate aminotransferase (AST), eGFR, and synuclein-alpha. The prediction model exhibited an area under the curve (AUC) of 0.929 for the training cohort and an AUC of 0.917 for the testing cohort. The decision curve analysis (DCA) plot displayed a good net benefit for this model, and external validation confirmed its reliability. The model also was translated into a web application that is freely available to the public.ConclusionThe prediction model that was developed based on laboratory and demographic variables obtained from ataxia patients at admission to the hospital might help improve the ability to differentiate MSA-C from spinocerebellar ataxia clinically.

Alpinia oxyphylla Miq. (Zingiberaceae) extract exerts protective activity against tert-butyl hydroperoxide-induced toxicity in HepG2 cells, and the antioxidant response element (ARE) luciferase activity increased 6-fold at 30 μg/mL in HepG2 cells transiently transfected with ARE-luciferase. To identify active molecules, activity-guided isolation of the crude extract led to four sesquiterpenes (1, 2, 5, 6) and two diarylheptanoids (3 and 4) from an n-hexane extract and six sesquiterpenes (7–12) from an ethyl acetate extract. Chemical structures were elucidated by one-dimensional, two-dimensional nuclear magnetic resonance (1D-, 2D-NMR), and mass (MS) spectral data. Among the isolated compounds, eudesma-3,11-dien-2-one (2) promoted the nuclear accumulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increased the promoter property of the ARE. Diarylheptanoids, yakuchinone A (3), and 5′-hydroxyl-yakuchinone A (4) showed radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Furthermore, optimization of extraction solvents (ratios of water and ethanol) was performed by comparison of contents of active compounds, ARE-inducing activity, radical scavenging activity, and HepG2 cell protective activity. As a result, 75% ethanol was the best solvent for the extraction of A. oxyphylla fruit. This study demonstrated that A. oxyphylla exerted antioxidant effects via the Nrf2/HO-1 (heme oxygenase-1) pathway and radical scavenging along with active markers eudesma-3,11-dien-2-one (2) and yakuchinone A (3).

Abstract Background Osteosarcoma is the most common primary bone tumor in children and adolescents. Unfortunately, osteosarcoma treatments often fail due to the development of chemoresistance, of which the underlying molecular mechanisms still remain unclear. In this study, we demonstrated that HSP90AA1 gene is responsible for drug resistance in osteosarcoma through an autophagy-related mechanism. Methods shRNAs were transfected into osteosarcoma cells for knockdown of HSP90AA1 gene. Stable HSP90AA1 overexpressing osteosarcoma cell lines were obtained by lentivirus infection. mRNA and protein expressions of HSP90AA1 in osteosarcoma cells were tested by quantitative real-time PCR and western blot, respectively. Autophagy of osteosarcoma cells was detected by western blot of LC3, transmission electron microscopy and fluorescence microscope. mRFP-GFP-LC3 lentiviral transfection was also performed to detect autophagic flux. NOD/SCID mices were inoculated with MG-63 tumor cells transfected with HSP90AA1 specific shRNA. TUNEL and LC3 staining were performed to detect apoptosis and autophagy of resected tumor tissues. Results Doxorubicin, cisplatin, and methotrexate, which are commonly used in chemotherapy, each induced HSP90AA1 upregulation in human osteosarcoma cells. Suppression of HSP90AA1 restored the sensitivity of osteosarcoma cells to chemotherapy both in vivo and in vitro. Mechanism study indicated that autophagy is responsible for the chemoresistance in osteosarcoma cells. HSP90AA1 increased drug resistance by inducing autophagy and inhibiting apoptosis. Suppression of HSP90AA1 diminished autophagic protection in response to chemotherapy in osteosarcoma cells. Moreover, HSP90AA1 promotes autophagy through PI3K/Akt/mTOR pathway and inhibits apoptosis through JNK/P38 pathway. Conclusion We showed that chemotherapy agents can induce HSP90AA1 expression in osteosarcoma cells. And HSP90AA1, acting as an important regulator of autophagy, is a critical factor in the development of osteosarcoma chemoresistance both in vitro and in vivo. HSP90AA1 provides a novel therapeutic target for improving osteosarcoma treatment.

In this study, a novel assisted liquid−phase plasma electrolysis was developed to realize one−step synthesis of popcorn biomass−derived porous carbon/cobalt tetroxide (popcorn−carbon/Co3O4) composites, effectively improving the structural stability and conductivity of Co3O4. The phase structure, morphologies, chemical composition, and weight ratio of the as−prepared popcorn−carbon/Co3O4 composites were systematically analyzed. The results of X−ray diffraction (XRD), Raman spectrometer, Fourier infrared spectrometer (FTIR), X−ray photoelectron spectrometer (XPS), and thermogravimetry analyzer (TG) proved the synthesis of the popcorn−carbon/Co3O4 composites. Co3O4 nanoparticles were distributed relatively uniformly on the popcorn−carbon surface. The electrochemical properties of the popcorn−carbon/Co3O4 composite electrode materials were analyzed for exploring the influence of different Co/C ratios on the electrochemical properties of composites. The results showed that the popcorn−carbon/Co3O4 composite electrode materials prepared under 200:1 mass ratio of Co(NO3)2·6H2O and popcorn−carbon possessed a specific capacitance and specific capacity of almost 1264 F/g (594 C/g) at a current density of 1 A/g, exhibiting a better electrochemical property. The efficient, fast, and novel assisted liquid−phase plasma electrolysis provides a new method for the preparation of composite electrode materials on the supercapacitors.

A wild Lonicera caerulea berry extract rich in polyphenols (LCBP) is widely used as a food supplement and additive. The main active components are cyanidin-3-glucoside, (+)-catechin, and chlorogenic acid. The aim of this study was to examine the hypocholesterolemic effects of LCBP in high cholesterol diet (HCD)-induced hypercholesterolemia in Sprague Dawley rats and the associated changes in cholesterol metabolism. Rats were fed an HCD with or without LCBP (75, 150, and 300 mg/kg body weight) for 12 weeks. LCBP at 150 and 300 mg/kg was effective for reducing cholesterol accumulation (p

The characteristics of elongated MnS have a critical effect on fatigue anisotropy and all mechanical anisotropies. A comparative investigation of nonmetallic inclusions in both stainless steels and tool steels has been carried out in this study. The inclusion characteristics were investigated using electrolytic extraction (EE) followed by scanning electron microscopy combined with energy-dispersive spectroscopy (SEM-EDS). Overall, three types of MnS inclusions (type I (regular), type II (irregular) and type III (Rod)) were found in tool steels in as-cast samples, which had not been heat-treated. Furthermore, three types of MnS inclusions (Rod-like sulfide (RS), Plate-like sulfide (PS) and Oxysulfide (OS)) were found in samples taken after rolling. Based on the breakability of the elongated MnS, three types of inclusions, Type UU, UB and BB, where U represents the undamaged or unbroken edge of an inclusion and B represents the fragment or broken edge of an inclusion, were studied in both stainless steels and tool steels both before and after additional heat treatment. The effect of heat treatment and dissolving the metal layer during the EE process is also discussed. The results show that both processes have a limited effect on the breakability of inclusions in steels with carbon contents

Randomly moving active particles can be herded into directed motion by asymmetric geometric structures. Although such a rectification process has been extensively studied due to its fundamental, biological, and technological relevance, a comprehensive understanding of active matter rectification based on single particle dynamics remains elusive. Here, by combining experiments, simulations, and theory, we study the directed transport and energetics of swimming bacteria navigating through funnel-shaped obstacles--a paradigmatic model of rectification of living active matter. We develop a microscopic parameter-free model for bacterial rectification, which quantitatively explains experimental and numerical observations and predicts the optimal geometry for the maximum rectification efficiency. Furthermore, we quantify the degree of time irreversibility and measure the extractable work associated with bacterial rectification. Our study provides quantitative solutions to long-standing questions on bacterial rectification and establishes a generic relationship between time irreversibility, particle fluxes, and extractable work, shedding light on the energetics of nonequilibrium rectification processes in living systems. [ABSTRACT FROM AUTHOR]

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate‐induced injury model of mouse hippocampal neurons HT‐22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate‐induced HT‐22 cells. The results showed that ISO inhibited glutamate‐induced ferroptosis of neuronal cells through nuclear factor E2‐related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT‐22 cells with ISO significantly reduced glutamate‐induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long‐chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT‐22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT‐22 cells was increased, and the expression of downstream heme oxygenase‐1 protein was upregulated. In summary, ISO protects HT‐22 cells from glutamate‐induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway. [ABSTRACT FROM AUTHOR]