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Long noncoding RNAs (lncRNAs) have been reported as critical modulators in many diseases including preeclampsia. Since the association between lncRNA BNIP3P1 and its cognate gene BNIP3 in preeclampsia has been revealed previously, this study aimed to further explore the function and mechanism of BNIP3P1 in preeclampsia. EdU and TUNEL assays revealed that BNIP3P1 or BNIP3 overexpression inhibited trophoblast cell proliferation and enhanced cell apoptosis in preeclampsia. As suggested by western blot analysis, the protein levels of apoptotic markers in the cells were affected by BNIP3P1 or BNIP3 overexpression. The binding between miR-128-3p and BNIP3P1 (or BNIP3) was explored by luciferase reporter assays. Mechanistically, BNIP3P1 bound to miR-128-3p to upregulate BNIP3 expression by acting as a competing endogenous RNA (ceRNA). Importantly, BNIP3P1 was found to inactivate the mTOR signaling pathway. In conclusion, BNIP3P1 inhibited trophoblast cell proliferation and enhanced cell apoptosis in preeclampsia by targeting the miR-128-3p/BNIP3/mTOR signaling pathway.

Immune checkpoint blockade (ICB) therapy has shown tremendous promises in the treatment of various types of tumors. However, ICB therapy with antibodies appears to be less effective for glioma, partly owing to the existence of the blood-brain barrier (BBB) that impedes the entrance of therapeutics including most proteins to the central nervous system (CNS). Herein, considering the widely existing nicotinic acetylcholine receptors (nAChRs) and choline transporters (ChTs) on the surface of BBB, a choline analogue 2-methacryloyloxyethyl phosphorylcholine (MPC) is employed to fabricate the BBB-crossing copolymerivia/ifree-radical polymerization, followed by conjugation with antiprogrammed death-ligand 1 (anti-PD-L1)ivia/ia pH-sensitive traceless linker. The obtained nanoparticles exhibit significantly improved BBB-crossing capability owing to the receptor-mediated transportation after intravenous injection in an orthotopic glioma tumor model. Within the acidic glioma microenvironment, anti-PD-L1 would be released from such pH-responsive nanoparticles, further triggering highly effective ICB therapy of glioma to significantly prolong animal survival. This work thus realizes glioma microenvironment responsive BBB-crossing delivery of ICB antibodies, promising for the next generation immunotherapy of glioma.

In order to investigate the nucleation behavior of arbidol hydrochloride monohydrate (AHM) in the aqueous THF (Tetrahydrofuran) solutions, metastable zone width (MSZW) was experimentally determined via the polythermal method, and then modified Sangwal’s theory was employed to explain the nucleation process. Via the MSZW investigation, the existence of hydrochloric acid might contribute to the nuleation of the AHM from the crystallization mother liquor, which accords with our previous experiment result that it is vital to manufacture AHM in a solvent system with hydrochloric acid. Based on the classic nucleation theory, modified Sangwal’s theory was also employed to estimate the solid-liquid interfacial tension, critical nucleus size and the nucleation Gibbs energy, severally. Moreover, it is also proved that the solid-liquid interfacial tension not only reliance on temperature, but also on nucleation driving force. The surface roughness factor fr was estimated to imply the occurrence of continuous growth at the crystal interface of AHM in aqueous THF solutions. Finally, the comparisons of the calculated and experimental induction time indicate that Kubota theory has a high applicability for AHM in the aqueous THF system.

Sepsis, a life-threatening organ dysfunction induced by severe infection and uncontrolled host immune response, threatens the health of people all over the world. Herein, a type of nanoparticle formulation with simple components is synthesized by encapsulating monophosphoryl lipid A (MPLA), a TLR4 agonist, with poly(lactic-co-glycolic acid) (PLGA) nanoparticle. The obtained nanoparticles (MPLA@PLGA) could provide Escherichia coli (E. coli)-induced sepsis protection by regulating the immune system after sepsis challenge, including promoting the levels of various cytokines, boosting the percentage of natural killer cells and accelerating bacterial clearance. Notably, the survival mice pre-treated with these nanoparticles could resist repeated E. coli-induced sepsis. Our work therefore provides the great promise of MPLA@PLGA nanoparticles as a simple yet effective nano-drug for prevention and protection against E. coli-induced sepsis.

Gestational diabetes mellitus (GDM) is a worldwide public health problem. MicroRNAs (miRNAs) have been reported to be associated with GDM progression. We intended to figure out the function of miR-342-3p in the insulin resistance (IR) and liver gluconeogenesis in GDM. GDM mouse models were established by intraperitoneal injection of streptozocin. The expression of miR-342-3p and regulatory factor X3 (Rfx3) in placenta and pancreatic tissues of GDM mice were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). GDM mice were treated with lentivirus-mediated antagomir-miR-342-3p for miR-342-3p downregulation. Enzyme-linked immunosorbent assay, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and periodic acid-Schiff staining were conducted to detect the influence of miR-342-3p knockdown on the levels of blood glucose, insulin, biochemical indices as well as the apoptosis and pathological changes in placenta or pancreatic tissues of GDM mice. The binding between Rfx3 and miR-342-3p was validated by dual luciferase reporter assays. miR-342-3p was upregulated and Rfx3 was downregulated in placenta and pancreatic tissues of GDM mice. Moreover, miR-342-3p bound with Rfx3 3'-UTR and therefore downregulated the expression of Rfx3. miR-342-3p expression was negatively correlated to Rfx3 expression in placenta tissues of GDM mice. In addition, miR-342-3p depletion decreased the levels of blood glucose, insulin, biochemical indices as well as restrained the apoptosis and pathological changes in GDM mouse placenta and pancreatic tissues. Furthermore, Rfx3 silencing countervailed the alleviative influence of miR-342-3p downregulation on IR and liver gluconeogenesis in GDM mice. Collectively, downregulation of miRNA-342-3p inhibits IR and liver gluconeogenesis in GDM by upregulating Rfx3, which may provide novel insight for GDM treatment.

A cotton fabric/titanium dioxide-nanocellulose (TiO2-Cot.) flexible and recyclable composite material with highly photocatalytic degradation of dyes and antibacterial properties was synthesized.

Intratumoral heterogeneity presents a major challenge to diagnosis and treatment of glioblastoma (GBM). Such heterogeneity is further exacerbated upon the recurrence of GBM, where treatment-induced reactive changes produce additional intratumoral heterogeneity that is ambiguous to differentiate on clinical imaging. There is an urgent need to develop non-invasive approaches to map the heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We propose to predictively fuse MRI with the underlying intratumoral heterogeneity in recurrent GBM using machine learning (ML) by leveraging unique image-localized biopsies with their associated locoregional MRI features. To this end, we develop BioNet, a biologically informed multi-task framework combining Bayesian neural networks and semi-supervised adversarial autoencoders, to predict regional distributions of three tissue-specific gene modules: proliferating tumor, reactive/inflammatory cells, and infiltrated brain tissue. BioNet provides insight into how to integrate implicit and hierarchical domain knowledge, which is difficult to incorporate into ML models through existing methods. The proposed architecture further addresses challenges in exploiting latent feature structures from limited labeled image-localized biopsy samples, which lead to improvements in prediction accuracy. BioNet performs significantly better than existing methods on cross-validation and blind test datasets, shows generalizability that surpasses other models, and is adaptable to different types of data or tasks. Prediction maps of gene modules from BioNet provide accurate predictions of intratumoral heterogeneity, which can improve surgical planning and localization of diagnostic biopsies, as well as inform neuro-oncological treatment assessment for each patient. These results also highlight the emerging role of ML in precision medicine.Significance StatementQuantitative assessments of intratumoral heterogeneity are limited by sparse biopsy sampling but is crucial for diagnosis, clinical management and treatment of (recurrent) glioblastoma. We propose leveraging a unique cohort of image-localized biopsies and their associated locoregional imaging features to develop a deep learning model, BioNet, that takes as input patient MRIs to predict output maps of the regional distributions of tissue-states. BioNet is able to (1) amplify the signal to noise ratio of the intratumoral genetic and cellular heterogeneity and (2) augment the learning capability of deep learning (DL) models through integrating implicit, hierarchical, but hard to be mathematically formulated domain knowledge. Our method performs significantly better than existing methods and is able to be adapted to related diseases.

Hofmann metal-organic frameworks (MOFs) are a variety of hybrid inorganic-organic polymers with a stable framework, plentiful adjustable pore size, and redox active sites, which display great application potential in energy storage. Unfortunately, the rapid and uncontrollable rate of coordination reaction results in a large size and an anomalous morphology, and the low electrical conductivity also severely limited further development, so there are few literature studies on Hofmann MOFs as anode materials for rechargeable batteries. Introducing graphene oxide can not only greatly facilitate the formation of a continuous conductive network but also effectively anchor and disperse MOF particles by utilizing the two-dimensional planar structure, thus reducing the sizes and agglomeration of particles. In this work, various mass ratios of graphene oxide with 3D Hofmann Ni-Pz-Ni MOFs were prepared via a simple one-pot solvothermal method. Benefiting from the gradually increasing capacitance characteristic during the continuous charge/discharge process, the Ni-Pz-Ni/GO-20% electrode exhibits a great reversible capacity of 896.1 mAh g

Background Clostridium perfringens is an important zoonotic microorganism, which can cause diseases in animals and humans under suitable conditions. Contamination of C. perfringens in chicken products has been reported worldwide, but the genetic diversity and relationship of isolates were seldom analyzed. Objectives The current study was undertaken to investigate the prevalence of C. perfringens from retail chicken products and sick chickens with suspected necrotic enteritis (NE) in Tai'an area, China. Methods In total, 295 samples were collected from Tai'an large poultry retail market and veterinary hospital in 2018, then the isolates were tested for toxin genes, drug resistance and multilocus sequence typing (MLST). Results Overall, 138 (46.78%) samples were determined to be positive for C. perfringens, and 99.37% of the isolates were identified as C. perfringens type A, with the remaining isolates being type F; 18.99% of the isolates were positive for cpb2 gene. Antimicrobial susceptibility testing revealed that 52.27% of the isolates from poultry retail market and diseased chickens showed multiple antibiotic resistance. MLST results showed that 50 analyzed isolates can be divided into 39 sequences types (STs), clustered in three clonal complexes (CCs) and 23 singletons. Although most of the isolates belong to type A, considerable genetic diversity can be observed, with the Simpson's diversity index up to 0.9181. MLST results and phylogenetic analysis showed that a portion of the isolates from humans and chickens were assigned to the same clusters in the phylogenetic tree or found to be in the same CCs, indicating the chicken isolates and the human isolates are related in certain stratification. Conclusions This study showed that the contamination rate of C. perfringens in the local retail chicken products was relatively high. Most of the isolates exhibit broad‐spectrum antimicrobial resistance. The high antibiotic resistance of C. perfringens isolates and the relationship between isolates from human and chicken indicated potential public health risks., The current study was undertaken to investigate the prevalence of C. perfringens from retail chicken products and suspected necrotic enteritis (NE) infected chickens in Tai'an area, China.

A Moon-based platform can provide efficient observations of large-scale geoscience phenomena on Earth. This study focuses on the global spatio-temporal sampling characteristics of Moon-based Earth ...

Based on the indentation fracture mechanics of brittle material, the correlations between the subsurface crack depth and the scratch depth induced by pyramidal, conical, and spherical indenters are established, respectively. Combined the kinematics of grinding process, the theoretical models of surface damage (SD) and subsurface damage (SSD) depths are developed considering the strain rate effect and the micro shape/geometry of abrasive grit. The mechanical properties of fused silica under different strain rates are measured by nanoindentation test. Many fused silica samples are processed under different grinding parameters, and their SD and SSD depths are measured. In combination with the experimental results, the theoretical models from differently shaped grits are assessed, and the effects of grinding/abrasive grit parameters are analyzed theoretically. The results show that compared with experimental SD and SSD depths, those calculated from spherical or pyramidal grit have average errors of less than 11.0% and 6.0%, respectively, while those from conical grit have average errors of more than 50.0% and 33.0%, respectively. The models from hybrid grit can be used to predict the SD and SSD depths efficiently, with average errors of 5.3% and 4.6%, respectively. The results also show that both SD and SSD depths increase with the grit apex angle, diameter, tip radius, or extraction depth. Moreover, the strain rate decreases with increasing grinding depth, feed speed, or grit diameter. The research is useful to optimize the grinding/abrasive grit parameters to reduce the damages in ground brittle materials.

Polysaccharide nanocrystals have led to the development of multifunctional and sustainable materials, but most are glucose-based carbohydrates derived from valuable natural sources. Here, we present a top-down strategy that enables one, for the first time, to isolate xylose-based hemicellulose nanocrystals from available industrial biowastes. By leveraging the selective oxidation of alkaline periodate, as high as 34 wt % solid yield is accessible. The hemicellulose nanocrystals exhibit platelet-like shapes (10-20 nm thickness, 30-80 nm wide), crystalline features, and superior dispersibility in water. We also showcase their successful interface applications for one-dimensional (1D) carbon nanotube (CNT) nanoinks and two-dimensional (2D) transition-metal dichalcogenide (TMD) nanozymes, which are comparable to the traditional cellulose nanocrystals. The scalable, low-cost, and sustainable hemicellulose nanocrystals can be envisioned to provide an alternative for glucose-based polysaccharide nanocrystals, as well as hold promise for the high-value utilization of biowastes.

With the continuation of the coronavirus disease 2019 pandemic and the emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, the control of the spread of the virus remains urgent. Various animals, including cats, ferrets, hamsters, nonhuman primates, minks, tree shrews, fruit bats, and rabbits, are susceptible to SARS-CoV-2 infection naturally or experimentally. Therefore, to avoid animals from becoming mixing vessels of the virus, vaccination of animals should be considered. In the present study, we report the establishment of an efficient and stable system using Newcastle disease virus (NDV) as a vector to express SARS-CoV-2 spike protein/subunit for the rapid generation of vaccines against SARS-CoV-2 in animals. Our data showed that the S and S1 protein was sufficiently expressed in rNDV-S and rNDV-S1-infected cells, respectively. The S protein was incorporated into and displayed on the surface of rNDV-S viral particles. Intramuscular immunization with rNDV-S was found to induce the highest level of binding and neutralizing antibodies, as well as strong S-specific T-cell response in mice. Intranasal immunization with rNDV-S1 provoked a robust T-cell response but barely any detectable antibodies. Overall, the NDV-vectored vaccine candidates were able to induce profound humoral and cellular immunity, which will provide a good system for developing vaccines targeting both T-cell and antibody responses.

Background Pyogenic liver abscess(PLA)is a potentially life-threatening disease associated with elevated risk of morbidity and mortality. Ultrasound or CT-guided percutaneous catheter drainage (PCD) and needle aspiration (PNA) are important surgical methods for the treatment of PLA. While their comparative efficacy is still debated, the aim of the study was to compare PCD and PNA in the treatment of liver abscesses. Methods Taking a retrospective comparative approach, 172 patients with liver abscesses from Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine Affiliated with Renji Hospital South Campus and Xinhua Hospital were studied between April 2015 and April 2021. These were modeled using an analysis of covariance (ANCOVA) with a-priori covariates: age, sex, general health, clinical symptoms, and Sequential Organ Failure Assessment (SOFA) score was collated from medical records. Results Liver abscess was more common in middle-aged men, occurring more frequently in the right hepatic lobe. Single abscess was common in both groups. The rate of blood culture that was positive for bacteria was higher in PCD-treated patients than those treated with PNA, with Klebsiella pneumonia the most common bacteria species identified in both groups. The side effect in PCD is worse than in PLA. Conclusion Patients with liver abscess use were more seriously ill, but their mortality or fever time did not significantly increase, suggesting that PLA is beneficial for severe patients for its safety.

Messenger RNA (mRNA) vaccines, while demonstrating great successes in the fight against COVID-19, have been extensively studied in other areas such as personalized cancer immunotherapy based on tumor neoantigens. In addition to the design of mRNA sequences and modifications, the delivery carriers are also critical in the development of mRNA vaccines. In this work, we synthesized fluoroalkane-grafted polyethylenimine (F-PEI) for mRNA delivery. Such F-PEI could promote intracellular delivery of mRNA and activate the Toll-like receptor 4 (TLR4)-mediated signaling pathway. The nanovaccine formed by self-assembly of F-PEI and the tumor antigen-encoding mRNA, without additional adjuvants, could induce the maturation of dendritic cells (DCs) and trigger efficient antigen presentation, thereby eliciting anti-tumor immune responses. Using the mRNA encoding the model antigen ovalbumin (mRNA

Geopolymer is an environment-friendly cementitious material, which can effectively immobilize heavy metals. However, the existing study on solidification/stabilization (S/S) of heavy metal contaminated soil using geopolymer is very limited. In order to investigate the effects of geopolymer produced by activating fly ash (FA) and ground granulated blast-furnace slag (GGBS) (FA + GGBS) with composite activator of Na2SiO3 and NaOH on environmental and engineering properties of Pb2+ and Cd2+ contaminated soil, a series of tests including soil pH, leachate pH and electrical conductivity (EC), toxicity leaching, UCS and pH-dependent tests were conducted at different curing times. Additionally, scanning electron microscopy/energy dispersive spectroscope (SEM/EDS), X-ray diffraction (XRD) and mercury intrusion porosimetry (MIP) tests were performed to analyze the micro mechanism of FA + GGBS based geopolymer solidified contaminated soil. The results indicated that the UCS and pH of soil increased steadily with FA + GGBS content and curing time increasing. Moreover, as FA + GGBS content and curing time increased, the leached Pb2+, Cd2+ concentration decreased significantly, and the concentration was closely related to the pH of leachate. Compared with Cd2+, the solidification ratio of FA + GGBS based geopolymer for Pb2+ was lower. Besides, the leached Pb2+ and Cd2+ concentrations decreased first and then increased with increasing pH of extraction fluid. Microscopic analysis showed that the gel products of FA + GGBS based geopolymer were mainly C-(N)-A-S–H gels. However, the geopolymer structure became looser due to the existence of Pb2+ or Cd2+. The formation of Cd(OH)2 was the primary solidification mechanism of Cd2+, while Pb2+ was mainly immobilized in geopolymer structure by ion exchange. The MIP results showed that the volume of inter-aggregate pores between 0.01 and 1 μm reduced with increasing FA + GGBS content of solidified soil.

More and more evidence has identified that long non-coding RNAs (lncRNAs) are involved in various biological process of numerous diseases. It has been reported that long intergenic non-protein coding RNA 473 (LINC00473) was associated with pre-eclampsia (PE) development. However, role and molecular mechanism of LINC00473 in PE remains elusive. Therefore, we designed this research to figure out the specific biological function of LINC00473 in trophoblasts. Firstly, we testified expressions of LINC00473 in trophoblasts of PE with RT-qPCR analysis. Then, to probe biological function of LINC00473 in trophoblasts of PE, CCK-8 assay, trans-well assays and western blot analysis were conducted in Wish and JAR cells. As for verifying interaction of microRNA-15a-5p (miR-15a-5p) and LINC00473 or lipopolysaccharide induced TNF factor (LITAF), RNA pull-down and luciferase reporter assays were carried out. Finally, rescue experiments were conducted to probe regulatory pattern of the LINC00473/miR-15a-5p/LITAF axis in trophoblasts of PE. As a result, LINC00473 presented a significant upregulation in trophoblasts of PE. Moreover, LINC00473 knockdown induced trophoblast viability, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in trophoblasts. Additionally, miR-15a-5p interacted with LINC00473 and miR-15a-5p was negatively regulated by LINC00473 in trophoblasts. Simultaneously, miR-15a-5p negatively modulated LITAF in trophoblasts. Moreover, LITAF overexpression or miR-15a-5p downregulation reversed the promotive impact of silenced LINC00473 on trophoblast viability, migration, invasion and EMT. In conclusion, LINC00473 regulated migration and invasion in trophoblasts via the miR-15a-5p/LITAF axis. Our study may provide a novel insight for clinical treatment of PE.

For advanced fibrosis, isoprene is a typical characteristic marker that could be used to quickly screen the population for chronic liver disease (CLD). To achieve trace detection of isoprene, different mol% Pt-decorated In2O3 and pure In2O3 samples were prepared with the commonly used hydrothermal method. The obtained characterization results show that the prepared Pt-decorated In2O3 (1 mol%) sample had Pt nanoparticles uniformly attached to the surface of porous hierarchical In2O3 nanosheets, and the specific surface area was 62.3 m2/g. Subsequently, these sensors based on Pt–In2O3 and pure In2O3 nanomaterials were prepared, and their response characteristics were studied. The results show that the response of 1 mol% Pt–In2O3 to isoprene gas was significantly enhanced, and the optimal working temperature was 200 °C. The response of 1 mol% Pt–In2O3 to 5 ppb and 5 ppm isoprene was approximately 3.2 times and 25.9 times that of pure In2O3, respectively. Meanwhile, the 1 mol% Pt-modified sample exhibited excellent selectivity for isoprene relative to other biomarkers (carbon monoxide, hydrogen, ethanol, and ammonia). The sensor shows good repeatability and long-term stability. Therefore, the developed 1 mol% Pt-decorated In2O3 was expected to be applied as a gas-sensitive material for breath isoprene, which could be suitable for large-scale CLD rapid breath detection.

Some human exhaled volatile organic compounds (VOCs) can be employed to diagnose related human endogenous diseases as characteristic biomarkers, which is expected to be applied to rapid screening and grading because of their non-invasive and cost-effective advantages. In this study, we developed a compact gas chromatography (GC) platform mainly composed of an integrated silicon-based micro-column chip using micro-electromechanical system techniques and a miniaturized metal oxide semiconductor gas detector. In addition, the sampling/switching valve with related components and embedded microcontrollers was used for airflow control. The fabricated system selectively detected the five VOCs (pentane, acetone, toluene, octane, and decane) considered the typical endogenous disease biomarkers. In the experiments, the functional parameters of the system were investigated, and the optimum temperature conditions of the system for separation were determined. The results show that the system can successfully test the studied five VOCs as low as 1 ppm. In addition, the influence of interfering gas (carbon dioxide and ammonia) on the system for the VOC mixture is also investigated. Moreover, to prove the possibility of breath analysis of the fabricated system, the detection performance of isoprene and acetone at the ppb level is studied. Then, the concentration changes of the isoprene at the ppb concentration for human breath are successfully detected in the system. Therefore, we believe that the prepared compact GC system has potential applications in the human endogenous disease diagnosis for the VOC biomarkers.

Recently, due to its advantages of inherent stability, non-toxicity, robustness, TiO2 has been used for the anode of lithium ion batteries (LIBs). Compared with TiO2, TiO has not only the above advantages of TiO2, but also a significantly better conductivity. However, on account of serious particle agglomeration, harsh and complex synthesis conditions, it is rarely reported as an electrode material. Hence, in this paper, we artfully develop an unique and facile synthetic route for the TiO/C hybrid nanotubes via the in-situ carbon reduction technology, where the TiO nanoparticles are embedded in carbon matrix. As the anode for LIBs, the hybrid porous TiO@C anode with a stable structure in the electrochemical reaction process, shows the high reversible capacity of 306 mA h g−1 at 0.2 A g−1 after 250 cycles, along with good rate capability and cycle performance. Meanwhile, the superior electrochemical properties of the electrode are attributed to the one-dimensional hybrid porous nanostructure that can prevent particle agglomeration and increase electrical conductivity.

Background: The main goal of process-related substances investigations is to understand how impurities should be controlled during the synthetic or purification process to produce a high-quality drug substance. The simultaneous determination of related substances is a very important factor in the quality control of API and pharmaceutical dosage forms. Methods: A new HPLC method was developed for the simultaneous analysis of Ipratropium bromide and its seven related substances. The separation was performed on a waters HPLC ZORBAX Eclipse XDB- C8 column (150 × 4.6 mm, 3.5 μm). The gradient method used mobile phases containing methanol, acetonitrile, trifluoroacetic acid (TFA), water: A: (methanol, acetonitrile, TFA, 500:500:0.3 v/v/v) and B (0.3% TFA in water v/v). The gradient elution conditions were as follows: 0-32.0 min, linear from 10% A to 35% A; 32.0-36.0 min isocratic 35% A; 36.0-42.0 min linear from 35% to 10%A. The wavelength by UV detector was 220 nm and the flow rate was 1.2 mL/min. The injection volume of sample was 20 μL, and the column temperature was 30 ºC. The proposed RP-HPLC method was applied for the determination of seven related substances. Results: All standard curves obtained exhibited good linear regression (r > 0.9939) within the tested range. The average recovery rates were in the range of 98.2-102.0% and RSD was less than 2.9% (n = 3). The process-related impurities were not observed in different batches ( Conclusion: The method was applied to determine 7 process-related substances in ipratropium bromide and proved to be robust, linear, repeatable, sensitive, selective and easy to perform. The results are valuable for quality control in the manufacturing of ipratropium bromide.

As to the problems of low data mining efficiency, less dimensionality, and low accuracy of traditional multidimensional association rules in the university big data environment, an OLAP-based multi-dimensional association rule mining method is proposed, which combines hash function and marked transaction compression technology to solve the problem of excessive or redundant candidate sets in the Apriori algorithm, and uses On Line Analytical Processing to manage the intermediate data in the association mining process , in order to reduce the time overhead caused by repeated calculations. To verify the validity of the proposed method, a learning situation analysis system is constructed in the field of colleges and universities. The multi-dimensional association rules mining method is used to analyze more than 21,000 desensitized real data, in order to mine the key factors affecting students' academic performance. The experimental results show that the proposed multi-dimensional mining model has good mining results and significantly improves the time performance.

Context Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. Objective To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. Materials and methods A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups (n = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining. Results The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression. Discussion and conclusions Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.

Background : Limited research has been conducted on afebrile pyogenic liver abscess (PLA). This poses a challenge in rapid diagnosis and early tailored care to physicians. In his study, we aimed to compare the clinical characteristics of afebrile and febrile patients with PLA. Methods : We retrospectively analyzed the data of patients with PLA who were admitted to the emergency departments of two university hospitals between January 2014 and March 2020. Patients were classified into afebrile and febrile groups by using body temperature higher than 38°C as the reference standard. The demographic, clinical, and laboratory characteristics of both groups were compared. The primary outcome was all-cause in-hospital mortality and length of hospital stay. Multivariate analysis was performed to define factors associated with afebrile PLA. Results : Of the 239 patients included in this study, 51 patients (21.3%) were afebrile and 188 patients (78.7%) were febrile. There were no differences between the abscess characteristics, laboratory manifestations, and disease severity of both groups; however, age and Charlson score differed between the groups (P = 0.009 and P = 0.011). The all-cause in-hospital mortality rate was much higher in the afebrile PLA group than in the febrile PLA group (9.8% vs. 2.1%, P = 0.011). Regarding the length of stay, no significant differences were noted in the febrile PLA group compared with the afebrile PLA group (18.5% vs 17.3%, P = 0.514). In multivariate analyses, only age greater than 65 years was significantly associated with afebrile PLA. Conclusions : Afebrile patients with PLA tend to be older, have higher Charlson scores, and in-hospital mortality rate than those with febrile patients. PLA patients older than 65 years are more likely to present without fever (

A triple stimuli-responsive nanoparticle derived from a noncovalently grafted amphiphilic copolymer was reported. The noncovalent graft copolymer, abbreviated as Dex-β-CD/Fc-PLA, was constructed by the host–guest interactions between β-cyclodextrin (β-CD) grafted dextran (Dex-β-CD) and ferrocene (Fc) terminated poly(lactide) (Fc-PLA). The synthetic Dex-β-CD/Fc-PLA copolymers and precursors were characterized by 1H NMR, FT-IR, UV-Vis, GPC, 2D NOESY 1H NMR and cyclic voltammetry (CV) analyses. The noncovalent amphiphilic copolymers could self-assemble into spherical nanoparticles (NPs) with dextran as the hydrophilic shell and PLA as the hydrophobic core in aqueous solution. The average particle size of Dex-β-CD/Fc-PLA NPs decreased from 118 nm to 79 nm with the increasing amount of hydrophobic PLA segments. Ascribed to the integration of many benzoic imine bonds and Fc groups, the NPs could remain stable at pH 7.4 but decomposed in the acidic and oxidizing (NaClO and positive voltage) media, as indicated by DLS and TEM measurements. The copolymer was used to encapsulate the hydrophobic anticancer drug doxorubicin (DOX) to achieve DOX-loaded NPs, which showed rather low drug release under simulated physiological conditions but significantly enhanced release in the simulated oxidizing and acidic media. MTT assays revealed that the pristine copolymer possessed low toxicity against both normal and cancer cells, but the DOX/Dex-β-CD/Fc-PLA NPs showed much higher selective toxicity on A549 cancer cells than normal HUVEC cells. Furthermore, the results from fluorescence microscopy demonstrated that these NPs could efficiently deliver and release DOX into the nuclei of A549 cells. The present biocompatible copolymers with triple stimuli-sensitivities are promising for the efficient intracellular delivery of hydrophobic anticancer drugs.

As strict measures were taken, the coronavirus disease 2019 (COVID-19) epidemic has been gradually brought under control. As a port city, Shanghai’s main problem has shifted from treating local cases to preventing foreign imports. To prevent the re-outbreak of COVID-19 caused by imported cases, the Shanghai government has set up central isolation sites for all people entering the country from abroad to be placed under medical observation. This report describes how to set up central isolation sites and run them effectively. We put isolation sites in transformed hotels, arranged personnel according to a huge data network, and set up specific procedures to manage guests. The epidemic situation in Shanghai has confirmed the feasibility and effectiveness of the methods that other jurisdictions can adapt for their use.

Ischemic stroke represents one of the leading causes of mortality worldwide and especially in developing countries. It is crucial for finding effective therapeutic targets that protect the brain against ischemic injury. Long noncoding RNAs (lncRNAs) have emerged as major regulators of neurological diseases, and clarifying their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke. We aimed to investigate the role of lncRNA-XLOC_035088 in middle cerebral artery occlusion (MCAO)-induced rat brain injury and oxygen-glucose deprivation (OGD)-reperfusion treated hippocampal neurons. In our findings, we found that XLOC_035088 expression was significantly upregulated in OGD-reperfusion treated hippocampal neurons and in different brain regions of MCAO-treated rats. XLOC_035088 silencing protected against MCAO-induced ischemic brain injury in vivo and OGD-induced hippocampal neuronal apoptosis in vitro. Intrahippocampal silencing of XLOC_035088 significantly decreased brain XLOC_035088 expression, reduced brain infarct size, and improved neurological function through inhibiting NOTCH1 following derepression of presenilin 2 (PSEN2). Taken together, this study provides evidence that the lncRNA XLOC_035088/PSEN2/Notch1 axis is involved in the pathogenesis of ischemic brain injury, and presents a promising therapeutic route for ischemic stroke.

Currently the diagnosis of schistosomiasis is mainly determined by observing the presence of eggs in host stool samples. Because of the overwhelming number of impurities in the stool, eggs are rarely observed. Therefore, the stool hatching method is used to observe the miracidia in the water. However, the miracidia of Schistosoma japonicum are small and difficult to detect, and missed detection is likely to occur when the infection level is low. In this study, recombinant streptococcal protein G-enhanced green fluorescent protein (rSPG-EGFP) was expressed, purified, and used as a fluorescence staining reagent for miracidia. A preliminary miracidium fluorescence staining method based on antigen and antibody bindingwas established by combining recombinant protein staining with the stool hatching method. The stool hatching method was used to collect the miracidia of S. japonicum, and Schistosoma-positive serum and the recombinant protein were mixed to assess the feasibility of fluorescence staining of miracidia. The miracidia of S. japonicum and Schistosoma turkestanicum were incubated with S. japonicum-positive serum and S. turkestanicum-positive serum, respectively, to identify miracidia species. When the fluorescence staining method was used to observe living miracidia, the miracidiawere labelled by the recombinant protein, and their motility status was not affected.