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Abstract Background Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S. aureus pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin α5β1, thus effectively addressing S. aureus-induced pneumonia. Methods C57 mice (8 week-old females) infected with S. aureus via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses. Results LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of S. aureus-induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination. Conclusions Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin α5β1 significantly diminished the S. aureus-mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections.

Abstract The complicated geological environment of deep rocks poses new challenges to tunnel and mining engineering. Some thorny disasters such as large deformation of soft rock and rockburst are becoming more and more prominent. However, the classic tunnelling methods represented by the mine tunnelling method and the new Austrian tunnelling method are generally unsatisfactory in addressing these issues due to the limited self-stability of surrounding rock mass. Therefore, the excavation compensation method (ECM) with the core of active stress compensation has been proposed and applied in practical engineering construction to solve the above problems. After extensive engineering practice, the theoretical foundation, key technologies, and construction system of ECM have been established and improved. This article provides a comprehensive overview of this novel tunnelling method. In addition, its controlling effects on surrounding rock are demonstrated by two typical engineering examples. It could provide some new ideas and references for the development of future tunnelling technology.

A novel meta steel with negative Poisson’s ratio effect (termed as micro-NPR steel) is developed for rock support in deep underground engineering. It possesses high strength, high ductility, and high energy absorption characteristics. In this paper, static tension and modified dynamic drop hammer tests are performed on this novel material to investigate its mechanical properties first. Then based on this material, a new generation of micro-NPR anchor cable is developed and applied in field tests subjected to blasting dynamic loads. The results of laboratory tests reveal that the ultimate elongation of micro-NPR steel under dynamic impacts is more than 30% and it is over 1.5 times that of Q235; the plastic and total energy absorption of micro-NPR are both significantly higher than that of Q235. Field test indicates the fine controlling effect of micro-NPR anchor cable on surrounding rock mass under dynamic loads. Axial force confirms that micro-NPR cables can distribute and absorb the dynamic energy uniformly around the supported rock when subjected to dynamic disturbance, avoiding local failure induced by excessive stress concentration. The excavation compensation principle and energy-absorbing characteristics are used to explain the support mechanisms. Thus, micro-NPR material and anchor cable can control and prevent dynamic disasters in deep underground engineering effectively.

ABSTRACT The global rise of antibiotic resistance has renewed interest in phage therapy, as an alternative to antibiotics to eliminate multidrug-resistant (MDR) bacterial pathogens. However, optimizing the broad-spectrum efficacy of phage therapy remains a challenge. In this study, we addressed this issue by employing strategies to improve antimicrobial efficacy of phage therapy against MDR Klebsiella pneumoniae strains, which are notorious for their resistance to conventional antibiotics. This includes the selection of broad host range phages, optimization of phage formulation, and combinations with last-resort antibiotics. Our findings unveil that having a broad host range was a dominant trait of isolated phages, and increasing phage numbers in combination with antibiotics significantly enhanced the suppression of bacterial growth. The decreased incidence of bacterial infection was explained by a reduction in pathogen density and emergence of bacterial resistance. Furthermore, phage-antibiotic synergy (PAS) demonstrated considerable broad-spectrum antibacterial potential against different clades of clinical MDR K. pneumoniae pathogens. The improved treatment outcomes of optimized PAS were also evident in a murine model, where mice receiving optimized PAS therapy demonstrated a reduced bacterial burden in mouse tissues. Taken together, these findings offer an important development in optimizing PAS therapy and its efficacy in the elimination of MDR K. pneumoniae pathogens.IMPORTANCEThe worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR) K. pneumoniae strains in in vitro and in vivo context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse K. pneumoniae pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.

Rockburst disasters occur frequently during deep underground excavation, yet traditional concepts and methods can hardly meet the requirements for support under high geo-stress conditions. Consequently, rockburst control remains challenging in the engineering field. In this study, the mechanism of excavation-induced rockburst was briefly described, and it was proposed to apply the excavation compensation method (ECM) to rockburst control. Moreover, a field test was carried out on the Qinling Water Conveyance Tunnel. The following beneficial findings were obtained: Excavation leads to changes in the engineering stress state of surrounding rock and results in the generation of excess energy ΔE, which is the fundamental cause of rockburst. The ECM, which aims to offset the deep excavation effect and lower the risk of rockburst, is an active support strategy based on high pre-stress compensation. The new negative Poisson’s ratio (NPR) bolt developed has the mechanical characteristics of high strength, high toughness, and impact resistance, serving as the material basis for the ECM. The field test results reveal that the ECM and the NPR bolt succeed in controlling rockburst disasters effectively. The research results are expected to provide guidance for rockburst support in deep underground projects such as Sichuan–Xizang Railway.

Abstract Background Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM. Methods RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood–brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein–protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results. Results RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 ~ -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway. Conclusion RPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.

Abstract The distribution of saline soil is wide and the area is large in China. The saline soil in different regions shows their own characteristics. The saline soil of single salt is configured by adding different contents of NaCl to the loess in Xi'an. The effects of chlorine content and water content on soil strength and volume change in a large water content range was studied, and the change mechanism was analyzed by scanning electron microscopy. The results show that the strength of chloride saline soil increases with the decrease of water content. The moisture content of 12% is the critical point of strength change of chloride saline soil. When the moisture content is greater than 12%, the strength of soil decreases with the increase of salt content. When the water content is less than 12%, the strength of saline soil is 3% NaCl content > 1% NaCl content > 5% NaCl content > 0% NaCl content. The volume change of the sample consists of three parts: elastic deformation during sample pressing, volume shrinkage during water loss and salt expansion. In the absence of NaCl and 1% NaCl content, the sample was in the state of shrinkage during the loading process, in which with the decrease of moisture content shrinkage rate slowed down. The volume change rate of 3% and 5% NaCl showed an inflection point from negative to positive when the water content was 15%. When the water content is less than 12%, the saline soil with 3% NaCl content has the characteristics of high strength and unobvious salt expansion. The method of adding 3% NaCl to loess in Xi 'an area can be used to simulate the cement between soil particles, which provides a reference for artificially preparing structural soil. According to the microstructure analysis, the higher the salt content of saline soil, the smaller the soil pores, and the contact form of soil particles gradually develops from the point contact between soil particles to the salt-wrapped structure.

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis. The spinal cord is a vital important part of the central nervous system; however, the underlying association between spinal cord injury and gut interactions remains unknown. Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis. Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury. This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury. Our research identified three key points. First, the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury. Second, following spinal cord injury, weakened intestinal peristalsis, prolonged intestinal transport time, and immune dysfunction of the intestine caused by abnormal autonomic nerve function, as well as frequent antibiotic treatment, may induce gut dysbiosis. Third, the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury; cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system. Fecal microbiota transplantation, probiotics, dietary interventions, and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota. Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

ObjectiveThis study aims to investigate the clinical application value of Metagenome Next-Generation Sequencing (mNGS) for pulmonary diffuse exudative lesions.MethodsFrom January 1, 2014, to November 31, 2021, 136 cases with chest radiologic presentations of pulmonary diffuse exudative lesions admitted to Fujian Provincial Hospital were included in the study; of those, 77 patients underwent mNGS pathogen detection. Based on the pathogen detection outcomes and clinical diagnoses, patients were categorized into an infection group (IG) and a non-infection group (NIG). A comparison was made between the diagnostic efficacy of the mNGS technique and traditional culture methods. Meanwhile, 59 patients clinically identified as having infectious pulmonary diffuse exudative lesions but who did not receive mNGS testing were designated as the non-NGS infection group (non-IG). A retrospective cohort study was conducted on patients in both the IG and non-IG, with a 30-day all-cause mortality endpoint used for follow-up.OutcomesWhen compared to conventional culture methods, mNGS demonstrated an approximate 35% increase in sensitivity (80.0% vs 45.5%, P

Abstract Background Spinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy. Methods In this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury. Results The NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction. Conclusions The DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.

Summary: Plasma proteins are promising biomarkers and potential drug targets in lung cancer. To evaluate the causal association between plasma proteins and lung cancer, we performed proteome-wide Mendelian randomization meta-analysis (PW-MR-meta) based on lung cancer genome-wide association studies (GWASs), protein quantitative trait loci (pQTLs) of 4,719 plasma proteins in deCODE and 4,775 in Fenland. Further, causal-protein risk score (CPRS) was developed based on causal proteins and validated in the UK Biobank. 270 plasma proteins were identified using PW-MR meta-analysis, including 39 robust causal proteins (both FDR-q

Loess has unique water sensitivity due to its distinct formation environment. The structure of loess is undercompactness, weak cementation, and porousness. The water sensitivity of loess directly leads to many environmental problems and geological hazards, including subgrade subsidences, slope collapse or failures, and building cracking. To reveal the relationship between water sensitivity and loess structure, confined-compression collapsibility tests and triaxial-collapsibility tests were performed on loess in different areas. The collapsibility coefficient, porosity ratio, and collapsibility rate were analyzed. Results show that the collapsibility process of loess can be divided into three stages: wetting, softening, and settling. The collapsibility sensitivity of loess is determined primarily by its structural and hydraulic state.

This study examines the widespread practice of upstream tailings dam construction in metallurgical mines in China, conducting comprehensive testing and research on tailings from various depositional zones of the Caijiagou tailings pond. Analysis of the test results from three types of tailings reveals a systematic relationship between the mechanical characteristics of tailings and their depositional zones: the farther from the dam, the finer the tailings particles, categorized as silty clay tailing, silt tailing, and sandy silt tailing. Consistent patterns were observed in the consolidated-drained shear strength and consolidated-undrained effective shear strength of these tailings. Among these, sandy silt tailing exhibited the highest strength, whereas silty clay tailing displayed the lowest. The dynamic stress–strain relationships of all three tailings types are described using the Hardin equivalent viscous-elastic model, where the initial dynamic shear modulus and the maximum dynamic shear stress in the model increased with effective confining pressure. The damping ratios exhibited a three-stage trend with increasing dynamic strain: gradual increase, rapid growth, and then gradual stabilization. Under various consolidated stress conditions, the ratio of the damping ratio to the maximum damping ratio versus the reduction in dynamic shear modulus showed a favorable linear relationship. Under vibration conditions, the dynamic shear stress corresponding to tailings failure increased with higher effective confining pressure and consolidated stress ratio. Finally, this study summarizes the parameters and indicators related to the saturated tailings of iron mines used in the research. Our work provides a foundation and reference for the design of tailings dams and the development and utilization of abandoned tailings ponds.

BackgroundWe previously found that the respiratory epithelial cells could eliminate the invaded group A streptococcus (GAS) through autophagy induced by binding a fibronectin (Fn) binding protein (FnBp) expressed on the surface of GAS to plasma protein Fn and its receptor integrin α5β1 of epithelial cells. Is autophagy initiated by FnBp+ bacteria via FnBp-Fn-Integrin α5β1 axis a common event in respiratory epithelial cells?MethodsWe chose Staphylococcus aureus (S. aureus/S. a) and Listeria monocytogenes (L. monocytogenes/L. m) as representatives of extracellular and intracellular FnBp+ bacteria, respectively. The FnBp of them was purified and the protein function was confirmed by western blot, viable bacteria count, confocal and pull-down. The key molecule downstream of the action axis was detected by IP, mass spectrometry and bio-informatics analysis.ResultsWe found that different FnBp from both S. aureus and L. monocytogenes could initiate autophagy through FnBp-Fn-integrin α5β1 axis and this could be considered a universal event, by which host tries to remove invading bacteria from epithelial cells. Importantly, we firstly reported that S100A8, as a key molecule downstream of integrin β1 chain, is highly expressed upon activation of integrin α5β1, which in turn up-regulates autophagy.ConclusionsVarious FnBp from FnBp+ bacteria have the ability to initiate autophagy via FnBp-Fn-Integrin α5β1 axis to promote the removal of invading bacteria from epithelial cells in the presence of fewer invaders. S100A8 is a key molecule downstream of Integrin α5β1 in this autophagy pathway.

Abstract The disintegration property of loess is the wetting and subsequent disintegration of loess in water, which is generally an important index for resistance to erosion and disintegration of wet loess slopes and foundations. In this study, a disintegration instrument is developed in this laboratory and used to study the disintegration properties of fly ash-modified loess in foundations and Roadyes-modified loess in subgrades. Disintegration tests are used to compare samples of loess modified with different amounts of fly ash and Roadyes, different water contents and different dry densities; the influence of fly ash and Roadyes content on the disintegration of modified loess is analyzed. The differences in disintegration properties between the pure loess and modified loess are compared to explore the evolution of disintegration properties of modified loess and the optimal incorporation levels of fly ash and Roadyes. The experimental results show that the incorporation of fly ash reduces the disintegration of loess, while the incorporation of Roadyes likewise decreases the disintegration of loess. The disintegration of the loess modified with the two curing agents is better than that of the pure loess and loess mixed with a single curing agent; the optimal incorporation levels are 15% fly ash and 0.5‰ Roadyes. Comparing the evolution of the disintegration curves of samples of loess with different modifications shows is a linear relationship between time and amount of disintegration for pure loess and Roadyes-modified loess. Thus, a linear disintegration model is established in which the parameter P is the disintegration rate. According to the exponential relationship between time and amount of disintegration of fly ash-modified loess and loess modified with both fly ash and Roadyes, an exponential disintegration model is established in which the water stability parameter Q affects the strong and weak disintegration of the modified loess. The relationship between the water stability of the loess (modified with added fly ash and Roadyes) in water and the initial water content and dry density is analyzed. The water stability of the loess first increases and then decreases with increasing initial water content and gradually increases with increasing dry density. When the sample density is the maximum dry density, the sample has the best water stability. These research results provide a basis for the application of loess modified with added fly ash and Roadyes.

Rockburst is becoming a huge challenge for the utilization of deep underground space. Extensive efforts have been devoted to investigating the rockburst behavior and mechanism experimentally, theoretically, and numerically. The aim of this review is to discuss the novel development and the state-of-the-art in experimental techniques, theories, and numerical approaches proposed for rockburst. The definition and classification of rockburst are first summarized with an in-depth comparison among them. Then, the available laboratory experimental technologies for rockburst are reviewed in terms of indirect and direct approaches, with the highlight of monitoring technologies and data analysis methods. Some key rockburst influencing factors (i.e. size and shape, rock types, stress state, water content, and temperature) are analyzed and discussed based on collected data. After that, rockburst theories and mechanisms are discussed and evaluated, as well as the microscopic observation. The simulation approaches of rockburst are also summarized with the highlight of optional novel numerical methods. The accuracy, stability, and reliability of different experimental, theoretical and numerical approaches are also compared and assessed in each part. Finally, a summary and some aspects of prospective research are presented.

Abstract Background Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. Methods A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. Results Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06–92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p

The Yumenkou Eastward-Expansion Water Pumping Project is an important pipeline for water network construction in Shanxi Province, China. This pipeline is vital for the development of cities and agricultural lands along its path. However, the foundation of the water delivery pipeline is mostly located in collapsible loess strata, thereby affecting project safety. To investigate the feasibility of foundation treatment schemes for the water delivery pipeline, a numerical analysis model is proposed in this study based on the analyzes of the leakage of water pipelines and different foundation treatment schemes through laboratory tests, field tests, and numerical simulations. Results show that the deeper the loess layer is, the smaller the collapsible deformation is and the greater the initial collapse pressure is. Furthermore, the deeper the buried pipeline is, the greater the collapsible deformation is after water leakage. A 0.5 m-thick lime-stabilized soil cushion layer is the most economically reasonable solution among the simulated scenarios. The collapsible deformation caused by pipeline leakage can be divided into three stages: start-up, development, and stabilization. Addressing the leakage point during the start-up stage is crucial. The proposed numerical analysis model can provide an important basis for similar engineering designs.

IntroductionThis study explored the differences in clinical characteristics between the 2009 pandemic influenza A (H1N1) and SARS-CoV-2 BA.2 variant (Omicron) infections in patients younger than age 65 years, to improve identification of these diseases and better respond to the current epidemic.MethodsData from 127 patients with the 2009 pandemic influenza A (H1N1) diagnosed between May and July of 2009 and 3,265 patients with Omicron diagnosed between March and May of 2022 were collected. Using a 1:2 match based on age (difference

Traumatic brain injury (TBI) has become one of the most important causes of death and disability worldwide. A series of neuroinflammatory responses induced after TBI are key factors for persistent neuronal damage, but at the same time, such inflammatory responses can also promote debris removal and tissue repair after TBI. The concept of pleiotropic neuroprotection delves beyond the single-target treatment approach, considering the multifaceted impacts following TBI. This notion embarks deeper into the research-oriented treatment paradigm, focusing on multi-target interventions that inhibit post-TBI neuroinflammation with enhanced therapeutic efficacy. With an enriched comprehension of TBI’s physiological mechanisms, this review dissects the advancements in developing pleiotropic neuroprotective pharmaceuticals to mitigate TBI. The aim is to provide insights that may contribute to the early clinical management of the condition.

Traumatic brain injury (TBI) is the leading cause for high morbidity and mortality rates in young adults, survivors may suffer from long-term physical, cognitive, and/or psychological disorders. Establishing better models of TBI would further our understanding of the pathophysiology of TBI and develop new potential treatments. A multitude of animal TBI models have been used to replicate the various aspects of human TBI. Although numerous experimental neuroprotective strategies were identified to be effective in animal models, a majority of strategies have failed in phase II or phase III clinical trials. This failure in clinical translation highlights the necessity of revisiting the current status of animal models of TBI and therapeutic strategies. In this review, we elucidate approaches for the generation of animal models and cell models of TBI and summarize their strengths and limitations with the aim of exploring clinically meaningful neuroprotective strategies.

The development of fractures in loess slopes often has a great influence on the stability of slopes. In this paper, taking the homogeneous slope model as an example, fractures with different distances and depths from the slope top angle are provided at the top of the slope. Firstly, the influence of single fracture location and depth on slope stability is analyzed, and after the most unfavorable location and depth of the fractures are determined, the influence of the slope top fractures on the slope seepage field and slope stability under the conditions with and without rainfall is studied secondly. The results show that with the increase of the distance from the fracture to the top angle of the slope, the safety coefficient of the slope shows the change law of decreasing first and then increasing. The critical fracture depth corresponding to the fractures at different locations is different, and when the critical fracture depth is exceeded, the slope safety factor tends to be stable. At the end of the rainfall moment through 1-1 section to analyze, it is found that at this time the pore water pressure and volume water content of the soil at the bottom of the fracture at different depths are greater than those of the upper soil, and the shallow fracture has less influence on the seepage field of the slope, and through 2-2 section it is found that the pore water pressure and volume water content in the soil far from the fracture are greater than those of the soil near the location of the fracture. When 288 h after the end of rainfall, the pore water pressure and volumetric water content of the soil around the fracture in section 2-2 were greater than those far from the fracture location. With the passage of time, the pore water pressure at the location of the fracture gradually dissipated and the corresponding volumetric water content gradually decreased, indicating that the fracture had an obvious influence on the characteristics of the seepage field in the soil at different times of rainfall. Under the condition of no rainfall, there exists a critical depth of fractures affecting slope safety stability, while under the condition of rainfall, the slope safety coefficient continuously decreases with the increase of fracture depth, and there is no critical fracture depth. The research results promote the understanding of the safety and stability of loess fracture slopes and provide a reference for slope management.

Gravity anchor blocks are a common type of ground anchor used for suspension bridges, whose bearing depends on its large body and gravity. As there is no stratum requirement, the safety of the anchor block is important for bridge stability. This study summarizes all available estimation indexes, calculating methods, and evaluation criteria for gravity anchor block safety for the Ruili bank of the Banjin Dam grand suspension bridge. The anti-overturning, anti-sliding, base stress, and deformation safeties were comprehensively evaluated using methods including the suggested specification method (SM), simplified mechanical method (SMM), and finite element method (FEM), the results of which were compared and analyzed. The reasons for errors and improved formulas and working conditions were presented. The main conclusions were as follows. 1) The methods for calculating different evaluation indexes according to specifications lack consistency. Moreover, FEM requires that designers have good computer skills and has low feasibility in practice. 2) The SMM for gravity anchor block safety estimation as described in this study, whose indexes cover systematic and overall, the computational formula is simple and speedy, with relatively conservative results and good practicability. 3) SM, SMM, and FEM were all used for the safety estimation of gravity anchor blocks in Ruili bank. The anti-overturning and anti-sliding stability coefficients must all meet the specification requirements of 2.0. SM cannot be used to estimate the base tensile stress under limited conditions. SMM denoted tensile stress at 2.5 times the main cable design force, compared to 3.2 P for FEM. Deformation calculation methods are not given by SM, but can be suggested by SMM based on the elastic mechanics. The horizontal displacements under design load conditions were 122 mm (SMM), 108 mm (FEM), and 44 mm (composite foundation treated by root piles), with a safety standard of

Aiming at the influence factors and their action regulation of the slope stability in the coal measure strata of Beijing–Hong Kong & Macao Expressway, the influence characteristics of injection dip angle of rock stratum, thickness and strength parameters of the soft interlayer, slope height and size of slope angle on the slope safety factor are systematically studied by using the limit equilibrium method theory. The influence of slope height, thickness of weak interlayer and shear strength parameters on the stability of slope in coal measure strata with different dip angles is that the safety factor decreases first and then increases with the increase of strata dip angle. The minimum safety factor of slope under the action of each factor is near the strata dip angle of 30°, which indicates that the stability of slope in coal measure strata is poor when the dip angle of rock stratum is about 30°. With the increase of slope angle, the minimum safety factor decreases. However, when the slope angle is less than 40°, the slope is in a stable state and the dip angle of the strata do not affect the stability of the slope. Slopes with different slope angles have the minimum safety factor that is not affected by slope height. The difference between analytical solution and numerical solution is analyzed. The research provides a theoretical basis for the treatment of slopes in coal measure strata and has certain practical significance.

Summary: Characterizing influences of DNA methylation (DNAm) on non-coding RNAs (ncRNAs) is important to understand the mechanisms of gene regulation and cancer outcome. In our study, we describe the results of ncRNA quantitative trait methylation sites (ncQTM) analyses on 8,545 samples from The Cancer Genome Atlas (TCGA), 763 samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and 516 samples from Genotype-Tissue Expression (GTEx) to identify the significant associations between DNAm sites and ncRNAs (miRNA, long non-coding RNA [lncRNA], small nuclear RNA [snRNA], small nucleolar RNA [snoRNA], and rRNA) across 32 cancer types. With more than 22 billion tests, we identify 302,764 cis-ncQTMs (6.28% of all tested) and 79,841,728 trans-ncQTMs (1.15% of all tested). Most DNAm sites (70.6% on average) are in trans association, while only 25.2% DNAm sites are in cis association. Further, we develop a subtype named ncmcluster based on cancer-specific ncRNAs thatis associated with tumor microenvironment, clinical outcome, and biological pathways. To comprehensively describe the ncQTM patterns, we developed a database named Pancan-ncQTM (http://bigdata.njmu.edu.cn/Pancan-ncQTM/).

Summary: The glucagon receptor (GCGR) is a member of the class B G protein-coupled receptor family. Many research works have been carried out on GCGR structure, glucagon signaling pathway, and GCGR antagonists. However, the expression and fine distribution of GCGR proteins in response to glucagon under high glucose remain unclear. Using direct stochastic optical reconstruction microscopy (dSTORM) imaging, nanoscale GCGR clusters were observed on HepG2 cell membranes, and high glucose promoted GCGR expression and the formation of more and larger clusters. Moreover, glucagon stimulation under high glucose did not inhibit GCGR levels as significantly as that under low glucose and did not increase the downstream cyclic 3,5′-adenosine monophosphate-protein kinase A (cAMP-PKA) signal, and there were still large-size clusters on the membranes, indicating that high glucose induced glucagon resistance. In addition, high glucose induced stronger glucagon resistance in hepatoma cells compared with hepatic cells. Our work will pave a way to further our understanding of the pathogenesis of diabetes and develop more effective drugs targeting GCGR.

The strength of loess in seasonal frozen soil areas decreases evidently due to the freeze-thaw cycle, which even leads to some engineering and geological problems. Fibre reinforcement is very effective in improving the mechanical properties of soil. Triaxial tests under different water contents, freezing temperatures, and number of freeze-thaw cycles were carried out for fibre-reinforced loess to study the ability of fibre reinforcement to improve the resistance of loess to freeze-thaw damage; scanning electron microscopy (SEM) was also conducted. The effects of freeze and thaw deterioration and reinforcement were discussed by comparing the strength parameters under different test conditions, and the influence mechanism of freezing temperature, number of freeze-thaw cycles, and reinforcement on loess strength was explained. Results show that a lower freezing temperature indicates a more evident decrease in strength after thawing. Under the action of the first five freeze-thaw cycles, the degree of decrease is more prominent. The fibre reinforcement can reduce the fragmentation of aggregates in loess, thereby effectively restraining the deterioration effect of loess during freeze-thaw cycles. Finally, the strength parameter prediction model under different freeze-thaw cycles of reinforced loess is established, thereby providing theoretical support for engineering application and numerical simulation of fibre-reinforced loess.

With the development of ultrahigh voltage transmission line construction in northwest China, an increasing number of overhead transmission lines are crossing the loess regions. Ensuring the stability of electricity transmission towers and mitigating the risk of collapse are crucial prerequisites for the construction of transmission lines. Taking the 750 kV demonstration electricity transmission line in Guanting–Lanzhou East as an example, representative loess samples were selected for compression and collapsing sensitivity tests. Four foundation treatment schemes were designed, and the wetting deformation characteristics were investigated through numerical simulation of the rainfall infiltration process. Corresponding optimisation schemes were proposed. The collapsing process was divided into four stages through laboratory collapsing tests. The relationship function between saturation and the Duncan–Chang model parameters of loess was established, which was introduced into the finite element model to consider the rainfall infiltration process. The analysis of the displacement field, and loess saturation field with time after rainfall infiltration for the four schemes showed that adding a lime-stabilised soil cushion layer and waterproof layer to the inclined column foundation had the best effect. Given that the design scheme needs to consider safety and economy, the thickness of the cushion layer was optimised, thereby reducing the use of lime-stabilised soil by 20%. Research findings provide meaningful guidance for the design of transmission tower foundations in loess areas.

Layers with low permeability are an important factor affecting the stability of tailings dams. In order to analyze the influence of the weak permeability interlayer on the seepage stability of the dam, this paper establishes a numerical analysis model of the tailings dam with the weak permeability interlayer. The seepage stability of the dam slope is calculated and analyzed for the location, thickness, number, and intervals of mud intercalation on the seepage stability of the dam slope. The weakly permeable interlayers at different locations form different saturation lines in the dam. When the weak permeability interlayer is located in the middle of the dam, the height of the saturation line is the highest, and the corresponding stability safety factor is the smallest. When the weak permeability interlayer moves up or down, the buried depth of the saturation line increases, and the safety factor increases. However, when the weak permeability interlayer is located above the drainage prism, the overall slip along the weak permeability interlayer is incidental to the increase in dam height. When the thickness of the weak permeability interlayer changes, the safety factor of the dam has a positively high significance related to the leakage. When the location of the weak permeability interlayer changes, the safety factor of the dam has no obvious correlation with the leakage. With the increase of the thickness and number of weak pemeability interlayer and the decrease of the intervals of mud intercalation, the height of the saturation line gradually increases, and the safety factor of the dam gradually decreases. Through the location of the sliding surface, it is found that the sliding surface eventually destabilizes through the lowest low-permeability interlayer.

Community-acquired pneumonia (CAP) is a lower respiratory tract infection. It is one of the commonest infectious diseases and the third leading cause of death worldwide. However, the epidemiological profiles of CAP in southeastern China are unknown. Data of inpatients and outpatients diagnosed with CAP from January 1, 2015 to December 31, 2020 were obtained from the National Healthcare Big Data in Fuzhou (Fuzhou Database). This database covers medical data from 37 hospitals and 159 community health service stations. The incidence rate, treatment pattern, and direct medical costs of CAP were assessed using clinical data. A total of 8,156,237 patients were enrolled, with a mean age of 33.72 ± 20.88 years. The overall incidence rate of CAP was 3.13 (95% confidence interval [CI]: 3.11–3.15) per 1000 person-years (PY), with 15.97 (95% CI: 15.85–16.08) per 1000 PY in children below 5 years old and 2.62 (95% CI: 2.57–2.66) per 1000 PY in the elderly ≥60 years. The cost per outpatient was $242.83 ± 341.62, and the cost per inpatient was $4,530.4 ± 9,151.68. The three most used therapeutic drugs in patients with CAP are cefotaxime, moxifloxacin, and azithromycin. In addition, despite the ability of both imported and domestic pneumococcal conjugate vaccines to reduce the incidence rate of CAP, the current vaccination coverage rates were relatively low. We suggest that more attention should be paid to the disease burden of CAP, especially due to its great economic burden in China.

Hypoglycemia is a limiting factor for blood glucose management. Serious symptoms such as seizures, and coma may occur during severe hypoglycemia, and nocturnal hypoglycemia is particularly dangerous for patients with type 1 diabetes (T1D). An effective early alarm method is essential for hypoglycemia prevention but challenging, as blood glucose is affected by many factors and the hypoglycemia sequence patterns vary from person to person. In this paper, we proposed a hypoglycemia early alarm method for mining the hidden information in blood glucose based on multi-dimensional sequential pattern mining. The blood glucose, meal, and insulin time series information were used to construct a multi-dimensional database, then the UniSeq algorithm was used to extract multi-dimensional hypoglycemia sequence patterns. Hypoglycemia early alarm was realized through pattern matching with real-time blood glucose. The public OhioT1DM dataset was used for performance evaluation. The experiment results were: 75.76% Sensitivity, 75% Precision, 75.38% F1 score, and 25.17 minutes early alarm time. The result verified that multi-dimensional sequential pattern mining can extract more hidden information and demonstrate more potential significance in providing comprehensive diagnosis support for personalized treatment. Furthermore, early alarms for potential hypoglycemia can also reserve sufficient time for blood glucose management.

ObjectThis study attempted to explore the effects of vaccination on disease severity and the factors for viral clearance and hospitalization in omicron-infected patients.MethodsThe clinical manifestations of 3,265 Omicron-infected patients (BA.2 lineage variant; the Omicron group) were compared with those of 226 Delta-infected patients (the Delta group). A Multi-class logistic regression model was employed to analyze the impacts of vaccination doses and intervals on disease severity; a logistic regression model to evaluate the risk factors for hospitalization; R 4.1.2 data analysis to investigate the factors for time for nucleic acid negativization (NAN).ResultsCompared with the Delta group, the Omicron group reported a fast transmission, mild symptoms, and lower severity incidence, and a significant inverse correlation of vaccination dose with clinical severity (OR: 0.803, 95%CI: 0.742-0.868, p

Abstract Background Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers. Methods We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein–protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD. Results Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor β (TGF-β) signaling pathway. Additionally, rescue experiments indicated that TGF-β signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells. Conclusions NCAPG may promote proliferation and migration via the TGF-β signaling pathway in LUAD.

Abstract Skin wound healing is a complicated and lengthy process, which is influenced by multiple factors and need a suitable cellular micro-environment. For skin wound, wound dressings remain a cornerstone of dermatologic therapy at present. The dressing material can create an effective protective environment for the wound, and the interactions between the dressing and the wound has a great impact on the wound healing efficiency. An ideal wound dressing materials should have good biocompatibility, moisturizing property, antibacterial property and mechanical strength, and can effectively prevent wound infection and promote wound healing. In this study, in order to design wound dressing materials endowed with excellent antibacterial and tissue repair properties, we attempted to load antimicrobial peptides onto dopmine-modified graphene oxide (PDA@GO) using lysozyme (ly) as a model drug. Then, functionalized GO was used to the surface modification of arginine-modified chitosan (CS-Arg) membrane. To evaluate the potential of the prepared nanocomposite membrane in wound dressing application, the surface morphology, hydrophilic, mechanical properties, antimicrobial activity, and cytocompatibility of the resulting nanocomposite membrane were analyzed. The results revealed that prepared nanocomposite membrane exhibited excellent hydrophilic, mechanical strength and antimicrobial activity, which can effectively promote cell growth and adhesion. In particular, using PDA@GO as drug carrier can effectively maintain the activity of antimicrobial peptides, and can maximize the antibacterial properties of the nanocomposite membrane. Finally, we used rat full-thickness wound models to observe wound healing, and the surface interactions between the prepared nanocomposite membrane and the wound. The results indicated that nanocomposite membrane can obviously accelerated wound closure, and the wounds showed reduced inflammation, improved angiogenesis and accelerated re-epithelialization. Therefore, incorporation of antimicrobial peptides-functionalize graphene oxide (ly-PDA@GO) into CS-Arg membrane was a viable strategy for fabricating excellent wound dressing. Together, this study not only prepared a wound dressing with excellent tissue repair ability, but also provided a novel idea for the development of graphene oxide-based antibacterial dressing.

The authors wish to make the following corrections to the original paper [...]

The Jiali fault is a large strike-slip fault that traverses the southeast of the Tibetan Plateau. It played an important role as an adjustment fault for adjusting stress balance both before and after the collision of the Indian and Eurasian plates. Based on early publications about the Jiali fault, this study systematically summarizes and analyzes its tectonic background, crustal and mantle structure, properties and rates of activity in the Late Quaternary and the present from the perspectives of geology and geophysics. Based on geological methods, we collected results related to dating in order to constrain the active age and rate of the fault. We newly tested optical stimulated luminescence dating for two areas near the Galong Temple, the northern branch of the eastern section of the Jiali fault to complement the measurement of activity rate. We compared the strike-slip rate and dislocation distance for different segments along the Jiali fault from west to east. Based on geophysical observations, we analyze the seismic activity, crustal and mantle velocity and seismic anisotropy. Using waveform modeling method, we newly determined focal mechanisms of 18 earthquakes with magnitudes between 3 and 5. We found that the current tectonic deformation of the Jiali fault is primarily the right-lateral strike-slip. However, there are different features at different segments. The newly activated Xixingla-Damu branch is the most active segment. On this basis, we discussed the tectonic evolution process of the Tibetan Plateau, and analyzed the structural stability of the eastern Himalaya syntaxis, which is needed for the geological hazard risk assessment of the Sichuan-Tibet railway engineering construction at the Yaan-Linzhi branch.

Abstract Background Early alarm of hypoglycemia, detection of asymptomatic hypoglycemia, and effective control of blood glucose fluctuation make a great contribution to diabetic treatment. In this study, we designed a multi-level hypoglycemia early alarm system to mine potential information in Continuous Glucose Monitoring (CGM) time series and improve the overall alarm performance for different clinical situations. Methods Through symbolizing the historical CGM records, the Prefix Span was adopted to obtain the early alarm/non-alarm frequent sequence libraries of hypoglycemia events. The longest common subsequence was used to remove the common frequent sequence for achieving the hypoglycemia early alarm in different clinical situations. Then, the frequent sequence pattern libraries with different risk thresholds were designed as the core module of the proposed multi-level hypoglycemia early alarm system. Results The model was able to predict hypoglycemia events in the clinical dataset of level-I (sensitivity 85.90%, false-positive 23.86%, miss alarm rate 14.10%, average early alarm time 20.61 min), level-II (sensitivity 80.36%, false-positive 17.37%, miss alarm rate 19.63%, average early alarm time 27.66 min), and level-III (sensitivity 78.07%, false-positive 13.59%, miss alarm rate 21.93%, average early alarm time 33.80 min), respectively. Conclusions The proposed approach could effectively predict hypoglycemia events based on different risk thresholds to meet different prevention and treatment requirements. Moreover, the experimental results confirm the practicality and prospects of the proposed early alarm system, which reflects further significance in personalized medicine for hypoglycemia prevention.

An automatic recognition of discontinuities in borehole images is a desirable way to overcome the inefficiency and inconsistency inherent in the conventional method of manual annotation. The rough borehole walls and prominent noise failed the application of existing recognition methods to borehole images taken in the coal-measure strata. This paper presents a novel approach to automatically convert coal-measure strata borehole images into identified discontinuity maps. The developed procedure formed an integrated feature representation for the borehole image through combining the color information of image and the textural features generated from multi-channel filtering. Image regions containing discontinuities are then separated from other regions by implementing fuzzy c-means clustering on the acquired feature representation. The identification of discontinuities is finally accomplished by searching for four predefined patterns (named topographic model) on the intensity transection of image regions. The proposed method is proven to be superior in the respects of noise suppression, discontinuity positioning, and recognition completeness.

ABSTRACT The HIV Env glycoprotein is the surface glycoprotein responsible for viral entry into CD4+ immune cells. During infection, Env also serves as a primary target for antibody responses, which are robust but unable to control virus replication. Immune evasion by HIV-1 Env appears to employ complex mechanisms to regulate what antigenic states are presented to the immune system. Immunodominant features appear to be distinct from epitopes that interfere with Env functions in mediating infection. Further, cell-cell transmission studies indicate that vulnerable conformational states are additionally hidden from recognition on infected cells, even though the presence of Env at the cell surface is required for viral infection through the virological synapse. Cell-cell infection studies support that Env on infected cells is presented in distinct conformations from that on virus particles. Here we review data regarding the regulation of conformational states of Env and assess how regulated sorting of Env within the infected cell may underlie mechanisms to distinguish Env on the surface of virus particles versus Env on the surface of infected cells. These mechanisms may allow infected cells to avoid opsonization, providing cell-to-cell infection by HIV with a selective advantage during evolution within an infected individual. Understanding how distinct Env conformations are presented on cells versus viruses may be essential to designing effective vaccine approaches and therapeutic strategies to clear infected cell reservoirs.

Abstract Traffic accidents, falls, and many other events may cause traumatic spinal cord injuries (SCIs), resulting in nerve cells and extracellular matrix loss in the spinal cord, along with blood loss, inflammation, oxidative stress (OS), and others. The continuous development of neural tissue engineering has attracted increasing attention on the application of fibrin hydrogels in repairing SCIs. Except for excellent biocompatibility, flexibility, and plasticity, fibrin, a component of extracellular matrix (ECM), can be equipped with cells, ECM protein, and various growth factors to promote damage repair. This review will focus on the advantages and disadvantages of fibrin hydrogels from different sources, as well as the various modifications for internal topographical guidance during the polymerization. From the perspective of further improvement of cell function before and after the delivery of stem cell, cytokine, and drug, this review will also evaluate the application of fibrin hydrogels as a carrier to the therapy of nerve repair and regeneration, to mirror the recent development tendency and challenge.

Abstract The materials used in bone tissue engineering (BTE) have been advancing with each passing day. With the continuous development of nanomedicine, gold nanoparticles (GNPs), which are easy to be synthesized and functionalized, have attracted increasing attention. Recent years have witnessed this amazing material, i.e., GNPs characterized with large surface area to volume ratio, biocompatibility, medical imaging property, hypotoxicity, translocation into the cells, high reactivity, and other properties, perform distinct functions in BTE. However, the low stability of GNPs in the biotic environment makes them in the requirements of modification or recombination before being used. After being combined with the advantages of other materials, the structures of GNPs have exhibited great potential in stem cells, scaffolds, delivery systems, medical imaging, and other aspects. This review will focus on the advances in the application of GNPs after modification or recombination with other materials to BTE.

ObjectiveTo evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China.MethodsA total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis.ResultsThe Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p

Most plasmalemmal proteins are organized into clusters to modulate various cellular functions. However, the machineries that regulate protein clustering remain largely unclear. Here, with EGFR as an example, we directly and in detail visualized the entire process of EGFR from synthesis to secretion onto the plasma membrane (PM) using a high-speed, high-resolution spinning-disk confocal microscope. First, colocalization imaging revealed that EGFR secretory vesicles underwent transport from the ER to the Golgi to the PM, eventually forming different distribution forms on the apical and basal membranes; that is, most EGFR formed larger clusters on the apical membrane than the basal membrane. A dynamic tracking image and further siRNA interference experiment confirmed that fusion of secretory vesicles with the plasma membrane led to EGFR clusters, and we showed that EGFR PM clustering may be intimately related to EGFR signaling and cell proliferation. Finally, we found that the size and origin of the secretory vesicles themselves may determine the difference in the distribution patterns of EGFR on the PM. More importantly, we showed that actin influenced the EGFR distribution by controlling the fusion of secretory vesicles with the PM. Collectively, a comprehensive understanding of the EGFR secretion process helps us to unravel the EGFR clustering process and elucidate the key factors determining the differences in the spatial distribution of EGFR PM, highlighting the correlation between EGFR secretion and its PM distribution pattern.

In high dynamic scenes, fringe projection profilometry (FPP) may encounter fringe saturation, and the phase calculated will also be affected to produce errors. This paper proposes a saturated fringe restoration method to solve this problem, taking the four-step phase shift as an example. Firstly, according to the saturation of the fringe group, the concepts of reliable area, shallow saturated area, and deep saturated area are proposed. Then, the parameter A related to the reflectivity of the object in the reliable area is calculated to interpolate A in the shallow and deep saturated areas. The theoretically shallow and deep saturated areas are not known in actual experiments. However, morphological operations can be used to dilate and erode reliable areas to produce cubic spline interpolation (CSI) areas and biharmonic spline interpolation (BSI) areas, which roughly correspond to shallow and deep saturated areas. After A is restored, it can be used as a known quantity to restore the saturated fringe using the unsaturated fringe in the same position, the remaining unrecoverable part of the fringe can be completed using CSI, and then the same part of the symmetrical fringe can be further restored. To further reduce the influence of nonlinear error, the Hilbert transform is also used in the phase calculation process of the actual experiment. The simulation and experimental results validate that the proposed method can still obtain correct results without adding additional equipment or increasing projection number, which proves the feasibility and robustness of the method.

Introduction Mining knowledge from continuous glucose monitoring (CGM) data to classify highly heterogeneous patients with type 2 diabetes according to their characteristics remains unaddressed. A refined clustering method that retrieves hidden information from CGM data could provide a viable method to identify patients with different degrees of dysglycemia and clinical phenotypes.Research design and methods From Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, we selected 908 patients with type 2 diabetes (18–83 years) who wore blinded CGM sensors (iPro2, Medtronic, California, USA). Participants were clustered based on CGM data during a 24-hour period by our method. The first level extracted the knowledge-based and statistics-based features to describe CGM signals from multiple perspectives. The Fisher score and variables cluster analysis were applied to fuse features into low dimensions at the second level. The third level divided subjects into subgroups with different clinical phenotypes. The four subgroups of patients were determined by clinical phenotypes.Results Four subgroups of patients with type 2 diabetes with significantly different statistical features and clinical phenotypes were identified by our method. In particular, individuals in cluster 1 were characterized by the lowest glucose level factor and glucose fluctuation factor, and the highest negative glucose factor and C peptide index. By contrast, cluster 2 had the highest glucose level factor and the lowest C peptide index. Cluster 4 was characterized by the greatest degree of glucose fluctuation factor, was the most insulin-sensitive, and had the lowest insulin resistance. Cluster 3 ranked in the middle concerning the CGM-derived metrics and clinical phenotypes compared with those of the other three groups.Conclusion A novel multilevel clustering approach for knowledge mining from CGM data in type 2 diabetes is presented. The results demonstrate that subgroups are adequately distinguished with notable statistical and clinical differences.

An improved three-frequency heterodyne synthesis phase unwrapping method is proposed to improve the measurement accuracy through phase difference and phase sum operations. This method can reduce the effect of noise and increase the equivalent phase frequency. According to the distribution found in the phase difference calculation process, the Otsu segmentation is introduced to judge the phase threshold. The equivalent frequency obtained from the phase sum is more than those of all projected fringe patterns. In addition, the appropriate period combinations are also studied. The simulations and related experiments demonstrate the feasibility of the proposed method and the ability to improve the accuracy of the measurement results further.

Abstract Rationale Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with “early” stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). Objectives To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. Methods Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. Results Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005–1.379], p = 0.043). Conclusions Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. Trial registration NCT01581229. Registered 19 April 2012