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Abstract Empirical maturation models (e.g., Johnson and Rhodin models) for glomerular filtration rate (GFR) are commonly used as scaling factors for predicting pediatric renal clearance, but their predictive performance for drugs featured with tubular reabsorption is poorly understood. This study investigated the adequacy of GFR‐based scaling models for predicting pediatric renal clearance in drugs with passive tubular reabsorption by comparing with a mechanistic kidney model (Mech‐KiM) that encompasses the physiological processes of glomerular filtration, tubular secretion, and reabsorption. The analysis utilized hypothetical drugs with varying fractions of tubular reabsorption (Freabs), alongside the model drug metronidazole, which has a Freabs of 96%. Our simulations showed that when Freabs is ≤70%, the discrepancies between the GFR‐based scaling methods and the Mech‐KiM model in predicting pediatric renal clearance were generally within a twofold range throughout childhood. However, for drugs with substantial tubular reabsorption (e.g., Freabs > 70%), discrepancies greater than twofold were observed between the GFR‐based scaling methods and the Mech‐KiM model in predicting renal clearance for young children. In neonates, the differences ranged from 5‐ to 10‐fold when the adult Freabs was 95%. Pediatric physiologically based pharmacokinetic (PBPK) modeling of metronidazole revealed that using a GFR‐based scaling method (Johnson model) significantly overestimated drug concentrations in children under 2 months, whereas utilizing the Mech‐KiM model for renal clearance predictions yielded estimates closely aligned with observed concentrations. Our study demonstrates that using GFR‐based scaling models to predict pediatric renal clearance might be inadequate for drugs with extensive passive tubular reabsorption (e.g., Freabs > 70%).

Abstract Background Recent phase III randomized controlled trials have demonstrated that first-line immune checkpoint inhibitors (ICIs) improve prognosis in advanced HER-2-negative gastric cancer patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) higher than 5. However, these findings are not confirmed in real-world settings, and the benefits in PD-L1 CPS

IntroductionLandscape changes resulting from urbanization have profound impacts on biodiversity, threatening the habitat of resident species. Birds are valuable research subjects because of their diversity, wide distribution, and particular sensitivity to environmental changes. Therefore, exploring the relationships between winter birds and environmental variables is essential for designing and managing green spaces during winter. However, the responses of the winter bird communities to environmental variables in cold regions remain unclear.MethodsIn this study, we investigated the winter bird community in the riparian zone of the Hun River in Shenyang. We selected 11 environmental variables of the riparian zone and conducted a principal component analysis to extract seven new components that represent environmental changes. Subsequently, we performed correlation and redundancy analyses on bird diversity indicators and environmental variables.ResultsThe results revealed that bird richness, Simpson’s diversity index and Shannon diversity index, was greater in the urban expansion area than in the urban core area. However, abundance was lower in the urban expansion area. Disturbance and built-up components were significantly associated with overall bird diversity, while disturbance, riparian, open vegetation, and suburban vegetation components were significantly linked to the diversity of resident and migratory birds. Birds in the urban expansion area exhibited greater sensitivity to environmental variables compared to those in the urban core area.DiscussionThis study recommend focusing on seasonal influence on birds’ resource use and urbanization level and bird species composition in riparian zones.

BackgroundDetecting programmed death ligand 1 (PD-L1) expression based on immunohistochemical (IHC) staining is an important guide for the treatment of lung cancer with immune checkpoint inhibitors. However, this method has problems such as high staining costs, tumor heterogeneity, and subjective differences among pathologists. Therefore, the application of deep learning models to segment and quantitatively predict PD-L1 expression in digital sections of Hematoxylin and eosin (H&E) stained lung squamous cell carcinoma is of great significance.MethodsWe constructed a dataset comprising H&E-stained digital sections of lung squamous cell carcinoma and used a Transformer Unet (TransUnet) deep learning network with an encoder-decoder design to segment PD-L1 negative and positive regions and quantitatively predict the tumor cell positive score (TPS).ResultsThe results showed that the dice similarity coefficient (DSC) and intersection overunion (IoU) of deep learning for PD-L1 expression segmentation of H&E-stained digital slides of lung squamous cell carcinoma were 80 and 72%, respectively, which were better than the other seven cutting-edge segmentation models. The root mean square error (RMSE) of quantitative prediction TPS was 26.8, and the intra-group correlation coefficients with the gold standard was 0.92 (95% CI: 0.90–0.93), which was better than the consistency between the results of five pathologists and the gold standard.ConclusionThe deep learning model is capable of segmenting and quantitatively predicting PD-L1 expression in H&E-stained digital sections of lung squamous cell carcinoma, which has significant implications for the application and guidance of immune checkpoint inhibitor treatments. And the link to the code is https://github.com/Baron-Huang/PD-L1-prediction-via-HE-image.

ABSTRACTMitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells’ mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.

Objective To investigate the serological changes of blood type and whether hemolytic reactions occurred in a patient with ABw subtype after type A therapeutic plasma exchange(TPE) retrospectively. Methods The ABO blood group identification and genotyping was carried out by microcolumn gel method, microcolumn glass bead method, saline tube method and absorption-elution test, and the laboratory results before and after TPE were analyzed. Results The patient underwent 2 000 mL type A TPE in other hospitals and was transferred to our hospital. On the second day of hospitalization, the test showed consistency between forward and reverse blood typing. On the third day, the detection showed that Bc was ±~1+ , and discrepancy was found between forward and reverse typing. The presence of B antigen was confirmed through tube method and human anti-B absorption-elution test, and was identified as ABw03 by molecular biological method. After type A TPE, Hb and Plt both temporarily decreased, creatinine slightly increased, ALT and AST continued to decrease, while TBIL, DBIL and IBIL showed a temporary decrease followed by an increase, indicating a slight hemolytic reaction. Conclusion Infusion of large volume of plasma may cause hemolytic reactions when ABO subtype patients contain weak A or B antigens.The blood type should be strictly identified according to the ABO blood type forward and reverse typing standards. Additional laboratory tests combined with molecular biology techniques are required for weak agglutination, which can reduce the missed detection of ABO subtypes and reduce the occurrence of transfusion reactions.

Objective To identify antibody specificity in an elderly patient with hydronephrosis accompanied by ureteral stones and shock who had multiple antibodies. Methods Microcolumn gel method was used to screen unexpected antibodies of red blood cells and identify antibodies. Enzyme method and antibody absorption method were used to help judge the specificity of antibodies in patients.The ABO blood type, Rh blood type and MNS blood type of patient were determined by saline tube method. Results The patient′s blood types were O, CCDee, NNss, and a combination of anti-E, anti-c, anti-M and anti-S antibodies was detected. Conclusion Repeated blood transfusion may lead to the presence of one or more unexpected antibodies in patients. Patients with multiple or high-frequency antibodies may experience difficulties in identification and delayed blood use.

Abstract This retrospective study aimed to investigate the impact of lumbar disc herniation (LDH) on vertebral axial rotation (VAR) in the lumbar spine, focusing on both close and distant neighboring vertebrae. A total of 516 patients with LDH and an equal number of healthy individuals were included in the study, matched for age and gender. The degree of axial rotation for each lumbar spine vertebra was assessed using the Nash–Moe index. The results revealed that the prevalence of VAR in the lumbar spine was significantly higher in the LDH group compared to the Control group (65.7% vs 46.7%, P

We investigated impulsive consensus in second-order nonlinear multi-agent systems (MASs) under Denial-of-Service (DoS) attacks. We consided scenarios where the communication network is subjected to DoS attacks, disrupting communication links and causing changes in the communication topology. An event-triggered impulsive control(ETIC) approach is proposed to flexibly address these issues. Additionally, an upper bound on the DoS attack period is introduced. Finally, a numerical example is given to verify the validity of the major results.

In this paper, we investigated leader-following consensus control for nonlinear multi-agent systems (MASs) experiencing denial-of-service (DoS) attacks. We proposed a distributed control strategy incorporating an adaptive scheme and a state feedback control gain to eliminate the effects of system nonlinear dynamics and uncertainties. In addition, we introduced a dynamic event-triggered control (DETC) to minimize the utilization of communication resources. Finally, we provided simulation results to show the validity of the proposed approach.

IntroductionPrevious studies have demonstrated that frailty is associated with depressive symptoms among older people and significantly increase the risk of difficulty in activities of daily living (ADL). However, uncertainties remain regarding the mechanisms behind such relationship. The aim of this study was to investigate the mediating effect of ADL in the relationship between frailty and depressive symptoms among older adults in China, and to explore to what extend sleep duration moderated the association between ADL and depressive symptoms.MethodsIn this study, we carried out cross-sectional descriptive analysis and 1,429 participants were included in the analysis. A survey was conducted using questionnaires and instruments measuring frailty, depressive symptoms, ADL and sleep duration. Bootstrap analyses served to explore the impact of ADL in mediating frailty and depressed symptoms, as well as the effect of sleep duration in moderating ADL and depressive symptoms.ResultsCompared to the robust group, the mediating effects of ADL between frailty and depressive symptoms were significant in the prefrail group and the frail group. The interaction term between sleep duration and ADL was significantly presented in the regression on depressive symptoms. Specifically, the Johnson–Neyman technique determined a range from 8.31 to 10.19 h for sleep duration, within which the detrimental effect of frailty on depressive symptoms was offset.ConclusionSleep duration moderated the indirect effect of ADL on the association between frailty and depressive symptoms. This provides support for unraveling the underlying mechanism of the association between frailty and depressive symptoms. Encouraging older adults to enhance ADL and obtain appropriate sleep duration might improve depressive symptoms for older adults with frailty and prefrailty.

Abstract Background Blood transfusion therapy is extremely important for certain neonatal diseases, but the threshold for neonatal blood transfusion is not the same in different countries. Until now, clinical studies to determine the suitable threshold for newborns in China are lacking. Therefore, it is of high importance to establish a multi-center cohort study to explore appropriate transfusion thresholds for newborns in China. Methods This retrospective cohort study investigated neonatal blood transfusion therapy administered from January 1, 2017 to June 30, 2018, with the aim of evaluating the effect of restricted and nonrestricted blood transfusion on neonatal health. The subjects were enrolled in 46 hospitals in China. A total of 5669 neonatal cases were included in the study. Clinical diagnosis and transfusion treatment of these neonates were collected and the data were retrospectively analyzed. The neonates were followed up 1 week and 1 month after leaving the hospital. The newborns’ and their mothers’ data were collected containing 280 variables in the database. The primary outcome of the study was mortality, and the secondary outcomes were complications, hospital stays, NICU hospital stays and hospital costs. Results Results from the

As an essential component of mechanical equipment, the fault diagnosis of rolling bearings may not only guarantee the systematic operation of the equipment, but also minimize any financial losses caused by equipment shutdowns. Fault diagnosis algorithms based on convolutional neural networks (CNN) have been widely used. However, traditional CNNs have limited feature representation capabilities, thereby making it challenging to determine their hyperparameters. This paper proposes a fault diagnosis method that combines a 1D-CNN with an attention mechanism and hyperparameter optimization to overcome the aforementioned limitations; this method improves the search speed for optimal hyperparameters of CNN models, improves the diagnostic accuracy, and enhances the representation of fault feature information in CNNs. First, the 1D-CNN is improved by combining it with an attention mechanism to enhance the fault feature information. Second, a swarm intelligence algorithm based on Differential Evolution (DE) and Grey Wolf Optimization (GWO) is proposed, which not only improves the convergence accuracy, but also increases the search efficiency. Finally, the improved 1D-CNN alongside hyperparameters optimization are used to diagnose the faults of rolling bearings. By using the Case Western Reserve University (CWRU) and Jiangnan University (JNU) datasets, when compared to other common diagnosis models, the results demonstrate the usefulness and dependability of the DE-GWO-CNN algorithm in fault diagnosis applications by demonstrating the increased diagnostic accuracy and superior anti-noise capabilities of the proposed method. The fault diagnosis methodology presented in this paper can accurately identify faults and provide dependable fault classification, thereby assisting technicians in promptly resolving faults and minimizing equipment failures and operational instabilities.

In this study, optimization of the microgreen space distribution through multistage regulation is investigated, with the goal of alleviating the imbalance between the supply and demand of green resources in the central urban area of Shenyang. An optimized evaluation model of green space supply and demand is employed to calculate the green space accessibility index at a 100-m grid scale and identify different levels of green space resource supply and demand. Priority is given to supplementing resources for the elderly population by balancing the green space supply in vulnerable areas. Particle swarm—ant colony optimization (PS-ACO) is used to select microgreen space sites within each priority level. On the basis of the “important-urgent” quadrant analysis, S1-priority residential areas account for 8.12% of the grid, S2-priority areas account for 67.01%, and S3-priority areas account for 24.87%. The PS-ACO algorithm outputs potential microgreen space sites within each priority level to accurately regulate the green space distribution in residential areas with different supply pressures and limited land availability. A spatial correlation analysis of the new sites reveals good spatial dispersion within service units, effectively alleviating demand pressures, and good aggregation at a regional scale to address imbalances in the supply of green space in a targeted manner. Thus, the optimized results of the PS-ACO algorithm are effective, providing reliable site-selection references for subsequent urban microgreen space distributions.

Abstract Background Sepsis is a systemic inflammatory response syndrome caused by severe infection in children, but cases of sepsis associated with human parainfluenza virus (HPIV) have been rarely reported in newborns. Case presentation We report a case of HPIV-3 positive full-term newborn admitted to the Neonatal Intensive Care Unit of Beijing Children’s Hospital due to hematuria, gloomy spirit, inactivity and loss of appetite for 6 h. He had septic shock when he arrived the Accident & Emergency Department requiring immediate intubation and mechanical ventilation. Intravenous antibiotics were started. He had completely negative response to all anti-shock treatments including fluid resuscitation and vasopressor supports, and died 14 h later. Viral nucleic acid detection and metagenomic next-generation sequencing (mNGS) analyses of nasopharyngeal aspirate and blood specimens verified an HPIV-3 infection, with negative bacterial culture results. The HPIV-3 strain detected in this patient was subtyped as HPIV C3a, and two unreported amino acid mutations were found in the HN protein region. Conclusion The patient had a severe infection associated with HPIV-3, which was the cause of sepsis and septic shock. This study showed the diagnostic value of mNGS in etiological diagnosis, especially in severe neonatal case.

Summary: Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.

Chitin is a polysaccharide similar to cellulose that contains abundant hydrogen bonds. Expansin-like proteins disrupt hydrogen bond networks, causing cellulose to swell and accelerating its degradation. We examined the effects of pretreatment with two expansin-like proteins, CxEXL22 (Arthrobotrys sp. CX1) and HcEXL (Hahella chejuensis), on chitin depolymerisation and enzymatic degradation. The efficiency of chitin degradation increased more than two-fold after pretreatment with expansin-like proteins. Following pretreatment with expansin-like proteins, chitin had a lower crystallinity index, greater d-spacing and crystallite size, and weaker hydrogen bonds, and the loosened porous microfibrils were more exposed than in untreated chitin. The rupture characterisation of crystalline chitin indicated that expansin-like proteins loosened the hydrogen bonds of the chitin polysaccharide chains, causing significant depolymerisation to expose more porous structures and enhance chitin accessibility.

Vascular-targeted photodynamic therapy (V-PDT) is an effective treatment for port wine stains (PWS). However, repeated treatment is usually needed to achieve optimal treatment outcomes, possibly due to the limited treatment light penetration depth in the PWS lesion. The optical clearing technique can increase light penetration in depth by reducing light scattering. This study aimed to investigate the V-PDT in combination with an optical clearing agent (OCA) for the therapeutic enhancement of V-PDT in the rodent skinfold window chamber model. Vascular responses were closely monitored with laser speckle contrast imaging (LSCI), optical coherence tomography angiography, and stereo microscope before, during, and after the treatment. We further quantitatively demonstrated the effects of V-PDT in combination with OCA on the blood flow and blood vessel size of skin microvasculature. The combination of OCA and V-PDT resulted in significant vascular damage, including vasoconstriction and the reduction of blood flow. Our results indicate the promising potential of OCA for enhancing V-PDT for treating vascular-related diseases, including PWS.

Abstract Cyclin dependent kinases (CDKs) are serine/threonine kinases that are proposed as promising candidate targets for cancer treatment. These proteins complexed with cyclins play a critical role in cell cycle progression. Most CDKs demonstrate substantially higher expression in cancer tissues compared with normal tissues and, according to the TCGA database, correlate with survival rate in multiple cancer types. Deregulation of CDK1 has been shown to be closely associated with tumorigenesis. CDK1 activation plays a critical role in a wide range of cancer types; and CDK1 phosphorylation of its many substrates greatly influences their function in tumorigenesis. Enrichment of CDK1 interacting proteins with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to demonstrate that the associated proteins participate in multiple oncogenic pathways. This abundance of evidence clearly supports CDK1 as a promising target for cancer therapy. A number of small molecules targeting CDK1 or multiple CDKs have been developed and evaluated in preclinical studies. Notably, some of these small molecules have also been subjected to human clinical trials. This review evaluates the mechanisms and implications of targeting CDK1 in tumorigenesis and cancer therapy.

With the wide application of intelligent manufacturing and the development of diversified functions of industrial manipulator, the requirements for the control accuracy and stability of the manipulator servo system are also increasing. The control of industrial manipulator is a time-varying system with nonlinear and strong coupling, which is often affected by uncertain factors, including parameter changing, environmental interference, joint friction and so on. Aiming at the problem of the poor control accuracy of the manipulator. Under the complex disturbance environment, control accuracy of the manipulator will be greatly affected, so this paper proposes an adaptive type-2 fuzzy sliding mode control (AT2FSMC) method applied to the servo control of the industrial manipulator, which realizes the adaptive adjustment of the boundary layer thickness to suppress the trajectory error caused by the external disturbance and weakens the chattering problem of the sliding mode control. The simulation results on a two-axis manipulator indicate that, with the presence of external disturbances, the proposed control method can help the manipulator maintain control signal stability and improve tracking accuracy. It also suppressed chattering produced by sliding mode control (SMC) and strengthening the robustness of the system. Compared with other conventional trajectory tracking control methods, the effectiveness of the proposed method can be reflected. Finally, the proposed method is tested in an actual manipulator to complete a practical trajectory to prove its feasibility.

Track irregularities directly affect the quality and safety of railway vehicle operations. Quantitative detection and real-time monitoring of track irregularities are of great importance. However, due to the frequent variable vehicle speed, vehicle operation is a typical non-stationary process. The traditional signal analysis methods are unsuitable for non-stationary processes, making the quantitative detection of the wavelength and amplitude of track irregularities difficult. To solve the above problems, this paper proposes a quantitative detection method of track irregularities under non-stationary conditions with variable vehicle speed by order tracking analysis for the first time. Firstly, a simplified wheel–rail dynamic model is established to derive the quantitative relationship between the axle-box vertical vibration and the track vertical irregularities. Secondly, the Simpson double integration method is proposed to calculate the axle-box vertical displacement based on the axle-box vertical acceleration, and the process error is optimized. Thirdly, based on the order tracking analysis theory, the angular domain resampling is performed on the axle-box vertical displacement time-domain signal in combination with the wheel rotation speed signals, and the quantitative detection of the track irregularities is achieved. Finally, the proposed method is validated based on simulation and field test analysis cases. We provide theoretical support and method reference for the quantitative detection method of track irregularities.

Summary: Gene silencing by P-element-induced wimpy testis-interacting RNAs is a mechanism to maintain genome integrity in germ cells. Here, we present a protocol for knockin or knockout editing of male germline genome mediated by CRISPR-Cas9 technology in Caenorhabditis elegans. We describe steps for constructing edited plasmids, microinjecting worms with these plasmids, and screening edited worms. We then detail procedures for dissecting released sperm and their observation with fluorescence microscopy. Engineered worms provide a model for studying hermaphrodite/male fertility or protein localization in vivo.For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Oil content (OC) is one of the important evaluation indicators in oilfield wastewater (OW) treatment. The purpose of this study is to realize online real-time detection of OC in OW by combining ultraviolet spectrophotometry with the convolutional neural network (CNN). In this paper, 80 groups of OW transmission data were measured for model establishment. Three CNN models with different structures are established to generalize the super parametric optimization process of the model. Furthermore, as a common method used in spectroscopy, the synergy interval partial least squares (siPLS) model is built in order to compare its accuracy with the CNN model. The results indicated the CNN model has a better performance than siPLS, in which the CNN model numbered Model 3 has the lowest root mean square error (MSE) of prediction (RMSEP) of 1.606 mg/L. As a consequence, the CNN model can be used in the monitoring of OW. This article will guide a rapid analysis of the OC of OW. HIGHLIGHTS Transmission spectra of the oil wastewater with different oil contents were determined.; Accuracy of the siPLS and CNN models for the prediction of the oil content in the oil wastewater was compared.; The CNN model is more suitable to analyze the oil content of oilfield wastewater than the siPLS model.; The CNN models with different depth structures were compared, and the deepest model exhibited the highest ability of prediction.;

Objective To investigate the causes of hemolytic transfusion reaction (HTR), identify clinical symptoms and severity, explore clinical detection methods, so as to provide reference for safe and rational blood use. Methods Clinical data of 3 cases of HTR in our hospital were analyzed. Blood type, unexpected antibody screening, antibody identification by serological method and elution test were reexamined in laboratory, and domestic literatures of HTR were reviewed. Results Case 1, 2, and 3 were diagnosed as DHTR (with anti-JKa antibody identified 7 days after transfusion), AHTR (with anti-Ce and anti-JKb antibodies respectively detected 5 and 7 days after transfusion) and HTR of unknown type (with anti-E antibody detected 3 days after transfusion). A total of 33 cases of HTR were reported from 2005 to 2021 in China, including 14 cases of AHTR, 18 cases of DHTR and 1 case as unknown type. The causes of HTR in 33 cases were as follows: ABO system antibodies in 4 cases, Rh system antibodies in 17 cases, 4 Kidd system antibodies in 4 cases, non-immune factors in 3 cases, and without antibody specificity in 5 cases. Conclusion Since various blood system antibodies may cause hemolysis reaction, it is of great significance to clarify the causes and identify the alloantibody for the safe use of blood in clinical practice.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Cold adaptation is essential to the protective effect of soft armor and other protective materials because of the potential for prolonged exposure to freezing conditions in service, while the properties of flexible matrices are always affected by low temperatures. To integrate the good protection efficiency and excellent anti-freezing properties, polyvinyl alcohol (PVA), sodium alginate (SA), and glycerol (Gly) were selected to prepare a frigostable hydrogel in this study. Afterward, the hydrogel was laminated with aramid fabric to obtain a flexible anti-puncture composite that can be used at low temperatures. At −30 °C, the breaking strength and elongation of PVA/SA/Gly hydrogel reached 1.32 MPa and 330%, which was basically the same as at room temperature, indicating its excellent cold adaptation. Meanwhile, the maximum puncture resistance force and energy dissipation of the aramid/hydrogel composite at −30 °C were 56.88 N and 263.07 mJ, respectively, 289% and 184% higher than that of neat fabric, while the weight gain rate of the composite was only 40%. At room and low temperatures, the flexibility of the composite was only 5% and 8% lower than that of the neat fabric, respectively, and a helix shape of 360° could be formed and maintained under a small torsional force even at −30 °C.

The growing number of long COVID cases has drawn clinical attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been spreading worldwide since winter 2019. Its symptoms are not limited to fatigue and shortness of breath but also affect daily life. We report the use of metagenomic next-generation sequencing (mNGS) to detect coinfection with SARS-CoV-2 and influenza A virus in a patient with long COVID. The patient was admitted with fever, expectoration, fatigue, and shortness of breath. The PCR test was negative due to possible clearance of SARS-Cov-2 in the upper respiratory tract of patients with long COVID. Other routine microbiological tests were also negative, making the clinical diagnosis difficult. Bronchoalveolar lavage fluid (BALF) samples were tested using mNGS. The patient was diagnosed and treated promptly, recovered quickly, and continued taking azvudine after discharge; his condition was stable. This study illustrates that mNGS may be valuable for the timely diagnosis of patients with long COVID and their mixed infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often absent or at low levels in the cerebrospinal fluid (CSF) of patients with previous SARS-CoV-2-associated Guillain-Barré syndrome (GBS). This has led to speculation that SARS-CoV-2-associated GBS is more likely mediated by post-infectious immunity or a parainfection. This understanding has influenced the development of treatment regimens for SARS-CoV-2-associated GBS. This paper reports our experience with four Chinese patients with SARS-CoV-2-associated GBS who tested positive for SARS-CoV-2 RNA in the CSF. They developed symptoms of peripheral nerve damage 4–15 days after fever and confirmed SARS-CoV-2 infection, all of whom presented with progressive weakness of both lower limbs; three with autonomic nerve function impairment such as constipation and urination disorder; and one with polycranial neuritis and Miller–Fisher syndrome. Three patients were tested for anti-ganglioside antibodies, and one tested positive for GD1a-IgG. Four patients recovered well after treatment with anti-viral drugs combined with intravenous immunoglobulin. The present results showed that SARS-CoV-2 RNA can be detected via mNGS in the CSF of some patients with SARS-CoV-2-associated GBS, suggesting that SARS-CoV-2-associated GBS may have multiple pathogeneses.

目的 对1例有输血史多次分娩史的RhD阴性孕妇D抗原进行血清学和分子生物学检测，明确RhD表型和基因型。方法 微柱凝胶技术进行母亲和新生儿Rh血型初筛，母亲红细胞经典抗人球蛋白技术进行RhD阴性确认，吸收放散试验确定是否为Del。基因检测确定孕妇RHD基因型。结果 该孕妇结果为Ccdee，RhD确证试验为D阴性，吸收放散试验阴性，基因检测为RHCE(2-9)-D变异，产生抗-D，抗-E。新生儿为CCDee表型，游离抗体检出抗-D和抗-E，放散液检出抗-D。患儿诊断为新生儿溶血病，进行输血、光疗和换血治疗。结论 RHCE(2-9)-D变异型血清学可能表现为D阴性，确证试验阴性，有产生抗-D并引起新生儿溶血病的风险。

The waterproofing capacity of segmental joints is an essential indicator for the long-term service performance of shield tunnels. The segmental joints with double gaskets have been adopted to improve the waterproof performance for certain tunnels with high water pressure, especially water-conveyance tunnels. This paper presents a series of waterproofing tests on joints with different settings of double gaskets via an improved test apparatus. Four cases are investigated, including (i) double gaskets with equal high/low waterproof capacity, (ii) the outer gasket with higher waterproof capacity, and (iii) the outer gasket with lower waterproof capacity. Different joint openings are also considered. Moreover, the water pressures at two cavities are continuously monitored to highlight the waterproofing mechanism and failure pattern of double gaskets. The results demonstrate that the gasket with the higher waterproofing capacity dominates the overall waterproofing capacity of joint with double gaskets; only a little enhancement of the waterproofing capacity is found for the joint with the same double gaskets. The waterproofing capacity of joints with double gaskets decreases with the increase of the joint opening. The failure pattern depends on the arrangement of double gaskets, and four stages can be identified during the whole failure process. The advantages of double gaskets in case of joint rotation are also discussed.

STFs impregnation is an effective method to prepare impact resistance fabrics without sacrificing their flexibility, and the structural features are essential factors affecting the puncture resistance behaviors of these fabrics. Since few studies focus on the quasi-static puncture resistance of 3D woven fabrics and their STFs-based composites, we developed a strategy to evaluate the anti-puncture efficiencies and established models to predict the puncture resistance characteristics of materials. The results show a significant linear relationship between the puncture resistance and layer numbers, and the maximum puncture force and energy dissipation could reach 1284.58 N and 7.22 J for the five-layer angle-interlock fabric after STFs impregnation. Given the inter-yarn slippage restriction by STFs, the maximum puncture force of the fabric with an FVF of 49.47% increases 132.84% after STFs treatment, but the anti-puncture efficiencies of fabrics, whose FVF is higher than 53.4%, drop more than 10% after impregnation. The layer-to-layer interweaving improves fabric's anti-puncture efficiency, but the overlarge binding warp inclination is detrimental to the mechanical usage of yarns and the maintenance of the compact structure.

Objective To identify and propose blood transfusion suggestions for 3 children suspected to have red blood cell T polyagglutination. Methods According to the RBC reactions with phytohemagglutinin, adult serum and cord blood serum, aggregation test with polybrene reagent and MN antigen phenotype test were carried out on 3 children to confirm the presence of T polyagglutination. The donor serum with negative or weak reactions was selected by minor cross matching for the 3 children who needed therapeutic plasma exchange(TPE). Results Three cases of RBC T polyagglutination were caused by bacterial infection, with transient appearance of MN antigen; the samples were reactive to peanut agglutinin, soybean agglutinin, adult serum but nonreactive to cord blood serum, and didn′t aggregate after adding polybrene reagent. After receiving timely TPE, the T polyagglutination gradually disappeared. Conclusion Some bacteria, such as Streptococcus pneumoniae, may cause polyagglutination of red blood cells. The patients with suspected T polyagglutination should be diagnosed in time. For T polyagglutination patients, the minor matched plasma should be used for avoiding the random plasma with anti-T antibody transfusion.

Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. The genome of EHEC O157:H7 contains 177 unique O islands (OIs). Certain OIs significantly contribute to the heightened virulence and pathogenicity exhibited by EHEC O157:H7. However, the function of most OI genes remains unknown. We demonstrated here that EHEC O157:H7 adherence to and colonization of the mouse large intestine are both dependent on OI-97. Z3495, which is annotated as a LysR-type transcriptional regulator and encoded in OI-97, contributes to this phenotype. Z3495 activated the locus of enterocyte effacement (LEE) gene expression, promoting bacterial adherence. Deletion of z3495 significantly decreased the transcription of ler and other LEE genes, the ability to adhere to the host cells, and colonization in the mouse large intestine. Furthermore, the ChIP-seq results confirmed that Z3495 can directly bind to the promoter region of rcsF, which is a well-known activator of Ler, and increase LEE gene expression. Finally, phylogenetic analysis revealed that Z3495 is a widespread transcriptional regulator in enterohemorrhagic and enteropathogenic Escherichia coli. As a result of this study, we have gained a deeper understanding of how bacteria control their virulence and provide another example of a laterally acquired regulator that regulates LEE gene expression in bacteria.

Abstract Strawberry vein banding virus (SVBV) is one of the serious viral pathogens infecting strawberry worldwide. To understand the molecular characterization of SVBV from China, complete genome sequences of sixteen SVBV isolates were cloned and sequenced. Sequence comparison showed they shared high nucleotide sequence identity (93.6–99.5%) with isolates from China and Japan (96.6–98.4%), while relatively low identity with the isolates from Canada (91.9–93.7%) and USA (85.5–85.9%). Phylogenetic analyses based on the complete genome sequence or coat protein (CP) gene showed the SVBV isolates clustered into three clades correlated with geographic distribution. Recombination analyses identified 13 recombinants and 21 recombinant events, indicating frequent and multiple recombinations in SVBV evolution. Furthermore, a sensitive loop-mediated isothermal amplification (LAMP) method was developed for rapid detection of SVBV isolates, which could be especially suitable for seedling propagation, virus-free culture and routine diagnostics in field investigation. This study offers new understanding of the molecular evolution and may help to improve the management of SVBV.

Abstract Background Field cancerization is the process in which a population of normal or pre-malignant cells is affected by oncogenic alterations leading to progressive molecular changes that drive malignant transformation. Aberrant DNA methylation has been implicated in early cancer development in non-small cell lung cancer (NSCLC); however, studies on its role in field cancerization (FC) are limited. This study aims to identify FC-specific methylation patterns that could distinguish between pre-malignant lesions and tumor tissues in NSCLC. Methods We enrolled 52 patients with resectable NSCLC and collected resected tumor (TUM), tumor-adjacent (ADJ) and tumor-distant normal (DIS) tissue samples, among whom 36 qualified for subsequent analyses. Methylation levels were profiled by bisulfite sequencing using a custom lung-cancer methylation panel. Results ADJ and DIS samples demonstrated similar methylation profiles, which were distinct from distinct from that of TUM. Comparison of TUM and DIS profiles led to identification of 1740 tumor-specific differential methylated regions (DMRs), including 1675 hypermethylated and 65 hypomethylated (adjusted P

In order to reduce the potential safety hazards in the operation of rail vehicles, a new parameter table optimization algorithm based on the particle swarm optimization algorithm is proposed to carry on the failure assessment and fatigue life calculation of welded joints. This algorithm reduces the number of iterations by adding connection pools to connect the parameter selection database. In addition, based on this algorithm, combined with Python language and BS7910 standard, a calculation program for failure assessment and fatigue crack growth life is written. The algorithm program is validated by taking the commonly used T-type, butt, and lap joints as examples. In terms of failure assessment, the calculation results of the algorithm program are securer and more conservative, and the safety accuracy of the algorithm program is improved by 8%–12%. In terms of fatigue crack growth life, the error between the calculated value of the algorithm program and the test data is within the engineering allowable range. At the same time, the algorithm program can give the evaluation calculation results more intuitively and quickly, which provides a reference for the failure assessment and life calculation of the welded structure.

BackgroundCoal workers' pneumoconiosis (CWP) is a serious occupational disease. Whether ferroptosis, a form of necrotic regulated cell death, is involved in coal dust induced mouse models of CWP needs further survey. ObjectiveThis experiment is designed to elucidate the role of ferroptosis in the formation of CWP induced by coal dust in mice. MethodsC57BL/6J mice were randomly assigned to a saline group or a CWP group, with eight mice in each group. The mice were treated with 0.1 mL normal saline or 0.1 mL coal dust suspensions (50g·L-1) via intra-tracheal instillation. HE staining and Masson staining were used to show lung injury and lung fibrosis. Iron concentration in mouse lung tissues was measured using iron assay kit. Lipid peroxidation was estimated in lung tissues by malondialdehyde (MDA) concentration and immunofluorescence intensity, and the ratio of glutathione (GSH) to L-glutathione oxidized (GSSG). Western blotting and real-time fluorescence-based quantitative PCR were used to test protein and mRNA expression levels of glutathione peroxidase 4 (GPX4) and ferritin in mice. ResultsCoal dust injured pulmonary structure, thickened alveolar wall, and caused collagen deposition and infiltration of inflammatory cells in the CWP group. The iron concentration in the CWP group [(10.75 ± 5.42) mg·L−1] was higher than that in the saline group [(1.14 ± 0.37) mg·L−1] (P < 0.01). The MDA concentration in the CWP group [(37.32 ± 12.18) μmol·L−1] was higher than that in the saline group [(18.70 ± 8.22) μmol·L−1] (P

ObjectivesWith the attention paid to the early diagnosis of depression, this study tries to use the biological information of speech, combined with deep learning to build a rapid binary-classification model of depression in the elderly who use Mandarin and test its effectiveness.MethodsDemographic information and acoustic data of 56 Mandarin-speaking older adults with major depressive disorder (MDD), diagnosed with the Mini-International Neuropsychiatric Interview (MINI) and the fifth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and 47 controls was collected. Acoustic data were recorded using different smart phones and analyzed by deep learning model which is developed and tested on independent validation set. The accuracy of the model is shown by the ROC curve.ResultsThe quality of the collected speech affected the accuracy of the model. The initial sensitivity and specificity of the model were respectively 82.14% [95%CI, (70.16–90.00)] and 80.85% [95%CI, (67.64–89.58)].ConclusionThis study provides a new method for rapid identification and diagnosis of depression utilizing deep learning technology. Vocal biomarkers extracted from raw speech signals have high potential for the early diagnosis of depression in older adults.

The degree of coordination between the supply and demand for urban green spaces serves as a vital metric for evaluating urban ecological development and the well-being of residents. An essential principle in assessing this coordination is the precise quantification of both the demand and supply of green spaces, as well as the differential representation of their spatiotemporal structures. This study utilizes the entropy weight method (EWM) and principal component analysis (PCA) to comprehensively measure supply indicators for green space quantity and quality in the central urban area of Shenyang, China. To establish reliable and quantifiable demand indicators, mobile signaling spatial-temporal data are corrected by incorporating static population cross-sectional data. The Gaussian two-step floating catchment area method (Ga2SFCA) is employed to calculate the accessibility of green spaces in each community with ArcGIS 10.2 software, while the Gini coefficient is utilized to assess the equity of green space distribution within the study area. This study employs location entropy to determine the levels of supply and demand for green spaces in each subdistrict. Furthermore, the priority of community-scale green space regulation is accurately determined by balancing vulnerable areas of green space supply and replenishing green space resources for the ageing population. The findings suggest a Gini coefficient of 0.58 for the supply and demand of green spaces in Shenyang’s central metropolitan region, indicating a relatively low level of equalization in overall green space allocation. Based on location entropy, the classification of supply and demand at the street level yields the following outcomes: balanced areas comprise 21.98%, imbalanced areas account for 26.37%, and highly imbalanced regions represent 51.65%. After eliminating the balanced regions, the distribution of the elderly population is factored in, highlighting the spatial distribution and proportions of communities with distinct regulatory priorities: Level 1 (S1) constitutes 7.4%, Level 2 (S2) accounts for 60.9%, and Level 3 (S3) represents 31.7%. Notably, the communities in the S1 category exhibit spatial distribution characteristics of aggregation within the inner ring and the northern parts of the third ring. This precise identification of areas requiring urgent regulation and the spatial distribution of typical communities can provide reliable suggestions for prioritizing green space planning in an age-friendly city.

Phase-pure α-(La,Yb,Er)2W2O9 upconversion (UC) phosphors were synthesized via room temperature coprecipitation and subsequent calcination at 1073–1273 K. The pH of the coprecipitation system and the RE3+ to WO42- ratio were found crucial for the formation of the target α phase. Phase transformation from cubic β-(La,Yb,Er)2W2O9 to triclinic α-(La,Yb,Er)2W2O9 occurred when calcination temperature was above 873 K. The UC luminescence including power/temperature dependent emission, decay kinetics of the main emission, emission color, and underlying UC mechanism were systematically investigated. The phosphor exhibited bright green luminescence under 978 nm laser excitation. The main emission (4S3/2→4I15/2) was analyzed to decay in a single exponential manner and have a decay time of 153.86 μs at room temperature. A three-photon mechanism was suggested responsible for the observed UC luminescence through analyzing the UC intensity against excitation power via logarithmic data transformation. The performance of optical temperature sensing was evaluated and compared with other typical UC phosphors. It was shown that the phosphor has relatively high maximum SA and SR values of 0.02694 K−1 (548 K) and 0.01699 K−1 (298 K) for the thermally coupled 2H11/2 and 4S3/2 energy levels in the 298–548 K temperature range.

BackgroundMost men who have sex with men (MSM), especially those with HIV infection, do not disclose their same-sex behaviors in China due to Chinese family values and fear of stigmatization, rejection, or prejudice. However, disclosure of same-sex behaviors to healthcare providers (HCPs) can be beneficial for reducing viral transmission and promoting their physical and mental health. In this study, by combining phylogenetic analysis with traditional epidemiological approaches, we tried to identify the MSM who do not disclose to HCPs in transmission networks and explored the factors related to the non-disclosed behaviors.MethodPhylogenetic analysis was conducted using HIV pol sequences obtained from the drug-resistant surveillance program, which was collected as part of routine clinical care since 2012. Sequences were linked to the demographic data collected in the Chinese HIV/AIDS Comprehensive Response Information Management System (CRIMS). First, male patients in whom genetic sequences were within the molecular transmission clusters involving self-reported MSM were identified as potential MSM (pMSM). Then, a cross-sectional survey was conducted to supplement behavioral information and attitudes toward MSM.ResultsOur sample consisted of 190 pMSM patients. In total, 43.16% of the patients were likely to conceal same-sex behaviors during the first-self-report, and 14.73% of patients might continue to conceal a history of same-sex behaviors even after receiving medical care. The pMSM who concealed their same-sex behaviors were reluctant to accept medical services such as Voluntary Counseling and Testing (VCT) and had a lower likelihood of condom use. In addition, the related factors for non-disclosed behavior were associated with current address, income before diagnosis, and attitudes toward MSM.ConclusionNon-disclosure of same-sex behaviors to HCPs may be a major obstacle for certain medical services for MSM who exhibit risky sexual behaviors. The pMSM from developing areas, with high monthly income, and with neutral or un-supportive attitudes toward MSM may represent non-disclosure of their same-sex behaviors. Thus, policies facilitating MSM to disclose their same-sex behaviors are recommended, such as legislations protecting homosexual rights on employment, education, marriage, and so on.

Rare earth double tungstates Na(Gd,RE)(WO4)2 (RE = Eu/Yb-Er) were successfully obtained from layered rare earth hydroxide precursors via sacrificial reaction at 200°C with molar ratio WO42-/RE3+ = 2.5 for 24 h reaction without calcination and the employment of any organic reagents. The temperature sensing performances of Na(Gd,RE)(WO4)2 (RE = Eu/Yb-Er) were comparatively investigated by analyzing the temperature-dependent down-conversion (DC) and up-conversion (UC) luminescence spectra. The DC phosphors Na(Gd,Eu)(WO4)2 were found to be well capable of sensing temperature via fluorescence lifetime (FL) mode. The UC phosphors Na(Gd,Yb,Er)(WO4)2 were capable of sensing temperature via both FL mode and fluorescence intensity ratio (FIR) mode through thermally coupled 2H11/2,4S3/2 levels (I520/I552), and non thermally coupled 2H11/2,4F9/2 energy levels (I520/I670). The UC phosphors Na(Gd,Yb,Er)(WO4)2 have maximum absolute sensitivity (SA) and maximum relative sensitivity (SR) of 174 × 10−4 K−1 (548 K) and 80 × 10−4 K−1 (298 K) for the thermally coupled 2H11/2,4S3/2 levels and maximum SA and SR of ~260 × 10−4 K−1 (300–550 K) and 96 × 10−4 K−1 (298 K) for the non-thermally coupled 2H11/2,4F9/2 energy levels.

Traditional electro-Fenton systems must continuously supply oxygen to the cathode, which leads to extensive volatilisation of benzene in solutions. In this study, we adopted a floating cathode electro-Fenton system without bubbling oxygen into the solution to treat benzene-containing wastewater. The effects of the floating cathode position and main reaction parameters on benzene degradation were analysed, and the degradation cost was estimated. The results indicated that the electro-Fenton system with floating cathode could effectively degrade benzene in solutions. For the cathode, the complete utilisation of air and oxygen released from the anode was crucial. The benzene degradation rate increased with an increase in benzene concentrations. Additionally, pH mainly affected the existing ionic state of iron and production ratio of active substances. The current intensity significantly influenced the reaction activity. Using the floating cathode electro-Fenton method, the benzene removal ratio in the solution could reach 74.80% after 60 min under the optimum reaction conditions. For the floating cathode electro-Fenton system, the cost of treating benzene-containing sewage per cubic metre was $1.2187, which is significantly lower than that for traditional electro-Fenton technology ($1.4000). Hence, the floating cathode electro-Fenton system is an economical and efficient method for benzene degradation in solutions. HIGHLIGHTS •A floating cathode electro-Fenton system was used for the treatment of benzene-containing wastewater.; •The problem of benzene volatilisation was solved during the electro-Fenton degradation process.; •The floating cathode electro-Fenton is an economical method for the wastewater treatment.;

The rational integration of many microfluidic chips and micropumps remains challenging. Due to the integration of the control system and sensors in active micropumps, they have unique advantages over passive micropumps when integrated into microfluidic chips. An active phase-change micropump based on complementary metal–oxide–semiconductor–microelectromechanical system (CMOS-MEMS) technology was fabricated and studied theoretically and experimentally. The micropump structure is simple and consists of a microchannel, a series of heater elements along the microchannel, an on-chip control system, and sensors. A simplified model was established to analyze the pumping effect of the traveling phase transition in the microchannel. The relationship between pumping conditions and flow rate was examined. Based on the experimental results, the maximum flow rate of the active phase-change micropump at room temperature is 22 µL/min, and long-term stable operation can be achieved by optimizing heating conditions.

Surfactant protein D (SP-D) is a C-type collectin and plays an important role in innate immunity and homeostasis in the lung. This study studied SP-D role in the nontypeable Haemophilus influenzae (NTHi)-induced otitis media (OM) mouse model. Wild-type C57BL/6 (WT) and SP-D knockout (KO) mice were used in this study. Mice were injected in the middle ear (ME) with 5 μL of NTHi bacterial solution (3.5 × 105 CFU/ear) or with the same volume of sterile saline (control). Mice were sacrificed at 3 time points, days 1, 3, and 7, after treatment. We found SP-D expression in the Eustachian tube (ET) and ME mucosa of WT mice but not in SP-D KO mice. After infection, SP-D KO mice showed more intense inflammatory changes evidenced by the increased mucosal thickness and inflammatory cell infiltration in the ME and ET compared to WT mice (p < 0.05). Increased bacterial colony-forming units and cytokine (IL-6 and IL-1β) levels in the ear washing fluid of infected SP-D KO mice were compared to infected WT mice. Molecular analysis revealed higher levels of NF-κB and NLRP3 activation in infected SP-D KO compared to WT mice (p < 0.05). In vitro studies demonstrated that SP-D significantly induced NTHi bacterial aggregation and enhanced bacterial phagocytosis by macrophages (p < 0.05). Furthermore, human ME epithelial cells showed a dose-dependent increased expression of NLRP3 and SP-D proteins after LPS treatment. We conclude that SP-D plays a critical role in innate immunity and disease resolution through enhancing host defense and regulating inflammatory NF-κB and NLRP3 activation in experimental OM mice.

This study is to evaluate the usefulness of pathogen detection using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) specimens from children with community-acquired pneumonia (CAP). We retrospectively collected BALF specimens from 121 children with CAP at Tianjin Children's Hospital from February 2021 to December 2021. The diagnostic performances of mNGS and conventional tests (CT) (culture and targeted polymerase chain reaction tests) were compared, using composite diagnosis as the reference standard. The results of mNGS and CT were compared based on pathogenic and non-pathogenic organisms. Pathogen profiles and co-infections between the mild CAP and severe CAP groups were also analyzed. The overall positive coincidence rate was 86.78% (105/121) for mNGS and 66.94% (81/121) for CT. The proportion of patients diagnosed using mNGS plus CT increased to 99.18%. Among the patients, 17.36% were confirmed only by mNGS; Streptococcus pneumoniae accounted for 52.38% and 23.8% of the patients were co-infected. Moreover, Bordetella pertussis and Human bocavirus (HBoV) were detected only using mNGS. Mycoplasma pneumoniae, which was identified in 89 (73.55%) of 121 children with CAP, was the most frequent pathogen detected using mNGS. The infection rate of M. pneumoniae in the severe CAP group was significantly higher than that in the mild CAP group (P = 0.007). The symptoms of single bacterial infections (except for mycoplasma) were milder than those of mycoplasma infections. mNGS identified more bacterial infections when compared to the CT methods and was able to identify co-infections which were initially missed on CT. Additionally, it was able to identify pathogens that were beyond the scope of the CT methods. The mNGS method is a powerful supplement to clinical diagnostic tools in respiratory infections, as it can increase the precision of diagnosis and guide the use of antibiotics.

Exosomes are extracellular vesicles that mediate cell-to-cell communication. Bioactive substances such as DNA, RNA, lipids, and proteins are present in it, and they play an essential role in the pathogenesis of colorectal cancer (CRC). The role of RNA and protein in exosomes has been extensively studied. Exosome DNA has recently attracted the attention of a great deal of scientists. According to studies, exosome DNA mainly contains genomic DNA (gDNA) and mitochondrial DNA (mtDNA), of which exosome gDNA is widely used in liquid biopsy of CRC. It includes a variety of clinically relevant tumor-specific mutation genes. In addition to liquid biopsy, researchers find that exosome gDNA regulates immune and metabolic functions in CRC, making it an important research object. However, the primary research on exosome gDNA is still limited. Here, we describe the occurrence and composition of exosomes. Summarize the essential characteristics and mode of action of exosome gDNA. Remarkably, this paper constitutes a comprehensive summary on the role of exosome gDNA on CRC with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.