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Abstract Background Patients with non‐small‐cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor‐related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small‐cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first‐line chemoimmunotherapy and to assess its relationship with prognosis. Methods We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first‐line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. Results A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574–18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506–18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179–3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001–1.002; p

BackgroundStroke is the leading cause of disability globally, with antiplatelet therapy being crucial for secondary prevention but also increasing bleeding risks. This requires careful dosage adjustments to balance thrombosis and bleeding risks.ObjectiveThis study compared the efficacy and safety of low-dose versus standard-dose antiplatelet therapy in stroke patients.MethodsWe conducted a comprehensive search across multiple databases, including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, CNKI, and the Wanfang Medical Database, up to March 2024. Only randomized controlled trials assessing low-dose antiplatelet therapy in stroke patients were considered. The Cochrane Risk of Bias Tool (RoB 2) was used for quality. Performed meta-analysis using Stata 15.0, with relative risk (RR) and 95% confidence interval (CI) as effect estimates.ResultsTen studies involving 7,703 Asia participants, mainly from China and Japan, were analyzed. The meta-analysis revealed that low-dose reduces the risk of bleeding (RR 0.51; 95% CI 0.27, 0.98) compared to standard dose, with similar risks for stroke (RR 1.04; 95% CI 0.69, 1.55), myocardial infarction (MI) (RR 1.91; 95% CI 0.88, 4.12), all-cause death (ACD) (RR 1.17; 95% CI 0.38, 3.62), and major bleeding (RR 0.74; 95% CI 0.16, 3.30). Subgroup analysis revealed that compared to standard-dose clopidogrel, low-dose clopidogrel increased the risk of MI. Notably, this increased risk was observed specifically within the Chinese population but not in the Japanese population. Low-dose clopidogrel and low-dose prasugrel reduce the risk of bleeding compared to standard-dose clopidogrel, but there is no statistically significant difference. Low-dose aspirin significantly reduces the risk of bleeding compared to standard-dose aspirin.ConclusionIn patients with stroke in Asia, low-dose antiplatelet therapy significantly reduces the risk of bleeding compared to standard doses, with consistent risks of stroke, MI, ACD, major bleeding, and discontinuation due to bleeding.

Objective To explore the enrichment conditions and main controlling factors of shale gas in the Lower Wuerhe Formation of the Permian System in the Junggar Basin, the Lower Wuerhe Formation in the Dongdaohaizi Sag was selected as the research object. Methods Based on the data of outcrop, core, well logging, well-calibrated seismic reflections and the technologies of total organic carbon (TOC) content determination, whole-rock X-ray diffraction, gas adsorption (N2, CO2), the distribution characteristics, organic matter development characteristics, reservoir characteristics, and gas bearing characteristics of the Lower Wuerhe Formation shale were studied. Results The results show that: (1) The organic matter of the Lower Wuerhe Formation shale is dominated by Ⅱ2 and Ⅲ types and shows an average TOC content of 1.58%. The average vitrinite reflectance (Ro) of organic matter is 1.46%, which indicates the mature stage. The average thickness of the source rock is 75 m. Summarily, the source rock is good and has a high gas potential. The basin simulation results show an average shale gas content of 1.89 m3/t in the Lower Wuerhe Formation. (2) The pores and microfractures in shale reservoirs are highly developed, and gas is primarily adsorbed in micropores and mesopores. The average porosity and permeability are 6.10% and 0.27×10-3 μm2 respectively, which are favourable for shale gas accumulation. (3) The shale has a high clay mineral content, with an average of 29.6%, providing a significant specific surface area and enhancing the gas adsorption capacity of the shale. Additionally, the average brittle mineral content is 50.9%, indicating good frackability. (4) Moreover, the shale reservoir exhibits a relatively large pressure coefficient of 1.58, indicating the favourable conservation conditions. The analysis of the regional tectonic-sedimentary environment and geochemical parameters indicates that the main factors controlling shale gas accumulation in the Lower Wuerhe Formation of the Dongdaohaizi Sag are geochemical parameters and preservation conditions. The key factors influencing shale gas accumulation include the high thermal evolution maturity of organic matter, large shale thickness, high TOC content, and good preservation conditions. These conditions suggest that the favourable area for shale gas exploration and development in the Dongdaohaizi Sag is located in the northeastern slope area of the sag's abdomen. Conclusion The results of this research reveal the enrichment conditions and main controlling factors of shale gas in the Lower Wuerhe Formation in the Dongdaohaizi Sag, which has reference value for deep oil and gas exploration in the abdominal area of the Junggar Basin.

Abstract Background To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy. Methods A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method. Results There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with

Host–parasitoid systems are an essential area of research in ecology and evolutionary biology due to their widespread occurrence in nature and significant impact on species evolution, population dynamics, and ecosystem stability. In such systems, the host is the organism being attacked by the parasitoid, while the parasitoid depends on the host to complete its life cycle. This paper investigates the effect of parasitoid aggregation attacks on a host in a host–parasitoid model with self-diffusion on two-dimensional coupled map lattices. We assume that in the simulation of biological populations on a plane, the interactions between individuals follow periodic boundary conditions. The primary objective is to analyze the complex dynamics of the host–parasitoid interaction model induced by an aggregation effect and diffusion in a discrete setting. Using the aggregation coefficient k as the bifurcating parameter and applying central manifold and normal form analysis, it has been shown that the system is capable of Neimark–Sacker and flip bifurcations even without diffusion. Furthermore, with the influence of diffusion, the system exhibits pure Turing instability, Neimark–Sacker–Turing instability, and Flip–Turing instability. The numerical simulation section explores the path from bifurcation to chaos through calculations of the maximum Lyapunov exponent and the construction of a bifurcation diagram. The interconversion between different Turing instabilities is simulated by adjusting the timestep and self-diffusion coefficient values, which is based on pattern dynamics in ecological modeling. This contributes to a deeper understanding of the dynamic behaviors driven by aggregation effects in the host–parasitoid model.

Although 5-fluorouracil (5-FU) is the primary chemotherapy treatment for colorectal cancer (CRC), its efficacy is limited by drug resistance. Ferroptosis activation is a promising treatment for 5-FU-resistant cancer cells; however, potential therapeutic targets remain elusive. This study investigated ferroptosis vulnerability and dihydroorotate dehydrogenase (DHODH) activity using stable, 5-FU-resistant CRC cell lines and xenograft models. Ferroptosis was characterized by measuring malondialdehyde levels, assessing lipid metabolism and peroxidation, and using mitochondrial imaging and assays. DHODH function is investigated through gene knockdown experiments, tumor behavior assays, mitochondrial import reactions, intramitochondrial localization, enzymatic activity analyses, and metabolomics assessments. Intracellular lipid accumulation and mitochondrial DHODH deficiency led to lipid peroxidation overload, weakening the defense system of 5-FU-resistant CRC cells against ferroptosis. DHODH, primarily located within the inner mitochondrial membrane, played a crucial role in driving intracellular pyrimidine biosynthesis and was redistributed to the cytosol in 5-FU-resistant CRC cells. Cytosolic DHODH, like its mitochondrial counterpart, exhibited dihydroorotate catalytic activity and participated in pyrimidine biosynthesis. This amplified intracellular pyrimidine pools, thereby impeding the efficacy of 5-FU treatment through molecular competition. These findings contribute to the understanding of 5-FU resistance mechanisms and suggest that ferroptosis and DHODH are promising therapeutic targets for patients with CRC exhibiting resistance to 5-FU.

Abstract We aim to investigate the influence of waist circumference and body mass index (BMI) on all‐cause death and cardiovascular‐specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all‐cause mortality and cardiovascular events. The waist circumference‐to‐BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan‐Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all‐cause mortality. Subsequently, Fine‐Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular‐specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups (P

Building extraction and change monitoring in remote sensing (RS) imagery play pivotal roles in various applications, including urban planning, disaster management, and infrastructure monitoring. While significant progress has been made in single and bitemporal RS images, effectively harnessing the rich temporal information of time series RS images remains a challenge. Time series RS images offer an extended temporal span for monitoring dynamic changes in building instances. However, they often exhibit noticeable appearance discrepancies and feature variations, presenting substantial obstacles to effective multitemporal information aggregation. To address these challenges, we introduce a Building Extraction and Change Monitoring Network (BuildMon), which jointly explores the segmentation masks, location tracking, and construction status of building instances. Our approach incorporates a spatial-temporal transformer to model relationships between images at different time spans. The windowed attention module within it can capture spatial-temporal context for a larger scope of feature aggregation. For enhancing the performance on both tasks, we adopted ground truth masks and semantic change information together as supervisory signals for BuildMon. This is complemented by the specially designed change-guided loss function, which specifically highlights regions of change and assigns targeted weights to building areas within the imagery. To validate the effectiveness of our method, we conduct comprehensive experiments on the SpaceNet 7 dataset. The results showcase the state-of-the-art performance of our approach, achieving mIoU and SpaceNet Change and Object Tracking metrics of 67.90 and 39.73, respectively.

Abstract The residual belief propagation (RBP) algorithm, which is the most classic informed dynamic scheduling strategy, achieves outstanding performance in error correction and can drastically accelerate convergence speed. However, the greedy algorithmic property of this iterative decoding will inevitably cause loss of decoding performance. To address this, a novel algorithm called the partial average bundle residual belief propagation (PABRBP) is proposed in this paper. According to the construction characteristics of a base matrix of protograph‐LDPC codes, informed dynamic scheduling (IDS) strategies are applied to an edge bundle of base matrices for the first time. This edge bundle of the base matrix can be applied to a corresponding cyclic permutation matrix. Furthermore, the update level of each bundle is determined by the value of the Partially Average Bundle Residual (PABR). Therefore, the edge message with the maximum residual in each bundle is updated in order, and the process of iterative decoding is less likely to become trapped in a local optimum. Additionally, the generation of silent nodes is reduced as much as possible. To further improve the PABRBP decoding performance for medium and long codes over the fading channel, the adjusted compensation term is periodically introduced. Analysis and simulation results show that PABRBP demonstrates a notable convergence quality and decoding performance improvement over the fading channels compared to existing state‐of‐art IDS algorithms.

As the flexible-controlled power source in the power system, the doubly fed-based variable-speed pumped storage unit (DF-VSPSU) has a significant role in the power rebalance and the reactive power support. However, as with the voltage sag in the remote grid side, the DF-VSPSU with the conventional low-voltage ride-through control may lose the synchronization and result in instability due to the absence of an equilibrium point. Thus, taking a DF-VSPSU infinite system as a case, the generator-side, and the grid-side model is well established. The large disturbance instability mechanism of doubly fed-based variable-speed pumped storage unit under remote grid faults is explained in detail, which is caused by the absence of the equilibrium point. Together with the key influencing factors, including the voltage depth and the short circuit ratio, the available gain of the reactive current control is presented. Finally, the availability of the theoretical analysis is demonstrated based on MATLAB/Simulink.

Abstract Background The contralateral seventh cervical (cC7) nerve root transfer represents a cornerstone technique in treating total brachial plexus avulsion injury. Traditional cC7 procedures employ the entire ulnar nerve as a graft, which inevitably compromises its restorative capacity. Objective Our cadaveric study seeks to assess this innovative approach aimed at preserving the motor branch of the ulnar nerve (MBUN). This new method aims to enable future repair stages, using the superficial radial nerve (SRN) as a bridge connecting cC7 and MBUN. Methods We undertook a comprehensive dissection of ten adult cadavers, generously provided by the Department of Anatomy, Histology, and Embryology at Fudan University, China. It allowed us to evaluate the feasibility of our proposed technique. For this study, we harvested only the dorsal and superficial branches of the ulnar nerve, as well as the SRN, to establish connections between the cC7 nerve and recipient nerves (both the median nerve and MBUN). We meticulously dissected the SRN and the motor and sensory branches of the ulnar nerve. Measurements were made from the reverse point of the SRN to the wrist flexion crease and the coaptation point of the SRN and MBUN. Additionally, we traced the MBUN from distal to proximal ends, recording its maximum length. We also measured the diameters of the nerve branches and tallied the number of axons. Results Our modified approach proved technically viable in all examined limbs. The distances from the reverse point of the SRN to the wrist flexion crease were 8.24 ± 1.80 cm and to the coaptation point were 6.60 ± 1.75 cm. The maximum length of the MBUN was 7.62 ± 1.03 cm. The average axon diameters in the MBUN and the anterior and posterior branches of the SRN were 1.88 ± 0.42 mm、1.56 ± 0.38 mm、2.02 ± 0.41 mm,respectively. The corresponding mean numbers of axons were 1426.60 ± 331.39 and 721.50 ± 138.22, and 741.90 ± 171.34, respectively. Conclusion The SRN demonstrated the potential to be transferred to the MBUN without necessitating a nerve graft. A potential advantage of this modification is preserving the MBUN’s recovery potential.

Abstract. Background:. Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 (CARD9) is critical for producing Aspergillus fumigatus-induced (Af-induced) T helper 2 (TH2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. Methods:. A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. Results:. The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus (aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N, which contributes to its functional alterations to facilitate Af-induced TH2-mediated ABPA development. In terms of mechanism, Card9 wild-type (Card9WT) expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9S12N. In addition, ABPA patients with heterozygous CARD9S12N had increased Af-induced interleukin-5 production. Conclusion:. Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N, followed by allele expression imbalance of CARD9S12N, facilitates the development of ABPA.

Although Mollisols are renowned for their fertility and high-productivity, high carbon (C) losses pose a substantial challenge to the sustainable provision of ecosystem services, including food security and climate regulation. Protecting these soils with a specific focus on revitalizing their C sequestration potential emerges as a crucial measure to address various threats associated with climate change. In this study, we employed a modeling approach to assess the impact of different fertilization strategies on crop yield, soil organic carbon (SOC) stock, and C sequestration efficiency (CSE) under various climate change scenarios (baseline, RCP 2.6, RCP 4.5, and RCP 8.5). The process-based SPACSYS model was calibrated and validated using data from two representative Mollisol long-term experiments in Northeast China, including three crops (wheat, maize and soyabean) and four fertilizations (no-fertilizer (CK), mineral nitrogen, phosphorus and potassium (NPK), manure only (M), and chemical fertilizers plus M (NPKM or NM)). SPACSYS effectively simulated crop yields and the dynamics of SOC stock. According to SPACSYS projections, climate change, especially the increased temperature, is anticipated to reduce maize yield by an average of 14.5% in Harbin and 13.3% in Gongzhuling, and soybean yield by an average of 10.6%, across all the treatments and climatic scenarios. Conversely, a slight but not statistically significant average yield increase of 2.5% was predicted for spring wheat. SOC stock showed a decrease of 8.2% for Harbin and 7.6% for Gonghzuling by 2,100 under the RCP scenarios. Future climates also led to a reduction in CSE by an average of 6.0% in Harbin (except NPK) and 13.4% in Gongzhuling. In addition, the higher average crop yields, annual SOC stocks, and annual CSE (10.15–15.16%) were found when manure amendments were performed under all climate scenarios compared with the chemical fertilization. Soil CSE displayed an exponential decrease with the C accumulated input, asymptotically approaching a constant. Importantly, the CSE asymptote associated with manure application was higher than that of other treatments. Our findings emphasize the consequences of climate change on crop yields, SOC stock, and CSE in the Mollisol regions, identifying manure application as a targeted fertilizer practice for effective climate change mitigation.

ABSTRACT: Background: Strain analysis offers a valuable tool to assess myocardial mechanics, allowing for the detection of impairments in heart function. This study aims to evaluate the pattern of myocardial strain in patients with heart failure (HF). Methods: In the present study, myocardial strain was measured by cardiac magnetic resonance imaging feature tracking in 35 control subjects without HF and 195 HF patients. The HF patients were further categorized as HF with preserved ejection fraction (HFpEF, n = 80), with mid-range ejection fraction (HFmrEF, n = 34), and with reduced ejection fraction (HFrEF, n = 81). Additionally, quantitative tissue evaluation parameters, including native T1 relaxation time and extracellular volume (ECV), were examined. Results: Compared to controls, patients in all HF groups (HFpEF, HFmrEF, and HFrEF) demonstrated impaired left ventricular (LV) strains and systolic and diastolic strain rates in all three directions (radial, circumferential, and longitudinal) (p

Aiming at the problem of power reduction when the transmitter and receiver coils are misaligned in wireless power transfer (WPT) system, a strategy to improve power by controlling the current phase of the array coils is proposed in this paper. Taking the square coil as an example, the expression of the magnetic field strength at a certain point in the array coil is discussed, and the parameters affecting the magnetic field distribution are determined. In order to improve the uniformity of the magnetic field distribution, the non-equidistant coil structure of the array coil is designed. BP neural network is introduced to learn the variation law of the magnetic flux with the current phase of the array coil in the specified area, and the phase difference between the coils when the magnetic flux is maximum is determined. Finally, the above concepts are realized through simulations and experiments. The results show that the proposed non-equidistant coil has more advantages in the uniformity of magnetic field distribution than the equidistant coil. Under the optimal phase configuration, the magnetic flux in the planar area of the array coil can be effectively improved.

Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have evolved to live entirely submerged in marine waters. Thus, these species are ideal for studying plant adaptation to marine environments. Herein, we sequenced the chloroplast (cp) genomes of two seagrass species (Zostera muelleri and Halophila ovalis) and performed a comparative analysis of them with 10 previously published seagrasses, resulting in various novel findings. Results The cp genomes of the seagrasses ranged in size from 143,877 bp (Zostera marina) to 178,261 bp (Thalassia hemprichii), and also varied in size among different families in the following order: Hydrocharitaceae > Cymodoceaceae > Ruppiaceae > Zosteraceae. The length differences between families were mainly related to the expansion and contraction of the IR region. In addition, we screened out 2,751 simple sequence repeats and 1,757 long repeat sequence types in the cp genome sequences of the 12 seagrass species, ultimately finding seven hot spots in coding regions. Interestingly, we found nine genes with positive selection sites, including two ATP subunit genes (atpA and atpF), three ribosome subunit genes (rps4, rps7, and rpl20), one photosystem subunit gene (psbH), and the ycf2, accD, and rbcL genes. These gene regions may have played critical roles in the adaptation of seagrasses to diverse environments. In addition, phylogenetic analysis strongly supported the division of the 12 seagrass species into four previously recognized major clades. Finally, the divergence time of the seagrasses inferred from the cp genome sequences was generally consistent with previous studies. Conclusions In this study, we compared chloroplast genomes from 12 seagrass species, covering the main phylogenetic clades. Our findings will provide valuable genetic data for research into the taxonomy, phylogeny, and species evolution of seagrasses.

Abstract Background Seagrasses are higher marine flowering plants that evolved from terrestrial plants, but returned to the sea during the early evolution of monocotyledons through several separate lineages. Thus, they become a good model for studying the adaptation of plants to the marine environment. Sequencing of the mitochondrial (mt) genome of seagrasses is essential for understanding their evolutionary characteristics. Results In this study, we sequenced the mt genome of two endangered seagrasses (Zostera japonica and Phyllospadix iwatensis). These data and data on previously sequenced mt genomes from monocotyledons provide new evolutionary evidence of genome size reduction, gene loss, and adaptive evolution in seagrasses. The mt genomes of Z. japonica and P. iwatensis are circular. The sizes of the three seagrasses (including Zostera marine) that have been sequenced to date are smaller than that of other monocotyledons. Additionally, we found a large number of repeat sequences in seagrasses. The most abundant long repeat sequences were 31–40 bp repeats. Our study also found that seagrass species lost extensive ribosomal protein genes during evolution. The rps7 gene and the rpl16 gene of P. iwatensis are exceptions to this trend. The phylogenetic analysis based on the mt genome strongly supports the previous results. Furthermore, we identified five positive selection genes (atp8, nad3, nad6, ccmFn, and matR) in seagrasses that may be associated with their adaptation to the marine environment. Conclusions In this study, we sequenced and annotated the mt genomes of Z. japonica and P. iwatensis and compared them with the genome of other monocotyledons. The results of this study will enhance our understanding of seagrass adaptation to the marine environment and can inform further investigations of the seagrass mt genome.

Abstract Background Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the “gut-lung axis”. However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. Methods Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). Results Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. Conclusion The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota’s potentiality as biomarkers for bronchiectasis. Trial registration: This study is registered with ClinicalTrials.gov, number NCT04490447.

BackgroundsThe safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.MethodsThis network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.ResultsNine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.ConclusionIn patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient’s profiles to maximize safety.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022334644.

Aerial images record the dynamic Earth terrain, reflecting changes in land cover patterns caused by natural processes and human activities. Nonetheless, prevailing aerial image classification methodologies predominantly function within a closed-set framework, thereby encountering challenges when confronted with the identification of newly emerging scenes. To address this, this paper explores an aerial image recognition scenario in which a dataset comprises both labeled and unlabeled aerial images, intending to classify all images within the unlabeled subset, termed Generalized Category Discovery (GCD). It is noteworthy that the unlabeled images may pertain to labeled classes or represent novel classes. Specifically, we first develop a contrastive learning framework drawing upon the cutting-edge algorithms in GCD. Based on the multi-object characteristics of aerial images, we then propose a slot attention-based GCD training process (Slot-GCD) that contrasts learning at both the object and image levels. It decouples multiple local object features from feature maps using slots and then reconstructs the overall semantic feature of the image based on slot confidence scores and the feature map. Finally, these object-level and image-level features are input into the contrastive learning module to enable the model to learn more precise image semantic features. Comprehensive evaluations across three public aerial image datasets highlight the superiority of our approach over state-of-the-art methods. Particularly, Slot-GCD achieves a recognition accuracy of 91.5% for known old classes and 81.9% for unknown novel class data on the AID dataset.

Calcineurin B homologous protein 3 (CHP3) is an EF-hand Ca2+-binding protein involved in regulation of cancerogenesis, cardiac hypertrophy, and neuronal development through interactions with sodium/proton exchangers (NHEs) and signalling proteins. While the importance of Ca2+ binding and myristoylation for CHP3 function has been recognized, the underlying molecular mechanism remained elusive. In this study, we demonstrate that Ca2+ binding and myristoylation independently affect the conformation and functions of human CHP3. Ca2+ binding increased local flexibility and hydrophobicity of CHP3 indicative of an open conformation. The Ca2+-bound CHP3 exhibited a higher affinity for NHE1 and associated stronger with lipid membranes compared to the Mg2+-bound CHP3, which adopted a closed conformation. Myristoylation enhanced the local flexibility of CHP3 and decreased its affinity to NHE1 independently of the bound ion, but did not affect its binding to lipid membranes. The data exclude the proposed Ca2+-myristoyl switch for CHP3. Instead, a Ca2+-independent exposure of the myristoyl moiety is induced by binding of the target peptide to CHP3 enhancing its association to lipid membranes. We name this novel regulatory mechanism ‘target-myristoyl switch’. Collectively, the interplay of Ca2+ binding, myristoylation, and target binding allows for a context-specific regulation of CHP3 functions.

It is generally known that soil organic carbon (SOC) stocks tend to increase with an increase in C input, whereas the C sequestration efficiency (CSE), i.e., the conversion ratio of C input to SOC, differs depending on the amount and type of C input. However, there is still a need to better understand the impact of various fertilization practices on CSE. We studied the data from eight long-term experiments located in the main dryland region of China in order to comprehensively assess the key drivers of CSE in the plow layer considering nearly four decades of various fertilizer treatments, i.e., no fertilizer (CK); chemical nitrogen, phosphorus, and potassium (NPK/NP); chemical fertilizers plus manure (NPKM/NPM/NM); and straw (NPKS/NPS/NS). Our results showed that manure amendment had the most significant fertilization effect on SOC sequestration with an average CSE of 14.9%, which was significantly higher than that of chemical fertilization (9.0%) and straw return treatments (7.9%). In addition, manure amendment also had the highest average SOC increase rate of 684 kg C ha-1 yr-1. Variance partitioning analysis (VPA) illustrated that the CSE of the main dryland region of China was mostly controlled by edaphic characteristics (32.2%), especially the soil C/N ratio and clay content. VPA and structural equation modeling revealed that the magnitude and influencing factors driving CSE varied among different fertilizer treatments. Soil total N was the limiting factor for CSE in the CK treatment, whereas the soil C/N ratio and pH were the main explanatory factors for CSE in the long-term chemical NPK fertilizer treatment. The negative impact of C input from straw was the main driver of CSE under straw return treatments, though C input had a positive effect on the improvement of soil physical properties. However, when considering manure amendments, the improvement of soil nutrients and clay content controlled CSE, underlining the main positive direct effect of soil chemical properties. In a nutshell, our results recommend manure plus chemical fertilizers as a sustainable practice for improving the C sequestration rate and efficiency in dryland cropping systems.

Enhancing soil organic carbon (SOC) stocks through fertilization and crop rotation will contribute to sustaining crop productivity and mitigating global warming. In this study, we analyzed the differences in total SOC stocks and their driving factors in the topsoil (0–20 cm) with various fertilization measures in two puddled lowland rice-based cropping systems (i.e., rice-wheat rotation and double rice rotation systems) over the last four decades from seven long-term experiments in the Yangtze River catchment. The soil types include Cambisol, Luvisol, and Anthrosol. The treatments include no fertilizer application (CK), application of chemical nitrogen, phosphorus and potassium fertilizers (NPK) and a combination of NPK and manure applications (NPKM). Every year, field was ploughed to a depth of 15–20 cm before wheat sowing and rice transplanting. Residue was removed after plant harvesting. Results showed that during the last four decades, the average crop grain yield ranged from 1,151 ± 504 kg ha−1 yr−1 under CK treatment to 7,553 ± 1,373 kg ha−1 yr−1 under NPKM treatment. The topsoil SOC stock significantly increased by 8.6 t ha−1 on average under NPKM treatment in rice-wheat system and by 2.5–6.4 t ha−1 on average under NPK and NPKM treatments in double rice system as compared with CK. A higher SOC sequestration rate and a longer SOC sequestration duration were found in NPKM treatment than that in NPK treatment in both cropping systems. The highest SOC stock ratio (SOC stock in fertilizer treatments to CK) was observed under the NPKM treatment in both cropping systems, though no significant difference was found between these two cropping systems. However, the fertilization-induced relative increase of the SOC stock was 109.5% and 45.8% under the NPK and NPKM treatments, respectively in the rice-wheat system than that in the double rice system. This indicates that the rice-wheat system is more conducive for SOC sequestration. RF and SEM analyses revealed that the magnitude and influencing factors driving SOC sequestration varied between two systems. In the double rice system, continuous flooding weakens the influence of precipitation on SOC sequestration and highlights the importance of soil properties and C input. In contrast, soil properties, C input and climate factors all have important impacts on SOC sequestration in rice-wheat system. This study reveals that the rice-wheat system is more favorable for SOC sequestration despite its lower C input compared to the double rice system in China’s paddies.

Abstract Background The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. Methods ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. Discussion ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

Abstract Background Diffusion tensor imaging (DTI) was used to quantitatively study the characteristics of the related spinal cord and nerve root compression parameters in patients with cervical spondylosis (CS), and diffusion tensor tractography (DTT) was used to visualize the spinal cord and nerve root and analyze their relevance to clinical evaluation. Methods A total of 67 patients with CS and 30 healthy volunteers received 3.0 T magnetic resonance imaging. Cervical DTI and DTT were performed in all the participants, where the b value of DTI was set at 800 s/mm2. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the spinal cord and cervical nerve roots were measured by using DTI. Patients with CS were scored according to the modified Japanese Orthopedic Association (mJOA) score. Results In all the participants, the spinal cord and cervical nerve roots were clearly visible by DTT. Compared to the healthy volunteers, the FA values were significantly decreased and ADC values were significantly increased in patients with CS. mJOA score was significantly correlated with the DTI index (ADC and FA) values. Receiver operator characteristic curve analysis revealed that FA and ADC could identify mild, moderate, and severe CS. Conclusions DTI parameters of cervical spinal cord and nerve root compression are associated with the clinical evaluation of patients with CS and may be helpful in assessing the severity of CS.

Abstract Background We aimed to analyze the distribution of knee cartilage degeneration in young patients with mild symptoms using quantitative magnetic resonance imaging (MRI) T2 mapping. Materials and methods This study included sixty six patients (case group) and twenty eight healthy volunteers (control group). The participants underwent 3.0 T conventional MRI plus a multi-echo sequence. The cartilage of each participant was divided into twenty eight subregions. We then calculated the T2 mean values and standard deviation or median and quartile range for each subregion according to whether the normal distribution was satisfied. Besides, we employed Kruskal–Wallis test to determine the statistical differences of each subregion in the control group while the Mann–Whitney U test was used to define the statistical difference between the case group and the control group and between the control group and subjects aged less than or equal to 35 years in the case group. Results In the case group, age of 30 male patients was 31.5 ± 9.3 and age of 36 female patients was 35.7 ± 8.3. In the two groups, the superficial central lateral femoral region exhibited relatively high T2 values (control/case group: 49.6 ± 2.7/55.9 ± 8.8), and the deep medial patellar region exhibited relatively low T2 values (control/case group: 34.2 ± 1.3/33.5(32.2, 35.5)). Comparison of the T2 values between the case and the control group demonstrated a statistically significant increase in nine subregions (P1

Abstract The charge transport and accumulation in oil–paper can cause the insulation degradation. So far, the most widely used model to simulate space charge transport and accumulation is the bipolar charge transport (BCT) model, which can well simulate the space charge dynamics. However, there are two shortcomings in the algorithms for solving the BCT model. One is that there is almost no use of vectorisation technology, which may increase the complexity of the algorithm, the other is the usage of fixed step size which might bring extra computation cost. In view of this, an adaptive time‐stepping transient upstream finite element method (FEM) is developed to solve the BCT model considering trapping/detrapping, as well as the recombination phenomenon under DC condition in this article. Then, a vectorisation technology is used in the method to optimise the algorithm. Moreover, the adaptive time‐stepping method is introduced in simulation to reduce computation time and calculation amount. Simulation results are obtained by programing and later presented, which are basically consistent with the corresponding experimental results. Therefore, the proposed method is expected to promote the optimization design of the oil–paper insulation system.

BackgroundAmong patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients.MethodsBetween January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression.ResultsOverall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden >70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92–6.44], a low-density non-calcified plaque (LDNCP) volume >30 mm3 (HR: 3.40, 95% CI: 2.07–5.56), a minimal luminal area (MLA)

BackgroundAtrial fibrillation (AF) has been a worldwide health issue with increasing prevalence and mortality. Recently, increasing attention has been gained to the relationship between heart rate variability (HRV) and the clinical prognosis of AF catheter ablation. We aimed to evaluate the prognostic value of HRV in AF recurrence.MethodsWe systematically searched Web of Science, PubMed, and Embase from inception until 17 August 2022 to conduct the systematic review and meta-analysis. We included the studies reporting the predictive value of HRV parameters for AF recurrence or in which HRV parameters in AF recurrence and non-recurrence groups were individually reported.ResultsFinally, we enrolled 16 studies, including 2,352 patients. Higher rMSSD could independently predict AF recurrence following catheter ablation (OR: 1.02, 95% CI: 1.00–1.04; p = 0.03). Higher HF (OR: 1.55, 95% CI: 1.05–2.28; p = 0.03) and lower LF/HF (OR: 1.12, 95% CI: 1.03–1.20; p = 0.004) could independently predict AF recurrence within 1 year. Higher SDNN (OR: 1.02, 95% CI: 101–1.02; p = 0.0006) could independently predict AF recurrence among patients with paroxysmal AF. Almost all HRV parameters within 3 days after catheter ablation and lnHF, lnLF, and rMSSD at 3 months after catheter ablation performed significant differences in AF recurrence and non-recurrence groups.ConclusionHeart rate variability, especially higher rMSSD (within short-term and long-term periods), was closely related to recurrent AF following catheter ablation, highlighting the clinical importance of HRV in the prognosis of AF following catheter ablation.

BackgroundThe high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient.MethodsWe retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months.ResultsThe HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1–2, 20.3% based on SPSP 1–3, and 20.8% based on SPSPII 1–3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months.ConclusionThe HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis.Trial registrationClinicalTrial.gov, identifier: NCT04516577.

Abstract Background Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient’s condition. Methods APAP patients numbering 151 were enrolled in this study. All patients’ severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1–2 and 3–5 through receiving operating characteristics (ROC) curve. Results Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1–2 and 3–5) showed an optimal cutoff of LDH of over 203 U/L ( 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748–0.882], sensitivity: 0.606, specificity: 0.877). Conclusion Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Abstract Background Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined. Methods Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro. Results The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU. Conclusions HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.

Abstract Background In recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear. Methods In this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated. Discussion The study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma. Trial registration: The trial was registered on the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/showprojen.aspx?proj=33231 ). Registration number: ChiCTR1800019990.

Chemoresistance against 5-fluorouracil (5-FU) is a major issue for colorectal cancer (CRC) patients. Increasing evidence for the roles of CD147 in glycolipid metabolic reprogramming and chemoresistance of tumor cells has emerged in recent years. However, whether CD147 contributes to 5-FU resistance in CRC and the role of abnormal glycolipid metabolism in this process remain poorly understood. We analyzed CD147 expression in primary tumor samples of CRC patients and found that upregulated CD147 correlated with decreased 5-FU chemosensitivity and an unfavorable prognosis of CRC patients. Moreover, in vivo and in vitro experiments confirmed that CD147 regulates glycolipid metabolism through two separate pathways. Mechanistically, CD147 upregulates HIF-1α-mediated glycolysis by activating the PI3K/AKT/mTOR pathway and CD147 also attenuates PPARα-mediated fatty acid oxidation by activation of the MAPK pathway. Most importantly, we found that CD147 confers 5-FU resistance in CRC via these glycolipid metabolic signatures. Our results demonstrated that CD147 is a potential 5-FU resistance biomarker for CRC patients and a candidate therapeutic target to restore 5-FU sensitivity of 5-FU-resistant CRC by remodeling glycolipid metabolism.

Hot spot temperature (HST) is an important parameter reflecting the working state of the traction transformer, and the load characteristics have a great influence on the HST. The current researches rarely consider the load characteristics of transformers in-depth, and most of the research on the temperature field focuses on steady load. Therefore, a prediction model of HST for the traction transformer considering the load characteristics is established by the finite element simulation in this paper. Considering the impact and nonlinearity of traction load, the influence of the load characteristics on the HST is studied. Analysis of the load curve revealed that the steady and step load combination could well simulate the traction load. Based on the analysis of traction transformer load characteristics, the temperature field coupling calculation of traction transformer is carried out according to the VI normative duty class. On this basis, the influence of load rate and time on HST is studied. The present findings show that the method can predict the HST of traction transformer under different working conditions and provide a reference for load dispatching of traction transformer. The simulation data are in good agreement with the test results, and the average relative error is 3.4%. The results verify the effectiveness of the proposed method.

Abstract Background Metabolic syndrome (MS) is a disorder, characterized by clusters of cardiovascular risk factors such as central obesity, insulin resistance, dyslipidemia and hypertension. Patients with MS may have a higher plaque burden that increases their risk of major adverse cardiovascular events (MACEs). This study aimed to analyze the prevalence of high-risk coronary plaques in patients with and without MS by coronary computed tomography angiography (CCTA) and to investigate the relationship between MS, high-risk coronary plaques, and their prognosis. Methods This was a retrospective cohort study of 1136 patients who underwent CCTA due to chest pain without obstructive heart disease (≥50% coronary stenosis) between January 2014 and December 2015 in our hospital. The relationships between high risk coronary plaques, MS, and other clinical factors were assessed. Multicollinearity analysis was performed to identify the collinearity between the variables. The proportional hazard assumption was checked and using Schoenfeld residual test. Cox proportional hazards model and Kaplan-Meier survival analysis assessed the relationship between MS, high-risk coronary plaques and MACEs. Results High-risk plaques were more frequent in the MS group than non-MS group (P = 0.004). MS (HR = 2.128, 95%CI: 1.524–2.970, P

Marine macrophytes (seagrasses and macroalgae) and their epiphytic microorganisms play an important role in the ecological and biochemical processes of coastal oceans. However, simultaneous comparative studies on the biodiversity and functions of epiphytic bacteria and fungi associated with marine macrophytes have not been conducted. In this study, high-throughput sequencing technology was used to describe the epiphytic bacterial and fungal communities of 11 common macroalgae and 2 seagrasses from an intertidal zone of northern China and compare them with seawater communities. The results showed that Proteobacteria and Bacteroidota were the dominant bacterial phyla in marine macrophytes, whereas Ascomycota, Chytridiomycota, and Basidiomycota were the dominant fungal phyla. The alpha diversity of the bacterial and fungal communities in seagrasses was the highest of all macrophyte samples. This may have been related to their ability to recruit microorganisms from multiple sources. Host phylogeny may influence bacterial community structure, and geographical differences may influence fungal community structure. The FAPROTAX data indicated that C metabolic microbes were enriched in marine macrophytes, while the FUNGuild data indicated that undefined saprotroph, which participated in organic matter degradation, were also enriched in marine macrophytes. These findings provide a theoretical basis regarding the epiphytic microorganisms of macrophytes and may offer new insights to support the improved ecological restoration of seagrass and macroalgae beds.

IntroductionTo evaluate the value of artificial intelligence (AI)-assisted software in the diagnosis of lung nodules using a combination of low-dose computed tomography (LDCT) and high-resolution computed tomography (HRCT).MethodA total of 113 patients with pulmonary nodules were screened using LDCT. For nodules with the largest diameters, an HRCT local-target scanning program (combined scanning scheme) and a conventional-dose CT scanning scheme were also performed. Lung nodules were subjectively assessed for image signs and compared by size and malignancy rate measured by AI-assisted software. The nodules were divided into improved visibility and identical visibility groups based on differences in the number of signs identified through the two schemes.ResultsThe nodule volume and malignancy probability for subsolid nodules significantly differed between the improved and identical visibility groups. For the combined scanning protocol, we observed significant between-group differences in subsolid nodule malignancy rates.ConclusionUnder the operation and decision of AI, the combined scanning scheme may be beneficial for screening high-risk populations.

Noise exposure causes noise-induced hearing loss (NIHL). NIHL exhibits loss of inner ear sensory hair cells and is often irreparable. Although oxidative stress is involved in hearing loss, the complex mechanisms involved in NIHL are unclear. Hypoxia-inducible factor 1α (HIF-1α) has been suggested to be essential for protecting sensory hair cells. Additionally, it has been shown that ROS is involved in modulating the stability of HIF-1α. To investigate the NIHL pathogenesis, we established a tert-butyl hydroperoxide (t-BHP)-induced oxidative stress damage model in hair-like HEI-OC1 cells and an NIHL model in C57BL/6 mice. Protein and mRNA expression were determined, and biochemical parameters including reactive oxygen species (ROS) accumulation, glucose uptake, adenosine triphosphat (ATP) production, and mitochondrial content were evaluated. In HEI-OC1 cells, t-BHP induced ROS accumulation and reduced mitochondrial content and oxygen consumption, but the ATP level was unaffected. Additionally, there was increased glucose uptake and lactate release along with elevated expression of HIF-1α, glucose transporter 1, and several glycolytic enzymes. Consistently, noise trauma induced oxidative stress and the expression of HIF-1α and glycolytic enzymes in mice. Thus, we concluded that ROS induced HIF-1α expression, which promoted glycolysis, suggesting a metabolic shift maintained the ATP level to attenuate hair cell damage in NIHL.

Background: Persistent cough and large amounts of purulent sputum affects many bronchiectasis patients. No studies have evaluated the efficacy and safety of bronchoscopic airway clearance therapy and bronchoalveolar lavage (B-ACT) for non-cystic fibrosis bronchiectasis patients with acute exacerbation. Methods: A randomised controlled trial was conducted to explore the efficacy and safety of B-ACT among 189 bronchiectasis inpatients from February 1, 2018 to February 28, 2019. The primary outcome was the time to first acute exacerbation. Secondary outcomes included changes of health-related scores, length of hospital stay, hospitalization expenses and incidences of adverse events. Findings: B-ACT therapy significantly prolonged the median days to first acute exacerbation when compared with control group (198 vs 168 days, HR 0·555 (0·322-0·958), p=0·012; effect size(r)= 0·94). Further analysis showed that B-ACT therapy was more beneficial for these patients with severe disease and greater symptoms. COPD Assessment Test (CAT) scores improved significantly on the third day (5·45 vs 4·85, 0·60 (0·09-1·11), p=0·023), and Leicester Cough Questionnaire (LCQ) scores improved obviously on the third and seventh days (1·53 vs 1·23, 0·30 (0·05-0·55), p=0·044; 1·66 vs 1·32, 0·34 (0·08-0·60), p=0·022; respectively) after B-ACT therapy. Adverse events associated with B-ACT were mostly transient and mild. Differences of the lengths of hospital stay and hospitalization expenses in both group was not significant. Interpretation: B-ACT therapy significantly prolonged the time to first acute exacerbation after discharge, highlighting the importance of B-ACT therapy focused on symptom improvements in preventing exacerbation. Funding: National Natural Science Foundation of China. Trial registry: ClinicalTrials.gov; No.:NCT03643302; URL: www.clinicaltrials.gov.

Seagrasses are marine flowering plants found in tropical and sub-tropical areas that live in coastal regions between the sea and land. All seagrass species evolved from terrestrial monocotyledons, providing the opportunity to study plant adaptation to sea environments. Here, we sequenced the chloroplast genomes (cpGenomes) of three Zostera species, then analyzed and compared their cpGenome structures and sequence variations. We also performed a phylogenetic analysis using published seagrass chloroplasts and calculated the selection pressure of 17 species within seagrasses and nine terrestrial monocotyledons, as well as estimated the number of shared genes of eight seagrasses. The cpGenomes of Zosteraceae species ranged in size from 143,877 bp (Zostera marina) to 152,726 bp (Phyllospadix iwatensis), which were conserved and displayed similar structures and gene orders. Additionally, we found 17 variable hotspot regions as candidate DNA barcodes for Zosteraceae species, which will be helpful for studying the phylogenetic relationships and interspecies differences between seagrass species. Interestingly, nine genes had positive selection sites, including two ATP subunit genes (atpA and atpF), two ribosome subunit genes (rps4 and rpl20), two DNA-dependent RNA polymerase genes (rpoC1 and rpoC2), as well as accD, clpP, and ycf2. These gene regions may have played key roles in the seagrass adaptation to diverse environments. The Branch model analysis showed that seagrasses had a higher rate of evolution than terrestrial monocotyledons, suggesting that seagrasses experienced greater environmental pressure. Moreover, a branch-site model identified positively selected sites (PSSs) in ccsA, suggesting their involvement in the adaptation to sea environments. These findings are valuable for further investigations on Zosteraceae cpGenomes and will serve as an excellent resource for future studies on seagrass adaptation to sea environments.

Abstract. Background:. Trocar-site hernia (TSH) is a serious complication after laparoscopic procedures. Although it is a rare entity, it can have life-threatening consequences. This study aimed to retrospectively analyze the potential associated factors for TSH following gynecologic laparoscopy and summarize prevention strategies based on our experience. Methods:. We searched for gynecological laparoscopic surgeries in the medical records system of Peking Union Medical College Hospital (PUMCH) from August 1998 to July 2018 and further sifted through the results for cases involving TSH. All included patients were divided into different groups according to patient characteristics, and the rate of TSH was compared among groups. Moreover, the detailed information of all patients with TSH was recorded and analyzed. Statistical analyses were performed with GraphPad Prism 6. Results:. The approximate total rate of post-operative TSH among gynecologic laparoscopy procedures performed at PUMCH in the last 20 years was 0.016% (9/55,244). The rate of TSH was significant higher in elder patients (≥60 years old; 3/2686, 0.112%) than in younger patients (

Background and aimsGlucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM).MethodsWe did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region.ResultsFourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P80% or ConclusionsThe predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.

OBJECTIVES: To evaluate the quantitative changes and diagnostic performance of volumetric capnography (VCap) parameters in patients with cough variant asthma. METHODS: This cross-sectional study enrolled 31 patients with cough variant asthma and 30 patients with chronic cough without asthma between November 2010 and March 2012. VCap measurements were recorded at baseline, during the five steps of the histamine challenge, and after bronchodilation with salbutamol. They were then compared between the baseline and histamine challenge, and between the two groups. Receiver operating characteristic curve analysis was performed for different VCap measurements. RESULTS: The slope of phase III (dc\dv3) and the ratio of phase III slope to phase II slope (SR23%) decreased from baseline upon challenge with 1.1 mg histamine in cough variant asthma patients but increased in patients with chronic cough without asthma. Additionally, the change upon challenge with 1.1 mg histamine in dc\dv3 from baseline (S6-S1dc\dv3) in cough variant asthma patients had the largest area under the curve (AUC) (0.814, 95% CI: 0.697-0.931; p

Abstract Aiming at how to improve the efficiency of image edge detection, an image edge detection method based on least squares support vector machine (LSSVM) and cellular automata is proposed. Firstly, a new kernel function is constructed based on the Gauss radial basis kernel and polynomial kernel, which enables the LSSVM to fit the gray values of the image pixels accurately. Then, the gradient operator of the image is deduced, and the gradient value of the image is obtained by convolution with the gray value of the image. Then, the cellular automata evolves the gradient value according to the designed local rules to locate and detect the image edge. Simulation results show that the proposed edge detection algorithm is effective, and the new algorithm has higher detection performance than Sobel and Canny algorithms.

In this paper, a digital metamaterial of arbitrary base based on liquid crystal (LC) is proposed. The digital metamaterial can be multiplexed for different desirable functions by properly biasing the LC for different code patterns. Simulation results of two common functions, beam steering with a steering elevation angle 27° and RCS reduction of at least 10 dB from 51 to 56 GHz, have been presented to prove the concept. The feasibility has been further confirmed by preliminary measurement.