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Abstract Early diagnosis and disease management based on risk stratification have a very positive impact on colon adenocarcinoma (COAD) prognosis. It is of positive significance to further explore risk stratification of COAD patients and identify predictive molecular biomarkers. PANoptosis is defined as a form of inflammatory cell death regulated by PANoptosome, with common features of pyroptosis, apoptosis and necroptosis. The role of PANoptosis in COAD has not been fully studied. In this study, we analyzed significant differences in the expression of PANoptosis-related gene (PRG) features in COAD. Subsequently, the PANoptosis associated lncRNAs (PALs) associated with PRGs were analyzed by LASSO algorithm and multivariate Cox analysis, and PALs related to the prognosis of COAD were selected. Based on the expression patterns of prognostic PAL features, we performed unsupervised consensus cluster analysis to categorize COAD samples into distinct PAL molecular subtypes and investigate their associated immune infiltration characteristics. We subsequently constructed PAL score model based on prognostic characteristics and verified its independent prognostic value for COAD. The nomogram diagnostic model was established to confirm the prognostic value of PAL scoring system again. Pathway enrichment analysis, somatic mutation profiling, and drug sensitivity analysis were employed to comprehensively assess the clinical value of the PAL score. Additionally, qRT-PCR was used to further validate the abnormal expression of the selected targets in COAD. Our results provide a new idea for clinical risk stratification and new evidence for the role of PANoptosis in COAD.

Abstract Early detection of lung function impairment is crucial. However, the sensitivity of spirometry in detecting early lung function deterioration is limited. In this study, lungs of 3180 healthy participants scheduled for annual health check were screened. Electrical impedance tomography measurements were conducted in 130 participants with normal spirometry for concept establishment phase and 105 for validation phase. A follow-up CT examination was suggested for participants with abnormal regional time constant or tobacco consumption ≥10 pack-years. Using CT as reference, the sensitivity and specificity of electrical impedance tomography-based screening were 81.3% and 50.0%, respectively in the concept establishment phase. In the validation phase, the sensitivity and specificity were 77.9% and 50.0%. In this study we show that conventional spirometry may not capture early changes that occur at a regional level. The regional time constant based on electrical impedance tomography can be a promising tool for early screening of lung function impairment. Clinical trial registration: ChiCTR2300076673, www.chictr.org.cn .

Abstract Background Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. Methods This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. Results A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. Conclusion This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. Trial registration Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .

Colorectal cancer is one of the most common and lethal malignancies, and various factors have been confirmed to contribute to its occurrence. However, the causal role of immune cell-specific changes in the development of colorectal cancer has not been investigated. The bidirectional two-sample Mendelian randomization analysis was performed to explore the association between 731 types of immune cell phenotypes-specific changes and colorectal cancer. The inverse variance weighting results indicated that a total of 31 and 28 immune cell phenotypes significantly associated with colorectal cancer in two different datasets, respectively. The primary results of inverse variance weighting Mendelian randomization suggested that the immune cell phenotypes BAFF-R on IgD+ CD38dim (OR = 1.033, 95%CI: 1.005–1.062) and SSC-A on monocyte (OR = 1.055, 95%CI: 1.016–1.096) served as risk factor for colorectal cancer. In addition, the meta-analysis further supports the causal link of BAFF-R on IgD+ CD38dim (pooled OR = 1.035, 95%CI: 1.013–1.059) and SSC-A on monocyte (pooled OR = 1.060, 95%CI: 1.026–1.095) with colorectal cancer. Finally, the inverse variance weighting Mendelian randomization result suggested that genetic determinants of colorectal cancer may decrease the level of HLA DR++ monocyte absolute count (OR = 0.686, 95%CI: 0.508–0.925). Our results indicated that the potential causal association of BAFF-R on IgD+ CD38dim and SSC-A on monocyte with colorectal cancer. The identified immune cells may be appealing drug targets for colorectal cancer, but lack confirmation from real clinical evidence. Further studies are needed to investigate the roles of these immune cells in colorectal cancer.

Abstract We aimed to determine the clinical characteristics of patient self-inflicted lung injury (P-SILI)-associated pneumothorax/pneumomediastinum, to reveal its risk factors, and to assess its impact on severe COVID-19 cases. In total, 229 patients were included in this case-control study. They were randomly divided into either the case group or the control group as per the inclusion and exclusion criteria. The two groups were further analyzed to reveal the risk factors of spontaneous pneumothorax/pneumomediastinum (SP/P). Finally, risk factors for death were analyzed in the case group and the relationship between death and SP/P was also analyzed among all patients. The mean age of patients was 59.69 ± 17.01 years, most of them were male (74.2%), and 62.0% of them had comorbidities upon admission. A respiratory rate higher than 30 BPM was a risk factor for SP/P (OR 7.186, 95% CI 2.414–21.391, P

Background: Spontaneous respiratory mechanical force interacted with the primary lung injury and aggravated the progression of ARDS clinically. But the exact role and involved mechanism of it in the pathogenesis of ARDS animal model remained obscure. Aim: This study was to investigate the effect of spontaneous respiratory mechanical force on lung injury of ARDS in mice. Methods: Female C57BL/6 mice were subjected to resistive spontaneous breathing (RSB) by tracheal banding after 4–6 h of intranasal inhalation of LPS. Pulmonary function was examined by Buxco system, partial pressures of oxygen and carbon dioxide (PO2 and PCO2) were measured by a blood gas analyzer, and lung pathological changes were analyzed with hematoxylin and eosin staining. The levels of inflammatory markers were quantified by ELISA, total protein assay, and FACS analysis. The expression levels of mechanosensitive ion channels were detected by qRT-PCR and immunohistochemistry. Results: The airway resistance (Raw) was increased and the tidal volume (TV) was decreased remarkedly in RSB group. RSB treatment did not affect PO2, PCO2, pathology and inflammation levels of lung in mice. The Raw increased and ventilatory indicators decreased in RSB + ARDS compared to ARDS significantly. Besides, RSB treatment deteriorated the changes of PO2, PCO2 and level of lactic acid induced by LPS. Meanwhile, RSB significantly promoted LPS-induced pulmonary histopathological injury, and elevated the levels of IL-1β, IL-6, TNF-α and total proteins, increased neutrophils infiltration. The expression level of Piezo1 in RSB + ARDS group was remarkably reduced compared to ARDS group and consistent with the severity of pulmonary damage. Conclusion: RSB exacerbated LPS-induced ARDS hypoxemia and hypercapnia, inflammation and damage. The mechanosensitive protein Piezo1 expression decreased and may play an important role in the process.

The Five-hundred-meter Aperture Spherical radio Telescope (FAST) is the world ’ s largest single-dish radio telescope. Its large reflecting surface achieves unprecedented sensitivity but is prone to damage, such as dents and holes, caused by naturally-occurring falling objects. Hence, the timely and accurate detection of surface defects is crucial for FAST’s stable operation. Conventional manual inspection involves human inspectors climbing up and examining the large surface visually, a time-consuming and potentially unreliable process. To accelerate the inspection process and increase its accuracy, this work makes the first step towards automating the inspection of FAST by integrating deep-learning techniques with drone technology. First, a drone flies over the surface along a predetermined route. Since surface defects significantly vary in scale and show high inter-class similarity, directly applying existing deep detectors to detect defects on the drone imagery is highly prone to missing and misidentifying defects. As a remedy, we introduce cross-fusion, a dedicated plug-in operation for deep detectors that enables the adaptive fusion of multi-level features in a point-wise selective fashion, depending on local defect patterns. Consequently, strong semantics and fine-grained details are dynamically fused at different positions to support the accurate detection of defects of various scales and types. Our AI-powered drone-based automated inspection is time-efficient, reliable, and has good accessibility, which guarantees the long-term and stable operation of FAST.

Abstract Background The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous. Methods A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis (P ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients. Results Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P

Thousand-kernel weight (TKW) is a measure of grain weight, a target of wheat breeding. The object of this study was to fine-map a stable quantitative trait loci (QTL) for TKW and identify its candidate gene in a recombinant inbred line (RIL) population derived from the cross of Kenong 9204 (KN9204) and Jing 411 (J411). On a high-density genetic linkage map, 24, 26 and 25 QTL were associated with TKW, kernel length (KL), and kernel width (KW), respectively. A major and stable QTL, QTkw-2D, was mapped to an 8.3 cM interval on chromosome arm 2DL. By saturation of polymorphic markers in its target region, QTkw-2D was confined to a 9.13 Mb physical interval using a secondary mapping population derived from a residually heterozygous line (F6:7). This interval was further narrowed to 2.52 Mb using QTkw-2D near-isogenic lines (NILs). NILsKN9204 had higher fresh and dry weights than NILsJ411 at various grain-filling stages. The TKW and KW of NILsKN9204 were much higher than those of NILsJ411 in field trials. By comparison of both DNA sequence and expression between KN9204 and J411, TraesCS2D02G460300.1 (TraesKN2D01HG49350) was assigned as a candidate gene for QTkw-2D. This was confirmed by RNA sequencing (RNA-seq) of QTkw-2D NILs. These results provide the basis of map-based cloning of QTkw-2D, and DNA markers linked to the candidate gene may be used in marker-assisted selection.

Abstract The heart primarily derives its energy through lipid oxidation. In cardiomyocytes, lipids are stored in lipid droplets (LDs) and are utilized in mitochondria, although the structural and functional connections between these two organelles remain largely unknown. In this study, visible evidence have presented indicating that a complex is formed at the mitochondria‐LD membrane contact (MLC) site, involving mitochondrion‐localized Mfn2 and LD‐localized Hsc70. This complex serves to tether mitochondria to LDs, facilitating the transfer of fatty acids (FAs) from LDs to mitochondria for β‐oxidation. Reduction of Mfn2 induced by lipid overload inhibits MLC, hinders FA transfer, and results in lipid accumulation. Restoring Mfn2 reinstates MLC, alleviating myocardial lipotoxicity under lipid overload conditions both in‐vivo and in‐vitro. Additionally, prolonged lipid overload induces Mfn2 degradation through the ubiquitin‐proteasome pathway, following Mfn2 acetylation at the K243 site. This leads to the transition from adaptive lipid utilization to maladaptive lipotoxicity. The experimental findings are supported by clinical data from patients with obesity and age‐matched non‐obese individuals. These translational results make a significant contribution to the molecular understanding of MLC in the heart, and offer new insights into its role in myocardial lipotoxicity.

BackgroundRetroperitoneal liposarcoma (RLS) is a rare but severe disease. Repeated postoperative recurrence with multiple tumors is a therapeutic dilemma. The clinical outcomes and survival predictors of recurrent RLS with multiple tumors remain to be explored.MethodsPatients with recurrent RLS were retrospectively analyzed. Univariate and multivariate analysis was performed to find independent prognostic factors that were correlated with Overall survival (OS) or progression-free survival (PFS). Factors significant in univariate analysis were further included into multivariate Cox proportional hazards regression model. The nomogram model was built to predict the survival status of patients. Variables that were significant in multivariable analysis were added to the internally validated nomogram models. The analysis of OS and PFS was performed by Kaplan–Meier analysis and log-rank test.ResultsA total of 113 recurrent RLS patients with multiple tumors were enrolled in the study. The 1-, 3-, and 5-years OS (PFS) rates were 70.7% (76.1%), 35.9% (76.1%), and 30.9% (76.1%), respectively. Univariate and multivariate analyses showed that number of surgeries, resection methods, tumor size, status of pathological differentiation, pathological subtypes, and recurrence patterns were important prognostic factors for OS or PFS (each p

Abstract Background Cardiac fibrosis is a leading cause of cardiac dysfunction in patients with diabetes. However, the underlying mechanisms of cardiac fibrosis remain unclear. This study aimed to investigate the role of the long non-coding RNA (LncRNA) Airn in the pathogenesis of cardiac fibrosis in diabetic cardiomyopathy (DCM) and its underlying mechanism. Methods Diabetes mellitus (DM) was induced in mice by streptozotocin injection. An intramyocardial adeno-associated virus (AAV) was used to manipulate Airn expression. The functional significance and underlying mechanisms in DCM fibrosis were investigated both in vitro and in vivo. Results Diabetic hearts showed a significant impairment in cardiac function, accompanied by obviously increased cardiac fibrosis. Interestingly, lncRNA Airn expression was significantly decreased in both diabetic hearts and high glucose (HG)-treated cardiac fibroblasts (CFs). AAV-mediated Airn reconstitution prevented cardiac fibrosis and the development of DCM, while Airn knockdown induced cardiac fibrosis phenotyping DCM. As in vitro, Airn reversed HG-induced fibroblast-myofibroblast transition, aberrant CFs proliferation and section of collagen I. In contrast, Airn knockdown mimicked a HG-induced CFs phenotype. Mechanistically, we identified that Airn exerts anti-fibrotic effects by directly binding to insulin-like growth factor 2 mRNA-binding protein 2 (IMP2) and further prevents its ubiquitination-dependent degradation. Moreover, we revealed that Airn/IMP2 protected p53 mRNA from degradation in m6A manner, leading to CF cell cycle arrest and reduced cardiac fibrosis. As a result, ablation of p53 blunted the inhibitory effects of Airn on fibroblast activation and cardiac fibrosis. Conclusions Our study demonstrated for the first time that Airn prevented the development of cardiac fibrosis in diabetic heart via IMP2-p53 axis in an m6A dependent manner. LncRNA Airn could be a promising therapeutic target for cardiac fibrosis in DCM. Graphical abstract

Abstract Sepsis is one of the most common causes of death, which is closely related to the uncontrolled systemic inflammation. Dysregulation of M1 macrophage polarization is the primary contributor to serious inflammation. In this study, it is revealed that the murine homologue of circRNA SCAR (steatohepatitis‐associated circRNA ATP5B regulator), denoted as circRNA mSCAR hereafter, decreases in the macrophages of septic mice, which correlates with the excessive M1 polarization. To restore circRNA mSCAR in mitochondria, exosomes encapsulated with circRNA mSCAR are further electroporated with poly‐D‐lysine‐graft‐triphenylphosphine (TPP‐PDL), and thus TPP‐PDL facilitates the bound circRNA delivered into mitochondria when the exosomes engulf by the recipient cells. In in vivo septic mouse model and in vitro cell model, it is shown that the exosome‐based mitochondria delivery system delivers circRNA mSCAR into mitochondria preferentially in the macrophages, favoring macrophage polarization toward M2 subtype. Accordingly, the systemic inflammation is attenuated by exosome‐based mitochondrial delivery of circRNA mSCAR, together with alleviated mortality. Collectively, the results uncover the critical role of circRNA mSCAR in sepsis, and provide a promising approach to attenuate sepsis via exosome‐based mitochondrial delivery of circRNA mSCAR.

IntroductionColon cancer is the 3rd most prevalent cancer worldwide, with more than 900,000 deaths annually. Chemotherapy, targeted treatment, and immunotherapeutic treatment are the three cornerstones of colon cancer treatment; however, the occurrence of immune therapy resistance is the most pressing problem to solve. Copper is a mineral nutrient that is both beneficial and potentially toxic to cells and is increasingly implicated in cell proliferation and death pathways. Cuproplasia is characterized by copper-dependent cell growth and proliferation. This term encompasses both neoplasia and hyperplasia and describes the primary and secondary effects of copper. The connection between copper and cancer has been noted for decades. However, the relationship between cuproplasia and colon cancer prognosis remains unclear.MethodIn this study, we applied bioinformatics approaches including WGCNA, GSEA and etc. to delineate cuproplasia characterization of colon cancer, set up a robust Cu_riskScore model based on cuproplasia-relevant genes and found its relevant biological processes use qRT-pCR to validate our results on our cohort.ResultThe Cu_riskScore is found to be relevant to Stage and MSI-H subtype, and some biological processes including MYOGENESIS and MYC TARGETS. The Cu_riskScore high and low groups also showed different immune infiltration pattern and genomic traits. Finally, the result of our cohort showed the Cu_riskScore gene RNF113A has a marked effect in predicting immunotherapy response.DiscussionIn conclusion, we identified a cuproplasia-related gene expression signature consisting of six genes and studied the landscape of the clinical and biological characterization of this model in Colon Cancer. Furthermore, the Cu_riskScore was demonstrated to be a robust prognostic indicator and predictive factor for the benefits of immunotherapy.

BackgroundImmune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.MethodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).ResultsA total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%–25.5%] and 44.0% (95% CI, 34.1%–53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%–94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%–66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%–99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].ConclusionThis systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.

BackgroundST-segment elevation myocardial infarction (STEMI) in young male patients accounts for a significant proportion of total heart attack events. Therefore, clinical awareness and screening for acute myocardial infarction (AMI) in asymptomatic patients at a young age is required. The gut microbiome is potentially involved in the pathogenesis of STEMI. The aim of the current study is to develop an early risk prediction model based on the gut microbiome and clinical parameters for this population.MethodsA total of 81 young males (age

Roots are the major organs for water and nutrient acquisition and substantially affect plant growth, development and reproduction. Improvements to root system architecture are highly important for the increased yield potential of bread wheat. QMrl-7B, a major stable quantitative trait locus (QTL) that controls maximum root length (MRL), essentially contributes to an improved root system in wheat. To further analyze the biological functions of QMrl-7B in root development, two sets of Triticum aestivum near-isogenic lines (NILs), one with superior QMrl-7B alleles from cultivar Kenong 9204 (KN9204) named NILKN9204 and another with inferior QMrl-7B alleles from cultivar Jing 411 (J411) named NILJ411, were subjected to transcriptomic analysis. Among all the mapped genes analyzed, 4871 genes were identified as being differentially expressed between the pairwise NILs under different nitrogen (N) conditions, with 3543 genes expressed under normal-nitrogen (NN) condition and 2689 genes expressed under low-nitrogen (LN) condition. These genes encode proteins that mainly include NO3− transporters, phytohormone signaling components and transcription factors (TFs), indicating the presence of a complex regulatory network involved in root determination. In addition, among the 13524 LN-induced differentially expressed genes (DEGs) detected in this study, 4308 and 2463 were specifically expressed in the NILKN9204 and NILJ411, respectively. These DEGs reflect different responses of the two sets of NILs to varying N supplies, which likely involve LN-induced root growth. These results explain the better-developed root system and increased root vitality conferred by the superior alleles of QMrl-7B and provide a deeper understanding of the genetic underpinnings of root traits, pointing to a valuable locus suitable for future breeding efforts for sustainable agriculture.

Abstract Background While hospital-acquired influenza A results in an additional cost burden and considerable mortality in patients, its risk factors are unknown. We aimed to describe the characteristics of patients vulnerable to hospital-acquired influenza A and to identify its risk factors to assist clinicians control hospital-acquired infections and reduce the burden of treatment. Methods A case-control study was conducted among hospitalized patients aged ≥18 years at a tertiary level teaching hospital during the 2018–2019 influenza A season. Patient data were retrieved from hospital-based electronic medical records. Hospital-acquired influenza A was defined as a case of influenza A diagnosed 7 days or more after admission, in a patient with no evidence of influenza A infection on admission. The controls without influenza A were selected among patients exposed to the same setting and time period. We identified risk factors using conditional logistic regression and described the characteristics of hospital-acquired influenza A by comparing the clinical data of infected patients and the controls. Results Of the 412 hospitalized patients with influenza A from all the departments in the study hospital, 93 (22.6%) cases were classified as hospital-acquired. The most common comorbidities of the 93 cases were hypertension (41.9%), coronary heart disease (21.5%), and cerebrovascular disease (20.4%). Before the onset of hospital-acquired influenza A, patients presented more lymphocytopenia (51.6% vs 35.5%, P = 0.027), hypoalbuminemia (78.5% vs 57.0%, P = 0.002), and pleural effusion (26.9% vs 9.7%, P = 0.002) than the matched controls. Infected patients also had longer hospital stays (18 days vs 14 days, P = 0.002), and higher mortality rates (10.8% vs 2.2%, P = 0.017) than the matched controls. Lymphocytopenia (odds ratio [OR]: 3.11; 95% confidence interval [CI]: 1.24–7.80; P = 0.016), hypoalbuminemia (OR: 2.24; 95% CI: 1.10–4.57; P = 0.027), and pleural effusion (OR: 3.09; 95% CI: 1.26–7.58; P = 0.014) were independently associated with hospital-acquired influenza A. Conclusions Lymphocytopenia, hypoalbuminemia and pleural effusion are independent risk factors that can help identify patients at high risk of hospital-acquired influenza A, which can extend hospital stay and is associated with a high mortality.

As one of the essential cereal crops, wheat provides 20% of the calories and proteins consumed by humans. Due to population expansion, dietary shift and climate change, it is challenging for wheat breeders to develop new varieties for meeting wheat production requirements. Marker-assisted selection (MAS) has distinct advantages over conventional selection in plant breeding, such as being time-saving, cost-effective and goal-oriented. This review makes attempts to give a description of different molecular markers: sequence tagged site (STS), simple sequence repeat (SSR), genotyping by sequencing (GBS), single nucleotide polymorphism (SNP) arrays, exome capture, Kompetitive Allele Specific PCR (KASP), cleaved amplified polymorphic sequence (CAPS), semi-thermal asymmetric reverse PCR (STARP) and genotyping by target sequencing (GBTS). We also summarize some quantitative trait loci (QTL)/genes as well as their linked markers, which are potentially useful in MAS. This paper provides updated information on some markers linked to critical traits and their potential applications in wheat breeding programs.

Accurate and reliable perception systems are essential for autonomous driving and robotics. To achieve this, 3D object detection with multi-sensors is necessary. Existing 3D detectors have significantly improved accuracy by adopting a two-stage paradigm that relies solely on LiDAR point clouds for 3D proposal refinement. However, the sparsity of point clouds, particularly for faraway points, makes it difficult for the LiDAR-only refinement module to recognize and locate objects accurately. To address this issue, we propose a novel multi-modality two-stage approach called FusionRCNN. This approach effectively and efficiently fuses point clouds and camera images in the Regions of Interest (RoI). The FusionRCNN adaptively integrates both sparse geometry information from LiDAR and dense texture information from the camera in a unified attention mechanism. Specifically, FusionRCNN first utilizes RoIPooling to obtain an image set with a unified size and gets the point set by sampling raw points within proposals in the RoI extraction step. Then, it leverages an intra-modality self-attention to enhance the domain-specific features, followed by a well-designed cross-attention to fuse the information from two modalities. FusionRCNN is fundamentally plug-and-play and supports different one-stage methods with almost no architectural changes. Extensive experiments on KITTI and Waymo benchmarks demonstrate that our method significantly boosts the performances of popular detectors. Remarkably, FusionRCNN improves the strong SECOND baseline by 6.14% mAP on Waymo and outperforms competing two-stage approaches.

The motivation of this research is to review all methods used in data compression of collected data in monitoring the condition of equipment based on the framework of edge computing. Since a large amount of signal data is collected when monitoring conditions of mechanical equipment, namely, signals of running machines are continuously transmitted to be crunched, compressed data should be handled effectively. However, this process occupies resources since data transmission requires the allocation of a large capacity. To resolve this problem, this article examines the monitoring conditions of equipment based on edge computing. First, the signal is pre-processed by edge computing, so that the fault characteristics can be identified quickly. Second, signals with difficult-to-identify fault characteristics need to be compressed to save transmission resources. Then, different types of signal data collected in mechanical equipment conditions are compressed by various compression methods and uploaded to the cloud. Finally, the cloud platform, which has powerful processing capability, is processed to improve the volume of the data transmission. By examining and analyzing the monitoring conditions and signal compression methods of mechanical equipment, the future development trend is elaborated to provide references and ideas for the contemporary research of data monitoring and data compression algorithms. Consequently, the manuscript presents different compression methods in detail and clarifies the data compression methods used for the signal compression of equipment based on edge computing.

Bacterial type IV secretion systems (T4SSs) play central roles in antibiotic resistance spread and virulence. By cryo-electron tomography (CryoET), we solved the structure of the plasmid pKM101-encoded T4SS in the native context of the bacterial cell envelope.

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

Summary: Pseudomonas species are a large class of gram-negative bacteria that exhibit significant biomedical, ecological, and industrial importance. Despite the extensive research and wide applications, genetic manipulation in Pseudomonas species, in particular in the major human pathogen Pseudomonas aeruginosa, remains a laborious endeavor. Here we report the development of a genome editing method pCasPA/pACRISPR by harnessing the CRISPR/Cas9 and the phage λ-Red recombination systems. The method allows for efficient and scarless genetic manipulation in P. aeruginosa. By engineering the fusion of the cytidine deaminase APOBEC1 and the Cas9 nickase, we further develop a base editing system pnCasPA-BEC, which enables highly efficient gene inactivation and point mutations in a variety of Pseudomonas species, such as P. aeruginosa, Pseudomonas putida, Pseudomonas fluorescens, and Pseudomonas syringae. Application of the two genome editing methods will dramatically accelerate a wide variety of investigations, such as bacterial physiology study, drug target exploration, and metabolic engineering. : Genetics; Microbial Genetics; Biotechnology; Genetic Engineering Subject Areas: Genetics, Microbial Genetics, Biotechnology, Genetic Engineering

ABSTRACT Helicobacter pylori colonizes about half of humans worldwide, and its presence in the gastric mucosa is associated with an increased risk of gastric adenocarcinoma, gastric lymphoma, and peptic ulcer disease. H. pylori strains carrying the cag pathogenicity island (cagPAI) are associated with increased risk of disease progression. The cagPAI encodes the Cag type IV secretion system (CagT4SS), which delivers the CagA oncoprotein and other effector molecules into human gastric epithelial cells. We visualized structures of native and mutant CagT4SS machines on the H. pylori cell envelope by cryoelectron tomography. Individual H. pylori cells contain multiple CagT4SS nanomachines, each composed of a wheel-shaped outer membrane complex (OMC) with 14-fold symmetry and an inner membrane complex (IMC) with 6-fold symmetry. CagX, CagY, and CagM are required for assembly of the OMC, whereas strains lacking Cag3 and CagT produce outer membrane complexes lacking peripheral components. The IMC, which has never been visualized in detail, is configured as six tiers in cross-section view and three concentric rings surrounding a central channel in end-on view. The IMC contains three T4SS ATPases: (i) VirB4-like CagE, arranged as a hexamer of dimers at the channel entrance; (ii) a hexamer of VirB11-like Cagα, docked at the base of the CagE hexamer; and (iii) VirD4-like Cagβ and other unspecified Cag subunits, associated with the stacked CagE/Cagα complex and forming the outermost rings. The CagT4SS and recently solved Legionella pneumophila Dot/Icm system comprise new structural prototypes for the T4SS superfamily. IMPORTANCE Bacterial type IV secretion systems (T4SSs) have been phylogenetically grouped into two subfamilies. The T4ASSs, represented by the Agrobacterium tumefaciens VirB/VirD4T4SS, include “minimized” machines assembled from 12 VirB- and VirD4-like subunits and compositionally larger systems such as the Helicobacter pylori CagT4SS. T4BSSs encompass systems closely related in subunit composition to the Legionella pneumophila Dot/IcmT4SS. Here, we present structures of native and mutant H. pylori Cag machines determined by in situ cryoelectron tomography. We identify distinct outer and inner membrane complexes and, for the first time, visualize structural contributions of all three “signature” ATPases of T4SSs at the cytoplasmic entrance of the translocation channel. Despite their evolutionary divergence, the CagT4SS aligns structurally much more closely to the Dot/IcmT4SS than an available VirB/VirD4 subcomplex. Our findings highlight the diversity of T4SSs and suggest a structural classification scheme in which T4SSs are grouped as minimized VirB/VirD4-like or larger Cag-like and Dot/Icm-like systems.

Genetic improvement of root systems is an efficient approach to improve yield potential and nitrogen use efficiency (NUE) of crops. QMrl-7B was a major stable quantitative trait locus (QTL) controlling the maximum root length in wheat (Triticum aestivum L). Two types of near isogenic lines (A-NILs with superior and B-NILs with inferior alleles) were used to specify the effects of QMrl-7B on root, grain output and nitrogen-related traits under both low nitrogen (LN) and high nitrogen (HN) environments. Trials in two consecutive growing seasons showed that the root traits, including root length (RL), root area (RA) and root dry weight (RDW), of the A-NILs were higher than those of the B-NILs at seedling stage (SS) before winter, jointing stage (JS), 10 days post anthesis (PA10) and maturity (MS), respectively. Under the LN environment, in particular, all the root traits showed significant differences between the two types of NILs (p < 0.05). In contrast, there were no critical differences in aerial biomass and aerial N accumulation (ANA) between the two types of NILs at SS and JS stages. At PA10 stage, the aerial biomass and ANA of the A-NILs were significantly higher than those of the B-NILs under both LN and HN environments (p < 0.05). At MS stage, the A-NILs also exhibited significantly higher thousand-grain weight (TGW), plot grain yield, harvest index (HI), grain N accumulation (GNA), nitrogen harvest index (NHI) and nitrogen partial factor productivity (NPFP) than the B-NILs under the corresponding environments (p < 0.05). In summary, the QMrl-7B A-NILs manifested larger root systems compared to the B-NILs which is favorable to N uptake and accumulation, and eventually enhanced grain production. This research provides valuable information for genetic improvement of root traits and breeding elite wheat varieties with high yield potential and NPFP.

High-density genetic linkage maps are essential for precise mapping quantitative trait loci (QTL) in wheat (Triticum aestivum L.). In this study, a high-density genetic linkage map consisted of 6312 SNP and SSR markers was developed to identify QTL controlling kernel size and weight, based on a recombinant inbred line (RIL) population derived from the cross of Shixin828 and Kenong2007. Seventy-eight putative QTL for kernel length (KL), kernel width (KW), kernel diameter ratio (KDR), and thousand kernel weight (TKW) were detected over eight environments by inclusive composite interval mapping (ICIM). Of these, six stable QTL were identified in more than four environments, including two for KL (qKL-2D and qKL-6B.2), one for KW (qKW-2D.1), one for KDR (qKDR-2D.1) and two for TKW (qTKW-5A and qTKW-5B.2). Unconditional and multivariable conditional QTL mapping for TKW with respect to TKW component (TKWC) revealed that kernel dimensions played an important role in regulating the kernel weight. Seven QTL-rich genetic regions including seventeen QTL were found on chromosomes 1A (2), 2D, 3A, 4B and 5B (2) exhibiting pleiotropic effects. In particular, clusters on chromosomes 2D and 5B possessing significant QTL for kernel-related traits were highlighted. Markers tightly linked to these QTL or clusters will eventually facilitate further studies for fine mapping, candidate gene discovery and marker-assisted selection (MAS) in wheat breeding.

Background: Asthma is a complex and heterogeneous chronic inflammatory disorder which is characterized by airway remodeling and airway inflammation, including goblet cell and airway smooth muscle cell hyperplasia, mucus hypersecretion and eosinophils infiltration. Epidermal growth factor receptor (EGFR) plays an important role in goblet cell hyperplasia and mucus hypersecretion. We aimed to investigate the effects of gefitinib, an EGFR inhibitor, on ovalbumin (OVA)-induced airway remodeling and inflammation of a mouse model of asthma. Methods: Pathological changes of OVA sensitization of BALB/c mice were measured by H&E and PAS staining; pEGFR, Bcl-2 and Bax expression was measured by western blot; ELISA was used to measure the level of muc5ac, IL-13 and IFN-γ; TUNEL staining was used to detect goblet cell apoptosis. Results: At the present study, H&E and PAS staining showed that mice pretreated with gefinitib developed fewer pathological changes compared with asthmatic mice and gefinitib treatment asthmatic mice, such as a remarkable reduction in airway inflammation, goblet cell and airway smooth muscle cell hyperplasia. Chronic gefitinib treatment or short-term gefitinib treatment significant down-regulate the expression of pEGFR compared with asthma group. Also, chronic gefitinib treatment markedly decreased the levels of muc5ac and IL-13 in BALF, whereas the level of IFN-γ did not change obviously. TUNEL staining showed that the goblet cell apoptosis rate was much higher in the short-term gefinitib treatment group compared with the asthma and chronic gefitinib treatment group which was accompanied by a decrease in Bcl-2 levels and an increase in Bax expression in goblet cells. Conclusion: In summary, our results suggested that gefinitib may have a potential role in airway remodeling and inflammation, and may be an effective pharmacotherapy for asthma.

Gastric cancer remains the main cause of cancer death allaround the world, and upregulated activation of thenonreceptor tyrosine kinase c-SRC (SRC) is a key player in thedevelopment. In this study, we found that expression of Src isalso increased in clinical gastric cancer samples, with theprotein level increased more significantly than that at the RNAlevel. Further study revealed that miR34a and miR203, twotumor suppressive miRNAs, inversely correlate with theexpression of Src. Restoration of miR34a and miR203 decreasedSrc expression in gastric cancer cell lines, which in turninhibited cell growth and cell migration. In summary, ourstudy here revealed that posttranscriptional regulation of Srccontributes to the deregulated cell growth and metastasis ingastric cancer, and targeting Src by miR34a or miR203 mimicswould be a promising strategy in therapy. [BMB Reports 2013;46(6): 316-321]

Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), a wild relative of common wheat, possesses many potentially valuable traits that can be transferred to common wheat through breeding programs. The wheat-A. cristatum disomic addition and translocation lines can be used as bridge materials to introduce alien chromosomal segments to wheat. Wheat-A. cristatum 2P disomic addition line II-9-3 was highly resistant to powdery mildew and leaf rust, which was reported in our previous study. However, some translocation lines induced from II-9-3 have not been reported. In this study, some translocation lines were induced from II-9-3 by 60Co-γ irradiation and gametocidal chromosome 2C and then identified by cytological methods. Forty-nine wheat-A. cristatum translocation lines were obtained and various translcoation types were identified by GISH (genomic in situ hybridization), such as whole-arm, segmental and intercalary translocations. Dual-color FISH (fluorescent in situ hybridization) was applied to identify the wheat chromosomes involved in the translocations, and the results showed that A. cristatum 2P chromosome segments were translocated to the different wheat chromosomes, including 1A, 2A, 3A, 4A, 5A, 6A, 7A, 3B, 5B, 7B, 1D, 4D and 6D. Many different types of wheat-A. cristatum alien translocation lines would be valuable for not only identifying and cloning A. cristatum 2P-related genes and understanding the genetics and breeding effects of the translocation between A. cristatum chromosome 2P and wheat chromosomes, but also providing new germplasm resources for the wheat genetic improvement.

Agropyron cristatum (L.) Gaertn. (2n = 4x = 28, PPPP) not only is cultivated as pasture fodder but also could provide many desirable genes for wheat improvement. It is critical to obtain common wheat-A. cristatum alien disomic addition lines to locate the desired genes on the P genome chromosomes. Comparative analysis of the homoeologous relationships between the P genome chromosome and wheat genome chromosomes is a key step in transferring different desirable genes into common wheat and producing the desired alien translocation line while compensating for the loss of wheat chromatin. In this study, six common wheat-A. cristatum disomic addition lines were produced and analyzed by phenotypic examination, genomic in situ hybridization (GISH), SSR markers from the ABD genomes and STS markers from the P genome. Comparative maps, six in total, were generated and demonstrated that all six addition lines belonged to homoeologous group 6. However, chromosome 6P had undergone obvious rearrangements in different addition lines compared with the wheat chromosome, indicating that to obtain a genetic compensating alien translocation line, one should recombine alien chromosomal regions with homoeologous wheat chromosomes. Indeed, these addition lines were classified into four types based on the comparative mapping: 6PI, 6PII, 6PIII, and 6PIV. The different types of chromosome 6P possessed different desirable genes. For example, the 6PI type, containing three addition lines, carried genes conferring high numbers of kernels per spike and resistance to powdery mildew, important traits for wheat improvement. These results may prove valuable for promoting the development of conventional chromosome engineering techniques toward molecular chromosome engineering.

BACKGROUND:Asthma is a complex and heterogeneous chronic inflammatory disorder that is associated with mucous cell metaplasia and mucus hypersecretion. Functional genomic analysis indicates that mucous cell metaplasia and mucus hypersecretion depend on members of the calcium-activated chloride channel (CLCA) gene family. It has been reported that the inhibition of CLCAs could relieve the symptoms of asthma. Thus, the mCLCA3 antibody may be a promising strategy to treat allergic diseases such as asthma. METHODS:We constructed asthmatic mouse models of OVA-induced chronic airway inflammatory disorder to study the function of the mCLCA3 antibody. Airway inflammation was measured by HE staining; goblet cell hyperplasia and mucus hypersecretion were detected by PAS staining; muc5ac, IL-13, IFN-γ levels in bronchoalveolar lavage fluid (BALF) were examined by ELISA; Goblet cell apoptosis was measured by TUNEL assay and alcian blue staining; mCLCA3, Bcl-2 and Bax expression were detected by RT-PCR, Western blotting and immunohistochemical analysis. RESULTS:In our study, mice treated with mCLCA3 antibody developed fewer pathological changes compared with control mice and asthmatic mice, including a remarkable reduction in airway inflammation, the number of goblet cells and mCLCA3 expression in lung tissue. The levels of muc5ac and IL-13 were significantly reduced in BALF. We also found that the rate of goblet cell apoptosis was increased after treatment with mCLCA3 antibody, which was accompanied by an increase in Bax levels and a decrease in Bcl-2 expression in goblet cells. CONCLUSIONS:Taken together, our results indicate that mCLCA3 antibody may have the potential as an effective pharmacotherapy for asthma.

The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome) carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by (60)Co-γirradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes.

Background: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). Method: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG (n =164) or TG (n=203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. Results: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P> 0.05). The TG group had a higher total number of lymph nodes retrieved (P<0.001) and longer operative time (P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) (P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group (P= 0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively (P= 0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. Conclusion: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option. [ABSTRACT FROM AUTHOR]