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Abstract Background Current cardiovascular prevention strategies are based on studies that seldom include valvular heart disease (VHD). The role of modifiable lifestyle factors on VHD progression and life expectancy among the elderly with different socioeconomic statuses (SES) remains unknown. Methods This cohort study included 164,775 UK Biobank participants aged 60 years and older. Lifestyle was determined using a five-factor scoring system covering smoking status, obesity, physical activity, diet, and sleep patterns. Based on this score, participants were then classified into “poor,” “moderate,” or “ideal” lifestyle groups. SES was classified as high or low based on the Townsend Deprivation Index. The association of lifestyle with major VHD progression was evaluated using a multistate mode. The life table method was employed to determine life expectancy with VHD and without VHD. Results The UK Biobank documented 5132 incident VHD cases with a mean follow-up of 12.3 years and 1418 deaths following VHD with a mean follow-up of 6.0 years. Compared to those with a poor lifestyle, women and men followed an ideal lifestyle had lower hazard ratios for incident VHD (0.66 with 95% CI, 0.59–0.73 for women and 0.77 with 95% CI, 0.71–0.83 for men) and for post-VHD mortality (0.58 for women, 95% CI 0.46–0.74 and 0.62 for men, 95% CI 0.54–0.73). When lifestyle and SES were combined, the lower risk of incident VHD and mortality were observed among participants with an ideal lifestyle and high SES compared to participants with an unhealthy lifestyle and low SES. There was no significant interaction between lifestyle and SES in their correlation with the incidence and subsequent mortality of VHD. Among low SES populations, 60-year-old women and men with VHD who followed ideal lifestyles lived 4.2 years (95% CI, 3.8–4.7) and 5.1 years (95% CI, 4.5–5.6) longer, respectively, compared to those with poor lifestyles. In contrast, the life expectancy gain for those without VHD was 4.4 years (95% CI, 4.0–4.8) for women and 5.3 years (95% CI, 4.8–5.7) for men when adhering to an ideal lifestyle versus a poor one. Conclusions Adopting a healthier lifestyle can significantly slow down the progression from free of VHD to incident VHD and further to death and increase life expectancy for both individuals with and without VHD within diverse socioeconomic elderly populations.

Abstract Chronic pain after lung transplantation (LTx) can substantially reduce quality of life (QoL), yet current consensus guidelines say little about how to prevent or manage it. Research on pain after LTx has tended to focus on acute rather than chronic pain, and it has not extensively examined the factors associated with onset or resolution of chronic pain, which differ from factors influencing chronic pain after general thoracic surgery. This narrative review explores what is known about the epidemiology and risk factors of chronic pain after LTx, as well as effective ways to treat or prevent it. The review identifies key questions and issues that should be the focus of future research.

Abstract Background Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. Results We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation “blacklist” in the BED region to reduce errors in downstream analyses. Conclusions We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

Abstract Background People with schizophrenia often face challenges such as lower psychological resilience, reduced self-worth, and increased social stigma, hindering their recovery. Mindfulness-Based Cognitive Therapy (MBCT) has shown promise in boosting psychological resilience and self-esteem while diminishing stigma. However, MBCT demands professional involvement and substantial expenses, adding to the workload of professionals and the financial strain on patients. Mixed-mode Mindfulness-Based Cognitive Therapy (M-MBCT) integrates both “face-to-face” and “self-help” approaches to minimize staff effort and costs. This study aims to assess the impact of M-MBCT on the psychological resilience, self-esteem, and stigma in schizophrenia patients. Methods This randomized, controlled, parallel-group, assessor-blinded clinical trial enrolled 174 inpatients with schizophrenia. Participants were randomly assigned to either the experimental or control group. The experimental group underwent an 8-week M-MBCT intervention, while the control group received standard treatment. Data collection employed the Connor-Davidson Resilience Scale (CD-RISC), Internalized Stigma of Mental Illness Scale (ISMI), and Rosenberg Self-Esteem Scale (RSES) before and after the intervention. Post-intervention, significant differences in ISMI, CD-RISC, and RSES scores were observed between the experimental and control groups. Results In the experimental group, ISMI scores notably decreased, while CD-RISC and RSES scores significantly increased (P

Osteoarthritis (OA) is a common chronic inflammatory disorder. Effective remodeling of inflammatory microenvironment in the joint is a promising strategy to prevent OA. However, current drugs remain unsatisfactory due to a lack of targeted and effective ways for relieving inflammatory conditions in OA joints. Bortezomib (BTZ), a proteasome inhibitor, could effectively inhibit proinflammatory cytokines but with poor accumulation in the inflammatory tissues. To overcome the shortcomings of BTZ delivery and to improve the efficacy of OA therapy, herein, we designed a novel nanomedicine (denoted as BTZ@PTK) by the co-assembly of BTZ and an amphiphilic copolymer (denoted as PTK) with ROS-cleaved thioketal (TK) linkages. The TK units in BTZ@PTK are first cleaved by the excessive ROS at OA sites, and then triggered the controlled release of BTZ, resulting in the accurate delivery and the inflammatory microenvironment remodeling. Accordingly, BTZ@PTK suppressed ROS generation and proinflammatory cytokines while promoting M1 macrophage apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 macrophages or LPS/IFN-γ-treated primary macrophages, which leads to a better effect than BTZ. In OA mice, BTZ@PTK passively accumulates into inflamed joints to attenuate pain sensitivity and gait abnormality. Importantly, BTZ@PTK treatment successfully ameliorates synovitis with the reduction of synovial hyperplasia and synovitis scores by suppressing M1 macrophage polarization and promoting M1 macrophage apoptosis in the synovium, thereby delaying cartilage damage. Collectively, BTZ@PTK can effectively modulate inflammatory microenvironment for OA recession by activating M1 macrophage apoptosis and inhibiting M1macrophage-mediated inflammatory response.

ABSTRACTRabbits produce robust antibody responses and have unique features in their antibody repertoire that make them an attractive alternative to rodents for in vivo discovery. However, the frequent occurrence of a non-canonical disulfide bond between complementarity-determining region (CDR) H1 (C35a) and CDRH2 (C50) is often seen as a liability for therapeutic antibody development, despite limited reports of its effect on antibody binding, function, and stability. Here, we describe the discovery and humanization of a human-mouse cross-reactive anti-programmed cell death (PD-1) monoclonal rabbit antibody, termed h1340.CC, which possesses this non-canonical disulfide bond. Initial removal of the non-canonical disulfide resulted in a loss of PD-1 affinity and cross-reactivity, which led us to explore protein engineering approaches to recover these. First, guided by the sequence of a related clone and the crystal structure of h1340.CC in complex with PD-1, we generated variant h1340.SA.LV with a potency and cross-reactivity similar to h1340.CC, but only partially recovered affinity. Side-by-side developability assessment of both h1340.CC and h1340.SA.LV indicate that they possess similar, favorable properties. Next, and prompted by recent developments in machine learning (ML)-guided protein engineering, we used an unbiased ML- and structure-guided approach to rapidly and efficiently generate a different variant with recovered affinity. Our case study thus indicates that, while the non-canonical inter-CDR disulfide bond found in rabbit antibodies does not necessarily constitute an obstacle to therapeutic antibody development, combining structure- and ML-guided approaches can provide a fast and efficient way to improve antibody properties and remove potential liabilities.

Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC. Neoadjuvant treatment for HCC has become a possibility—findings from the IMbrave 050 trial indicated that ICIs offer the benefit of recurrence-free survival for high-risk HCC patients post-resection or local ablation. However, only a small fraction of individuals benefit from systemic therapy. Consequently, there is an urgent need to identify predictive biomarkers for treatment response and outcome assessment. This study reviewed the historical progression of systemic therapy for HCC, highlighting notable therapeutic advancements. This study examined the development of systemic therapies involving conventional drugs and clinical trials utilized in HCC treatment, as well as potential predictive biomarkers for advanced and/or locally advanced HCC. Various studies have revealed potential biomarkers in the context of HCC treatment. These include the association of dendritic cells (DCs) with a favorable response to neoadjuvant therapy, the presence of enriched T effector cells and tertiary lymphoid structures, the identification of CD138+ plasma cells, and distinct spatial arrangements of B cells in close proximity to T cells among responders with locally advanced HCC receiving neoadjuvant cabozantinib and nivolumab treatment. Furthermore, pathological response has been associated with intratumoral cellular triads consisting of progenitor CD8+ T cells and CXCL13+ CD4+ T helper cells surrounding mature DCs in patients receiving neoadjuvant cemiplimab for resectable HCC. Despite no widely recognized predictive biomarkers for HCC individualized treatment, we believe neoadjuvant trials hold the most promise in identifying and validating them. This is because they can collect multiple samples from resectable HCC patients across stages, especially with multi-omics, bridging preclinical and clinical gaps.

Abstract The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an attractive therapeutic approach, but the molecular basis for chemokine-mediated activation and antibody-mediated inhibition of CCR8 are not fully elucidated. Here, we obtain an antagonist antibody against human CCR8 and determine structures of CCR8 in complex with either the antibody or the endogenous agonist ligand CCL1. Our studies reveal characteristic antibody features allowing recognition of the CCR8 extracellular loops and CCL1-CCR8 interaction modes that are distinct from other chemokine receptor - ligand pairs. Informed by these structural insights, we demonstrate that CCL1 follows a two-step, two-site binding sequence to CCR8 and that antibody-mediated inhibition of CCL1 signaling can occur by preventing the second binding event. Together, our results provide a detailed structural and mechanistic framework of CCR8 activation and inhibition that expands our molecular understanding of chemokine - receptor interactions and offers insight into the development of therapeutic antibodies targeting chemokine GPCRs.

Entity–relationship extraction plays a pivotal role in the construction of domain knowledge graphs. For the aquatic disease domain, however, this relationship extraction is a formidable task because of overlapping relationships, data specialization, limited feature fusion, and imbalanced data samples, which significantly weaken the extraction’s performance. To tackle these challenges, this study leverages published books and aquatic disease websites as data sources to compile a text corpus, establish datasets, and then propose the Fd-CasBGRel model specifically tailored to the aquatic disease domain. The model uses the Casrel cascading binary tagging framework to address relationship overlap; utilizes task fine-tuning for better performance on aquatic disease data; trains on specialized aquatic disease corpora to improve adaptability; and integrates the BRC feature fusion module—which incorporates self-attention mechanisms, BiLSTM, relative position encoding, and conditional layer normalization—to leverage entity position and context for enhanced fusion. Further, it replaces the traditional cross-entropy loss function with the GHM loss function to mitigate category imbalance issues. The experimental results indicate that the F1 score of the Fd-CasBGRel on the aquatic disease dataset reached 84.71%, significantly outperforming several benchmark models. This model effectively addresses the challenges of ternary extraction’s low performance caused by high data specialization, insufficient feature integration, and data imbalances. The model achieved the highest F1 score of 86.52% on the overlapping relationship category dataset, demonstrating its robust capability in extracting overlapping data. Furthermore, We also conducted comparative experiments on the publicly available dataset WebNLG, and the model in this paper obtained the best performance metrics compared to the rest of the comparative models, indicating that the model has good generalization ability.

PurposePolypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment.MethodsWe conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response.ResultsThe results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group.ConclusionsOur study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.

As advanced functional materials, piezoelectric ceramics are widely used in various fields, including the medical, aviation, and military industries. With the advancement of science and technology, the piezoelectric ceramics needed in special fields have become more intelligent, diverse and lightweight. The shapes and structures of piezoelectric ceramics are becoming more complex. Traditional piezoelectric ceramic preparation technology has been unable to meet the high-speed and complex production demands of various industries. Considering this situation, 3D printing technology has attracted much attention in the field of piezoelectric ceramics. In this paper, the applications of several main 3D printing techniques in the field of piezoelectric ceramics are mainly introduced, and their development statuses, process characteristics and achievements are summarized. The advantages and disadvantages of each printing technique are summarized and compared. The challenges and possible future trends of 3D printing when manufacturing piezoelectric ceramics are summarized and proposed.

Hemostatic disturbances after cardiac surgery can lead to excessive postoperative bleeding. Thromboelastography (TEG) was employed to evaluate perioperative coagulative alterations in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), investigating the correlation between factors concomitant with cardiac surgery and modifications in coagulation. Coagulation index as determined by TEG correlated significantly with postoperative bleeding at 24-72 h after cardiac surgery ( P

This article presents a new method for model-free verification of a general class of control systems with unknown nonlinear dynamics, where the state space has both a continuum-based and a discrete component. Specifically, we focus on finding what choices of initial states or parameters maximize a given probabilistic objective function over all choices of initial states or parameters from such hybrid state space, without having exact knowledge of the system dynamics. We introduce the notion of set initialized Markov chains to represent such systems. Our method utilizes generalized techniques from multi-armed bandit theory on the continuum, in an attempt to make an efficient use of the available sampling budget. We introduce a new algorithm called the Hybrid Hierarchical Optimistic Optimization (HyHOO) algorithm, which is designed to address the problem outlined in this paper. The algorithm combines elements of the existing Hierarchical Optimistic Optimization (HOO) bandit algorithm with carefully chosen parameters to create a fresh perspective on the problem. By viewing the problem as a multi-armed bandit problem, we are able to provide theoretical regret bounds on sample efficiency of our tool, $\mathsf{HyHooVer}$. This is achieved by making assumptions about the smoothness of the underlying system. The results of experiments in formal verification and parameter synthesis of variety of scenarios, indicate that the proposed method is effective and efficient when applied to realistic-sized problems and it performs well compared to other methods, specifically PlasmaLab, BoTorch, and the baseline HOO algorithm. Specifically, it demonstrates better efficiency when employed on models with large state space and when the objective function has sharp slopes in comparison with other tools.

Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overexpression or underexpression of certain HOX genes is linked to the occurrence and prognosis of gliomas. This aberrant expression may contribute to the dysregulation of important pathological processes such as cell proliferation, differentiation, and metastasis. This study aimed to propose a novel HOX-related signature to predict patients’ prognosis and immune infiltrate characteristics in PGs.Methods: The data of PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes (HFGs), prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. The HFGs were utilized to identify heterogeneous subtypes using consensus clustering. Then random forest-supervised classification algorithm and nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training set. Finally, the signature was validated in an internal testing set and an external independent cohort.Results: Firstly, we identified HFGs significantly differentially expressed in PGs compared to normal tissues. The individuals with PGs were then divided into two heterogeneous subtypes (HOX-SI and HOX-SII) based on HFGs expression profiles. HOX-SII showed higher total mutation counts, lower immune infiltration, and worse prognosis than HOX-SI. Then, we constructed a HOX-related gene signature (including HOXA6, HOXC4, HOXC5, HOXC6, and HOXA-AS3) based on the cluster for subtype prediction utilizing random forest supervised classification and nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis.Conclusion: Our study provides a novel method for the prognosis classification of PGs. The findings also suggest that the HOX-related signature is a new biomarker for the diagnosis and prognosis of patients with PGs, allowing for more accurate survival prediction.

Objective To develop a nomogram for the prediction of tracheostomy in patients with traumatic cervical spinal cord injury (TCSCI). Methods A total of 689 TCSCI patients were included in our study. First, the variable selection was performed using between-group comparisons and LASSO regression analysis. Second, a multivariate logistic regression analysis (MLRA) with a step-by-step method was performed. A nomogram model was developed based on the MLRA. Finally, the model was validated on the training set and validation set. Results The nomogram prediction model incorporated 5 predictors, including smoking history, dislocation, thoracic injury, American Spinal Injury Association (ASIA) grade, and neurological level of injury (NLI). The area under curve in the training group and in the validation group were 0.883 and 0.909, respectively. The Hosmer-Lemeshow test result was p = 0.153. From the decision curve analysis curve, the model performed well and was feasible to make beneficial clinical decisions. Conclusion The nomogram combining dislocation, thoracic injury, ASIA grade A, NLI, and smoking history was validated as a reliable model for the prediction of tracheostomy.

Abstract Background Early prediction of tracheostomy in traumatic cervical spinal cord injury (TCSCI) patients is often difficult. This study aims to clarify the association between shoulder abductor strength (SAS) and tracheostomy in patients with TCSCI. Methods We retrospectively analyzed 513 TCSCI patients who were treated in our hospital. All patients were divided into a tracheostomy group and a non-tracheostomy group. The SAS was assessed using the Medical Research Council (MRC) Scale for Muscle Strength grading. Potential predictors were assessed for their association with tracheostomy in patients. A nomogram was developed based on multivariable logistic regression analysis (MLRA) to visualize the predictive ability of the SAS. Validation of the nomogram was performed to judge whether the nomogram was reliable for visual analysis of the SAS. Receiver operating characteristics curve, specificity, and sensitivity were also performed to assess the predictive ability of the SAS. Results The proportion of patients with the SAS grade 0–2 was significantly higher in the tracheostomy group than in the non-tracheostomy group (88.1% vs. 54.8%, p = 0.001). The SAS grade 0–2 was identified as a significant predictor of the tracheostomy (OR: 4.505; 95% CI: 2.080–9.758; p = 0.001). Points corresponding to both the SAS grade 0–2 and the neurological level of injury at C2-C4 were between 60 and 70 in the nomogram. The area under the curve for the SAS grade 0–2 was 0.692. The sensitivity of SAS grade 0–2 was 0.239. The specificity of SAS grade 0–2 was 0.951. Conclusions SAS is a novel predictor of tracheostomy in patients after TCSCI. The SAS grade 0–2 had a good predictive ability of tracheostomy.

This study aimed to explore the underlying reasons for the differences in egg production in Chinese Chahua chickens. The Chahua chicken population was divided into two groups, namely a high-yielding group (H) and a low-yielding group (L). The egg-laying performance, ovarian morphology, histological characteristics, and serum hormone concentrations in the H and L groups were analysed. The results revealed that there were significant differences (P < 0.01) between the two groups for the age at the first egg and the number of eggs. The H group showed significantly more (P < 0.01) hierarchical follicles and small yellow follicles than the L group. While several secondary follicles and primary follicles were observed in the ovaries of the H group, only a few secondary follicles were observed in the ovaries of the L group. The serum concentrations of the follicle-stimulating hormone, the luteinising hormone, and oestradiol were significantly higher in the H group compared to that in the L group (P < 0.01). Next, we sequenced and analysed the ovarian expression profiles in the two groups using RNA-seq. The transcriptome sequencing revealed 875 differentially expressed genes (DEGs) between the H and L groups. Of the 875 DEGs, 624 were up-regulated, and 251 were down-regulated. The DEGs were mapped to 31 Gene Ontology (GO) terms and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for the ovarian tissue. The KEGG pathway analysis mainly revealed the involvement of focal adhesion, cytokine-cytokine receptor interaction, and the TGF-beta signalling pathway, while the GO analysis mainly showed involvement of the hormonal activity, extracellular matrix, and extracellular region. Our results showed that understanding the differences in the gene expressions between the ovarian tissues of high- and low-yielding hens may provide a useful reference for improving the egg-laying performance in Chahua chickens.

A high-throughput cell-based platform is developed for systematic investigation of receptor-ligand interactions and applied to identify cell-surface proteins that bind to SARS CoV-2.

BackgroundObservational studies have suggested an association between obesity and iron deficiency anemia, but such studies are susceptible to reverse causation and residual confounding. Here we used Mendelian randomization to assess whether the association might be causal.MethodsData on single-nucleotide polymorphisms that might be associated with various anthropometric indicators of obesity were extracted as instrumental variables from genome-wide association studies in the UK Biobank. Data on genetic variants in iron deficiency anemia were extracted from a genome-wide association study dataset within the Biobank. Heterogeneity in the data was assessed using inverse variance-weighted regression, Mendelian randomization Egger regression, and Cochran's Q statistic. Potential causality was assessed using inverse variance-weighted, Mendelian randomization Egger, weighted median, maximum likelihood and penalized weighted median methods. Outlier SNPs were identified using Mendelian randomization PRESSO analysis and “leave-one-out” analysis.ResultsInverse variance-weighted regression associated iron deficiency anemia with body mass index, waist circumference, trunk fat mass, body fat mass, trunk fat percentage, and body fat percentage (all odds ratios 1.003–1.004, P ≤ 0.001). Heterogeneity was minimal and no evidence of horizontal pleiotropy was found.ConclusionOur Mendelian randomization analysis suggests that obesity can cause iron deficiency anemia.

Wound healing has been a great challenge throughout human history. Improper treatment for wounds is so easy to lead to infection and a series of serious symptoms, even death. Because of the ability of absorbing fluid and keeping a moist environment, the hydrogel with 3D networks is ideal candidate for wound dressing. More important, it has good biocompatibility. However, most of the hydrogel dressings reported have weak mechanical properties and adhesion properties, which greatly limit their clinical application. Herein, a tough adhesive hydrogel with good mechanical stability for non-invasive wound repair is reported. The hydrogel is composed of polyethylene glycol dimethacrylate (PEGDA), chitosan (CS) and chitin nano-whisker (CW). PEGDA and CS form interpenetrating network hydrogel through free radical polymerization reaction under the UV light. The introduction of CW further enhances the toughness of the hydrogel. The pH-sensitive CS can form adhesion to various materials through topological adhesion. As a wound closure repair material, PEGDA/CS/CW hydrogel not only has the characteristic of effectively closing the wound, defending against invading bacteria, and keeping the wound clean, but also has good tensile and mechanical stability, which is expected to realize the closure and repair of joints and other moving parts of the wound. This adhesive hydrogel is proven a promising material for wound closure repair.

Single-port robotic technique combines the benefits of minimally invasive outcome, improved visualization and fine surgical movement. This case report describes a 33-year-old patient with bilateral ovarian cysts suspected of teratoma who received single-port robotic trans-umbilical endoscopic bilateral cystectomy. This case shows that single-port robotic-assisted laparoscopic surgery is feasible and could be safe using the Shurui® system in select patients.

Silique morphology is an important trait that determines the yield output of oilseed rape (Brassica napus L.). Segmenting siliques and quantifying traits are challenging because of the complicated structure of an oilseed rape plant at the reproductive stage. This study aims to develop an accurate method in which a skeletonization algorithm was combined with the hierarchical segmentation (SHS) algorithm to separate siliques from the whole plant using 3-dimensional (3D) point clouds. We combined the L1-median skeleton with the random sample consensus for iteratively extracting skeleton points and optimized the skeleton based on information such as distance, angle, and direction from neighborhood points. Density-based spatial clustering of applications with noise and weighted unidirectional graph were used to achieve hierarchical segmentation of siliques. Using the SHS, we quantified the silique number (SN), silique length (SL), and silique volume (SV) automatically based on the geometric rules. The proposed method was tested with the oilseed rape plants at the mature stage grown in a greenhouse and field. We found that our method showed good performance in silique segmentation and phenotypic extraction with R2 values of 0.922 and 0.934 for SN and total SL, respectively. Additionally, SN, total SL, and total SV had the statistical significance of correlations with the yield of a plant, with R values of 0.935, 0.916, and 0.897, respectively. Overall, the SHS algorithm is accurate, efficient, and robust for the segmentation of siliques and extraction of silique morphological parameters, which is promising for high-throughput silique phenotyping in oilseed rape breeding.

Chiton teeth in the radula are one of the hardest biomaterials in nature. Chiton uses radula to scrape algae on hard surfaces. The ultrastructure and composition of teeth are well known while how they move is less clear. This study used an array of material characterizations including soft-tissue micro-computed tomography (micro-CT), histology, scanning electron microscopy, and proteomics to investigate the tissue that may control the movement of the radula of Acanthopleura loochooana. Surprisingly, unusually complex muscle fibers were found around the radula. 54 muscle fibers with diameters of around 130 µm were anchored to the second and third shell plates. These muscle fibers are in close contact with the radula and cartilage beneath the radula. Proteomics using a recently published chiton genome as a reference confirmed the proteins related to energy metabolism, calcium metabolism, as well as a cartilage oligomeric matrix protein in the muscle. qPCR found that the above proteins were highly expressed in the radula muscle compared to the foot. Taken together, this study provides insights into the complex tissue structures that control the movement of the radula, which may inspire robotics design relating to hard-soft tissue interfaces.

Multifunctional materials have more extensive applications than their counterpart single-functional materials due to their superior polyfunctions, among which fluorescent-conductive-magnetic (FCM) multifunctional materials have been extensively investigated for their unique performance and application value. However, the material properties may be degraded due to the adverse interactions among the fluorescent, conductive and magnetic materials with three different functions when they are directly blended. Hence, such adverse interactions brought by the direct contact of different functional materials should be avoided by designing and preparing unique structures. In this study, a one-dimensional (1D) tri-coaxial microbelt is innovatively designed, which can effectively separate and integrate different materials at the micro-level to obtain excellent macroscopic polyfunction. Generally, the preparation of tri-coaxial structure requires multistep procedures. To facilely construct the designed tri-coaxial microbelt, as a case study, a novel [CoFe2O4/polymethyl methacrylate (PMMA)]@[polyaniline (PANI)/PMMA]@[Tb(acac)3bpy/PMMA] (defined as [M@C@F]) tri-coaxial microbelts and arrays are synthesized through the one-pot direct electrospinning (ES) process. The tri-coaxial microbelts are assembled by the CoFe2O4/PMMA magnetic core layer, the PANI/PMMA conductive intermediate layer, and the Tb(acac)3bpy/PMMA insulated-fluorescent shell layer. It is the first time to integrate three different functions into the tri-coaxial microbelts and restrict three functions into three independent zones in the microbelt to shun adverse mutual interferences. The function of each layer can be regulated by adjusting the position and content of the three functional materials. Comparison with the control samples indicates that the property of the tri-coaxial microbelts array is directly impacted by structure and the arrangement modes of the building units. Hence, excellent macroscopic polyfunctions are obtained via designing and preparing microscopic partitioned building units and arranged modes. Array displays superior green fluorescence at 549 nm, tunable electrical conduction and magnetism. The new technique of one-pot direct construction of the tri-coaxial microbelts is significant and can be extended to for assemble other multifunctional materials. Moreover, the constructed [M@C@F] tri-coaxial microbelts and arrays have applications in various fields, such as micro-integrated circuits, microchips, and micro/nanodevices.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. More than 30% of patients with diagnosed HCC have abnormally high expression of fibroblast growth factor receptor 4 (FGFR4). Currently, clinical trials for a variety of FGFR4-specific inhibitors have started. However, the effect of these inhibitors is not ideal, and it is necessary to find a drug combination to synergistically exert anti-tumor effects. We found strong correlations between FGFR4 and HCC clinicopathological characteristics in the present study. After grouping patients according to FGFR4 expression, the key gene signatures were inputted the drug-gene related databases, which predicted several potential drug candidates. More importantly, to achieve the reliable and high throughput drug cytotoxicity assessment, we developed an efficient and reproducible agarose hydrogel microwells to generate uniform-sized multicellular tumor spheroids, which provide better mimicry of conventional solid tumors that can precisely represent anticancer drug candidates’ effects. Using high content screening, we quickly evaluated the enhanced anti-tumor effects of these combinations. Finally, we demonstrated that Parthenolide is a potential drug that can significantly enhance the clinical efficacy of FGFR4 receptor inhibitors. In general, we offered a new therapeutic way for FGFR4 positive HCC patients.

Accurate canopy mapping and head-volume estimation of large areas of broccoli is an important prerequisite for precision farming since it provides important phenotypic traits associated with field management, environmental control, and yield prediction. Currently, the detection and characterization of broccoli mostly rely on ground surveys and human interpretation, which is often time- and labor-intensive. Recent developments based on unmanned aerial vehicle (UAV) remote sensing offer low cost, timely, and flexible data acquisition, thereby providing a potential alternative technique to enhance in situ field surveys. The combination of UAV data and deep learning has led to a series of breakthroughs in rapid and automated collection of simultaneous multisensor and multimodal plant phenotyping data. However, their application for monitoring broccoli remains problematic when faced with the significant spatial scale involved and the variety of vegetation species. To address this problem, we propose herein a fast and reliable semi-automatic workflow based on deep learning to process UAV RGB imagery and LiDAR point clouds and thereby remotely detect and characterize broccoli canopy and heads. First, we explore the use of TransUNet to differentiate canopy and non-canopy regions in RGB images at the individual-plant scale. The results demonstrate that TransUNet consistently achieves the highest accuracy (average returned Precision, Recall, F1 score, and IoU of 0.917, 0.864, 0.901, and 0.895, respectively) compared with three CNN-based and two shallow learning-based approaches. In addition, TransUNet performs best in terms of robustness against variations in training samples. Subsequently, to estimate the volume of broccoli heads, a point cloud transformer (PCT) network is developed for point cloud segmentation. Improving upon the results of three existing methods PointNet, PointNet++, and K-means that were applied to the same datasets, the best-performing PCT produced a precision of 0.914, an overall recall of 0.899, an overall F1 score of 0.901, and an overall IoU of 0.879. A regression analysis indicates that the PCT estimates had R2 = 0.875, RMSE = 18.62, and rRMSE = 3.64 %, which is also superior to the results from other comparison approaches. Collectively, the wide application of such technology would facilitate applied research in plant phenotyping and precision agro-ecological applications and field management.

Neovascularization is one of the many manifestations of ocular diseases, including corneal injury and vascular diseases of the retina and choroid. Although anti-VEGF drugs have been used to effectively treat neovascularization, long-term use of anti-angiogenic factors can cause a variety of neurological and developmental side effects. As a result, better drugs to treat ocular neovascularization are urgently required. There is mounting evidence that epigenetic regulation is important in ocular neovascularization. DNA methylation and histone modification, non-coding RNA, and mRNA modification are all examples of epigenetic mechanisms. In order to shed new light on epigenetic therapeutics in ocular neovascularization, this review focuses on recent advances in the epigenetic control of ocular neovascularization as well as discusses these new mechanisms.

Lenvatinib is the first-line treatment for hepatocellular carcinoma (HCC), the most common type of primary liver cancer; however, some patients become refractory to lenvatinib. The underlying mechanism of lenvatinib resistance (LR) in patients with advanced HCC remains unclear. We focused on exploring the potential mechanism of LR and novel treatments of lenvatinib-resistant HCC. In particular, we established a Huh7 LR cell line and performed in vitro, bioinformatic, and biochemical assays. Additionally, we used a Huh7-LR cell-derived xenograft mouse model to confirm the results in vivo. Following LR induction, multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) transporters were markedly upregulated, and the epidermal growth factor receptor (EGFR), MEK/ERK, and PI3K/AKT pathways were activated. In vitro, the co-administration of elacridar, a dual MDR1 and BCRP inhibitor, with lenvatinib inhibited proliferation and induced apoptosis of LR cells. These effects might be due to inhibiting cancer stem-like cells (CSCs) properties, by decreasing colony formation and downregulating CD133, EpCAM, SOX-9, and c-Myc expression. Moreover, the co-administration of gefitinib, an EGFR inhibitor, with lenvatinib retarded proliferation and induced apoptosis of LR cells. These similar effects might be caused by the inhibition of EGFR-mediated MEK/ERK and PI3K/AKT pathway activation. In vivo, co-administration of lenvatinib with elacridar or gefitinib suppressed tumour growth and angiogenesis. Therefore, inhibiting MDR1 and BCRP transporters or targeting the EGFR/PI3K pathway might overcome LR in HCC. Notably, lenvatinib should be used to treat HCC after LR induction owing to its role in inhibiting tumour proliferation and angiogenesis. Our findings could help develop novel and effective treatment strategies for HCC.

Tengchong Snow chickens are one of the most precious, black-boned chickens in Yunnan province and usually produce black meat. However, we found a small number of white meat traits in the chicken population during feeding. In order to determine the pattern of melanin deposition and the molecular mechanism of formation in the Tengchong Snow chicken, we measured the luminance value (L value) and melanin content in the skin of black meat chickens (Bc) and white meat chickens (Wc) using a color colorimeter, ELISA kit, and enzyme marker. The results showed that the L value of skin tissues in black meat chickens was significantly lower than that of white meat chickens, and the L value of skin tissues gradually increased with an increase in age. The melanin content of skin tissues in black meat chickens was higher than that of white meat chickens, and melanin content in the skin tissues gradually decreased with an increase in age, but this difference was not significant (p > 0.05); the L value of skin tissues in black meat chickens was negatively correlated with melanin content, and the correlation coefficient was mostly above −0.6. In addition, based on the phenotypic results, we chose to perform the comparative transcriptome profiling of skin tissues at 90 days of age. We screened a total of 44 differential genes, of which 32 were upregulated and 12 were downregulated. These DEGs were mainly involved in melanogenesis, tyrosine metabolism and RNA transport. We identified TYR, DCT, and EDNRB2 as possible master effector genes for skin pigmentation in Tengchong Snow black meat chickens through DEGs analysis. Finally, we measured the mRNA of TYR, DCT, MC1R, EDNRB2, GPR143, MITF, and TYRP1 genes through a quantitative real-time polymerase chain reaction (qPCR) and found that the mRNA of all the above seven genes decreased with increasing age. In conclusion, our study initially constructed an evaluation system for the black-boned traits of Tengchong Snow chickens and found key candidate genes regulating melanin deposition, which could provide an important theoretical basis for the selection and breeding of black-boned chickens.

Abstract Background The present study aims to provide a comparative analysis of the etiologies of female infertility between Dehong, on the Yunnan Frontier, and Kunming. Methods A retrospective study, which included 941 infertile females in Kunming who were treated in the First People’s Hospital of Yunnan Province and infertile females who were treated in the local hospital in Dehong from January 2016 to November 2018, was conducted. A comparative analysis of the etiologies of infertility in the two regions was then carried out. Results In patients with primary infertility, ovulation disorder (15.03%) was the main cause of infertility in Kunming, and pelvic inflammatory disease (25.59%) was the main cause in Dehong. With regard to secondary infertility, although pelvic inflammatory disease was the main cause of infertility in both regions, the incidence of intrauterine adhesions in Kunming was significantly higher than in Dehong. Conclusions The etiology of infertility showed different epidemiological characteristics depending on the region, hence individualized treatment should be given accordingly

The combined utilization of mineral accelerators and nano-seeding materials is a novel method to promote the early strength of cement-based materials. In this paper, the effects of nano-C-S-H seed (NCS) on the early compressive strength of the Portland cement (PC)– calcium sulfoaluminate cement (CSA) binder were investigated. The results showed that NCS and CSA synergistically contributed to the early strength of PC. In detail, a 326.3% increase in the 10 h compressive strength of PC paste was obtained through the addition of NCS (2 wt%) and CSA (5%) in common. This was higher than the sum of the increases observed with the single additions of CSA (157.9%) or NCS (87.6%), with the same above dosage, in PC. Meanwhile, the early strength enhancement effects of NCS and CSA, when used together in PC, lasted longer than the effects of either used alone. Moreover, the synergetic effect mechanism was analyzed by isothermal calorimeter, QXRD, TGA, MIP, and SEM techniques. The calorimetry, XRD, and TGA results demonstrated that the synergistic mechanism was associated with the synergistic promotion effects of CSA and NCS on the hydrates. The fast hydration of CSA produced large amounts of ettringite and also consumed partial free water to promote the performance of the seeding effect of NCS which, simultaneously, further accelerated the precipitation of C-S-H gel and CH. The high alkie environment was also beneficial for the continuous generation of ettringite. In addition, the results of MIP and SEM measurements showed that the micro-filling effect of NCS significantly optimized the pore structure of a PC-CSA blend-hardened paste. Thus, the synergistic strength enhancement effects of CSA and NCS on PC were attributed to the matching of the promotion of hydration generation and the optimization of pore structures in hardening cement paste. The results of this article provide a new approach to achieving the rapid development of the early strength of cementitious materials, with potential applications in precast concrete and low-temperature construction.

Intrahepatic cholangiocarcinoma (iCCA) is a complex malignancy carrying poor prognosis. Liver transplantation (LT) was historically contraindicated for iCCA, due to poor outcomes after LT. However, an increasing number of studies have challenged this premise, because LT alone or combined with neoadjuvant chemotherapy has achieved relatively satisfactory transplant outcomes in well selected iCCA cases. This current review based on existing clinical researches, evinced that LT might serve as a viable option in iCCA cases as follows: ① unresectable tumor restricted to 2 cm, along with context of chronic liver diseases; and ② unresectable tumor locally advanced within the liver (without extrahepatic metastasis or vascular invasion) but responses to tumor down-staging treatments (namely, systemic neoadjuvant therapy and/or locoregional therapy). On the contrary, it is recommended as contraindications in iCCA cases as follows: ① patients with tumor progression while waiting for a transplant (increase of diameter, macrovascular invasion, new nodules, escalation of carbohydrate antigen 19-9, or extrahepatic spread); ② patients with iCCA recurrence. Conclusively, tumor burden, tumor biology, and response to down-staging strategies should be taken into consideration before LT. Whereas, the concept of “locally advanced stage” remains to be defined in the future, especially the optimized combination of “maximum size of largest lesion”, “number of lesions”, with/without “tumor differentiation”, just like the Milan criteria which is widely used for hepatocellular carcinoma. Given the scarcity of donor organ, and also the debate about LT in iCCA, accurate consensus about LT for iCCA patients is still urgently warranted.

Modular structures are premanufactured off-site and assembled on-site, leading to reduced on-site works and construction periods and improved quality compared to conventional prefabricated steel structures and reinforced concrete structures. Meanwhile, steel frame-light gauge slotted steel stud (LGSS) walls have been considered to be assembled into the modules due to their excellent thermal- and sound-insulation properties. These structural components will also contribute to the resistance of the modular system when subjected to lateral loads/actions, especially seismic actions. A finite element model was developed to investigate the seismic performance of high-rise modular steel structures with LGSS shear walls. Then, parametric studies were conducted to investigate the influences of the layouts of the LGSS shear walls and structure heights on the lateral stiffness, the deformation modes, and the stress states of the modular steel structures. Observed from the results of a ten-storey modular steel structure infilled with LGSS shear walls, the maximum storey drift reduced by 50.1–79.50% compared to the corresponding pure steel frame structure under the selected high-intensity seismic waves. The results indicate that the studied modular steel structure with LGSS shear walls possesses good seismic resistance and could be a practical and economical choice for future modular constructions.

Android applications are developing rapidly across the mobile ecosystem, but Android malware is also emerging in an endless stream. Many researchers have studied the problem of Android malware detection and have put forward theories and methods from different perspectives. Existing research suggests that machine learning is an effective and promising way to detect Android malware. Notwithstanding, there exist reviews that have surveyed different issues related to Android malware detection based on machine learning. We believe our work complements the previous reviews by surveying a wider range of aspects of the topic. This paper presents a comprehensive survey of Android malware detection approaches based on machine learning. We briefly introduce some background on Android applications, including the Android system architecture, security mechanisms, and classification of Android malware. Then, taking machine learning as the focus, we analyze and summarize the research status from key perspectives such as sample acquisition, data preprocessing, feature selection, machine learning models, algorithms, and the evaluation of detection effectiveness. Finally, we assess the future prospects for research into Android malware detection based on machine learning. This review will help academics gain a full picture of Android malware detection based on machine learning. It could then serve as a basis for subsequent researchers to start new work and help to guide research in the field more generally.

With the rapid development of inverter-based generators (IGs), power grid is faced with critical frequency stability challenges because the existing IGs have no inertia. To equip IGs with inertial response, researchers have proposed several virtual inertia control methods, which can be classified into two categories: virtual synchronous generator (VSG) control and droop control based on rate of change of frequency (ROCOF-droop control). In this paper, the comparison between both virtual inertia control methods is conducted from three perspectives: mathematical model, output characteristic and small-signal stability. State-space models are firstly built to analyze the control mechanism of VSG control and ROCOF-droop control methods. Simulation and eigenvalue analysis are conducted to study the transient responses and oscillation characteristics of both methods, which is helpful to understand the advantages and limitations of existing virtual inertia control methods. Finally, the obtained theoretical results are validated through realtime laboratory (RT-LAB) hardware-in-loop simulation platform.

Objectives: To investigate the clinical characteristics, treatment and prognosis of leiomyomatosis peritonealis disseminata (LPD) following laparoscopic surgery with uncontained morcellation and to summarize clinical features of iatrogenic LPD based on published literature together with our own experience.Methods: A cohort of 13 cases with iatrogenic LPD diagnosed and treated in Peking Union Medical College Hospital from 2011 to 2020 was reported focusing on clinical characteristics, treatment and prognosis.Results: All the patients had a history of laparoscopic myomectomy with uncontained morcellation. The average age was 35.6 (range 25–47) years. The interval between initial laparoscopic surgery and first diagnosis of LPD was 6.08 years on average (range 1–12). Most of the patients had no obvious symptoms. The accuracy of pre-operative diagnosis was low. Two patients had been treated with gonadotropin-releasing hormone agonist (GnRH-a) before surgery without obvious effect. The nodules of LPD are usually located in the lower half of the peritoneal cavity. The most commonly involved site was the pouch of Douglas. The number of nodules ranged from 3 to over 10, and they ranged in size ranged from 0.3 to 22 cm. All patients underwent surgical treatment: six patients underwent laparoscopy and seven underwent laparotomy. Pathology results confirmed LPD. The immunohistochemical profile indicated LPD tends to be positive strongly for desmin, caldesmon, ER, PR and SMA. Only one patient underwent post-operative treatment with GnRH-a. All patients were followed for an average period of 49 months without recurrence.Conclusion: Iatrogenic LPD is a relatively rare condition. Patients usually exhibit no hormonal stimulation factors. Surgery is the main method of treatment, and hormone suppressive therapy is only rarely used. The nodules are usually large and less numerous, and most involve the pelvis. The prognosis of iatrogenic LPD seems good.

Human organoid systems recapitulate key features of organs offering platforms for modelling developmental biology and disease. Tissue-derived organoids have been widely used to study the impact of extrinsic niche factors on stem cells. However, they are rarely used to study endogenous gene function due to the lack of efficient gene manipulation tools. Previously, we established a human foetal lung organoid system (Nikolić et al., 2017). Here, using this organoid system as an example, we have systematically developed and optimised a complete genetic toolbox for use in tissue-derived organoids. This includes ‘Organoid Easytag’, our efficient workflow for targeting all types of gene loci through CRISPR-mediated homologous recombination followed by flow cytometry for enriching correctly targeted cells. Our toolbox also incorporates conditional gene knockdown or overexpression using tightly inducible CRISPR interference and CRISPR activation which is the first efficient application of these techniques to tissue-derived organoids. These tools will facilitate gene perturbation studies in tissue-derived organoids facilitating human disease modelling and providing a functional counterpart to many ongoing descriptive studies, such as the Human Cell Atlas Project.

BackgroundLung cancer is the leading cause of death from cancer, and lung adenocarcinoma (LUAD) is the most common form. Despite the great advances that has been made in the diagnosis and treatment for LUAD, the pathogenesis of LUAD remains unclear. In this study, we aimed to identify the function of circKEAP1 derived from the exon of KEAP1 in LUAD.MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The levels and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR (qRT-PCR). Subsequently, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, the dual luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its host gene, which activated the KEAP1/NRF2 signal pathway, and finally suppresses the tumor progress. Our findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a novel method for the treatment of LUAD.

Abstract Background The advances of hyperspectral technology provide a new analytic means to decrease the gap of phenomics and genomics caused by the fast development of plant genomics with the next generation sequencing technology. Through hyperspectral technology, it is possible to phenotype the biochemical attributes of rice seeds and use the data for GWAS. Results The results of correlation analysis indicated that Normalized Difference Spectral Index (NDSI) had high correlation with protein content (PC) with RNDSI2 = 0.68. Based on GWAS analysis using all the traits, NDSI was able to identify the same SNP loci as rice protein content that was measured by traditional methods. In total, hyperspectral trait NDSI identified all the 43 genes that were identified by biochemical trait PC. NDSI identified 1 extra SNP marker on chromosome 1, which annotated extra 22 genes that were not identified by PC. Kegg annotation results showed that traits NDSI annotated 3 pathways that are exactly the same as PC. The cysteine and methionine metabolic pathway identified by both NDSI and PC was reported important for biosynthesis and metabolism of some of amino acids/protein in rice seeds. Conclusion This study combined hyperspectral technology and GWAS analysis to dissect PC of rice seeds, which was high throughput and proven to be able to apply to GWAS as a new phenotyping tool. It provided a new means to phenotype one of the important biochemical traits for the determination of rice quality that could be used for genetic studies.

Abstract Objectives To analyze the clinicopathological characteristics of subsequent pelvic masses after hysterectomy for benign diseases, and to compare the masses following hysterectomy with or without simultaneous bilateral salpingectomy. Methods This study retrospectively analyzed patients undergone reoperation for pelvic mass subsequently to previous hysterectomy for benign disease from January 2012 to December 2016 in Peking Union Medical College Hospital. Results A total of 247 patients were enrolled in this study, of which 80.16% (n = 198) received simple hysterectomy, and 5.67% (n = 14) underwent hysterectomy with bilateral salpingectomy. The clinicopathological data of patients undergone simple hysterectomy or simultaneous bilateral salpingectomy was compared. In the former group, we found that 68.18% (n = 135) of the pelvic massed were benign, and the remaining 31.82% (n = 63) were malignant. In latter group, 57.10% (n = 8) were benign (8%) and 42.90% (n = 6) were malignant. Univariate analysis showed that the age of surgery for pelvic masses in patients undergoing hysterectomy with simultaneous bilateral salpingectomy was significantly younger than that in patients without salpingectomy (median, 44.5 vs 50 years, P

Accurate acquisition of plant phenotypic information has raised long-standing concerns in support of crop breeding programs. Different methods have been developed for high throughput plant phenotyping, while they mainly focused on the canopy level without considering the spatiotemporal heterogeneity at different canopy layers and growth stages. This study aims to phenotype spatiotemporal heterogeneity of chlorophyll (Chl) content and fluorescence response within rice leaves and canopies. Multipoint Chl content and high time-resolved Chl a fluorescence (ChlF) transient (OJIP transient) of rice plants were measured at different nitrogen levels and growth stages. Results showed that the Chl content within the upper leaves exhibited an increasing trend from the basal to the top portions but a decreasing pattern within the lower leaves at the most growth stages. Leaf Chl content within the rice canopy was higher in the lower leaves in the vegetative phase, while from the initial heading stage the pattern gradually reversed with the highest Chl content appearing in the upper leaves. Nitrogen supply mainly affects the occurrence time of the reverse vertical pattern. This could be the result of different nutritional demands of leaves transforming from sinks to sources, and it was further confirmed by the fall of the JI phase of OJIP transient in the vegetative phase and the rise in the reproductive phase. We further deduced that the vertical distribution of Chl content could have a defined pattern at a specific growth stage. Furthermore, the reduction of end acceptors at photosystem I (PSI) electron acceptor side per cross section (RE0/CS) was found to be a potential sensitive predictor for identifying the vertical heterogeneity of leaf Chl content. These findings provide prior knowledge on the vertical profiles of crop physiological traits, which explore the opportunity to develop more efficient plant phenotyping tools for crop breeding.

Noise-induced-hearing-loss(NIHL) is a common occupational disease caused by various environmental and biological factors. To investigate the association between TAB2 and the susceptibility of NIHL of people exposed to occupational environments, a genetic association study was performed on selected companies with 588 cases and 537 healthy control subjects. Five selected single nucleotide polymorphisms (SNPs) in TAB2,incoluding rs2744434, rs521845, rs652921, rs7896, rs9485372, were genotyped after a collection of DNA samples. Evident differences in participants between the case group and the control group reveals the result that people with the TAB2 has a high probability of getting NIHL. The results show that rs521845 is deeply associated with the risk of NIHL and is available for the diagnosis in the future.

Objective: The aim of this research was to study the factors contributing to the survival rate of in-hospital cardiac arrest (IHCA) and to determine whether the incidence density of fever (IDF) acts as a mediator.Methods: Data from patients with IHCA who survived more than 48 h were collected from 2011 to 2017. IDF was defined as the fever duration divided by the hospitalization duration, prolonged fever was defined as fever lasting for more than 5 days, and early fever was defined as an initial onset within the first 2 days of IHCA. Possible clinical variables associated with IDF were examined by linear regression, and possible clinical variables associated with survival rate were examined by univariate and multivariate analyses. IDF was investigated as a mediator of the indirect effects of the risk factors on survival.Results: In our retrospective study, the median IDF was 0, with an interquartile range from 0 to 0.42. Prolonged fever was noted in 16% (97/605) of the total, and early fever was noted in 17.2% (104/605) of the total. Linear regression results showed that positive chest X-ray, central venous catheter and Glasgow Coma Score (GCS) ≤ 8 were related to IDF. The IDF (OR: 0.36, 95% CI, 0.13–0.97, P = 0.04), prolonged fever (adjusted OR = 0.13, 95% CI, 0.06–0.29, P < 0.001), positive chest X-ray (OR: 0.67, 95% CI, 0.46–0.98, P = 0.04), central venous catheter placement (OR: 0.54, 95% CI, 0.34–0.89, P = 0.01), and endotracheal intubation (OR: 0.47, 95% CI, 0.33–0.69, P < 0.001) were also related to the negative outcome of hospital discharge after adjustment. Additionally, positive chest X-ray had a 19% effect on survival outcome through IDF as a mediator, and the indirect effect of central venous catheter mediated by IDF accounted for 10% of the total.Conclusions: A higher IDF, prolonged fever, a positive chest X-ray, the use of a central venous catheter and endotracheal intubation reduced the survival rate of these patients, and the detrimental impacts of a positive chest X-ray and the use of a central venous catheter on survival outcomes were partially mediated by IDF.

Background/Aims: Assistance with tumor-associated vascularization is needed for the growth and invasion of non-small cell lung cancer (NSCLC). Recently, it was shown that placental growth factor (PLGF) expressed by NSCLC cells had a critical role in promoting the metastasis of NSCLC cells. However, the underlying molecular mechanisms remain elusive. Methods: Here, we first established a NSCLC model in mice that allows us not only to isolate tumor cells from non-tumor cells in the tumor, but also to trace tumor cells in living animals. Levels of PLGF, its unique receptor Flt-1, as well as transforming growth factor β1 (TGFβ1) was examined in tumor cells and tumor-associated macrophages (TAM) by RT-qPCR. A transwell well co-culture system and HUVEC assay were applied to study the crosstalk between NSCLC cells and TAM. Results: NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through surface expression of Flt-1 on macrophages. In a transwell co-culture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete TGFβ1 to enhance the growth of endothelial cells in a HUVEC assay. Conclusion: The cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFβ receptor signaling may promote the growth and vascularization of NSCLC.