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Per- and poly-fluoroalkyl substances (PFAS) are a new type of persistent organic pollutants that have received extensive attention in recent years. This article reviewed the population characteristics of environmental exposure to PFAS, as well as the potential health effects. Previous studies have verified that people are exposed to PFAS mainly through ingestion, and food and water are the dominant contributors. In terms of exposure characteristics, geographical, gender, age, and occupational differences have an impact on the level of PFAS exposure in the corresponding populations by influencing their behavioral characteristics and metabolic levels, with occupational exposure receiving more attention, especially in the exploration of novel PFAS. PFAS associate with a variety of adverse health effects caused by hepatorenal toxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and carcinogenicity. However, some of the conclusions are not completely consistent, and the published epidemiological studies have focused on children and young people, lacking relevant data of the elderly. Future research can pay more attention to the elderly population and carry out validation exploration on controversial conclusions.

Abstract Background This study targeted at developing a robust, prognostic signature based on super-enhancer-related genes (SERGs) to reveal survival prognosis and immune microenvironment of breast cancer. Methods RNA-sequencing data of breast cancer were retrieved from The Cancer Genome Atlas (TCGA), 1069 patients of which were randomly assigned into training or testing set in 1:1 ratio. SERGs were downloaded from Super-Enhancer Database (SEdb). After which, a SERGs signature was established based on the training set, with its prognostic value further validated in the testing set. Subsequently, we identified the potential function enrichment and tumor immune infiltration of the model. Moreover, in vitro experiments were completed to further explore the biological functions of ZIC2 gene (one of the risk genes in the prognostic model) in breast cancer. Results A risk score system of prognostic value was constructed with 6 SERGs (ZIC2, NFE2, FOXJ1, KLF15, POU3F2 and SPIB) to find patients in high-risk group with significantly worse prognosis in both training and testing sets. In addition, a multivariate regression was established via integrating the 6 genes with age and N stage, indicating well performance by calibration, time-dependent receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Further analysis demonstrated that tumor-associated pathological processes and pathways were significantly enriched in the high-risk group. In general, the novel SERGs signature could be applied to screen breast cancer with immunosuppressive microenvironment for the risk score was negatively correlated with ESTIMATE score, tumor-infiltration lymphocytes (such as CD4 + and CD8 + T cell), immune checkpoints and chemotactic factors. Furthermore, down-regulation of ZIC2 gene expression inhibited the cell viability, cellular migration and cell cycle of breast cancer cells. Conclusions The novel SERGs signature could predict the prognosis of breast cancer; and SERGs might serve as potential therapeutic targets for breast cancer.

Abstract Glasshouse plants are species that trap warmth via specialized morphology and physiology, mimicking a human glasshouse. In the Himalayan alpine region, the highly specialized glasshouse morphology has independently evolved in distinct lineages to adapt to intensive UV radiation and low temperature. Here we demonstrate that the glasshouse structure – specialized cauline leaves – is highly effective in absorbing UV light but transmitting visible and infrared light, creating an optimal microclimate for the development of reproductive organs. We reveal that this glasshouse syndrome has evolved at least three times independently in the rhubarb genus Rheum. We report the genome sequence of the flagship glasshouse plant Rheum nobile and identify key genetic network modules in association with the morphological transition to specialized glasshouse leaves, including active secondary cell wall biogenesis, upregulated cuticular cutin biosynthesis, and suppression of photosynthesis and terpenoid biosynthesis. The distinct cell wall organization and cuticle development might be important for the specialized optical property of glasshouse leaves. We also find that the expansion of LTRs has likely played an important role in noble rhubarb adaptation to high elevation environments. Our study will enable additional comparative analyses to identify the genetic basis underlying the convergent occurrence of glasshouse syndrome.

Background and Aim: Porcine circovirus 3 (PCV3) was recently reported in Malaysian commercial pig population in 2020 by conventional polymerase chain reaction (PCR), revealing a molecular prevalence of 17.02% in the sampled domestic pig population. This study aims to describe a chromogenic in situ hybridization (ISH) technique using digoxigenin (DIG)- labeled cloned PCV3 open reading frame 1 (ORF1) fragment DNA to detect and localize the PCV3 antigen in formalin-fixed, paraffin-embedded lung, and lymphoid tissue specimens. Materials and Methods: Since PCV3 was mainly detected in lung and lymphoid tissues, we obtained tissue specimens from these organs from the previous Malaysian PCV3 study. Digoxigenin-labeled ISH probes were designed to target a 69 bp region of PCV3 ORF1 spanning from the nucleotide positions (282–350). Results: Light microscopy analysis revealed that chromogenic staining of PCV3 antigens was visualized within the cytoplasm of pneumocytes and lymphocytes, indicating positive ISH results. The results of molecular detection of PCV3 using PCR and ISH showed a high agreement of 90.91%, including for the negative PCV3 status for all samples. Conclusion: This study reports a chromogenic ISH technique using DIG-labeled probes targeting PCV3 ORF1 to detect PCV3 antigens in lung and lymphoid tissues. Despite the limited availability of PCV3 antibodies, ISH remains relevant for investigating PCV3 replication and pathogenesis and can be used complementarily with PCR for evaluating the localization of antigens in infected tissues.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug–drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

Abstract O-Methylated stilbenes are prominent nutraceuticals but rarely produced by crops. Here, the inherent ability of two Saccharinae grasses to produce regioselectively O-methylated stilbenes is reported. A stilbene O-methyltransferase, SbSOMT, is first shown to be indispensable for pathogen-inducible pterostilbene (3,5-bis-O-methylated) biosynthesis in sorghum (Sorghum bicolor). Phylogenetic analysis indicates the recruitment of genus-specific SOMTs from canonical caffeic acid O-methyltransferases (COMTs) after the divergence of Sorghum spp. from Saccharum spp. In recombinant enzyme assays, SbSOMT and COMTs regioselectively catalyze O-methylation of stilbene A-ring and B-ring respectively. Subsequently, SOMT-stilbene crystal structures are presented. Whilst SbSOMT shows global structural resemblance to SbCOMT, molecular characterizations illustrate two hydrophobic residues (Ile144/Phe337) crucial for substrate binding orientation leading to 3,5-bis-O-methylations in the A-ring. In contrast, the equivalent residues (Asn128/Asn323) in SbCOMT facilitate an opposite orientation that favors 3ʹ-O-methylation in the B-ring. Consistently, a highly-conserved COMT is likely involved in isorhapontigenin (3ʹ-O-methylated) formation in wounded wild sugarcane (Saccharum spontaneum). Altogether, our work reveals the potential of Saccharinae grasses as a source of O-methylated stilbenes, and rationalize the regioselectivity of SOMT activities for bioengineering of O-methylated stilbenes.

Abstract Background Ulmus mianzhuensis is an endemic tree species in China with high ornamental and economic value. Currently, little is known regarding its genomic architecture, phylogenetic position, or adaptive evolution. Here, we sequenced the complete chloroplast genome (cp genome) of U. mianzhuensis and further compared the variations in gene organization and structure within Ulmus species to define their genomic evolution, then reconstructed the phylogenomic relationship of 31 related Ulmus species to explore the systematic position of U. mianzhuensis and the utility of cp genome for resolving phylogenetics among Ulmus species. Results Our results revealed that all the Ulmus species exhibited a typical quadripartite structure, with a large single copy (LSC) region of 87,170 − 88,408 bp, a small single copy (SSC) region of 18,650 − 19,038 bp and an inverted repeat (IR) region of 26,288 − 26,546 bp. Within Ulmus species, gene structure and content of cp genomes were highly conserved, although slight variations were found in the boundary of SC/IR regions. Moreover, genome-wide sliding window analysis uncovered the variability of ndhC-trnV-UAC, ndhF-rpl32, and psbI-trnS-GCU were higher among 31 Ulmus that may be useful for the population genetics and potential DNA barcodes. Two genes (rps15 and atpF) were further detected under a positive selection of Ulmus species. Comparative phylogenetic analysis based on the cp genome and protein-coding genes revealed consistent topology that U. mianzhuensis is a sister group to U. parvifolia (sect. Microptelea) with a relatively low-level nucleotide variation of the cp genome. Additionally, our analyses also found that the traditional taxonomic system of five sections in Ulmus is not supported by the current phylogenomic topology with a nested evolutionary relationship between sections. Conclusions Features of the cp genome length, GC content, organization, and gene order were highly conserved within Ulmus. Furthermore, molecular evidence from the low variation of the cp genome suggested that U. mianzhuensis should be merged into U. parvifolia and regarded as a subspecies of U. parvifolia. Overall, we demonstrated that the cp genome provides valuable information for understanding the genetic variation and phylogenetic relationship in Ulmus.

Healthy coral reefs provide diverse habitats for marine life, playing a crucial role in marine ecosystems. Coral health is under threat due to global climate change, ocean pollution, and other environmental stressors, leading to coral bleaching. Coral bleaching disrupts the symbiotic relationship between corals and algae, ultimately impacting the entire marine ecosystem. Processing complex underwater images manually is time-consuming and burdensome for marine experts. To rapidly locate and monitor coral health, deep neural networks are employed for identifying coral categories, which can facilitate the automated processing of extensive underwater imaging data. However, these classification networks may overlook critical classification criteria like color and texture. This paper proposes a multi-local perception network (ML-Net) for image classification of healthy and bleached corals. ML-Net focuses on local features of coral targets, leveraging valuable information for image classification. Specifically, the proposed multi-branch local adaptive block extracts image details through parallel convolution kernels. Then, the proposed multi-scale local fusion block integrates features of different scales vertically, enhancing the detailed information within the deep network. Residual structures in the shallow network transmit local information with more texture and color to the deep network. Both horizontal and vertical multi-scale fusion blocks in deep networks are used to capture and retain local details. We evaluated ML-Net using six evaluation metrics on the Bleached and Unbleached Corals Classification dataset. In particular, ML-Net achieves an ACC result of 86.35, which is 4.36 higher than ResNet and 8.5 higher than ConvNext. Experimental results demonstrate the effectiveness of the proposed modules for coral classification in underwater environments.

Background and aim: Rivaroxaban is an emerging oral anticoagulant for postoperative anticoagulation after percutaneous left atrial appendage closure (LAAC). Because a once-daily dosing regimen of rivaroxaban causes fluctuations in the drug plasma concentration, we studied the feasibility and safety of twice-daily rivaroxaban as a postoperative anticoagulation regimen for patients with atrial fibrillation (AF) undergoing LAAC.Methods: This study involved patients with AF who underwent LAAC and took rivaroxaban postoperatively. A total of 326 patients who received a standard total dose (15 or 20 mg) of rivaroxaban based on their creatinine clearance rate were divided into the twice-daily (BID) rivaroxaban group (n = 208) and once-daily (QD) rivaroxaban group (n = 118) according to their anticoagulation strategy. Transesophageal echocardiography was recommended at 3–6 months postoperatively to check for device-related thrombosis (DRT). Clinical outcomes were evaluated during postoperative anticoagulation.Results: The median CHA2DS2-VASc score (4 [3, 5] vs. 4 [3, 5], p = 0.28) and HAS-BLED score (2 [2, 3] vs. 2 [2, 3], p = 0.48) were not significantly different between the groups. During the anticoagulation period (4.1 ± 0.7 vs. 4.1 ± 0.9 months, p = 0.58), 148 (71.2%) patients in the BID group and 75 (63.6%) in the QD group underwent follow-up transesophageal echocardiography. There were no statistically significant differences between the two groups in terms of DRT (1.4% vs. 2.7%, p = 0.60), minor bleeding (8.2% vs. 11.0%, p = 0.39), thromboembolic events (1.0% vs. 0.8%, p = 1.00), major bleeding (0.5% vs. 0.8%, p = 1.00), or death.Conclusion: A short course of twice-daily rivaroxaban following LAAC is a feasible alternative regimen with a low rate of major bleeding events, DRT, and thromboembolic events for patients with AF.

Abstract Background Children affected by tethered cord syndrome (TCS) encounter multifaceted challenges encompassing educational, familial and social spheres, underscoring the significance of a holistic comprehension of their subjective emotional well‐being and life encounters. Nonetheless, healthcare professionals tend to prioritise the physical functionality of the afflicted individuals throughout the treatment and rehabilitation process, often neglecting the emotional experiences and requirements of these children as they transition into posthospitalization phases. Aim To advance the subjective experiences and perceptions of children with TCS upon reintegration into their families, educational institutions and wider societal contexts subsequent to their discharge from medical facilities. Methods The study was conducted at the Children's Hospital in Zhejiang. Twelve children aged 8–15 with TCS were included in the study. The research design used an interpretative qualitative approach, utilising semi‐structured interviews as the primary data collection method. Data analysis was performed using reflexive thematic analysis, facilitating a comprehensive exploration of emerging themes and patterns. Results Four major themes (and seven subthemes) were identified from the findings: (1) growing pains (a shameful secret, distance between ideal and reality); (2) inappropriate expressions of familial affection (knowing is not understanding, unspeakable guilt); (3) social estrangement (uncomfortable distinctions, familiar stranger) and (4) striving for independence and consistency. Conclusions Children affected by TCS exhibit internal sensitivity and challenges in self‐development, family dynamics and social interactions. They aspire to attain a future characterised by independence and freedom, akin to that of their typically developing peers. These findings can help health professionals, families and educators gain a deeper understanding of what it takes to be a child with TCS, and the findings can also serve as a platform for interventions that seek to promote self‐expression in these children so that they can experience life as a meaningful and positive process. Patient or Public Contribution This study received support from children with TCS and their guardians during data collection, as well as from the head nurse of the unit. Coresearchers also contributed to design, data collection, analysis and writing.

Carbendazim, a widely used fungicide in China, has been found to have reproductive toxicity and mutagenic effects. However, information on the spatial-temporal variations of carbendazim residues in food in China is limited. Here, we investigated the presence of carbendazim in China's plant-based foods from 2011 to 2020, evaluated the spatial-temporal characteristics, and assessed the associated exposure risks in the Chinese diet. The results revealed a high detection frequency of carbendazim in fruits (26.4%) and high concentrations in vegetables (∼110 mg kg−1), indicating widespread misuse of the fungicide. The acute risks of consuming certain vegetables and cereals exceeded the recommended limits by up to 12 and 5 times, respectively. Although there has been a decline in carbendazim residue levels in food since the implementation of the Chinese government's action plan for zero growth of pesticide use in 2015, some provinces still exhibited high levels of carbendazim in multiple food categories, which were positively correlated with annual pesticide application. We highlight that carbendazim contamination reflects the broader issue of pesticide use in China. It emphasizes the need for committed and targeted national policies to reduce carbendazim residues in food and suggests that such measures could also regulate the use of other pesticides, given that pesticide abuse in China is not limited to specific types. We call for the re-evaluation of maximum residue limits of carbendazim, particularly in highly consumed foods such as cereals.

Abstract Objectives We systematically reviewed how investigators argued for and justified the validity of their instrumental variables (IV) in clinical studies of dementia and neurodegenerative disease. Methods We included studies using IV analysis with observational data to investigate causal effects in clinical research studies of dementia and neurodegenerative disease. We reported the subject‐matter argumentation, falsification test, and study design strategies used to satisfy the three assumptions of a valid IV: relevance, exclusion restriction, and exchangeability. Results Justification for the relevance assumption was performed in all 12 included studies, exclusion restriction in seven studies, and exchangeability in nine studies. Two subject‐matter argumentation strategies emerged from seven studies on the relevance of their IV. All studies except one provided quantitative evidence for the strength of the association between the IV and exposure variable. Four argumentation strategies emerged for exclusion restriction from six studies. Four falsification tests were performed across three studies. Three argumentation strategies emerged for exchangeability across four studies. Nine falsification tests were performed across nine studies. Two notable study design strategies were reported. Conclusion Our results reinforce IV analysis as a feasible option for clinical researchers in dementia and neurodegenerative disease by clarifying known strategies used to validate an IV.

This study investigates the frequency of a clinically reported variant in PMS2, NM_000535.7:c.2523G>A p.(W841∗), from next-generation sequencing studies in 2 racially diverse cohorts. We identified clinical reports of the PMS2 c.2523G>A p.(W841∗) variant in the National Precision Oncology Program’s somatic testing database (n = 25,168). We determined frequency of the variant in germline exome sequencing from the Penn Medicine BioBank (n = 44,256) and in gnomAD. The PMS2 c.2523G>A p.(W841∗) was identified as a homozygous variant on tumor testing in an adult patient of self-identified Black race/ethnicity with no evidence of constitutional mismatch repair deficiency. The variant was clinically reported on 35 total tumor and liquid biopsy tests (0.1%), and all individuals with the variant were of self-identified Black race/ethnicity (0.6% of n = 5787). In individuals of African genetic ancestry (AFR), the variant's germline frequency was reported to be 0.2% and 1.3% in the Penn Medicine BioBank (PMBB) and gnomAD, respectively. The variant cannot be found in any individuals of European genetic ancestry (EUR) from either of the databases. The variant is found in a region of PMS2 with 100% homology to the PMS2CL pseudogene. PMS2 c.2523G>A p.(W841∗), when identified, is typically an African-ancestry-specific PMS2CL pseudogene variant, which should be recognized to prevent misdiagnosis of Lynch syndrome in Blacks.

Recently, with the vigorous development of the Internet of Things (IoT) technology, all kinds of intelligent home appliances in the market are constantly innovating. The public requirements for residential safety and convenience are also increasing. Meanwhile, with the improvement of indigenous medical technology and quality of life, people’s average lifespan is gradually increasing. However, countries around the world are facing the problem of aging societies. Hand gesture recognition is gaining popularity in the fields of gesture control, robotics, or medical applications. Therefore, how to create a convenient and smart control system of home appliances for the elderly or the disabled has become the objective of this study. It aims to use Google MediaPipe to develop a hand tracking system, which detected 21 key points of a hand through the camera lens of a mobile device and used a vector formula to calculate the angle of the intersection of two lines based on four key points. After the angle of bending finger is obtained, users’ hand gesture can be recognized. Our experiments have confirmed that the recognition precision and recall values of hand gesture for numbers 0–9 reached 98.80% and 97.67%, respectively; and the recognition results were used to control home appliances through the low-cost IoT-Enabled system.

Macroscopic tensile tests are conventionally used to obtain mechanical properties of aged polyethylene (PE) gas pipes, but cannot characterize the inhomogeneous aging behavior of the specimens caused by diffusion-limited oxidation (DLO). Nanoindentation test procedures have, therefore, been adopted to obtain time- and space-dependent mechanical properties of small-sized PE pipe samples, especially, creep properties directly from two types of the PE pipes in accelerated aging and natural conditions. The results indicate that the energy-based method to calculate the initial contact stiffness is not only suitable for cementitious materials and rocks, but also for PE materials. The combination of nanoindentation creep test and generalized Kelvin model can extract detailed parameters that are more representative of the differences in material deformation. The change of crystallinity with aging times probably leading to the difference of mechanical properties was revealed by physical and chemical properties obtained by the DSC and FITR technique. In addition, the correlation between nanoindentation results and structural information also indicates crystallinity plays a dominant role on mechanical performances of the PE pipe. This method using nanoindentation can significantly promote the accuracy of mechanical properties characterization and possess well fitness for PE pipes in accelerated aging conditions or in-service.

Abstract Background In the current study, seizure semiology and potential predictive factors of seizure outcomes in glutamic acid decarboxylase antibody (GAD Ab)-associated neurological syndrome were investigated. Methods In this study, 32 Chinese patients with GAD Ab-associated neurological syndrome who presented with seizures at Peking Union Medical College Hospital from January 2017 to October 2022 were reviewed; 30 had a follow-up duration of more than 1 year. Results Among the 32 patients, 10 presented with epilepsy alone. Concomitant neurological syndromes were observed in 22 patients, including limbic encephalitis (n = 20), stiff-person syndrome (SPS, n = 1), and cerebellar ataxia (n = 1). Bilateral tonic–clonic seizures were observed in 21 patients (65.6%). Focal seizures occurred in 27 patients (84.4%); 17 had focal motor seizures and 18 focal non-motor seizures. Among 30 patients with long-term follow-up, 11 (36.7%) were seizure-free. Acute/subacute onset (p = 0.049) and comorbidity of limbic encephalitis with epilepsy (p = 0.023) led to better seizure outcomes. Patients with persistent epilepsy were more likely to have focal seizure (p = 0.003) and higher frequency of seizure (p = 0.001). Furthermore, these patients tended to have longer intervals from onset to immunomodulatory treatments. Early immunotherapy (within 6 months from onset) was administered in 81.8% of seizure-free patients but only in 42.1% of patients with persistent seizures. However, steroid and immunosuppressant duration did not differ in the two groups. Repeated serum GAD Ab tests during the follow-up showed no association with seizure outcomes. Conclusions The seizure manifestations are diverse and variable. Approximately one third of patients achieved seizure remission during long-term follow-up. The type and frequency of seizures may influence the seizure outcomes. Early immunotherapy, especially within 6 months, may lead to better seizure outcomes.

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

Abstract Background Breast cancer (BRCA) is the most common malignancy with high morbidity and mortality in women, and transcription factor (TF) is closely related to the occurrence and development of BRCA. This study was designed to identify a prognostic gene signature based on TF family to reveal immune characteristics and prognostic survival of BRCA. Methods In this study, RNA-sequence with corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and GSE42568. Prognostic differentially expressed transcription factor family genes (TFDEGs) were screened to construct a risk score model, after which BRCA patients were stratified into low-risk and high-risk groups based on their corresponding risk scores. Kaplan–Meier (KM) analysis was applied to evaluate the prognostic implication of risk score model, and a nomogram model was developed and validated with the TCGA and GSE20685. Furthermore, the GSEA revealed pathological processes and signaling pathways enriched in the low-risk and high-risk groups. Finally, analyses regarding levels of immune infiltration, immune checkpoints and chemotactic factors were all completed to investigate the correlation between the risk score and tumor immune microenvironment (TIME). Results A prognostic 9-gene signature based on TFDEGs was selected to establish a risk score model. According to KM analyses, high-risk group witnessed a significantly worse overall survival (OS) than low-risk group in both TCGA-BRCA and GSE20685. Furthermore, the nomogram model proved great possibility in predicting the OS of BRCA patients. As indicted in GSEA analysis, tumor-associated pathological processes and pathways were relatively enriched in high-risk group, and the risk score was negatively correlated with ESTIMATE score, infiltration levels of CD4+ and CD8+T cells, as well as expression levels of immune checkpoints and chemotactic factors. Conclusions The prognostic model based on TFDEGs could distinguish as a novel biomarker for predicting prognosis of BRCA patients; in addition, it may also be utilized to identify potential benefit population from immunotherapy in different TIME and predict potential drug targets.

Abstract Background Early prediction of treatment response is crucial for the optimal treatment of advanced breast cancer. We aimed to explore whether monitoring early changes in plasma human epidermal growth factor receptor 2 (HER2) levels using digital PCR (dPCR) could predict the treatment response in advanced breast cancer. Methods This was a multicenter, prospective, noninterventional clinical study of patients with advanced breast cancer. All enrolled patients underwent blood testing to measure the HER2 levels by digital PCR before treatment initiation and once every 3 weeks during the study. The primary endpoints werea the diagnostic value of dPCR for detecting HER2 status in the blood andb the relevance of potential changes in the plasma HER2 level at 3 weeks from baseline for predicting treatment response. Results Overall, 85 patients were enrolled between October 9, 2018, and January 23, 2020. dPCR had a specificity of 91.67% (95% CI: 80.61% to 97.43%) for detecting HER2 amplification, and the area under the receiver operating characteristic (ROC) curve was 0.84 (p

Due to their good impact resistance, foam metal composite plates are widely used in the lightweight multi-structure design of cars, and nickel foam is one of the commonly used foam metals. In this paper, the nickel foam composite plates were manufactured, and the self-piercing riveting was used to join the nickel foam composite plates with AA5052 aluminum alloy. The impacts of different energies and times ont the joints were investigated, and the mechanical properties and failure forms of the impacted joints were analyzed. The results show that self-piercing riveting can realize the connection between the composite plate and AA5052 aluminum alloy, and the variation of impact force with displacement is different at various impact energies and times. The higher the impact energy, the deeper the damage to the joint. At 5 J, the impact times have no significant effect on the residual strength, while at 10 J and 15 J, the residual strength decreases with the increased impact times. The failures are all manifested by tearing the lower panel of the composite plate and the rivet head is pulled out from the composite plate, and the impacts do not affect the tensile failure forms of the joints. The aluminum alloy panel shows a ductile fracture, and mixed damage occurs for the adhesive layer.

The stability of nano-TATB in an environment of long-term storage or service is currently one concern since it will affect the reliability of weapon systems. To explore the effects of the residual dimethyl sulfoxide (DMSO) solvent generated during synthesis on the storage performance of nano-TATB, this study proposed a new strategy that utilized solvent atmosphere induction to simulate the effects of residual solvents for the first time and quantified the residual solvents using the equilibrium adsorption capacity (Qe) obtained from the pseudo-first-order adsorption kinetic model. Moreover, this study investigated the storage performance of nano-TATB in the DMSO atmosphere using techniques of scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy (Raman), and infrared (IR) spectroscopy. The results show that the residual DMSO can induce nano-TATB growth more significantly than stimuli in a hot and humid environment. After aging at 60 ​°C for 1 ​d in the DMSO atmosphere, a large number of particles with relatively a regular shape and a particle size of about 1 ​μm were generated in the DMSO atmosphere, with a Qe of DMSO of (1.045 ​± ​0.026) mg·g−1. After aging for 5 ​d, some nano-TATB particles grew and had a particle size of up to 5–6 ​μm, and the average density and cohesive strength of nano-TATB greatly increased. As shown by the analysis of the growth mechanism of nano-TATB in the DMSO atmosphere based on the above experimental results, the main reason for the self-assembly of nano-TATB is the surface DMSO induction caused by the interactions between nano-TATB and DMSO molecules. These results show that the key to improving the storage stability of nano-TATB is to reduce the content of residual solvents.

Selenized whey protein isolate (Se-WPI) was prepared by dry heating and its physicochemical properties such as organic selenium percentage, selenate stability, digestibility, and 77Se-nuclear magnetic resonance (NMR) characteristics as well as anti-prostate cancer activity were evaluated. The results showed that the content of organic selenium in Se-WPI prepared by heating at 80 ℃ for 24 h at pH 3.0 was 2.09%. According to the results of 77Se-NMR and selenate stability, selenium in Se-WPI existed in the form of selenite ester. The biological activities of WPI were improved after selenization. The digestibility of Se-WPI was significantly improved. Like sodium selenite (SS), Se-WPI also showed inhibitory activity against the proliferation of human prostate cancer cell lines LNCaP and DU145, and it could promote the apoptosis of LNCap cells in terms of the cell cycle, apoptosis and caspase-3 activity. In addition, Se-WPI could also inhibit the adhesion of cancer cells to basement membrane components. These results can provide a basis for further research on the anticancer mechanism of organic selenium compounds.

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Abstract Evidence from psychology and cognitive neuroscience indicates that the human brain’s semantic system contains several specific subsystems, each representing a particular dimension of semantic information. Word ratings on these different semantic dimensions can help investigate the behavioral and neural impacts of semantic dimensions on language processes and build computational representations of language meaning according to the semantic space of the human cognitive system. Existing semantic rating databases provide ratings for hundreds to thousands of words, which can hardly support a comprehensive semantic analysis of natural texts or speech. This article reports a large database, the Six Semantic Dimension Database (SSDD), which contains subjective ratings for 17,940 commonly used Chinese words on six major semantic dimensions: vision, motor, socialness, emotion, time, and space. Furthermore, using computational models to learn the mapping relations between subjective ratings and word embeddings, we include the estimated semantic ratings for 1,427,992 Chinese and 1,515,633 English words in the SSDD. The SSDD will aid studies on natural language processing, text analysis, and semantic representation in the brain.

Abstract High tumor mutation load (TMB-H, or TMB ≥ 10) has been approved by the U.S. FDA as a biomarker for pembrolizumab treatment of solid tumors, including non‑small cell lung cancer (NSCLC). Patients with cancer who have immunotherapy-resistant gene mutations cannot achieve clinical benefits even in TMB-H. In this study, we aimed to identify gene mutations associated with immunotherapy resistance and further informed mechanisms in NSCLC. A combined cohort of 350 immune checkpoint blockade-treated patients from Memorial Sloan Kettering Cancer Center (MSKCC) was used to identify genes whose mutations could negatively influence immunotherapy efficacy. An external NSCLC cohort for which profession-free survival (PFS) data were available was used for independent validation. CIBERSORT algorithms were used to characterize tumor immune infiltrating patterns. Immunogenomic features were analysed in the TCGA NSCLC cohort. We observed that PBRM1 mutations independently and negatively influence immunotherapy efficacy. Survival analysis showed that the overall survival (OS) and PFS of patients with PBRM1 mutations (MT) were significantly shorter than the wild type (WT). Moreover, compared with PBRM1-WT/TMB-H group, OS was worse in the PBRM1-MT/TMB-H group. Notably, in patients with TMB-H/PBRM1-MT, it was equal to that in the low-TMB group. The CIBERSORT algorithm further confirmed that the immune infiltration abundance of CD8+ T cells and activated CD4+ memory T was significantly lower in the MT group. Immunogenomic differences were observed in terms of immune signatures, T-cell receptor repertoire, and immune-related genes between WT and MT groups. Nevertheless, we noticed an inverse relationship, given that MT tumors had a higher TMB than the WT group in MSKCC and TCGA cohort. In conclusion, our study revealed that NSCLC with PBRM1 mutation might be an immunologically cold phenotype and exhibited immunotherapy resistance. NSCLC with PBRM1 mutation might be misclassified as immunoresponsive based on TMB.

ObjectiveThis study aimed to explore the effects of eye masks on the sleep quality and pain of children over 5 years old with humeral supracondylar fracture after surgery.MethodsFifty children with humeral supracondylar fracture who underwent closed reduction and percutaneous pinning (CRPP) in the Pediatric orthopaedic Department of a provincial hospital in China from February 2020 to December 2021 were selected. The children were randomly divided into the experimental group (n = 25) and the control group (n = 25). Children in the control group were given routine sleep care, and the children in the experimental group were given a sleep intervention with eye masks for three nights after surgery. The Pittsburgh Sleep Quality Index was used to evaluate the sleep quality of the children. The Children’s Pain Behaviour Scale was used to evaluate the pain of the children.ResultsAfter three nights of receiving the eye mask intervention, the children in the experimental group had significantly lower sleep quality scores than those in the control group; the difference was statistically significant (p

Soil organic matter (SOM) is important for the global carbon cycle, and hyperspectral remote sensing has proven to be a promising method for fast SOM content estimation. However, because of the neglect of the spectral response of soil physical properties, the accuracy and spatiotemporal transferability of the SOM prediction model are poor. This study aims to improve the spatiotemporal transferability of the SOM prediction model by alleviating the coupling effect of soil physical properties on spectra. Based on satellite hyperspectral images and soil physical variables, including soil moisture (SM), soil surface roughness (root-mean-square height, RMSH), and soil bulk weight (SBW), a soil spectral correction model was established based on the information unmixing method. Two important grain-producing areas in Northeast China were selected as study areas to verify the performance and transferability of the spectral correction model and SOM content prediction model. The results showed that soil spectral corrections based on fourth-order polynomials and the XG-Boost algorithm had excellent accuracy and generalization ability, with residual predictive deviations (RPDs) exceeding 1.4 in almost all the bands. In addition, when the soil spectral correction strategy was adopted, the accuracy of the SOM prediction model and the generalization ability after the model migration were significantly improved. The SOM prediction accuracy based on the XG-Boost-corrected spectrum was the highest, with a coefficient of determination (R2) of 0.76, a root-mean-square error (RMSE) of 5.74 g/kg, and an RPD of 1.68. The prediction accuracy, R2 value, RMSE, and RPD of the model after the migration were 0.72, 6.71 g/kg, and 1.53, respectively. Compared with the direct migration prediction of the model, adopting the soil spectral correction model based on fourth-order polynomials and XG-Boost reduced the RMSE of the SOM prediction results by 57.90% and 60.27%, respectively. This performance comparison highlighted the advantages for considering soil physical properties in regional-scale SOM predictions.

The ancient Chinese medical book “Compendium of Materia Medica” records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1β, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

Heavy metal pollution in farmland soil threatens soil environmental quality. It is an important task to quickly grasp the status of heavy metal pollution in farmland soil in a region. Hyperspectral remote sensing technology has been widely used in soil heavy metal concentration monitoring. How to improve the accuracy and reliability of its estimation model is a hot topic. This study analyzed 440 soil samples from Sihe Town and the surrounding agricultural areas in Yushu City, Jilin Province. Considering the differences between different types of soils, a local regression model of heavy metal concentrations (As and Cu) was established based on projection pursuit (PP) and light gradient boosting machine (LightGBM) algorithms. Based on the estimations, a spatial distribution map of soil heavy metals in the region was drawn. The findings of this study showed that considering the differences between different soils to construct a local regression estimation model of soil heavy metal concentration improved the estimation accuracy. Specifically, the relative percent difference (RPD) of As and Cu element estimations in black soil increased the most, by 0.30 and 0.26, respectively. The regional spatial distribution map of heavy metal concentration derived from local regression showed high spatial variability. The number of characteristic bands screened by the PP method accounted for 10–13% of the total spectral bands, effectively reducing the model complexity. Compared with the traditional machine model, the LightGBM model showed better estimation ability, and the highest determination coefficients (R2) of different soil validation sets reached 0.73 (As) and 0.75 (Cu), respectively. In this study, the constructed PP–LightGBM estimation model takes into account the differences in soil types, which effectively improves the accuracy and reliability of hyperspectral image estimation of soil heavy metal concentration and provides a reference for drawing large-scale spatial distributions of heavy metals from hyperspectral images and mastering soil environmental quality.

Controlling overlay in lithography is crucial for improving the yield of integrated circuit manufacturing. The process disturbances can cause undesirable morphology changes of overlay targets (such as asymmetric grating), which can significantly impact the accuracy of overlay metrology. It is essential to decouple the overlay target asymmetry from the wafer deformation, ensuring that the overlay metrology is free from the influence of process-induced asymmetry (e.g., grating asymmetry and grating imbalance). Herein, we use an asymmetric grating as a model and show that using high-diffraction-order light can mitigate the impact of asymmetric grating through the rigorous coupled-wave analysis (RCWA) method. In addition, we demonstrate the diffraction efficiency as a function of the diffraction order, wavelength, and pitch, which has guiding significance for improving the measurement accuracy of diffraction-based overlay (DBO) metrology.

Maize residue cover (MRC) is an important parameter to quantify the degree of crop residue cover in the field and its spatial distribution characteristics. It is also a key indicator of conservation tillage. Rapid and accurate estimation of maize residue cover (MRC) and spatial mapping are of great significance to increasing soil organic carbon, reducing wind and water erosion, and maintaining soil and water. Currently, the estimation of maize residue cover in large areas suffers from low modeling accuracy and poor working efficiency. Therefore, how to improve the accuracy and efficiency of maize residue cover estimation has become a research hotspot. In this study, adaptive threshold segmentation (Yen) and the CatBoost algorithm are integrated and fused to construct a residue coverage estimation method based on multispectral remote sensing images. The maize planting areas in and around Sihe Town in Jilin Province, China, were selected as typical experimental regions, and the unmanned aerial vehicle (UAV) was employed to capture maize residue cover images of sample plots within the area. The Yen algorithm was applied to calculate and analyze maize residue cover. The successive projections algorithm (SPA) was used to extract spectral feature indices from Sentinel-2A multispectral images. Subsequently, the CatBoost algorithm was used to construct a maize residue cover estimation model based on spectral feature indices, thereby plotting the spatial distribution map of maize residue cover in the experimental area. The results show that the image segmentation based on the Yen algorithm outperforms traditional segmentation methods, with the highest Dice coefficient reaching 81.71%, effectively improving the accuracy of maize residue cover recognition in sample plots. By combining the spectral index calculation with the SPA algorithm, the spectral features of the images are effectively extracted, and the spectral feature indices such as NDTI and STI are determined. These indices are significantly correlated with maize residue cover. The accuracy of the maize residue cover estimation model built using the CatBoost model surpasses that of traditional machine learning models, with a maximum determination coefficient (R2) of 0.83 in the validation set. The maize residue cover estimation model constructed based on the Yen and CatBoost algorithms effectively enhances the accuracy and reliability of estimating maize residue cover in large areas using multispectral imagery, providing accurate and reliable data support and services for precision agriculture and conservation tillage.

Abstract The neural representation of concepts is a focus of many cognitive neuroscience studies. Prior works studying concept representation with neural imaging data have been largely limited to concrete concepts. The use of relatively small and constrained sets of stimuli leaves open the question of whether the findings can generalize other concepts. We share an fMRI dataset in which 11 participants thought of 672 individual concepts, including both concrete and abstract concepts. The concepts were probed using words paired with images in which the words were selected to cover a wide range of semantic categories. Furthermore, according to the componential theories of concept representation, we collected the 54 semantic features of the 672 concepts comprising sensory, motor, spatial, temporal, affective, social, and cognitive experiences by crowdsourcing annotations. The quality assessment results verify this as a high-quality neuroimaging dataset. Such a dataset is well suited to study how the brain represents different semantic features and concepts, creating the essential condition to investigate the neural representation of individual concepts.

Background/purpose: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. Methods: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. Results: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). Conclusions: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.