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ABSTRACT: Colorectal cancer (CRC) arises from the accumulation of abnormal mutations in colorectal cells during prolonged inflammation. This study aimed to investigate the potential of probiotic fermented milk containing the probiotic strain, Bifidobacterium animalis ssp. lactis BX-245 (BX-245), in alleviating tumor burden in CRC mice induced by azoxymethane and dextran sodium sulfate. The study monitored changes in tumor size and number, gut microbiota, metabolomics, and inflammation levels before and after the intervention. Our findings indicate that intragastric administration of BX245-fermented milk effectively modulated the intratumor microbiota, as well as the gut microbiota and its metabolism. We also observed a decreased relative abundance of intratumor Akkermansia in the CRC mice, while the intratumor Parabacteroides exhibited a significant positive correlation with tumor number and weight. Moreover, administering BX245-fermented milk significantly reduced gut barrier permeability, alleviated gut barrier damage, and increased serum IL-2 and IFN-γ levels compared with the ordinary fermented milk group. Collectively, our data suggest that administering probiotic fermented milk containing specific functional strains such as BX245 could result in a reduction in tumor burden in CRC mice. Conversely, ordinary fermented milk did not show the same tumor-inhibiting effects. The current results are preliminary, and further confirmation is necessary to establish the causal relationship among probiotic milk, changes in gut microbiota, and disease alleviation.

Abstract Background Gestational hypertension and preeclampsia are potentially linked to similar pathophysiological processes. Maternal preeclampsia increases the occurrence of early-onset neonatal thrombocytopenia. We hypothesized that maternal gestational hypertension may impact the incident early-onset neonatal thrombocytopenia. Methods We included 538 neonates, comprising 318 and 220 neonates born to healthy mothers and those with pregnancy-induced hypertension. The minimum platelet count within 72 h of birth was recorded for these neonates. The incidence of early-onset thrombocytopenia in neonates in relation to maternal gestational hypertension, preeclampsia, and health status was evaluated. Logistic regression analysis was conducted to assess the relationship between maternal gestational hypertension and the risk of early-onset neonatal thrombocytopenia. Results The incidence of early-onset thrombocytopenia was significantly higher in neonates born to mothers with preeclampsia than in those born to mothers with gestational hypertension or healthy mothers. Significant differences were observed among the three groups (30.0% vs. 13.3% vs. 7.9%, p

The application of machine learning, particularly deep learning methods, is becoming increasingly widespread in seismology, achieving near-human accuracy in tasks such as phase detection and event classification. However, most neural network models in seismology currently focus on single tasks. Based on the CSNCD dataset released by the China Earthquake Networks Center, we have developed a bi-directional neural network pre-trained model for single-station data analysis. This model uses three-component seismic waveform data as input and employs convolutional neural networks and bi-directional Transformer models for feature extraction and processing. It not only performs routine tasks such as Pg, Sg, Pn and Sn phase detection, P-wave first-motion direction determination, and event type classification but can also be adapted to other seismic waveform data analysis tasks through transfer learning.

Abstract The global flood risk urges an improved understanding of flood magnitude and its mechanism, which needs insights from pre-instrumental flood investigations. Due to data scarcity, reconstructing pre-instrumental flood magnitudes relies on statistical downscaling, failing to capture nonlinear and dynamic characteristics. We developed a dynamical approach, NorESM-WRF-SWAT, integrating a global climate, a regional, and a hydrologic model to investigate the 1931 Yangtze River flood (the deadliest in the world) and compared it with the 1998’s. Through validation, our method outperforms the statistical method in simulating precipitations and river discharges. For the first time, we presented detailed insights into the intensity and duration of the 1931 flood, revealing a smaller magnitude but associated with an amplified loss, likely due to social vulnerability and reduced societal resilience compared to the 1998’s. While successful simulation can be interfered with by model variability, our dynamical method shows promise for simulating pre-instrumental flood and building a long-term pre-instrumental-hydrology database.

Abstract Objective The objective of this study is to investigate the effect after the application of Failure Model and Effect Analysis (FMEA) in nursing care for patients who have undergone endoscopic submucosal dissection (ESD). Methods A cohort of 40 patients who underwent ESD between July and September 2023 were selected as the control group, while 42 patients who underwent ESD between October 2023 and June 2024 after implementing FMEA were selected as the observation group. A multidisciplinary team was established based on the FMEA model to analyze and create a nursing flowchart. The 3 primary processes and 13 sub-processes were thoroughly analyzed and assessed to identify potential failure models, possible causes of failure, and consequences for each sub-process. Risk Priority Numbers (RPNs) were calculated to determine priority failure models, including medication and item preparation, specimen collection, equipment/instrument/accessory preparation, and nursing coordination. Corresponding improvement measures were formulated and implemented followed by a subsequent analysis of the effects. Results After implementing the improvement measures, there was a significant decrease in RPNs in the observation group when compared with the control group. A statistical significance was observed in context of medication and item preparation (P

Abstract With the rapid advancement of technologies like the Internet, big data, and AI, various apps have impacted the daily lives of the elderly, widening the generational “digital divide.” Adapting apps for elderly users is crucial to addressing this issue. To address this challenge, we first focused on the middle-aged and elderly population, verifying the reliability and validity of the survey results. Then, descriptive statistics were used to analyze user behavior and preferences for the APP aging mode. Finally, ACSI path analysis and the fuzzy-IPA model were applied to assess user satisfaction. The key findings are as follows: (1) The APP aging mode is quite popular; (2) middle-aged and elderly users hesitate to use the aging mode due to “loss of original functions” and “secondary interface layout and font adjustments”; (3) better user experience in the aging mode leads to higher satisfaction, whereas higher initial expectations lead to lower satisfaction; (4) four aspects-“simple operation,” “ease of learning,” “understanding of function descriptions,” and “effective help system”-have high importance but low satisfaction levels. Overall, middle-aged and elderly users find the aging mode satisfactory but with room for improvement.

Abstract Using metal oxides to disperse iridium (Ir) in the anode layer proves effective for lowering Ir loading in proton exchange membrane water electrolyzers (PEMWE). However, the reported low-Ir-based catalysts still suffer from unsatisfying electrolytic efficiency and durability under practical industrial working conditions, mainly due to insufficient catalytic activity and mass transport in the catalyst layer. Herein we report a class of porous heterogeneous nanosheet catalyst with abundant Ir-O-Mn bonds, achieving a notable mass activity of 4 A mgIr −1 for oxygen evolution reaction at an overpotential of 300 mV, which is 150.6 times higher than that of commercial IrO2. Ir-O-Mn bonds are unraveled to serve as efficient charge-transfer channels between in-situ electrochemically-formed IrOx clusters and MnOx matrix, fostering the generation and stabilization of highly active Ir3+ species. Notably, Ir/MnOx-based PEMWE demonstrates comparable performance under 10-fold lower Ir loading (0.2 mgIr cm−2), taking a low cell voltage of 1.63 V to deliver 1 A cm−2 for over 300 h, which positions it among the elite of low Ir-based PEMWEs.

Abstract Background Phaius Lour. (Collabieae, Orchidaceae) is a small genus consisting of about 45 species, with highly ornamental and medicinal values. However, the phylogenetic relationship of Phaius among Calanthe s. l. has been highly debated based on morphological and molecular data. The complete chloroplast (cp) genome has been widely used as a useful molecular marker for resolving phylogenetic problems, while few genomic data on Phaius was available. Therefore, complete cp genomes of eight Phaius species were sequenced and characterized in detail to provide a better understanding of its phylogenetics in Calanthe s. l. Results The cp genomes of eight species investigated exhibited conserved quadripartite structures with varied lengths ranging between 157,997 bp to 158,735 bp. The overall GC content of these genomes ranged between 36.82 and 36.97%. Gene annotation revealed 136 genes in all eight genomes, of which 21 were duplicated in inverted regions and 15 with introns. Comparative analysis of eight cp genomes revealed stable sequence identity with greater variation in the single-copy regions, alongside notable differences in the genes at the LSC/IRb and IRb/SSC junctions, as well as in the number of SSRs. The phylogenetic analysis based on CDS from 49 complete cp genomes of Collabieae indicated that the eight Phaius species, together with other two species P. philippinensis and P. hainanensis, were clustered into a monophyletic clade among Calanthe s. l. and divided into two subclades with strong supports. Additionally, it was also supported that Calanthe s. l. should be divided into five genera with strong supports, including Calanthe s. s., Cephalantheropsis, Styloglossum, Phaius, and Preptanthe. Conclusions It was the first report on the complete cp genome of six Phaius species (P. columnaris, P. mishmensis, P. takeoi, P. tonkinensis, P. wallichii and P. wenshanensis) and has been comparatively analyzed in detail with P. flavus and P. tancarvilleae. It provided a comprehensive investigation of various cp genomic features for phylogenetic implications, including overall genome structure, codon usage, repeat sequences, IR boundaries, DNA polymorphisms, and phylogenetic reconstruction. It was suggested that Phaius and Calanthe s. s. should be treated as two independent genera. The concept of new genus Paraphaius was not confirmed by complete cp genomic data here. The intergeneric relationship of Phaius and its alliance in Calanthe group could be understood better by more cp genomic data.

Abstract Ampullary carcinoma (AC) of the intestinal type represents a distinct variant within the broader category of ampullary neoplasms. The scarcity of pertinent cellular models has constrained investigations centered on this particular malignancy. This research effectively generated a cell line (CL) of intestinal-type AC (DPC-X3). This newly developed CL has been continuously cultured for 1 year and has demonstrated stable passaging exceeding 60 generations. Morphologically, DPC-X3 exhibited characteristic attributes of an epithelial tumor. The cell proliferation rate of DPC-X3 exhibited a doubling interval of 79 h. Short tandem repeat (STR) analysis validated the high consistency between DPC-X3 and the patient’s primary tumor. Characteristically, DPC-X3 displayed sub diploid karyotypes, primarily featuring 44, XY inv (9), -18, -20, -22, and + mar. Under suspension culture conditions, DPC-X3 could efficiently form organoids, and DPC-X3 cells inoculated subcutaneously into NXG mice could form transplanted tumors. Drug susceptibility assays demonstrated that DPC-X3 resisted paclitaxel, oxaliplatin, 5-fluorouracil(5-FU), and gemcitabine. Immunohistochemical (IHC) evaluation revealed affirmative reactivity for CK7 and CK20 within DPC-X3 cells, while CDX2 exhibited no detectable expression. E-cadherin and Vimentin demonstrated positive immunoreactivity, whereas CEA and CA19-9 displayed faint positivity. The Ki-67 proliferation index was determined to be approximately 40%. DPC-X3 presents a valuable experimental platform for elucidating the pathogenesis of intestinal-type AC and can serve as a driver for drug development efforts.

Abstract Background Non-suicidal self-injury (NSSI) emerged as an escalating health concern in youths worldwide, particularly in the vulnerable. In China, a burgeoning internal migration in human history has been tearing families apart, generating a surging number of left-behind children (LBC) with a lack of parental supervision. Despite the empirical acknowledgment of parental migration as a risk predictor of the NSSI among LBC, there remains a lack of understanding of the specific role of the maternal migration experience. Objective This study sought to determine the association of maternal migration experience and its characteristics in terms of age at initiation and length with 12-month NSSI among school-aged children. Participants and setting Data were collected by a self-administrated questionnaire survey conducted among a school-based sample of students in the Anhui province, China. Methods A total of 2476 participants were analyzed, and the Chi-squared tests and binary logistic regression analysis were employed. Results Compared with children whose father is currently migrating and the mother never migrated for work (FM-MN), children whose father never migrated but the mother previously migrated for work (FN-MP, OR = 2.21, 95% CI [1.27–3.84], p

Abstract Thyroid nodules are a common endocrine condition with an increasing incidence over the decades. Data-independent acquisition has been widely utilized in discovery proteomics to identify disease biomarkers and therapeutic targets. To analyze the thyroid disease-related proteome in a high-throughput, reproducible and reliable manner, we introduce thyroid-specific peptide spectral libraries. Here, we generated four deep-coverage libraries through four mass spectrometers comprising Q Exactive HF, Orbitrap Exploris 480, ZenoTOF 7600, and timsTOF Pro. These libraries encompass over 215,000 precursors, 172,000 peptides, and 12,000 proteins, derived from 245 tissue samples across nine histological types and 50 cell lines across six histological types. Moreover, the spectral libraries are applied to nine types of thyroid samples to facilitate the exploration of disease-specific proteins. Our spectral libraries serve as a valuable resource for analyzing thyroid protein content, facilitating deeper insights into thyroid disorders.

Abstract Artificial Intelligence (AI) assumes a pivotal role in Earth science, leveraging deep learning’s predictive capabilities. Despite its prevalence, the impact of AI on scientific discovery remains uncertain. In Earth sciences, the emphasis extends beyond mere accuracy, striving for groundbreaking discoveries with distinct physical properties essential for driving advancements through thorough analysis. Here, we introduce a novel knowledge-guided deep symbolic regression model (KG-DSR) incorporating prior knowledge of physical process interactions into the network. Using KG-DSR, we successfully derived the Penman-Monteith (PM) equation and generated a novel surface resistance parameterization. This new parameterization, grounded in fundamental cognitive principles, surpasses the conventional theory currently accepted in surface resistance parameterization. Importantly, the explicit physical processes generated by AI can generalize to future climate scenarios beyond the training data. Our results emphasize the role of AI in unraveling process intricacies and ushering in a new paradigm in tasks related to “AI for Land Surface Modeling.”

Objective To explore the mediating effect of marital support between the correlation of fear of cancre recurrence (FCR) and the level of mindfulness in patients with gastric cancer.Methods Gastric cancer patients admitted to the department of gastroenterology in the Second Affiliated Hospital of Xuzhou Medical University from August 2020 to August 2022 were selected, and all patients underwent radical gastrectomy treatment. A general information survey, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the Marital Support Questionnaire, and the Mindfulness Attention Awareness Scale (MAAS) were used to investigate the included study subjects. Spearman rank correlation analysis was used to explore the relationship between FCR, mindfulness level, and marital support. The Bootstrap method was used to verify the mediating effect of marital support on the FCR and mindfulness level in gastric cancer patients.Results A total of 120 patients were included. The total FoP-Q-SF score was (27.37±6.03), of which 22 patients had psychological dysfunction due to fear of disease progression. The total score of marital support was (56.81±18.03). The total MAAS score was (54.72±7.75). The results of correlation analysis showed that the FCR and its scores were negatively correlated with the scores of the patients' mindfulness level and total score and scores for each dimension of spousal support (P

Abstract Stroke has become the leading cause of disability in adults worldwide. Early precise rehabilitation intervention is crucial for the recovery of stroke patients, with the key lying in accurately identifying patients’ physical characteristics during the rehabilitation phase. Compared to diagnostic techniques such as medical neuroimaging, traditional Chinese medicine(TCM) tongue diagnosis offers good accessibility and ease of application. However, conventional TCM tongue diagnosis relies on the experience of doctors, which introduces a degree of subjectivity, especially since stroke patients exhibit unique characteristics in tongue texture, shape, and coating, making accurate diagnosis more challenging. To address this issue, this paper proposes a deep learning-based automatic recognition approach for the tongue images of stroke patients, aiming to improve the accuracy of automatic extraction and recognition of stroke-related tongue features through image processing and machine learning techniques. First, this study performs image cropping and data augmentation on tongue images. Then, considering that tongue color, coating color, and coating texture are interrelated in TCM theory and jointly reflect the body’s physiological and pathological state, a label-guided multi-label recognition model for tongue images is designed. This model extracts features from the tongue images of stroke patients, learns the correlations among the features, and performs classification to automatically identify key characteristics such as tongue shape, color, and coating. Finally, the model’s performance is quantitatively evaluated. Experimental results show that the proposed deep learning model outperforms several advanced deep learning models, such as resnet and densenet, and existing single-task tongue classification models in automatically recognizing stroke patients’ tongue images. This research improves the accuracy of feature extraction and recognition of tongue characteristics in stroke patients during rehabilitation, providing a convenient and feasible technical approach for real-time evaluation and diagnosis in the stroke rehabilitation process. It has significant clinical application value and research significance.

Abstract Two-dimensional (2D) semiconductors, combining remarkable electrical properties and mechanical flexibility, offer fascinating opportunities for flexible integrated circuits (ICs). Despite notable progress, so far the showcased 2D flexible ICs have been constrained to basic logic gates and ring oscillators with a maximum integration scale of a few thin film transistors (TFTs), creating a significant disparity in terms of circuit scale and functionality. Here, we demonstrate medium-scale flexible ICs integrating both combinational and sequential elements based on 2D molybdenum disulfide (MoS2). By co-optimization of the fabrication processes, flexible MoS2 TFTs with high device yield and homogeneity are implemented, as well as flexible NMOS inverters with robust rail-to-rail operation. Further, typical IC modules, such as NAND, XOR, half-adder and latch, are created on flexible substrates. Finally, a medium-scale flexible clock division module consisting of 112 MoS2 TFTs is demonstrated based on an edge-triggered Flip-Flop circuit. Our work scales up 2D flexible ICs to medium-scale, showing promising developments for various applications, including internet of everything, health monitoring and implantable electronics.

In order to understand the change of water state and quality characteristics of longan during practical drying production and discover the pivotal drying stages, the dynamic changes of moisture content and state, color, 5-HMF, main nutritional and functional qualities, and antioxidant capacity were monitored through whole intermittent heat pump drying and equilibrium stages. The results showed that the moisture content of longan decreased rapidly during drying stages, and decreased slowly during the equilibrium stages. After through drying stage 2, the free water of longan was removed and transferred coupled with the immobilized water increased. With the drying and equilibrium progress going, the color, browning degree and 5-HMF of longan increased in a step manner, color changes were most significantly occurred in drying stage 3, and the content of 5-HMF was dramatically increased to 55.40 μg/g DW after drying stage 1. On the contrary, the total phenols, total flavonoids, total free amino acids were decreased in a step manner, and decreased to 35.23%, 41.05%, and 42.13% after drying stage 3, respectively, when compared with fresh sample. Moreover, the degradation of total free amino acids was mainly decreased in drying stage 1 and 3. According to antioxidant analysis, the antioxidant capacity of longan was mainly decreased in drying stage 2, which was in conformity with the change of total phenols. Overall, drying stage 1 and 3 were the key stages during the intermittent heat pump drying process, which affected quality characteristics of longan mostly.

In this study, the change of Msalais quality and antioxidant capacity during storage were investigated. The experiments were carried out over a period of 9 months, and analyses were performed monthly. The results showed that the pH, total sugar, and alcohol content of Msalais during the storage period exhibited a decreasing trend, while the total acid content increased. The antioxidant capacity indicated that the contents of total phenols and flavonoids and the scavenging ability of Msalais for DPPH and ABTS decreased markedly with storage time, and stabilizing after 9 months of storage. Furthermore, a total of 27 aroma components, including alcohols, aldehydes, ketones, esters and acids, were detected. After 9 months of storage, the content of most aroma components in Msalais had changed. Among them, the values of the characteristic aroma ingredient phenylethyl alcohol decreased during storage. However, the contents of diisobutyl phthalate, hexadecanoic acid ethyl ester, and octadecanoic acid ethyl ester increased substantially with the following 9 months of storage time. Overall, during the storage process, alcohols, aldehydes and ketones continued to decrease, while esters and acids continued to increase; it was determined that within the 9 month storage period, the longer the storage time, the greater the difference. The obtained findings provide reference data for the optimization of Msalais storage.

Colorectal cancer (CRC) is the third most diagnosed cancer and the second deadliest cancer worldwide representing a major public health problem. In recent years, increasing evidence has shown that microRNA (miRNA) can control the expression of targeted human messenger RNA (mRNA) by reducing their abundance or translation, acting as oncogenes or tumor suppressors in various cancers, including CRC. Due to the significant up-regulation of oncogenic miRNAs in CRC, elucidating the underlying mechanism and identifying dysregulated miRNA targets may provide a basis for improving current therapeutic interventions. In this paper, we proposed Gra-CRC-miRTar, a pre-trained nucleotide-to-graph neural network framework, for identifying potential miRNA targets in CRC. Different from previous studies, we constructed two pre-trained models to encode RNA sequences and transformed them into de Bruijn graphs. We employed different graph neural networks to learn the latent representations. The embeddings generated from de Bruijn graphs were then fed into a Multilayer Perceptron (MLP) to perform the prediction tasks. Our extensive experiments show that Gra-CRC-miRTar achieves better performance than other deep learning algorithms and existing predictors. In addition, our analyses also successfully revealed 172 out of 201 functional interactions through experimentally validated miRNA-mRNA pairs in CRC. Collectively, our effort provides an accurate and efficient framework to identify potential miRNA targets in CRC, which can also be used to reveal miRNA target interactions in other malignancies, facilitating the development of novel therapeutics. The Gra-CRC-miRTar web server can be found at: http://gra-crc-mirtar.com/.

In this study, we utilized material extrusion (MEX) molding additive manufacturing and debinding sintering technology to create pure copper parts with high density and exceptional conductivity. This was achieved using self-developed MEX raw materials with pure copper powder accounting for 60 vol %. The macroscopic and microscopic characteristics of green, debound and sintered parts were comprehensively characterized. The relationship between density and different sizes of nozzles and different layer heights was examined. After immersing the green body in an n-hexane solution at 40 °C for 12 h, a debinding rate of 95 % was achieved. The debounded parts were then sintered at 1050 °C in argon-hydrogen (H∼10 vol %) mixed gas. The results show that the copper parts produced with a 0.6 mm nozzle and 0.1 mm layer height exhibited the best performance, achieving a density greater than 98 %, conductivity of ∼93 % IACS, ultimate tensile strength of 198 MPa, and elongation at break of 34 %. This study offers a novel MEX printing approach for the additive manufacturing of pure copper, focusing on raw material formulation and optimizing experimental parameters.

Abstract Cardiac differentiation of human pluripotent stem cells is not only a new strategy of regenerative therapy for cardiovascular disease treatment but also provides unique opportunities for the study of in vitro disease models and human heart development. To elucidate the dynamic gene regulatory networks and pivotal regulators involved in the cardiomyocyte differentiation process, we conducted an analysis of single-cell RNA sequencing data obtained from the reprogramming of two human induced pluripotent stem cell (iPSC) lines into cardiomyocytes. The data were collected from 32,365 cells at 4 stages of this process. We successfully identified cardiomyocyte clusters and several other cell clusters with different molecular characteristics derived from iPSC and described the differentiation trajectory of cardiomyocytes during differentiation in vitro. Through differential gene analysis and SCENIC analysis, we identified several candidate genes including CREG and NR2F2 that play an important regulatory role in cardiomyocyte lineage commitment. This study provides the key differentiation trajectory of heart differentiation in vitro at single-cell resolution and reveals the molecular basis of heart development and differentiation of iPSC-derived cardiomyocytes.

Abstract Respiratory infections caused by coronaviruses have posed serious and unpredictably public health threats; reliable animal models continue to be essential for advancing our understanding of the virus’s transmission, pathophysiology, and immunological mechanisms. In response to the critical need for centralized resources in coronavirus research, the COVID-AMD database (Coronavirus Disease Animal Model Database, https://www.uc-med.net/CoV-AMD ) has been developed as an integrated platform. Data was gathered from public literature databases, refined and integrated using ETL (Extract, Transform, Load) methodology. After data conversion and cleaning, COVID-AMD was implemented using MySQL relational database with jQuery and JBoss. COVID-AMD database consolidates comprehensive data on animal models infected with various CoVs, including MERS-CoV, SARS-CoV, and SARS-CoV-2, featuring methodologies for establishing infection models, clinical features, and phenotypic data. It catalogs 869 animal models across 29 species and 312 virus strains, covering five diseases and ten infection routes. With global and advanced search capabilities, it facilitated data preprocessing, integration, analysis, and visualization, and provided tools for comparative analysis, model recommendation and omics analysis based on model and phenotype data. The open access to this rich repository aims to enable rapid identification of animal models for CoVs, thereby accelerating the development and clinical trial progression of prospective therapeutics and vaccines.

Abstract Objective Effective postoperative pain management is critical for pediatric craniotomies. Scalp nerve block (SNB) interventions present a potential solution, yet their comparative benefits in preoperative and postoperative settings remain unclear. This study investigated the analgesic effects of SNB in pediatric craniotomy patients by comparing preoperative versus postoperative administration. Methods This randomized trial included 180 children (1–12 years) who underwent elective craniotomy and were assigned to the preoperative, postoperative, or nonblocking control group. The outcomes included cumulative sufentanil use, pain scores (1, 2, 4, 24, 48 h postoperation), rescue medicine utilization, postoperative complications (24, 48 h), and hospitalization length. The primary outcome was total sufentanil use within 24 h postsurgery. Results Total sufentanil use (µg·kg− 1) in the postoperative block group was significantly lower than that in the nonblocking control group at 1 h (P

Abstract Late complications of radiotherapy can include a variety of issues, such as xerostomia, dysphagia, taste changes, digestive and absorption dysfunction. These late complications can seriously impact the nutritional status and quality of life of patients following radiotherapy, and may even adversely affect tumor control and patient survival. Comprehensive nutritional management strategies should be implemented to address these late complications. For radiation-induced xerostomia, salivary stimulant drugs, saliva substitutes, and hyperbaric oxygen therapy have demonstrated efficacy in alleviating dry mouth symptoms. The management of post-radiation trismus remains challenging, with functional training, including active jaw exercises, passive motor devices, and splints, being the primary interventions. In the case of radiation-induced dysphagia, a multidisciplinary team approach is recommended, incorporating malnutrition risk assessment, personalized nutritional treatment, nursing care, rehabilitation training, and patient education. Protecting normal organs, such as the tongue and oral cavity, during radiotherapy planning can help prevent and mitigate taste changes, which can be further managed with zinc supplements, oral care, and lactoferrin supplementation. For post-radiation digestive and absorption dysfunction, a comprehensive assessment of the patient's nutritional status, site of gastrointestinal injury, and potential complications (e.g., bleeding, perforation) is crucial in guiding the selection of appropriate nutritional support, ranging from enteral nutrition as the first-line approach to supplemental or even exclusive parenteral nutrition. Surgical intervention may be necessary in some cases. By implementing these multifaceted nutritional management strategies, healthcare professionals can optimize the care of cancer patients undergoing radiotherapy and mitigate the adverse impact of late radiation complications on their overall well-being and treatment outcomes.

Abstract Background DNA methylation is an epigenetic modification that plays an important role in animal and plant development. Among the diverse types of DNA methylation modifications, methylation of cytosines catalyzed by DNA cytosine methyltransferases (DNMTs) is the most common. Recently, we characterized DNA methyltransferase genes including HlDnmt1 and HlDnmt from the Asian longhorned tick, Haemaphysalis longicornis. However, the dynamic expression and functions of these DNMTs at different developmental stages and feeding statuses of the important vector tick H. longicornis remain unknown. Results The expression levels of HlDnmt1 and HlDnmt were significantly different at the four developmental stages: eggs, larvae, nymphs, and adults, with the highest expression levels observed in the larval stage. HlDnmt1 and HlDnmt showed different expression trends in the midguts, ovary, Malpighian tubules, and salivary glands of engorged adults, with the highest expression of HlDnmt1 observed in the ovary and the lowest in the midguts; HlDnmt expression was the highest in the midguts and the lowest in the Malpighian tubules. After RNA interference, the relative expression of HlDnmt1 and HlDnmt in H. longicornis decreased significantly, resulting in a significant decrease in the biting rate of H. longicornis. RNA-seq revealed that the differentially expressed genes were mainly enriched in the biological processes of peptide biosynthesis and the cell components of ribosomes. Molecular functions were mainly concentrated on oxidoreductase activity, ribosome structure composition, serine-type endopeptidase activity, molecular function regulators, and endopeptidase inhibitor activity. KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in autophagy and lysosome pathways, amino sugar and nucleotide sugar metabolism, glyceride metabolism, ribosomes, and other pathways. Conclusions HlDnmt1 and HlDnmt played an important role during development and feeding of H. longicornis, and their functions were potentially associated with lysosome pathways. These results provide basic knowledge for understanding the epigenetic regulation of the development of the tick H. longicornis, which sheds light on control strategies for ticks and tick-borne diseases.

Abstract Background Spinal orthoses are commonly prescribed for adolescent idiopathic scoliosis (AIS), yet their three-dimensional correction was not fully understood. The amount of deformity control largely depends on the corrective forces applied, which remain empirically based due to a lack of consensus on optimal force application. This study investigated the effects of different corrective force directions exerted by spinal orthoses on patients with AIS. Methods A retrospective analysis was conducted on 78 subjects. The trunk was segmented into four quadrants using coronal and sagittal planes from a top-down perspective. Each left or right posterolateral quadrant (with 90°) was further subdivided into zones 1–4, from the sagittal to coronal planes. Based on the zone where the resultant corrective force direction fell, the subjects were categorized into Group 1 (zone 1), Group 2 (zone 2), Group 3 (zone 3), or Group 4 (zone 4). The direction of the corrective force was estimated using modified models of the subjects’ bodies, designed through a computer-aided design and manufacturing system integral to the orthosis fabrication process. The effects of corrective forces in different zones on scoliotic spine were assessed. Results Among the subjects, 3 were in Group 1, 17 in Group 2, 52 in Group 3, and 6 in Group 4. Due to the limited number of subjects, data from Groups 1 and 4 were not analysed. Groups 2 and 3 showed significant reductions in Cobb angle in the coronal plane and plane of maximum curvature (PMC) following orthosis fitting (p 5º in thoracic kyphosis (p 0.05) but was notably higher in Group 2 after orthosis fitting (p

Abstract Ruthenium (Ru) is widely recognized as a low-cost alternative to iridium as anode electrocatalyst in proton-exchange membrane water electrolyzers (PEMWE). However, the reported Ru-based catalysts usually only operate within tens of hours in PEMWE because of their intrinsically high reactivity of lattice oxygen that leads to irrepressible Ru leaching and structural collapse. Herein, we report a design concept by employing large-sized and acid-resistant lattice lead (Pb) as a second element to induce a pinning effect for effectively narrowing the moving channels of oxygen atoms, thereby lowering the reactivity of lattice oxygen in Ru oxides. The Pb-RuO2 catalyst presents a low overpotential of 188 ± 2 mV at 10 mA cm−2 and can sustain for over 1100 h in an acid medium with a negligible degradation rate of 19 μV h−1. Particularly, the Pb-RuO2-based PEMWE can operate for more than 250 h at 500 mA cm−2 with a low degradation rate of only 17 μV h−1. Experimental and theoretical calculation results reveal that Ru-O covalency is reduced due to the unique 6s−2p−4d orbital hybridization, which increases the loss energy of lattice oxygen and suppresses the over-oxidation of Ru for improved long-term stability in PEMWE.

Background and objective: Stress urinary incontinence (SUI) in women is a common condition that affects middle-aged and elderly women. Currently, there are still many limitations in the epidemiological research on SUI. This study aims to address the gap in the prevalence of female SUI in mainland China and provide theoretical support for the prevention and treatment of SUI. Methods: A comprehensive literature search was conducted on the prevalence of female SUI in mainland China, systematically searching Chinese and English databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Weipu Database as of April 1, 2024. Detailed criteria for screening and exclusion were established. The prevalence of SUI in the selected studies was synthesized using Stata MP (version 15) software, and a multisubgroup analysis, a sensitivity analysis, and publication bias detection of the prevalence of SUI were also performed using the software. Additionally, ArcGIS software (version 10.8) and Geoda software (version 1.2) were utilized to explore the geographical distribution characteristics of the prevalence of female SUI in mainland China. Key findings and limitations: A total of 688 articles were screened, and finally 85 articles were included. The overall rate of female SUI in mainland China was 24.5% (95% confidence interval: 22.5–26.5%). The heterogeneity of the study is statistically significant (I2 = 99.0%, p

Abstract The deep learning (DL)-based prediction of accurate lymph node (LN) clinical target volumes (CTVs) for nasopharyngeal carcinoma (NPC) radiotherapy (RT) remains challenging. One of the main reasons is the variability of contours despite standardization processes by expert guidelines in combination with scarce data sharing in the community. Therefore, we retrospectively generated a 262-subjects dataset from four centers to develop the DL models for LN CTVs delineation. This dataset included 440 computed tomography images from different scanning phases, disease stages and treatment strategies. Three clinical expert boards, each comprising two experts (totalling six experts), manually delineated six basic LN CTVs on separate cohorts as the ground truth according to LN involvement and clinical requirements. Several state-of-the-art segmentation algorithms were evaluated on this benchmark, showing promising results for LN CTV segmentation. In conclusion, this work built a multicenter LN CTV segmentation dataset, which may be the first dataset for automatic LN CTV delineation development and evaluation, serving as a benchmark for future research.

Abstract Background Olezarsen is a GalNAc3-conjugated, hepatic-targeted antisense oligonucleotide that lowers apolipoprotein C-III (apoC-III) and triglyceride levels. The efficacy and safety of olezarsen has not previously been studied in ethnically diverse American populations. The aim of this study is to assess the effect of olezarsen in healthy Japanese Americans. Methods A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 weeks for 4 doses). The primary, secondary, and exploratory objectives were safety and tolerability, pharmacokinetics, and effects of olezarsen on fasting serum triglycerides and apoC-III, respectively. Results There were 20 participants (16 active:4 placebo) in the SAD part of the study, and 8 participants (6 active:2 placebo) in the MD part of the study. For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported. The majority of olezarsen plasma exposure occurred within 24 h post-dose. In the SAD cohorts at Day 15 the percentage reduction in apoC-III/TG was − 39.4%/ − 17.8%, − 60.8%/ − 52.7%, and − 68.1%/ − 39.2% in the 30, 60 and 90 mg doses, respectively, vs 2.3%/44.5% increases in placebo. In the MD cohort, at Day 92 the percentage reduction in apoC-III/TG was − 81.6/ − 73.8% vs − 17.2/ − 40.8% reduction in placebo. Favorable changes were also present in VLDL-C, apoB and HDL-C. Conclusions Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans.

Abstract Background There are no standard treatment options for bilateral multiple pulmonary nodules requiring resection. This study aimed to summarize the experience of simultaneous bilateral uniportal video-assisted thoracoscopic surgery for the treatment of bilateral multiple primary pulmonary nodules. Methods The clinical data of 65 cases of simultaneous bilateral uniportal thoracoscopic surgery for bilateral multiple primary pulmonary nodules treated were retrospectively analyzed. These cases were treated within The Ninth Medical Center of PLA General Hospital between January 2018 and November 2020. Parameters related to the surgery, perioperative aspects, surgical techniques, pathology results, and postoperative complications were examined. Results All surgeries were conducted through uniportal video-assisted thoracoscopic surgery, with no instances of intraoperative conversion to thoracotomy. Fifty-three patients further underwent CT-guided Hookwire localization for the localization of pulmonary nodules. A total of 189 nodules were resected using multiple surgical procedures, with a malignancy rate of 86.2%. The average operation time was 226 ± 77.4 min, the average thoracic drainage duration was 3.1 ± 1.5 days, the average 24 h pleural drainage was 385.9 ± 157.4 mL, the average postoperative hospital stay was 8.6 ± 2.4 days, and the average blood loss was 77.2 ± 33.8 mL. Post-surgery, all patients were transferred to the ward safely within 12 h. 15.38% of patients have prolonged drainage time, and 12.31% of patients experience complications such as lung infection, arrhythmia, and venous thrombosis. Conclusion The selected cases undergoing simultaneous bilateral uniportal video-assisted thoracoscopic surgery for the management of bilateral multiple primary pulmonary nodules demonstrated favorable outcomes. Our observations indicate the safety and feasibility of this procedure, providing an individualized and precise treatment approach for affected patients.

Abstract Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and COVID-19 patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.

Pediatric intracranial germ cell tumors (GCT) are clinically rare but highly heterogeneous tumors, primarily occurring in children and adolescents. The treatment method depends on the tumor type. Pure germinoma can be cured with radiotherapy and chemotherapy, while mature teratomas can be cured with surgical resection. Non-germinomatous germ cell tumors (NGGCT) require comprehensive treatment. Current domestic and international guidelines or expert consensus recommend initial chemotherapy, followed by surgical resection for those not achieving complete remission. However, clinical practice has found that surgery risks increase after chemotherapy, leading some experts to advocate for direct surgery. Beijing Tiantan Hospital, Capital Medical University proposed a clinical diagnosis and treatment strategy for pediatric intracranial NGGCT (2023 Tiantan version), recommending joint evaluation by neurosurgeons and oncologists for individualized treatment to provide better treatment plans for children.

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Using Taraxacum kok-saghyz Rodin (TKS) roots as the raw material, the liquid-solid ratio, ultrasonic power, extraction temperature, and extraction time were selected as experimental factors. On the basis of single factor experiments, the response surface methodology was used to optimize the ultrasonic-assisted extraction process of polyphenols from the TKS roots. The in vitro antioxidant and hypoglycemic activity of the polyphenols extracted from TKS roots were measured. The results showed that the optimal extraction conditions were liquid-solid ratio of 33:1 mL/g, ultrasonic power of 270 W, extraction temperature of 61 ℃, and extraction time of 31 min. Under these conditions, the yield of polyphenols from TKS roots was 1.46%±0.03%. The in vitro activity test showed that the half inhibitory concentrations (IC50) of polyphenol extracts on DPPH and ABTS+ radicals were 54.06 and 39.27 µg/mL, respectively, the IC50 values for α-amylase and α-glucosidase were 133.26 and 50.22 µg/mL, respectively. This indicated that the polyphenols from TKS roots had strong antioxidant and hypoglycemic activities in vitro. This study can provide theoretical basis for the comprehensive development and utilization of TKS.

Abstract In order to ensure the filling integrity of complex counter-gravity casting and improve metallurgical quality, it is necessary to shorten the filling time while avoiding air entrainments. To address this contradiction, a novel nonlinear pressurization method was proposed in this study. Through systematically analyzing the relationship between critical gating velocity and stable filling height, a criterion for iterative calculation of nonlinear pressurization curve was established, and an empirical expression between nonlinear pressurizing speed and the filling height was obtained. Based on the empirical expression, a nonlinear pressurization curve can be designed according to the casting structures and initial pressurizing speeds. The above nonlinear pressure curve design method was validated through water filling experiments. It was proved that the nonlinear pressure curve can shorten the filling time while avoiding air entrainments. It provides important processing control method for improving the low-pressure casting performance of complex castings.

Abstract Background Catheter-associated urinary tract infection (CAUTI) remains the most significant challenge among hospital-acquired infections (HAIs), yet still unresolved. The present study aims to evaluate the preventive effectiveness of JUC Spray Dressing (name of U.S. FDA and CE certifications, while the medical device name in China is Long-acting Antimicrobial Material) alone for CAUTI without combining with antibiotics and to evaluate the impact of bacterial biofilm formation on CAUTI results on the inserted catheters of patients. Methods In this multicenter, randomized, double-blind study, we enrolled adults who suffered from acute urinary retention (AUR) and required catheterization in 6 hospitals in China. Participants were randomly allocated 1:1 according to a random number table to receive JUC Spray Dressing (JUC group) or normal saline (placebo group). The catheters were pretreated with JUC Spray Dressing or normal saline respectively before catheterization. Urine samples and catheter samples were collected after catheterization by trial staff for further investigation. Results From April 2012 to April 2020, we enrolled 264 patients and randomly assigned them to the JUC group (n = 132) and the placebo group (n = 132). Clinical symptoms and urine bacterial cultures showed the incidence of CAUTI of the JUC group was significantly lower than the placebo group (P

Abstract In this study, we successfully established a novel gallbladder cancer cell line, designated as GBC-X1, derived from a primary tumor of a gallbladder cancer patient. By comprehensively analyzing the cell line’s phenotype, molecular characteristics, biomarkers, and histological characteristics, we confirmed that GBC-X1 serves as a valuable model for investigating the pathogenesis of gallbladder cancer and developing therapeutic agents. GBC-X1 has been continuously cultured for one year, with over 60 stable passages. Morphologically, GBC-X1 exhibits typical features of epithelial tumors. The population doubling time of GBC-X1 is 32 h. STR analysis validated a high consistency between GBC-X1 and the patient’s primary tumor. Karyotype analysis revealed an abnormal hypertetraploid karyotype for GBC-X1, characterized by representative karyotypes of 98, XXXX del (4) p (12) del (5) p (21) der (10). Under suspension culture conditions, GBC-X1 efficiently forms tumor balls, while subcutaneous inoculation of GBC-X1 cells into NXG mice leads to xenograft formation with a rate of 80%. Drug sensitivity testing demonstrated that GBC-X1 is resistant to oxaliplatin and sensitive to 5-FU, gemcitabine, and paclitaxel. Immunohistochemistry revealed positive expression of CK7, CK19, E-cadherin, MMP-2, CD44, SOX2, and TP53 in GBC-X1 cells, weak positive expression of Vimentin, and a Ki67 positive rate of 35%. Our research highlights GBC-X1 as a novel gallbladder cancer cell line and emphasizes its potential as an effective experimental model for investigating the pathogenesis of gallbladder cancer and drug development.

Abstract The individuals often show consolation to distressed companions or show aggression to the intruders. The circuit mechanisms underlying switching between consolation and aggression remain unclear. In the present study, using male mandarin voles, we identified that two distinct subtypes of oxytocin receptor (OXTR) neurons in the medial amygdala (MeA) projecting to the anterior insula (AI) and ventrolateral aspect of ventromedial hypothalamus (VMHvl) response differently to stressed siblings or unfamiliar intruders using c-Fos or calcium recording. Oxytocin release and activities of PVN neurons projecting to MeA increased upon consoling and attacking. OXTR antagonist injection to the MeA reduced consoling and attacking. Apoptosis, optogenetic or pharmacogenetic manipulation of these two populations of neurons altered behavioral responses to these two social stimuli respectively. Here, we show that two subtypes of OXTR neurons in the MeA projecting to the AI or VMHvl causally control consolation or aggression that may underlie switch between consolation and aggression.

Abstract Purpose To explore the effects of a single dose of uridine adenosine tetraphosphate (Up4A) administered through the tail vein, on the blood pressure of mice. Methods The mice were separated into three groups: the Up4A group, the norepinephrine (NA) group, and the α, β-methylene adenosine triphosphate (α, β-meATP) group. Each group of mice were injected drugs through the tail vein at 1, 3, 10, and 30 nmol/kg doses in an ascending order. Additionally, six mice were injected Up4A through the tail vein at 20, 40, 60, and 80 nmol/kg doses in an ascending order. The administration intervals for each dose were 20 min. Results Mice in these groups experienced a rapid increase in blood pressure, reaching its peak within 10 s after drug administration. It took approximately 120 s for the blood pressure to return to baseline levels after the administration of the drugs in both the NA and α, β-meATP groups. After higher doses of Up4A were administered to the mice, their blood pressure exhibited biphasic changes. Initially, blood pressure of the mice rapidly dropped to a minimum within 10 s, then rose rapidly to a peak within 30 s. Subsequently, it gradually declined, taking around 10 min to return to the levels before the drug administration. Conclusion Compared to NA and α, β-meATP, Up4A, which contains purine and pyrimidine components, displayed a weaker blood pressure-elevating potency. Through its corresponding structure, Up4A exerted vasodilatory and vasoconstrictive effects throughout the entire experiment resulting in biphasic changes in blood pressure.

Abstract Background Combining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors. Methods Data were obtained from the US Food and Drug Administration Adverse Event Reporting System from 2014 to 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratios (RORs) with 95% confidence intervals (95%Cls). The adjusted RORs (RORadj) were then analysed using logistic regression analysis, considering age, sex, and reporting year. Drug-drug interactions occur when a combination treatment enhances the frequency of an event. Further confirmation of the robustness of the findings was achieved using additive and multiplicative models, which are the two statistical methodologies for signal detection of DDIs using spontaneous reporting system. Results The total number of reports on immune checkpoint combined with proton pump inhibitors was 4,276. Median patient age was 66 years (interquartile range [IQR]: 60–74 years). Significant interaction signals were observed for congenital, familial and genetic disorders (RORadj = 2.66, 95%CI, 1.38–5.14, additive models = 0.7322, multiplicative models = 3.5142), hepatobiliary disorders (RORcrude = 6.64, 95%CI, 5.82–7.58, RORadj = 7.10, 95%CI, 6.16–8.18, additive models = 2.0525, multiplicative models = 1.1622), metabolism and nutrition disorders (RORcrude = 3.27, 95%CI, 2.90–3.69, RORadj = 2.66, 95%CI, 2.30–3.08, additive models = 0.6194), and skin and subcutaneous tissue disorders (RORcrude = 1.41, 95%CI, 1.26–1.58, RORadj = 1.53, 95%CI, 1.34–1.75, additive models = 0.6927, multiplicative models = 5.3599). Subset data analysis showed that programmed death-1 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders; hepatobiliary disorders; and skin and subcutaneous tissue disorders. Programmed death ligand-1 combined with proton pump inhibitors was associated with adverse reactions of metabolism and nutrition disorders. Cytotoxic T-lymphocyte antigen-4 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders, and skin and subcutaneous tissue disorders. Conclusions Based on real-world data, four Standardized MedDRA Query System Organ Class toxicities were identified as drug-drug interactions associated with combining immune checkpoint and proton pump inhibitors. Clinicians should be cautious when administering these drugs concomitantly. Preclinical trials and robust clinical studies are required to explore the mechanisms and relationships underlying interactions, thus improving understanding of drug-drug interactions associated with this combination therapy.

Lauded for its capacity to curtail building energy consumption and enhance environmental performance compared to traditional mineral-based materials, wood has gained substantial traction in the construction sector. Timber construction, which is a focal point of growing interest in both industry and academia, warrants a reassessment of its historical trajectory and future prospects. This study examines publications on timber construction from 1990 to 2022 to analyze the growth path, shifting hotspots, and potential research directions in this field. By employing scientometric analysis, influential journals, articles, countries, and keywords are identified. Integration into a logistic growth model (LGM) showcases publication trends, while the Prophet model forecasts global growth. Research frontiers and emerging themes are revealed through keyword bursts surge evolution. This study offers a visualized knowledge framework, bridging current research with future trends and enabling practitioners and researchers to comprehensively grasp the evolution of timber construction.

【Objective】The study was conducted to analyze the effects of single and mixed fermentation of Dendrocalamus latiflorus with Lactiplantibacillus plantarum and Limosilactobacillus fermentum on their quality, to explore suitable fermentation agents for D. latiflorus.【Method】L. plantarum S1 and L. fermentum G9 were used as fermentation strains to study the effects of single and mixed fermentation of the two Lactobacillus strains on the lactic acid bacteria count, reducing sugars, pH values, total acids, nitrites, antioxidants, organic acids, biogenic amines and volatile compounds of fermented D. latiflorus.【Result】Compared with the natural fermentation group, fermentation with L. plantarum S1 and L. fermentum G9 significantly increased the lactic acid bacteria count, total acids, organic acids and antioxidant activity (P < 0.05) of fermented D. latiflorus, while its pH value and reducing sugar content were reduced. At the 4th day of fermentation, the lactobacillus count in G9 fermentation group was the highest, 8.70 lg (CFU/mL), and at the end of fermentation, the lactobacillus count in inoculated fermentation group was higher than 6.31 lg (CFU/mL), which was significantly higher than that in natural fermentation group. Moreover, the inoculated fermentation groups showed higher total acids and lactic acid contents in comparison with the naturally fermented D. latiflorus. The highest total acid (5.86 g/kg) and lactic acid content (3.66 g/kg) were both found in S1 fermentation group. In addition, inoculated fermentation with lactic acid bacteria could effectively reduce the nitrite and biogenic amine contents of fermented D. latiflorus, and the nitrite and biogenic amine contents of inoculated fermentation groups were significantly lower than those of natural fermentation group during the fermentation. The results of volatile flavor substances analysis showed that 26, 33, 29 and 31 compounds were detected in the natural, S1, G9 and mixed fermentation groups with the relative contents of 12.75, 22.58, 15.15 and 20.81 mg/kg, respectively. Compared with the inoculated fermentation group, the natural fermentation group had relatively fewer types of volatile substances, and the relative content of volatile substances (12.75 mg/kg) was lower than that of other fermentation groups.It was shown that inoculated fermentation could effectively enhance the types and relative contents of volatile flavor substances in fermented D. latiflorus.【Conclusion】The above findings indicated that both L. plantarum S1 and L. fermentum G9 could better enhance the quality and flavor of fermented D. latiflorus, which could be used as potential fermentation agents for D. latiflorus.

Immune checkpoint inhibitors (ICIs) become integral in clinical practice, yet their application in cancer therapy is constrained by low overall response rates and the primary resistance of cancers to ICIs. Herein, this study proposes aggregation-induced emission (AIE)-based nanoparticles (NPs) for a more effective and synergistic approach combining immunotherapy and photodynamic therapy (PDT) to achieve higher responses than anti-PD-L1 monotherapy. The TBP@aPD-L1 NPs are constructed by functionalizing azide group-modified TBP-2 (TBP-N3) with anti-PD-L1 antibodies via the DBCO-S-S-PEG2000-COOH linker. The anti-PD-L1 target the tumor cells and promote the TBP-N3 accumulation in tumors for enhanced PDT. Notably, the TBP-N3, featuring aggregation-induced emission, boosts reactive oxygen species (ROS) generation through both type I and type II processes for enhanced PDT. The TBP@aPD-L1-mediated PDT induces more powerful effects of direct tumor cell-killing and further elicits effective immunogenic cell death (ICD), which exerts anti-tumor immunity by activating T cells for ICI treatment and reshapes the tumor immune microenvironment (TIME), thereby enhancing the efficacy of PD-L1 blockade of anti-PD-L1. Consequently, TBP@aPD-L1 NPs demonstrated significantly enhanced inhibition of tumor growth in the mouse model of malignant melanoma (MM). Our NPs act as a facile and effective drug delivery platform for enhanced immunotherapy combined with enhanced PDT in treating MM.

ABSTRACT Aim This study was to establish a scientific and sensitive index system of the biosafety incident response competence for clinical nursing staff to provide a reference for the evaluation of nurses' biosafety incident response competence. Design A modified recommendation for the conducting and reporting of Delphi studies was used to guide this study. Methods According to the literature review, preliminary biosafety incident response competence indicators for nursing staff were established, and an expert survey questionnaire was designed. The evaluation system for clinical nurses' biosafety incident response competence indicators was determined using the Delphi method. Results After two‐round Delphi survey, 28 nursing specialists from six provinces and cities around China, with expertise in three prevention research, epidemiology, military health service and biosafety incident rescue, established the index system of the biosafety incident response competence for nursing staff from April to May 2023. The final index system of the biosafety incident response competence was composed of four primary indicators, namely, biosafety incident preparedness, monitoring competence, protection ability and nursing disposal abilities; 10 secondary indicators and 49 tertiary indicators. The effective recovery rates of the two rounds of expert survey questionnaires were 93.33% and 100%, respectively. The authority coefficient, judgement coefficient and familiarity degree of Delphi experts were 0.877, 0.911 and 0.843, respectively. The Kendall's harmony coefficients of the two rounds of expert consultation were 0.301–0.384 and 0.401–0.424, respectively, with statistical significance (p

IntroductionDiagnosing the types of malignant lymphoma could help determine the most suitable treatment, anticipate the probability of recurrence and guide long-term monitoring and follow-up care.MethodsWe evaluated the differences in benign, lymphoma and metastasis superficial lymph nodes using ultrasonography and tissue metabolomics.ResultsOur findings indicated that three ultrasonographic features, blood supply pattern, cortical echo, and cortex elasticity, hold potential in differentiating malignant lymph nodes from benign ones, and the shape and corticomedullary boundary emerged as significant indicators for distinguishing between metastatic and lymphoma groups. Metabolomics revealed the difference in metabolic profiles among lymph nodes. We observed significant increases in many amino acids, organic acids, lipids, and nucleosides in both lymphoma and metastasis groups, compared to the benign group. Specifically, the lymphoma group exhibited higher levels of nucleotides (inosine monophosphate and adenosine diphosphate) as well as glutamic acid, and the metastasis group was characterized by higher levels of carbohydrates, acylcarnitines, glycerophospholipids, and uric acid. Linear discriminant analysis coupled with these metabolites could be used for differentiating lymph nodes, achieving recognition rates ranging from 87.4% to 89.3%, outperforming ultrasonography (63.1% to 75.4%).DiscussionOur findings could contribute to a better understanding of malignant lymph node development and provide novel targets for therapeutic interventions.

Introduction and Objectives: Liver plays a key role in sepsis, a systemic inflammatory response syndrome caused by infection. Ferroptosis is involved in sepsis-induced liver injury. We aimed to assess the changes in ferroptosis in cecal ligation and puncture (CLP)-induced septic mice, and determine the role of lipocalin-2 (LCN2) in liver ferroptosis. Materials and Methods: CLP was used to induce sepsis in mice. The morphological changes in liver tissues and mitochondrial structure were observed using hematoxylin and eosin staining and transmission electron microscopy. The levels of serum alanine transaminase, aspartate aminotransferase, superoxide dismutase, and malondialdehyde were detected using the corresponding kits. The changes of reactive oxygen species level in liver tissues were detected using dihydroethidium as a fluorescence probe. LCN2, cysteine-glutamate reverse transport system, and dihydroorotate dehydrogenase protein levels in the liver were detected by western blotting. The ferroptosis inhibitor ferrostatin-1 (Fer-1), iron chelator dexrazoxane (DXZ), iron-dextran, and LCN2 knockdown studies were performed to determine role of ferroptosis and LCN2 in liver injury during sepsis. Results: Ferroptosis levels increased in the liver tissues of CLP-induced septic mice. Both Fer-1 and DXZ suppressed ferroptosis and attenuated liver injury following sepsis challenge, whereas iron-dextran increased ferroptosis and liver injury in mice with sepsis. LCN2 knockdown suppressed ferroptosis and reduced oxidative stress in the liver. Conclusions: Ferroptosis inhibition attenuates septic liver injury. LCN2 knockdown alleviates sepsis-induced liver injury by inhibiting ferroptosis and reducing oxidative stress.

During investigations of freshwater fungi in Hunan and Yunnan provinces, China, Chaetopsina yunnanensis sp. nov. (Nectriaceae), Parafuscosporella hunanensis sp. nov. (Fuscosporellaceae), and Pleurotheciella yunnanensis sp. nov. (Pleurotheciaceae) were discovered on submerged decaying wood and branches. Based on phylogenetic analyses, C. yunnanensis formed a separate branch with Chaetopsina pinicola and nested among other Chaetopsina species in Nectriaceae (Hypocreales). Furthermore, hitherto known Chaetopsina beijingensis shared the same branch with Chaetopsina fulva, a type species of the genus, demonstrating their conspecific status. Therefore, C. beijingensis is formally synonymized under C. fulva, with an amended species circumscription. Pa. hunanensis formed a well-separated subclade with the ex-type strain of Parafuscosporella mucosa and clustered with other Parafuscosporella within Fuscosporellaceae (Fuscosporellales). In addition, the genus Parafuscosporella is treated as distinct from Vanakripa due to a lack of phylogenetic evidence in clarifying their congeneric status with the latter. Pl. yunnanensis is found to be sister to Pleurotheciella saprophytica, forming a subclade with Pleurotheciella dimorphospora within the Pleurotheciaceae (Pleurotheciales). Morphologically, C. yunnanensis fits well with the generic concept of Chaetopsina in forming a holomorphic state with hyphomycetous asexual morph producing pigmented, setiform conidiophores, phialidic conidiogenous cells, hyaline conidia, and nectria-like sexual morph. Pa. hunanensis fits well with Parafuscosporella in having acrogenous, apiosporous, versicolored, obovoid to obpyriform conidia. In contrast, Pl. yunnanensis resembles Pl. dimorphospora in forming asexual dimorphism with two types of conidia (Type I, brown, muriform/phragmosporous conidia; Type II, hyaline, amerosporous/didymorsporous conidia). The novelty of taxa is explained with detailed descriptions, photo-micrographic illustrations, polymorphism, and multigene phylogenetic analyses of Bayesian inference and maximum likelihood criteria.

Ischemia-reperfusion injury is a serious clinical pathology involving multiple organs such as the heart and brain. The injury results from oxidative stress, inflammatory response and cell death triggered by restoring tissue blood flow after ischemia, leading to severe cell and tissue damage. In recent years, the volume-regulated anion channel (VRAC) has gained attention as an important membrane protein complex. VRAC plays a dual role in ischemia-reperfusion injury: on the one hand, activated VRAC promotes the release of intracellular chloride and glutamate, exacerbating cellular swelling and excitotoxicity, and on the other hand, the regulatory effect of VRAC may also provide protection to cardiomyocytes. This article reviews the pathophysiological mechanisms of ischemia-reperfusion injury, existing therapeutic strategies and their limitations, focuses on the molecular structure of VRAC, its activation mechanism, and its role in ischemia-reperfusion injury, and concludes with a discussion of the potential of targeted inhibition of VRAC as an emerging therapeutic strategy and the challenges it faces. A deeper understanding of the role of VRAC in ischemia-reperfusion injury is expected to provide new therapeutic ideas to improve patient prognosis.

Abstract This study introduces a novel fluorescent light‐up electrospun membrane, integrating PbBr2, which serves as an exceptionally selective probe for the detection of cesium ions (Cs+). Leveraging the superior optical properties of CsPbBr3 perovskite nanocrystals (PNCs), the researchers employ electrospinning technology to fabricate a test strip, namely PbBr2@polyacrylonitrile (PbBr2@PAN) nanofiber membranes, capable of swiftly detecting Cs+ in water merely by observing changes in the nanocrystals' luminescence with the naked eye. By the introduction of NH4+‐modified montmorillonite (NH4+‐MMT), PbBr2‐MT@PAN nanofiber membranes is obtained. The selectivity and sensitivity to Cs+ can be further improved because NH4+‐MMT endows PbBr2‐MT@PAN nanofiber membranes with the hydrophilic property and selective adsorption toward Cs+ ions. The membrane's fabrication is simple, scalable, and cost‐effective, with high cesium selectivity and sensitivity down to 44 ppb. This innovation enables efficient, on‐site cesium monitoring critical for environmental safety and nuclear waste management.