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Abstract In the evolving landscape of smart libraries, this research pioneers an IoT-based low-cost architecture utilizing Software-Defined Networking (SDN). The increasing demand for more efficient and economical solutions in library management, particularly in the realm of RFID-based processes such as authentication, property circulation, and book loans, underscores the significance of this study. Leveraging the collaborative potential of IoT and SDN technologies, our proposed system introduces a fresh perspective to tackle these challenges and advance intelligent library management. In response to the evolving landscape of smart libraries, our research presents an Internet of Things (IoT)-based low-cost architecture utilizing SDN. The exploration of this architectural paradigm arises from a recognized gap in the existing literature, pointing towards the necessity for more efficient and cost-effective solutions in managing library processes. Our proposed algorithm integrates IoT and SDN technologies to intelligently oversee various library activities, specifically targeting RFID-based processes such as authentication, property circulation management, and book loan management. The system's architecture, encompasses components like the data center, SDN controllers, RFID tags, tag readers, and other network sensors. By leveraging the synergy between RFID and SDN, our innovative approach reduces the need for constant operator supervision in libraries. The scalability and software-oriented nature of the architecture cater to extensive library environments. Our study includes a two-phase investigation, combining practical implementation in a small-scale library with a simulation environment using MATLAB 2021. This research not only fills a crucial gap in current knowledge but also lays the foundation for future advancements in the integration of IoT and SDN technologies for intelligent library management.

Abstract Background Pancreatic cancer stem cells are crucial for tumorigenesis and cancer metastasis. Presently, long non-coding RNAs were found to be associated with Pancreatic Ductal Adenocarcinoma stemness characteristics but the underlying mechanism is largely known. Here, we aim to explore the function of LINC00909 in regulating pancreatic cancer stemness and cancer metastasis. Methods The expression level and clinical characteristics of LINC00909 were verified in 80-paired normal pancreas and Pancreatic Ductal Adenocarcinoma tissues from Guangdong Provincial People’s Hospital cohort by in situ hybridization. RNA sequencing of PANC-1 cells with empty vector or vector encoding LINC00909 was experimented for subsequent bioinformatics analysis. The effect of LINC00909 in cancer stemness and metastasis was examined by in vitro and in vivo experiments. The interaction between LINC00909 with SMAD4 and the pluripotency factors were studied. Results LINC00909 was generally upregulated in pancreatic cancer tissues and was associated with inferior clinicopathologic features and outcome. Over-expression of LINC00909 enhanced the expression of pluripotency factors and cancer stem cells phenotype, while knock-down of LINC00909 decreased the expression of pluripotency factors and cancer stem cells phenotype. Moreover, LINC00909 inversely regulated SMAD4 expression, knock-down of SMAD4 rescued the effect of LINC00909-deletion inhibition on pluripotency factors and cancer stem cells phenotype. These indicated the effect of LINC00909 on pluripotency factors and CSC phenotype was dependent on SMAD4 and MAPK/JNK signaling pathway, another downstream pathway of SMAD4 was also activated by LINC00909. Specifically, LINC00909 was localized in the cytoplasm in pancreatic cancer cells and decreased the stability the SMAD4 mRNA. Finally, we found over-expression of LINC00909 not only accelerated tumor growth in subcutaneous mice models, but also facilitated tumorigenicity and spleen metastasis in orthotopic mice models. Conclusion We demonstrate LINC00909 inhibits SMAD4 expression at the post-transcriptional level, which up-regulates the expression of pluripotency factors and activates the MAPK/JNK signaling pathway, leading to enrichment of cancer stem cells and cancer metastasis in pancreatic cancer.

The objective of this study was to determine the differences of aroma and taste in three black sesame originsbefore and after processing via flavor and widely metabolomics. By analyzing the sensory characteristics and metabolites of raw and treated black sesame from China, Vietnam, and Myanmar, treated Chinese sesame have the most significant change in hardness after thermal processing, low viscosity and was easy to chew. The electronic nose could distinguish between raw and treated sesame due to the aroma distribution. The reason of treated sesame from China was “fragrant” is due to the highest content (2545.50 ​μg/kg) of total pyrazines including 2,5-dimethylpyrazine, 2-ethyl-5-methylpyrazine, 2,3,5-trimethylpyrazine, 3-ethyl-2,5-dimethylpyrazine. 933 metabolites were detected via a wide targeted metabolomics in the taste of raw and treated sesame. Based on the analysis of metabolites related to bitterness, 145 substances were selected. The main bitter contributors may be amino acids, dipeptides and organic acids.

The aerodynamic drag of a high-speed train has a significant impact on its energy consumption. At high speeds, the pantograph is one of the primary sources of aerodynamic drag for the train. To enhance train operation characteristics and reduce aerodynamic drag, two optimized pantograph models with bionic non-smooth grooves beneath carbon slide plates were designed based on bionic non-smooth theories, using shark skin as the bionic object. The Navier-Stokes equation and k-ϵ turbulence model were adopted to simulate the flow field structure of two pantograph optimized models. The results show the structure of pantograph head has a significant effect on its separation point of the boundary layer, the wake flow and the tail vortex area. Compared to the pantograph head with arc-shaped grooves, the pantograph head with V-shaped grooves exhibits a more significant backward movement of the boundary layer of separation point. This results in a more stable wake flow and a more pronounced reduction in the area of the tail vortex. Furthermore, incorporating V-shaped grooves beneath the carbon slide plate resulted in an average rate of drag reduction increase of 4.9% for the pantograph head and 4.7% for the pantograph compared to the original pantograph.

This is an article in the field of earth sciences. Manganese ore is one of the strategic minerals in short supply in China. The area of Northern Guizhou-Eastern Yunnan is the most typical distribution area of manganese ore in Permian, which is also rare in the Late Paleozoic in the world. It is rich in manganese ore resources and has great prospecting potential, so it is called "Zunyi type manganese ore". The results show that the manganese ore is produced in the late Permian Maokou, and its distribution is strictly controlled by the northern Guizhou rift basin. The manganese ore is formed in the center of graben basin by exhalation deposition, but no manganese ore is distributed in the barrier area, and the ore-body spatial distribution direction is basically consistent with the basin distribution direction. Among them, manganese ore in Zunyi - western Guizhou area is spatially distributed in the basin facies area, and can be divided into three manganese ore facies belts, namely, the central phase, the transition phase and the edge, which further indicates the specific metallogenic location of manganese ore and shows that the manganese ore is controlled by the center of the basin. Based on the Zunyi-Xuanwei manganese ore belt, it can be divided into four manganese ore concentration areas in the Zunyi-Qianxi manganese ore mineralization subzone: Shenxi-Bali, Longping-Xinglong, Tuanxi-Shangji and Qianxi, and two manganese ore concentration areas in shuicheng - Xuanwei manganese ore mineralization subzone: Shuicheng - Nayong and Gexue.The research results are of great significance to search for Permian concealed manganese deposits in northern Guizhou and eastern Yunnan and to carry out metallogenic prediction.

Abstract Bone marrow ablation is routinely performed before hematopoietic stem cell transplantation (HSCT). Hematopoietic stem and progenitor cells (HSPCs) require a stable bone marrow microenvironment to expand and refill the peripheral blood cell pool after ablation. Roundabout guidance receptor 4 (Robo4) is a transmembrane protein exclusive to endothelial cells and is vital in preserving vascular integrity. Hence, the hypothesis is that Robo4 maintains the integrity of bone marrow endothelial cells following radiotherapy. We created an endothelial cell injury model with γ-radiation before Robo4 gene manipulation using lentiviral-mediated RNAi and gene overexpression techniques. We demonstrate that Robo4 and specific mesenchymal proteins (Fibronectin, Vimentin, αSma, and S100A4) are upregulated in endothelial cells exposed to irradiation (IR). We found that Robo4 depletion increases the expression of endoglin (CD105), an auxiliary receptor for the transforming growth factor (TGF-β) family of proteins, and promotes endothelial-to-mesenchymal transition (End-MT) through activation of both the canonical (Smad) and non-canonical (AKT/NF-κB) signaling pathways to facilitate Snail1 activation and its nuclear translocation. Endothelial Robo4 overexpression stimulates the expression of immunoglobulin-like adhesion molecules (ICAM-1 and VCAM-1) and alleviates irradiation-induced End-MT. Our coculture model showed that transcriptional downregulation of endothelial Robo4 reduces HSPC proliferation and increases HSC quiescence and apoptosis. However, Robo4 overexpression mitigated the damaged endothelium’s suppressive effects on HSC proliferation and differentiation. These findings indicate that by controlling End-MT, Robo4 preserves microvascular integrity after radiation preconditioning, protects endothelial function, and lessens the inhibitory effect of damaged endothelium on hematopoietic reconstitution.

To fully leverage the application potential of distributed energy storage systems (DESS) and network reconfiguration, a coordinated optimization method is proposed to enhance the economic efficiency of distribution networks under normal conditions and the reliability of a power supply during fault conditions. First, a scenario-generation method is developed based on Latin hypercube sampling and Kantorovich distance synchronous back-substitution reduction is used to obtain the typical scenario of wind and solar output. Next, a planning operation coordinated optimization framework and model are established, considering both normal and fault states of the distribution network. In the planning layer, the objective is to minimize the annual comprehensive capital expenditures for the distribution network to improve the economic efficiency of the distribution network. The operation layer includes both normal operation and fault operation states, with the optimization goal of minimizing the sum of normal operation costs and the fault costs associated with load shedding. Subsequently, a hybrid optimization algorithm combining an improved Aquila Optimizer-Second-Order Cone Programming (IAO-SOCP) is proposed to solve the coordinated optimization model. Finally, the proposed coordinated optimization method is validated using an enhanced IEEE 33-bus distribution network case study. The results demonstrate that the method effectively reduces network losses and minimizes load shedding costs during fault conditions, thereby ensuring a balance between the economic efficiency and reliability of the distribution network.

Abstract Bedload transport is a natural process that strongly affects the Earth's surface system. An important component of quantifying bedload transport flux and establishing early warning systems is the identification of the onset of bedload motion. Bedload transport can be monitored with high temporal resolution using passive acoustic methods, for example, hydrophones. Yet, an efficient method for identifying the onset of bedload transport from long‐term continuous acoustic data is still lacking. Benford's Law defines a probability distribution of the first‐digit of data sets and has been used to identify anomalies. Here, we apply Benford's law to continuous acoustic recordings from Baiyang hydrometric station, a tributary of Liwu River, Taroko National Park, Taiwan at the frequency of 32 kHz from stationary hydrophones deployed for 3 years since 2019. We construct a workflow to parse sound combinations of bedload transportation and analyze them in the context of hydrometric sensing constraining the onset, and recession of bedload transport. We identified three separate sound classes in the data related to the noise produced by the motion of pebbles, water flow, and air. We identify two bedload transport events that lasted 17 and 45 hr, respectively, covering about 0.35% of the total recorded time. The workflow could be transferred to other different catchments, events, or data sets. Due to the influence of instrument and background noise on the regularity of the residuals of the first‐digit, we recommend identifying the first‐digit distribution of the background noise and ruling it out before implementing this workflow.

Short neuropeptide F (sNPF) is a neuropeptide that widely distributed among arthropods. This neuropeptide has been proposed to play pleiotropic roles in insects, but its physiological functions in crustaceans are poorly understood. Here, we cloned the cDNA sequences of sNPF and its putative receptor (sNPFR) from the swimming crab, Portunus trituberculatus, and determined their possible roles during ovarian development. PtsNPF encodes three sNPF mature peptides with a conserved C-terminal “RLRFG” motif. All three PtsNPF peptides concentration-dependently activated PtsNPFR expressed in HEK293T cells, with EC50 values in the nanomolar range. PtsNPF and PtsNPFR transcripts showed a broad distribution among neural and non-neural tissues. During the ovarian development, expression of PtsNPF and PtsNPFR in hepatopancreas and ovary both increased to the highest levels at the late-vitellogenic stage, a period for rapid vitellogenesis. The in vitro experiments further showed that, among the three sNPF peptides, sNPF3 treatments can induce the vitellogenin (Vg) gene and protein levels in the hepatopancreas, as well as the Vg receptor (VgR) gene and protein levels and vitellogenin (Vn) deposition in the ovary. Opposing effects were observed for the dsPtsNPFR treatments, suggesting that PtsNPFR plays a role in the PtsNPF-mediated vitellogenesis. Additionally, it was found that the PtsNPF/PtsNPFR system can activate different second messengers species in hepatopancreas and ovary, suggesting it may act via different G proteins.

In bronchial ultrasound elastography, accurately segmenting mediastinal lymph nodes is of great significance for diagnosing whether lung cancer has metastasized. However, due to the ill-defined margin of ultrasound images and the complexity of lymph node structure, accurate segmentation of fine contours is still challenging. Therefore, we propose a dual-stream feature-fusion attention U-Net (DFA-UNet). Firstly, a dual-stream encoder (DSE) is designed by combining ConvNext with a lightweight vision transformer (ViT) to extract the local information and global information of images; Secondly, we propose a hybrid attention module (HAM) at the bottleneck, which incorporates spatial and channel attention to optimize the features transmission process by optimizing high-dimensional features at the bottom of the network. Finally, the feature-enhanced residual decoder (FRD) is developed to improve the fusion of features obtained from the encoder and decoder, ensuring a more comprehensive integration. Extensive experiments on the ultrasound elasticity image dataset show the superiority of our DFA-UNet over 9 state-of-the-art image segmentation models. Additionally, visual analysis, ablation studies, and generalization assessments highlight the significant enhancement effects of DFA-UNet. Comprehensive experiments confirm the excellent segmentation effectiveness of the DFA-UNet combined attention mechanism for ultrasound images, underscoring its important significance for future research on medical images.

PurposeThe development of multiple system diseases is increased by obesity. However, the connection between obesity and developmental disabilities (DDs) in children is unclear. As an obesity index, the weight-adjusted waist index (WWI) assessed fat distribution and muscle mass. In this study, we examined the correlation between WWI and DDs among children 6 to 17 years of age.MethodsThis study used data from the National Health and Nutrition Examination Survey database (NHANES) covering 2003 to 2018, which included the data of 17,899 participants between 6 and 17 years of age. Data regarding their waist circumference, weight, and DDs were collected via physical examinations and questionnaire, respectively. A person’s WWI is calculated by dividing their waist circumference by their weight squared. The correlation between WWI and DDs was studied using weighted multiple logistic regression models. Additionally, a sensitivity analysis was conducted utilizing a generalized additive model and smooth curve fitting.ResultsAfter adjusting for all covariates, WWI was positively related to DDs in children ages 6-17. Based on the sensitivity analysis, the correlation between the WWI and prevalence of DDs remained consistent across subgroups. Additionally, there was a J-shaped correlation between the WWI and the prevalence of DDs in children ages 6 through 11.ConclusionChildren 6–17 years of age with a high WWI were at greater risk for DDs; however, the causal relationships and potential mechanisms require further exploration.

Summary: Recent phenomena such as pandemics, geopolitical tensions, and climate change-induced extreme weather events have caused transportation network interruptions, revealing vulnerabilities in the global supply chain. A salient example is the March 2021 Suez Canal blockage, which delayed 432 vessels carrying cargo valued at $92.7 billion, triggering widespread supply chain disruptions. Our ability to model the spatiotemporal ramifications of such incidents remains limited. To fill this gap, we develop an agent-based complex network model integrated with frequently updated maritime data. The Suez Canal blockage is taken as a case study. The results indicate that the effects of such blockages go beyond the directly affected countries and sectors. The Suez Canal blockage led to global losses of about $136.9 ($127.5–$147.3) billion, with India suffering 75% of these losses. Global losses show a nonlinear relationship with the duration of blockage and exhibit intricate trends post blockage. Our proposed model can be applied to diverse blockage scenarios, potentially acting as an early-alert system for the ensuing supply chain impacts. Furthermore, high-resolution daily data post blockage offer valuable insights that can help nations and industries enhance their resilience against similar future events.

Background and aimsPatients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure.MethodsThis retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab).ResultsA total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p

IntroductionThe air-curing process of cigar tobacco, as a key step in enhancing the quality of cigars, is often susceptible to contamination by mold spores, which severely constrains the quality of cigar tobacco.MethodsThis study employed high-throughput Illumina sequencing technology and a continuous flow analysis system to analyze the differences between the microbial communities and physicochemical components of moldy and healthy cigar tobacco leaves. Furthermore, correlation analysis was performed to reveal the impact of mold on the quality of cigar tobacco.ResultsThe differences between the microbial flora and physicochemical compositions of moldy (MC) and healthy (HC) tobacco leaves were analyzed, revealing significant disparities between the two groups. Aspergillus spp. represented the dominant mold in MC, with nine out of twelve isolated molds showing higher quantities on MC than on HC. Mold contamination notably decreased the total nitrogen (TN), total phosphorus (TP), total alkaloids (TA), starch, protein, and flavor constituents while increasing the total fatty acid esters (TFAA), which was accompanied by a shift towards weakly acidic pH in the leaves. Fungal community analysis indicated a significant reduction in the fungal operational taxonomic unit (OUT) numbers and diversity indices in MC, contrasting with the bacterial trends. Aspergillus exhibited significantly higher relative abundance in MC, with LEfSe analysis pinpointing it as the primary driver of differentiation. Furthermore, significant negative correlations were observed between Aspergillus and TP, starch, TA, and protein, while a significant positive association was evident with TFAA. Network analysis underscored the pivotal role of Aspergillus as the species influencing disparities between HC and MC, with its abundance serving as a critical determinant during the air-curing process.DiscussionThis study elucidated substantial quality distinctions between MC and HC during air-curing, with Aspergillus emerging as the key species contributing to leaf mold.

Abstract CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy.

Infection by the novel duck reovirus (NDRV) in ducklings causes high mortality, which leads to substantial economic losses in the duck industry in China. To date, no commercial vaccine is available for this disease. In this study, linear B cell epitopes of the σB protein of the NDRV were predicted and recombinant multiple linear B cell epitopes (MLBEs) were constructed through linkers. The recombinant MLBEs were then expressed and purified. One-day-old Muscovy ducklings were immunized with different doses of MLBEs and challenged with 5 × 104 ELD50 of the virulent CHY strain of NDRV 14 days after immunization. The ducklings vaccinated with 20 and 40 μg of MLBE performed no clinical signs or gross or histopathological lesions, indicating 100% protection against infection. The viral load in the liver and spleens of these birds was significantly lower than that in the control group. Additionally, these ducklings exhibited positive seroconversion at 7 days after vaccination on enzyme-linked immunosorbent assay. These results indicate that MLBE of σB could be used as a candidate for developing vaccines against NDRV infection.

Abstract Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat diseases. However, concerns over the safety and efficacy require to be further addressed in order to realize their full potential. Synthetic receptors, a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules, have been rapidly developed and applied as a powerful solution. Delicately designed and engineered, they can be applied to finetune the therapeutic activities, i.e., to regulate production of dosed, bioactive payloads by sensing and processing user-defined signals or biomarkers. This review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical research. With a special focus on four synthetic receptor systems at the forefront, including chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, we address the generalized strategies to design, construct and improve synthetic receptors. Meanwhile, we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

Objectives: This study aimed to explore the public and medical professionals’ concerns and attitudes toward nurse prescribing using text-mining method to analyze social media data. Methods: Python was used to automatically mine data related to the keywords “nurse prescribing” and “prescription” that were posted on four Chinese internet platforms between January 1, 2017, and November 1, 2022. The four Chinese internet platforms included social media sites such as Zhihu and Weibo, as well as medical forums like Aiaiyi Medical Hotspot and Dingxiangyuan Medicine. We conducted personnel, topic, and sentiment analysis techniques using SnowNLP, Bayesian Latent Dirichlet Allocation (LDA), and BosonNLP. Finally, we conducted content analysis using Nvivo 11 based on the results of the topic and sentiment analysis to obtain comprehensive and insightful results. Results: We acquired 2,823 comments totaling 92,859 words on the four Internet platforms to conduct analysis. The analyze result showed that many public and medical professionals held a negative attitude toward nurse prescribing, and few had a prudent positive attitude. The public is concerned about the impact of nurse prescribing on medical professionals and the competency requirements for nurses. Medical professionals are concerned about the current and future status of nurse prescribing in China and the difficulties in implementing nurse prescribing. Conclusion: Nurses should gradually gain recognition for their expertise and win the acceptance of the public and medical professionals on their ability of nursing prescribing by striving to enhance their professional capacity and self-authorization capabilities. Nurse administrators and educators need to recognize the advantages of nurse prescribing and address the challenges and issues in its implementation through promoting legislation, education, and heightening public awareness of its benefits.

Abstract The evaluation of plant-based feedstocks is an important aspect of biorefining. Nicotiana glauca is a solanaceous, non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions. In the present article, compatible sequential solvent extractions were applied to N. glauca leaves to enable the generation of enriched extracts containing higher metabolite content comparing to direct leaf extracts. Typically, between 60 to 100 metabolite components were identified within the fractions. The occurrence of plant fatty acids, fatty acid alcohols, alkanes, sterols and terpenoids was detected by gas liquid chromatography–mass spectrometry (GC–MS) and metabolite identification was confirmed by comparison of physico-chemical properties displayed by available authentic standards. Collectively, co-products such waxes, oils, fermentable sugars, and terpenoids were all identified and quantified. The enriched fractions of N. glauca revealed a high level of readily extractable hydrocarbons, oils and high value co-products. In addition, the saccharification yield and cell wall composition analyses in the stems revealed the potential of the residue material as a promising lignocellulosic substrate for the production of fermentable sugars. In conclusion a multifractional cascade for valuable compounds/commodities has been development, that uses N. glauca biomass. These data have enabled the evaluation of N. glauca material as a potential feedstock for biorefining. Graphical Abstract

PARP inhibitors (PARPi) are a kind of cancer therapy that targets poly (ADP-ribose) polymerase. PARPi is the first clinically approved drug to exert synthetic lethality by obstructing the DNA single-strand break repair process. Despite the significant therapeutic effect in patients with homologous recombination (HR) repair deficiency, innate and acquired resistance to PARPi is a main challenge in the clinic. In this review, we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance, aiming at extending PARPi application and improving patient outcomes.

Cultural landscape is a social natural process under which people actively participate in thinking, feeling, and acting. On this basis, their connection with a certain part of the environment in turn affects people's perception of the world and the products of their actions. Trails is a representative and complex practice of integrating nature into society and transforming it into a mixed entity. However, the dynamic and diverse relationships of cultural landscapes represented by this interactive process have not been well interpreted in landscape research. The research first discusses the conceptualization and value theory of cultural landscape, and develops the methodology of cultural landscape interaction process research combining typology and Network theory. Taking the trails spontaneously formed around the Zhengqi Pavilion of Sun Yat-sen Mausoleum in Nanjing as an example, this paper discusses the interaction process of trails as a cultural landscape. Based on the analysis results, we obtained the dynamic characteristics of cultural landscapes by treating trails as a network, while obtaining the value expression created by typology.

Abstract Background Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes after ischemic stroke. This study aimed to estimate the association between adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke. Methods Patients with ischemic stroke without a history of diabetes mellitus in the Third China National Stroke Registry were included. Adipose tissue specific insulin resistance index (Adipo-IR) was calculated by fasting serum insulin and free fatty acids and categorized into 5 groups according to the quintiles. Outcomes included stroke recurrence (ischemic or hemorrhagic), combined vascular events, all-cause death, and poor outcome (modified Rankin Scale, 3–6) at 12 months after stroke onset. We assessed the association between Adipo-IR and risk of prognosis by multivariable Cox/logistic regression models adjusted for potential covariates. Results Among 2,222 patients, 69.0% were men with a mean age of 62.5 years. At 12 months, 185 (8.3%) patients had recurrent stroke, 193 (8.7%) had combined vascular events, 58 (2.6%) died, and 250 (11.5%) had a poor outcome. Compared with patients with the lowest quintile, patients with the second, third, fourth, fifth quintiles of the Adipo-IR were associated with an increased risk of stroke recurrence (hazard ratio [HR], 1.77; 95% CI, 1.04–3.03; P = 0.04; HR, 2.19; 95% CI, 1.30–3.68; P = 0.003; HR, 1.84; 95% CI, 1.06–3.21; P = 0.03; HR, 2.11; 95% CI, 1.20–3.71; P = 0.01, respectively) and marginally associated with an increased risk of combined vascular events ( HR, 1.60; 95%CI, 0.97–2.64; P = 0.07; HR, 1.91; 95% CI, 1.17–3.13; P = 0.01; HR, 1.62; 95% CI, 0.96–2.75; P = 0.07; HR, 1.80; 95% CI, 1.05–3.09; P = 0.03, respectively) at 12 months after adjustment for potential covariates. Adipo-IR was not associated with mortality and poor outcome at 12 months. Conclusions These findings suggest that adipose tissue specific insulin resistance is independently associated with recurrent stroke and combined vascular events after acute ischemic stroke in nondiabetic patients.

Abstract Introduction Goniosynechialysis (Phaco-GSL) is a logical therapeutic approach for patients with primary angle-closure glaucoma (PACG) and cataract. The aim of this study was to compare the long-term effectiveness and safety of Phaco-GSL and trabeculectomy (TRB) in the management of PACG with coexisting cataract. Methods A review was conducted on 96 Chinese patients (96 eyes) with PACG and cataract from Peking Union Medical College Hospital (PUMCH). Among them, 56 patients underwent Phaco-GSL, while 40 underwent TRB. Intraocular pressure (IOP), best corrected visual acuity (BCVA), use of supplemental antiglaucoma medical therapy, surgery success rates, and complications for both procedures were assessed. Results The average follow-up period was 50.3 ± 18.7 months in the Phaco-GSL group and 61.2 ± 15.1 months in the TRB group. At the final follow-up, IOP decreased from 27.0 ± 11.1 mmHg to 13.5 ± 2.1 mmHg in the Phaco-GSL group and in the TRB group IOP decreased from 27.1 ± 7.7 mmHg to 16.5 ± 5.5 mmHg. The long-term postoperative IOP in the Phaco-GSL group was significantly lower than that in the TRB group. There was a statistically significant reduction in medication usage in both groups, with the TRB group having a higher number of postoperative medications at the final follow-up. The incidence of postoperative complications was significantly higher in the TRB group compared to the Phaco-GSL group. Conclusions Phaco-GSL is the recommended surgical approach for Chinese patients with primary angle-closure glaucoma (PACG) and cataract. Compared to traditional TRB, eyes undergoing Phaco-GSL show a reduced requirement for antiglaucomatous medications, improved management of IOP, decreased risk of complications, and higher long-term cumulative probability of treatment success for patients with PACG.

Abstract Background Aberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. We aimed to explore the potential role of Wnt5a expression in liver injury caused by chronic HBV infection. Methods Wnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemical staining. Results Wnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to healthy controls and correlated positively with liver injury markers. Additionally, there was a significant correlation between Wnt5a mRNA expression and HBV DNA load in all patients and CHB patients but not in ACHBLF patients. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression compared with lower hepatic inflammatory grades. In addition, the cut-off value of 12.59 for Wnt5a mRNA level was a strong indicator in predicting ACHBLF in CHB patients. Conclusions We found that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in exacerbation of chronic HBV infection.

Abstract Proton-conducting materials are essential to the emerging hydrogen economy. Covalent triazine frameworks (CTFs) are promising proton-conducting materials at high temperatures but need more effective sites to strengthen interaction for proton carriers. However, their construction and design in a concise condition are still challenges. Herein, we show a low temperature approach to synthesize CTFs via a direct cyclotrimerization of aromatic aldehyde using ammonium iodide as facile nitrogen source. Among the CTFs, the perfluorinated CTF (CTF-TF) was successfully synthesized with much lower temperature ( ≤ 160 °C) and open-air atmosphere. Due to the additional hydrogen-bonding interaction between fluorine atoms and proton carriers (H3PO4), the CTF-TF achieves a proton conductivity of 1.82 × 10−1 S cm−1 at 150 °C after H3PO4 loading. Moreover, the CTF-TF can be readily integrated into mixed matrix membranes, displaying high proton conduction abilities and good mechanical strength. This work provides an alternative strategy for rational design of proton conducting media.

Abstract Background With the development of cancer precision medicine, a huge amount of high-dimensional cancer information has rapidly accumulated regarding gene alterations, diseases, therapeutic interventions and various annotations. The information is highly fragmented across multiple different sources, making it highly challenging to effectively utilize and exchange the information. Therefore, it is essential to create a resource platform containing well-aggregated, carefully mined, and easily accessible data for effective knowledge sharing. Methods In this study, we have developed “Consensus Cancer Core” (Tri©DB), a new integrative cancer precision medicine knowledgebase and reporting system by mining and harmonizing multifaceted cancer data sources, and presenting them in a centralized platform with enhanced functionalities for accessibility, annotation and analysis. Results The knowledgebase provides the currently most comprehensive information on cancer precision medicine covering more than 40 annotation entities, many of which are novel and have never been explored previously. Tri©DB offers several unique features: (i) harmonizing the cancer-related information from more than 30 data sources into one integrative platform for easy access; (ii) utilizing a variety of data analysis and graphical tools for enhanced user interaction with the high-dimensional data; (iii) containing a newly developed reporting system for automated annotation and therapy matching for external patient genomic data. Benchmark test indicated that Tri©DB is able to annotate 46% more treatments than two officially recognized resources, oncoKB and MCG. Tri©DB was further shown to have achieved 94.9% concordance with administered treatments in a real clinical trial. Conclusions The novel features and rich functionalities of the new platform will facilitate full access to cancer precision medicine data in one single platform and accommodate the needs of a broad range of researchers not only in translational medicine, but also in basic biomedical research. We believe that it will help to promote knowledge sharing in cancer precision medicine. Tri©DB is freely available at www.biomeddb.org , and is hosted on a cutting-edge technology architecture supporting all major browsers and mobile handsets.

Tongxie Yaofang (TXYF) has therapeutic effect on the ulcerative colitis (UC) with liver depression and spleen deficiency syndrome. This study investigated the changes in the gut microbiota of UC rats treated with TXYF. Wistar rats were divided into three groups: Control, dinitrobenzene sulfonic acid (DNBS)-colitis, and DNBS + TXYF (n = 8 per group). UC model was constructed via intrarectally injection of DNBS (25 mg DNBS and 0.25 mL 50% ethanol); rats in DNBS + TXYF group were administered with TXYF (20.8 g/kg) for 21 days. Physiological parameters were measured. Five samples from each group were selected for metagenomic analysis. TXYF treatment significantly reduced disease activity index, colon mucosal damage index, and tumor necrosis factor-alpha level. TXYF treatment prevented DNBS-induced dysregulation of gut microbial communities. Compared with DNBS-colitis group, the abundance of Firmicutes increased significantly and that of Bacteroidetes and Proteobacteria decreased in DNBS + TXYF group. Pathways such as protein processing in the endoplasmic reticulum pathway was enriched in the DNBS-colitis group, whereas it was decreased in the DNBS + TXYF group. Thus, TXYF treatment could effectively restore the dysregulation of intestinal flora induced by UC.

Abstract Background Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge. Results Here we defined an adapted differentiation protocol to generate induced corneal endothelial cells (iCECs) consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved iCECs. Cells express high levels of typical CECs markers and exhibit transendothelial potential properties in vitro typical of iCECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving iCECs ameliorated edema and recovered corneal opacity. Conclusions Our work provides an efficient approach for generating iCECs and demonstrates the safety and efficacy of iCECs in disease modeling. Therefore, clinical-grade iCECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Abstract Angelica sinensis roots (Angelica roots) are rich in many bioactive compounds, including phthalides, coumarins, lignans, and terpenoids. However, the molecular bases for their biosynthesis are still poorly understood. Here, an improved chromosome-scale genome for A. sinensis var. Qinggui1 is reported, with a size of 2.16 Gb, contig N50 of 4.96 Mb and scaffold N50 of 198.27 Mb, covering 99.8% of the estimated genome. Additionally, by integrating genome sequencing, metabolomic profiling, and transcriptome analysis of normally growing and early-flowering Angelica roots that exhibit dramatically different metabolite profiles, the pathways and critical metabolic genes for the biosynthesis of these major bioactive components in Angelica roots have been deciphered. Multiomic analyses have also revealed the evolution and regulation of key metabolic genes for the biosynthesis of pharmaceutically bioactive components; in particular, TPSs for terpenoid volatiles, ACCs for malonyl CoA, PKSs for phthalide, and PTs for coumarin biosynthesis were expanded in the A. sinensis genome. These findings provide new insights into the biosynthesis of pharmaceutically important compounds in Angelica roots for exploration of synthetic biology and genetic improvement of herbal quality.

Abstract Thrombospondin1 (TSP1) is a multifunctional matricellular protein. Previously, we demonstrated that TSP1 plays a pivotal role in obesity-related inflammation and insulin resistance (IR) by modulating macrophage accumulation and activation in adipose tissue. Moreover, in our in vitro studies, a CD36-derived peptide, functioning as a TSP1 antagonist, effectively inhibited TSP1-induced proinflammatory macrophage activation. However, whether this CD36 peptide can inhibit obesity-induced inflammation and IR in vivo is unknown and determined in this study in a high fat diet-induced obese mouse model (DIO). CD36 peptide or control peptide was intraperitoneally administered into the established obese mice triweekly for 6 weeks. We found that CD36 peptide treatment didn’t affect obesity or weight gain but significantly reduced proinflammatory cytokine production systemically and in visceral fat tissue. Adipose tissue exhibited fewer crown-like structures and reduced macrophage infiltration. CD36 peptide treatment also attenuated the proinflammatory phenotype of bone marrow derived macrophages from obese mice. Furthermore, CD36 peptide treatment improved glucose tolerance and insulin sensitivity, and mitigated obesity-related fatty liver disease and kidney damage. Collectively, this study suggests that the CD36 peptide, as a TSP1 antagonist, shows promise as a novel therapeutic approach for managing obesity-related metabolic disorders.

In the field of object detection, enhancing algorithm performance in complex scenarios represents a fundamental technological challenge. To address this issue, this paper presents an efficient optimized YOLOv8 model with extended vision (YOLO-EV), which optimizes the performance of the YOLOv8 model through a series of innovative improvement measures and strategies. First, we propose a multi-branch group-enhanced fusion attention (MGEFA) module and integrate it into YOLO-EV, which significantly boosts the model’s feature extraction capabilities. Second, we enhance the existing spatial pyramid pooling fast (SPPF) layer by integrating large scale kernel attention (LSKA), improving the model’s efficiency in processing spatial information. Additionally, we replace the traditional IOU loss function with the Wise-IOU loss function, thereby enhancing localization accuracy across various target sizes. We also introduce a P6 layer to augment the model’s detection capabilities for multi-scale targets. Through network structure optimization, we achieve higher computational efficiency, ensuring that YOLO-EV consumes fewer computational resources than YOLOv8s. In the validation section, preliminary tests on the VOC12 dataset demonstrate YOLO-EV’s effectiveness in standard object detection tasks. Moreover, YOLO-EV has been applied to the CottonWeedDet12 and CropWeed datasets, which are characterized by complex scenes, diverse weed morphologies, significant occlusions, and numerous small targets. Experimental results indicate that YOLO-EV exhibits superior detection accuracy in these complex agricultural environments compared to the original YOLOv8s and other state-of-the-art models, effectively identifying and locating various types of weeds, thus demonstrating its significant practical application potential.

The accurate estimation of soil plant analytical development (SPAD) values in cotton under various intercropping patterns with soybean is crucial for monitoring cotton growth and determining a suitable intercropping pattern. In this study, we utilized an unmanned aerial vehicle (UAV) to capture visible (RGB) and multispectral (MS) data of cotton at the bud stage, early flowering stage, and full flowering stage in a cotton–soybean intercropping pattern in the Yellow River Delta region of China, and we used SPAD502 Plus and tapeline to collect SPAD and cotton plant height (CH) data of the cotton canopy, respectively. We analyzed the differences in cotton SPAD and CH under different intercropping ratio patterns. It was conducted using Pearson correlation analysis between the RGB features, MS features, and cotton SPAD, then the recursive feature elimination (RFE) method was employed to select image features. Seven feature sets including MS features (five vegetation indices + five texture features), RGB features (five vegetation indices + cotton cover), and CH, as well as combinations of these three types of features with each other, were established. Voting regression (VR) ensemble learning was proposed for estimating cotton SPAD and compared with the performances of three models: random forest regression (RFR), gradient boosting regression (GBR), and support vector regression (SVR). The optimal model was then used to estimate and visualize cotton SPAD under different intercropping patterns. The results were as follows: (1) There was little difference in the mean value of SPAD or CH under different intercropping patterns; a significant positive correlation existed between CH and SPAD throughout the entire growth period. (2) All VR models were optimal when each of the seven feature sets were used as input. When the features set was MS + RGB, the determination coefficient (R2) of the validation set of the VR model was 0.902, the root mean square error (RMSE) was 1.599, and the relative prediction deviation (RPD) was 3.24. (3) When the features set was CH + MS + RGB, the accuracy of the VR model was further improved, compared with the feature set MS + RGB, the R2 and RPD were increased by 1.55% and 8.95%, respectively, and the RMSE was decreased by 7.38%. (4) In the intercropping of cotton and soybean, cotton growing under 4:6 planting patterns was better. The results can provide a reference for the selection of intercropping patterns and the estimation of cotton SPAD.

To enhance agricultural productivity through the accurate detection of pests under the constrained resources of mobile devices, we introduce LP-YOLO, a bespoke lightweight object detection framework optimized for mobile-based insect pest identification. Initially, we devise lightweight components, namely LP_Unit and LP_DownSample, to serve as direct substitutes for the majority of modules within YOLOv8. Subsequently, we develop an innovative attention mechanism, denoted as ECSA (Efficient Channel and Spatial Attention), which is integrated into the network to forge LP-YOLO(l). Moreover, assessing the trade-offs between parameter reduction and computational efficiency, considering both the backbone and head components of the network, we use structured pruning methods for the pruning process, culminating in the creation of LP-YOLO(s). Through a comprehensive series of evaluations on the IP102 dataset, the efficacy of LP-YOLO as a lightweight object detection model is validated. By incorporating fine-tuning techniques during training, LP-YOLO(s)n demonstrates a marginal mAP decrease of only 0.8% compared to YOLOv8n. However, it achieves a significant reduction in parameter count by 70.2% and a remarkable 40.7% increase in FPS, underscoring its efficiency and performance.

The neuropeptide corazonin (Crz) exerts diverse physiological effects in insects, yet its role in crustaceans remains elusive. The abundant expression of Crz receptor (CrzR) in the Y-organs of several crustaceans suggests a potential involvement of Crz in regulating ecdysteroid synthesis. In this study, we examined the effects of PtCrz on ecdysteroid synthesis during the molting period of Portunus trituberculatus through PtCrz treatments and PtCrzR silencing. Our results showed that PtCrz peptide stimulates ecdysteroid levels and the gene expression involved in ecdysteroidogenesis both in vitro and in vivo, whereas dsPtCrzR treatments had opposite effects on ecdysteroid levels and associated gene expression. Thus, our study suggests that PtCrz may modulate ecdysteroid synthesis via Y-organ-expressed PtCrzR. Furthermore, we also discovered the involvement of PtCrz/PtCrzR signaling in regulating PtETH expression. Notably, the inhibitory effect of dsPtCrzR on ecdysteroid synthesis or PtETH expression can be reversed by PtCrz treatment, suggesting the potential existence of multiple receptors for PtCrz. This study provides new insights into the function of crustacean Crz and, for the first time, elucidates the presence of a neuropeptide that can stimulate ecdysteroid synthesis in crustaceans.

Rapeseed oil is a widely consumed edible oil that contains varieties of beneficial micronutrients such as tocopherols and phytosterols; however, the high acid value due to increased free fatty acid can imperil the oil quality and safety. This paper proposed the enzymatic deacidification for high-acid rapeseed oil and simultaneous production of functional diacylglycerols (DAGs) catalyzed by self-made immobilized lipase CALB@MCM-41-C8. The results indicate that the carrier of molecular sieve MCM-41 exhibited a sufficient surface area of 1439.9 m2/g and a proper pore size of 3.5 nm, promoting the immobilization of lipase CLAB. Under the optimal reaction conditions, the acid value of rapeseed oil was largely decreased from 15.3 mg KOH/g to 1.7 mg KOH/g within 3 h, while DAG content was increased from 1.2% to 40.2%. The antioxidant stability of rapeseed oil was also increased from 4.3 h to 7.6 h after enzymatic deacidification. Besides, the deacidified rapeseed oil exhibited fatty, bitter almond aromas, compared to the picked-vegetable, spicy, and pungent aromas for high-acid oil. Finally, the catalytic stability and applicability of CALB@MCM-41-C8 was validated, thus demonstrating the great potential of CALB@MCM-41-C8 in green refining of edible oils and sustainable synthesis of functional lipids.

Synthetic Aperture Radar (SAR) imagery presents significant advantages for observing ocean surface winds owing to its high spatial resolution and low sensitivity to extreme weather conditions. Nevertheless, signal noise poses a challenge, hindering precise wind retrieval from SAR imagery. Moreover, traditional geophysical model functions (GMFs) often falter, particularly in accurately estimating high wind speeds, notably during extreme weather phenomena like tropical cyclones (TCs). To address these limitations, this study proposes a novel hybrid model, CMOD-Diffusion, which integrates the strengths of GMFs with data-driven deep learning methods, thereby achieving enhanced accuracy and robustness in wind retrieval. Based on the coarse estimation of wind speed by the traditional GMF CMOD5.N, we introduce the recently developed data-driven method Denoising Diffusion Probabilistic Model (DDPM). It transforms an image from one domain to another domain by gradually adding Gaussian noise, thus achieving denoising and image synthesis. By introducing the DDPM, the noise from the observed normalized radar cross-section (NRCS) and the residual of the GMF methods can be largely compensated. Specifically, for wind speeds within the low-to-medium range, a DDPM is employed before proceeding to another CMOD iteration to recalibrate the observed NRCS. Conversely, a posterior-placed DDPM is applied after CMOD to reconstruct high-wind-speed regions or TC-affected areas, with the prior information from regions characterized by low wind speeds and recalibrated NRCS values. The efficacy of the proposed model is evaluated by using Sentinel-1 SAR imagery in vertical–vertical (VV) polarization, collocated with data from the European Centre for Medium-Range Weather Forecasts (ECMWF). Experimental results based on validation sets demonstrate significant improvements over CMOD5.N, particularly in low-to-medium wind speed regions, with the Structural Similarity Index (SSIM) increasing from 0.76 to 0.98 and the Root Mean Square Error (RMSE) decreasing from 1.98 to 0.63. Across the entire wind field, including regions with high wind speeds, the validation data obtained through the proposed method exhibit an RMSE of 2.39 m/s, with a correlation coefficient of 0.979.

Abstract Background We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine. Case presentation A 42-year-old male patient with nanophthalmos experienced sudden blurred vision in the right eye after using topical brimonidine when picking up tennis balls repeatedly 6 weeks after bilateral YAG peripheral iridotomy. Ocular examination showed wide choroidal and exudative retinal detachment in the temporal and inferior region, involving the macula. Acute uveal effusion in the right, bilateral nanophthalmos was diagnosed. Oral and topical corticosteroids, combined with topical nonsteroids and atropine led to a complete resolution of the uveal effusion after one month. Conclusion This case suggested a possible causal relationship between the topical use of brimonidine and acute uveal effusion in patients with nanophthalmos. Topical brimonidine should be used with caution in nanophthalmic eyes.

Abstract Background Chimeric antigen receptor NK (CAR-NK) cell therapy is one of the most promising immunotherapies. Although it has shown a significant therapeutic effect in hematologic malignancies, few successes have been obtained in solid tumors including esophageal squamous cell carcinoma (ESCC). The major reasons are lack of specific cell surface antigens and complex tumor microenvironment. Here we identify CD22, a well-known tumor surface marker in hematologic malignancies, is expressed in ESCC, possibly serving as a potential target of CAR-NK cell therapy. Methods The expression of 13 tumor cell surface antigens used clinically was analyzed in patients from The Cancer Genome Atlas (TCGA) database. Also, mRNA expression were detected in 2 ESCC cell lines and 2 patients samples by qCPR. Then according to Venn diagram, CD22 was selected for further investigation. Following this, the expression of CD22 by immunofluorescence (IF) in ESCC cell lines and by immunohistochemistry (IHC) in 87 cases of human ESCC samples was detected respectively. On the basis of H-score results, the correlation between CD22 expression and clinical parameters was analyzed. As a proof, the efficacy of CD22-targeted CAR-NK cells against ESCC cell lines was performed by a real-time cell analyzer (RTCA) platform. Results KYSE-140 and KYSE-150 cell lines displayed surface expression of CD22. IHC showed an 80.46% (70/87) positive rate in ESCC patient samples. Among these, cell membranous expression of CD22 was observed in 27.59% (24/87) patient samples. Through chi-square test, expression of CD22 in ESCC was associated with lymph node metastasis while it was no related to the depth of tumor invasion and clinical stage. Engineered CD22-targeted CAR-NK cells exhibited inhibitory growth capability against ESCC cell lines (p

Abstract Aims Robot-assisted total hip arthroplasty (rTHA) boasts superior accuracy in implant placement, but there is a lack of effective assessment in perioperative management in the context of enhanced recovery after surgery (ERAS). This study aimed to compare the effectiveness and safety of rTHA versus conventional total hip arthroplasty (cTHA) in ERAS-managed patients. Methods In this prospective trial, a total of 60 eligible patients aged between 18 and 80 years were randomly divided into two groups to undergo either rTHA or cTHA. The primary outcomes included blood loss parameters. Secondary outcomes were the duration of the operation, surgical time, WOMAC pain score, WOMAC stiffness score, WOMAC physical function score, Harris score, and postoperative complications. Results The study cohort analyzed 59 eligible participants, 30 of whom underwent rTHA and 29 of whom underwent cTHA. Analysis could not be conducted for one patient due to severe anemia. Notably, the cTHA group had a significantly shorter surgical time than the rTHA group (69.49 ± 18.97 vs. 104.20 ± 19.63 min, P

Abstract To investigate the hot topics and attitudes of autism in the larger community. In this study, we analyzed and summarized experimental texts from the social media platform Zhihu using the TF-IDF algorithm and K-means clustering approach. Based on the analysis of the 1,740,826-word experimental text, we found that the popularity of autism has steadily risen over recent years. Sufferers and their parents primarily discuss autism. The K-means clustering algorithm revealed that the most popular topics are divided into four categories: self-experience of individuals with autism, external views of individuals with autism, caring and stressful behaviors of caregivers, and information about autism. This study concluded that people with autism face more incredible negative emotions, external cognitive evaluations of the autistic group reflect stereotypes, the caregiver’s family suffers high financial and psychological stress, and disorders caused by disease in autistic individuals.

In broad sense, beverages made from nuts and plant fruits/pulp, as well as other plant-derived materials including proteins etc. are collectively known as plant-based milk. Plant-based milk has multiple advantages such as lactose free, cholesterol free, hormone free, low saturated fat, antibiotics free, special sensory flavor, as well as unique nutritional functions, which fit with the diversified needs of consumers. The market size of plant-based milk in China is huge, which also has great development potential. However, there are still many unsolved problems, such as backward processing technology, insufficient raw material development, unsatisfied sensory properties, vague nutritional and digestive characteristics, and incomplete academic discipline etc. From this, the processing problems of plant-based milk, new processing technology and equipment, innovative technology development trend, industrialization policy comprehensively are described and discussed in this paper. This paper will contribute to the industrial development of domestic plant-based milk, and further satisfying people's growing demand for nutrition and health.

ObjectiveTo construct a prediction model for the intention of accepting recombinant zoster vaccine(RZV) vaccination among community residents based on reasoned action approach for promoting RZV vaccination in the population. MethodsTotally 1 480 attendees of four community health service centers were recruited with accidental sampling in three districts of Shanghai city for an online survey conducted during October – November 2022. The vaccination intention scale developed by Vissor et al was translated into Chinese and modified to collect participants′ information relevant to accept RZV vaccination. Of the 1 471 individual data from eligible respondents, 981 and 490 were randomly assigned into a training set and a test set. Lasso regression analysis on the data of training set was performed to explore the determinants of RZV vaccination intention. A nomogram prediction model for RZV vaccination intention was constructed using multivariate logistic regression analysis on the data of training set and the performance of the established model was evaluated with the receiver operating characteristic curve (ROC). ResultsThe intention to have RZV vaccination within 6 months was reported by 8.36% (123) of the eligible respondents. The results of Lasso regression analysis screened out nine predictive factors of RZV vaccination intention, including perception ability (β = 0.149), perceived infection risk (β = 0.074), moral norm (β = 0.061), decisional uncertainty (β = – 0.060), general vaccination beliefs (β = – 0.007), never having herpes zoster infection (β = 0.812), perceived cost-benefit (β = – 0.014), social norm (β = 0.019), and attitude (β = 0.003) and the nine factors were used to construct the prediction model. Based on the nomogram of the established prediction model, the possibility to have RZV vaccination within next 6 months is 9.00% for the respondents never having herpes zoster infection and with following scale items′ scores: 7 for perception ability, 7 for perceived infection risk, 7 for moral norm, 7 for decisional uncertainty, 42 for general vaccination beliefs, 28 for perceived cost-benefit, 49 for social norm, and 42 for the attitude towards RZV vaccination. The results of internal and external validation analysis showed that the established model is of good differentiation and calibration（the area under the curve [AUC]training set = 0.717, AUCtest set = 0.689; χ2training set = 9.061, degree of freedom [df]training set = 8, p training set = 0.337, χ2test set = 12.024, dftest set = 8, ptest set = 0.150）. ConclusionPerception ability, perceived infection risk, moral norm, decisional uncertainty, general vaccination beliefs, whether or not having herpes zoster infection, perceived cost-benefit, social norm, and attitude towards RZV vaccination are main predictive factors for RZV vaccination intention among community residents of Shanghai city.

Abstract Background Patients with acute pancreatitis (AP) exhibit specific phenotypes of gut microbiota associated with severity. Gut microbiota and host interact primarily through metabolites; regrettably, little is known about their roles in AP biological networks. This study examines how enterobacterial metabolites modulate the innate immune system in AP aggravation. Methods In AP, alterations in gut microbiota were detected via microbiomics, and the Lactobacillus metabolites of tryptophan were identified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). By culturing Lactobacillus with tryptophan, differential metabolites were detected by LC–MS/MS. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and mice with cerulein plus LPS-induced AP were used to evaluate the biological effect of norharman on M1 macrophages activation in AP development. Further, RNA sequencing and lipid metabolomics were used for screening the therapeutic targets and pathways of norharman. Confocal microscopy assay was used to detect the structure of lipid rafts. Molecular docking was applied to predict the interaction between norharman and HDACs. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to explore the direct mechanism of norharman promoting Rftn1 expression. In addition, myeloid-specific Rftn1 knockout mice were used to verify the role of Rftn1 and the reversed effect of norharman. Results AP induced the dysfunction of gut microbiota and their metabolites, resulting in the suppression of Lactobacillus-mediated tryptophan metabolism pathway. The Lactobacillus metabolites of tryptophan, norharman, inhibited the release of inflammatory factor in vitro and in vivo, as a result of its optimal inhibitory action on M1 macrophages. Moreover, norharman blocked multiple inflammatory responses in AP exacerbation due to its ability to maintain the integrity of lipid rafts and restore the dysfunction of lipid metabolism. The mechanism of norharman’s activity involved inhibiting the enzyme activity of histone deacetylase (HDACs) to increase histone H3 at lysine 9/14 (H3K9/14) acetylation, which increased the transcription level of Rftn1 (Raftlin 1) to inhibit M1 macrophages’ activation. Conclusions The enterobacterial metabolite norharman can decrease HDACs activity to increase H3K9/14 acetylation of Rftn1, which inhibits M1 macrophage activation and restores the balance of lipid metabolism to relieve multiple inflammatory responses. Therefore, norharman may be a promising prodrug to block AP aggravation. Graphical Abstract

Abstract Aims Heart failure (HF) is one of the common adverse cardiovascular events after acute myocardial infarction (AMI), but the predictive efficacy of numerous machine learning (ML) built models is unclear. This study aimed to build an optimal model to predict the occurrence of HF in AMI patients by comparing seven ML algorithms. Methods Cohort 1 included AMI patients from 2018 to 2019 divided into HF and control groups. All first routine test data of the study subjects were collected as the features to be selected for the model, and seven ML algorithms with screenable features were evaluated. Cohort 2 contains AMI patients from 2020 to 2021 to establish an early warning model with external validation. ROC curve and DCA curve to analyze the diagnostic efficacy and clinical benefit of the model respectively. Results The best performer among the seven ML algorithms was XgBoost, and the features of XgBoost algorithm for troponin I, triglycerides, urine red blood cell count, γ-glutamyl transpeptidase, glucose, urine specific gravity, prothrombin time, prealbumin, and urea were ranked high in importance. The AUC of the HF-Lab9 prediction model built by the XgBoost algorithm was 0.966 and had good clinical benefits. Conclusions This study screened the optimal ML algorithm as XgBoost and developed the model HF-Lab9 will improve the accuracy of clinicians in assessing the occurrence of HF after AMI and provide a reference for the selection of subsequent model-building algorithms.

Abstract Background Rehabilitation improves functional recovery in subarachnoid hemorrhage (SAH) patients, and assessing patients for rehabilitation is the first step in this process. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation for patients with SAH. Methods To identify patients hospitalized with SAH and to analyze rehabilitation assessment rates, we used data for 11,234 SAH patients admitted to 861 hospitals from the China Stroke Center Alliance from August 2015 to July 2019. We examined factors for rehabilitation assessment and analyzed the relationship between rehabilitation assessment and outcomes in these patients. Results Among 11,234 patients with SAH, 6,513 (58.0%) were assessed for rehabilitation. Assessed patients had an increased length of stay (mean ± SD days: 17.3 ± 12.5 versus 11.6 ± 10.5, P = 49.4), a higher Glasgow Coma Scale (GCS) score on admission (mean ± SD GCS score: 12.3 ± 3.8 versus 11.8 ± 4.4, P = 12.2), and were more likely to be admitted to the stroke unit (19.6% versus 13.8%, P = 15.6). In multivariable analysis, factors associated with an increased likelihood of a rehabilitation assessment (p

Diabetic retinopathy(DR)is a neurovascular disease caused by the neurovascular unit(NVU)impairment. Immune imbalance and inflammation are key factors that affect the normal function of NVU and lead to the progression of DR. Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is indicated as an important component of the inflammatory response, and it can identify endogenous danger signals, leading to the activation of caspase-1 and then activating a series of inflammatory cytokines and pyroptosis. Early activation of inflammasome maintains and promotes innate immunity against bacterial and viral infections, while excessive inflammasome activation results in excessive expression and ongoing action of inflammatory proteins, which in turn triggers off immune disorders and an inflammatory cascade that seriously harms the body. This review summarizes the recent research progress on the mechanism of NLRP3 inflammasome in NVU impairment of DR, including the related drugs targeting NLRP3 pathways.

Background In papillary thyroid carcinoma (PTC) patients with Hashimoto’s thyroiditis (HT), preoperative ultrasonography frequently reveals the presence of enlarged lymph nodes in the central neck region. These nodes pose a diagnostic challenge due to their potential resemblance to metastatic lymph nodes, thereby impacting the surgical decision-making process for clinicians in terms of determining the appropriate surgical extent. Methods Logistic regression analysis was conducted to identify independent risk factors associated with central lymph node metastasis (CLNM) in PTC patients with HT. Then a prediction model was developed and visualized using a nomogram. The stability of the model was assessed using ten-fold cross-validation. The performance of the model was further evaluated through the use of ROC curve, calibration curve, and decision curve analysis. Results A total of 376 HT PTC patients were included in this study, comprising 162 patients with CLNM and 214 patients without CLNM. The results of the multivariate logistic regression analysis revealed that age, Tg-Ab level, tumor size, punctate echogenic foci, and blood flow grade were identified as independent risk factors associated with the development of CLNM in HT PTC. The area under the curve (AUC) of this model was 0.76 (95% CI [0.71–0.80]). The sensitivity, specificity, accuracy, and positive predictive value of the model were determined to be 88%, 51%, 67%, and 57%, respectively. Conclusions The proposed clinic-ultrasound-based nomogram in this study demonstrated a favorable performance in predicting CLNM in HT PTCs. This predictive tool has the potential to assist clinicians in making well-informed decisions regarding the appropriate extent of surgical intervention for patients.