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Abstract Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m2) on Days 1 and 8 and oxaliplatin (85 mg/m2) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825). Trial registration Clinical trials: NCT03951597.

The main purpose of this study was to investigate the improvement effect of Mesona chinensis Benth polysaccharide (MP) on cyclophosphamide (CTX) induced liver injury in mice. To explore metabolic profile of liver tissue and feces among normal group, CTX-induced group and MP management group based on metabolomics method by using UPLC-Q-TOF/MS. The results showed that MP could alleviate liver injury and promote the production of short chain fatty acids (SCFAs), with the best dose of 200 mg/kg·body weight (bw). The principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) scores plots of the liver and feces samples showed a clear separation among normal, model and high-dose of MP (MPH). There were 18 endogenous metabolites in liver and 29 endogenous metabolites in feces, which were mainly involved in 8 metabolic pathways: taurine and hypotaurine metabolism, phenylalanine metabolism, α-linolenic acid metabolism, tricarboxylic acid (TCA) cycle, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, sphingolipid metabolism as well as tryptophan metabolism. Moreover, a common metabolite arachidonic acid was observed in liver and feces samples. These endogenous metabolites may be considered to be MP's response to liver protection. It will help to further understand the mechanism of MP and provide a basis for further research.

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus and potentially leads to significant visual impairment and blindness. The complex mechanisms involved in the pathological changes in DR make it challenging to achieve satisfactory outcomes with existing treatments. Diets conducive to glycemic control have been shown to improve outcomes in diabetic patients, thus positioning dietary interventions as promising avenues for DR treatment. Investigations have demonstrated that natural products (NPs) may effectively manage DR. Many types of natural compounds, including saponins, phenols, terpenoids, flavonoids, saccharides, alkaloids, and vitamins, have been shown to exert anti-inflammatory, antioxidant, anti-neovascular, and antiapoptotic effects in vivo and in vitro. Nevertheless, the clinical application of NPs still faces challenges, such as suboptimal specificity, poor bioavailability, and a risk of toxicity. Prospective clinical studies are imperative to validate the therapeutic potential of NPs in delaying or preventing DR.

Zinc ions (Zn2+) play a key role in maintaining and regulating protein structures and functions. To better understand the intracellular Zn2+ homeostasis and signaling role, various fluorescent sensors have been developed that allow the monitoring of Zn2+ concentrations and bioimaging in live cells in real time. This review highlights the recent development of organic fluorescent probes for the detection and imaging of intracellular Zn2+, including the design and construction of the probes, fluorescent response mechanisms, and their applications to intracellular Zn2+ detection and imaging on-site. Finally, the current challenges and prospects are discussed.

The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes obtained from the beef production chain (cattle farms, abattoirs, and retail outlets) in Gauteng province, South Africa. The sequence types (STs), clonal complexes (CCs), and the lineages of the isolates were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses/prophages, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were seven STs, six CCs, forty-four putative virulence factors, two resistance genes, one plasmid with AMR genes, and three with conjugative genes, one CRISPR gene, and all 60 isolates were positive for proviruses/prophages. Among the seven STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p < 0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (p < 0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in three (5%) isolates. A CRISPR-Cas system was detected in six (10%), and all the isolates carried proviruses/prophages. The source and sample type significantly affected the frequencies of STs and virulence factors in the isolates of L. monocytogenes. The presence of fosX and vga(G) genes in all L. monocytogenes isolates obtained from the three industries of the beef production chain can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain, is the first time genomics was performed on this type of data set in the country, and this provides insights into the health implications of Listeria.

This study aimed to improve the safety and economy of cement production and to investigate the gasification performance and tar properties of wheat straw in a small electrically heated bubbling fluidized bed by varying three factors, namely, gasification reaction conditions, fuel quality and type, and the natural environment, so as to promote the application of the low-temperature gasification of biomass in the cement industry. The gasification experiment was carried out at temperatures of 550–700 °C, air equivalence ratios of 0.1–0.2, moisture contents of 5.25–24%, blended rubber ratios of 0–100%, and furnace vacuums of 0–0.03 within the parameter ranges, and the component analyses of the produced gases and tars were carried out by gas chromatography (GC) and gas chromatography–mass spectrometry (GC-MS). The experimental findings revealed that the optimal operating conditions for gasification were attained at a temperature of 650 °C, an equivalence ratio of 0.15, a moisture content of 5.25%, a rubber blending ratio of 0, and a vacuum degree of 0. Under these conditions, the concentrations of combustible components (H2, CH4, and CO) in the produced gas were 4.01%, 4.60%, and 21.05%, respectively. The carbon conversion rate was 62.40%, with the cold gas efficiency of 39.37%. The lower heating value of the produced gas was 5.915 MJ/Nm3, accompanied by a tar yield of 118.15 g/Nm3 and lower heating value of 3.385 MJ/Nm3.

Functional foods have potential health benefits for humans. Lotus seeds (LS) as functional foods have excellent antioxidant activities. However, the differences in chemical composition of different LS cultivars may affect their antioxidant activities. This study comprehensively analyzed the differences among five LS cultivars based on metabolomics and further revealed the effects of metabolites on antioxidant activities by correlation analysis. A total of 125 metabolites were identified in LS using UPLC-Q/TOF-MS. Then, 15 metabolites were screened as differential metabolites of different LS cultivars by chemometrics. The antioxidant activities of LS were evaluated by DPPH•, FRAP, and ABTS•+ assays. The antioxidant activities varied among different LS cultivars, with the cultivar Taikong 66 showing the highest antioxidant activities. The correlation analysis among metabolites and antioxidant activities highlighted the important contribution of phenolics and alkaloids to the antioxidant activities of LS. Particularly, 11 metabolites such as p-coumaric acid showed significant positive correlation with antioxidant activities. Notably, 6 differential metabolites screened in different LS cultivars showed significant effects on antioxidant activities. These results revealed the important effects of phytochemicals on the antioxidant activities of different LS cultivars. This study provided evidence for the health benefits of different LS cultivars.

Human–robot collaboration stands as one of the research frontiers in industrial applications due to the possibility for human operators to be supported by robots in carrying out their tasks in a shared workspace. However, advances in this field can be slowed down by the lack of standards regarding the safety and ergonomics of such applications. This article aims at reducing this gap by presenting an adaptation of the standard ISO 11228-3 for the ergonomic evaluation of hand-guiding applications through the OCRA index. This innovative methodology is innovatively applied to a drilling application in which a human operator hand-guides a collaborative robotic system consisting of a Franka Emika Panda robot, a force/torque sensor and an IMU suit to track the motion of the operator’s body. The SaRAH app, a MATLAB 2020a-based software tool developed on purpose, implements the ergonomic assessment procedure, allowing the proper redesign of the working shift (offline mode) or providing the worker suggestions to improve his/her behavior (online mode) so as to reduce the ergonomic risk.

The decipherment of ancient Chinese scripts, such as oracle bone and bronze inscriptions, holds immense significance for understanding ancient Chinese history, culture, and civilization. Despite substantial progress in recognizing oracle bone script, research on the overall recognition of ancient Chinese characters remains somewhat lacking. To tackle this issue, we pioneered the construction of a large-scale image dataset comprising 9233 distinct ancient Chinese characters sourced from images obtained through archaeological excavations. We propose the first model for recognizing the common ancient Chinese characters. This model consists of four stages with Linear Embedding and Swin-Transformer blocks, each supplemented by a CoT Block to enhance local feature extraction. We also advocate for an enhancement strategy, which involves two steps: firstly, conducting adaptive data enhancement on the original data, and secondly, randomly resampling the data. The experimental results, with a top-one accuracy of 87.25% and a top-five accuracy of 95.81%, demonstrate that our proposed method achieves remarkable performance. Furthermore, through the visualizing of model attention, it can be observed that the proposed model, trained on a large number of images, is able to capture the morphological characteristics of ancient Chinese characters to a certain extent.

With the rapid development of economic globalization and green manufacturing, traditional flexible job shop scheduling has evolved into the low-carbon heterogeneous distributed flexible job shop scheduling problem (LHDFJSP). Additionally, modern smart manufacturing processes encounter complex and diverse contingencies, necessitating the ability to address dynamic events in real-world production activities. To date, there are limited studies that comprehensively address the intricate factors associated with the LHDFJSP, including workshop heterogeneity, job insertions and transfers, and considerations of low-carbon objectives. This paper establishes a multi-objective mathematical model with the goal of minimizing the total weighted tardiness and total energy consumption. To effectively solve this problem, diverse composite scheduling rules are formulated, alongside the application of a deep reinforcement learning (DRL) framework, i.e., Rainbow deep-Q network (Rainbow DQN), to learn the optimal scheduling strategy at each decision point in a dynamic environment. To verify the effectiveness of the proposed method, this paper extends the standard dataset to adapt to the LHDFJSP. Evaluation results confirm the generalization and robustness of the presented Rainbow DQN-based method.

Food-derived peptides have been extensively studied for their benefits in humans. Hen eggs, characterized by high protein and digestibility, are an excellent source of food-derived bioactive peptides. This review summarizes the preparation methods, purification, and identification of hen egg-derived peptides (HEPs). The preparation methods mainly include enzymatic hydrolysis, microbial fermentation, and chemical synthesis. Genetic engineering is an emerging trend of HEP preparation. Then, we summarize the biological activities of HEPs, such as antioxidant activities, enzyme inhibitory activity, and antibacterial activity, of which the enzyme inhibitory activity is comprehensively summarized for the first time. The structure–activity relationship and underlying mechanism of the HEPs are further elucidated. Finally, the applications, future challenges, and opportunities of HEPs were mainly discussed in the food and non-food sectors. We focus on the potential applications of HEPs in intestinal health and assembly delivery and provide a reference for the further utilization and commercial development of HEPs.

Flexible thermoelectric generators (FTEGs), which can overcome the energy supply limitations of wearable devices, have received considerable attention. However, the use of toxic Te-based materials and fracture-prone electrodes constrains the application of FTEGs. In this study, a novel Ag2Se and Poly (3,4-ethylene dioxythiophene): poly (styrene sulfonate) (PEDOT:PSS)/multi-walled carbon nanotube (MWCNT) FTEG with a high output performance and good flexibility is developed. The thermoelectric columns formulated in the work are environmentally friendly and reliable. The key enabler of this work is the use of embedded EGaIn electrodes, which increase the temperature difference collected by the thermoelectric column, thereby improving the FTEG output performance. Additionally, the embedded EGaIn electrodes could be directly printed on polydimethylsiloxane (PDMS) molds without wax paper, which simplifies the preparation process of FTEGs and enhances the fabrication efficiency. The FTEG with embedded electrodes exhibits the highest output power density of 25.83 μW/cm2 and the highest output power of 10.95 μW at ΔT = 15 K. The latter is 31.6% higher than that of silver-based FTEGs and 2.5% higher than that of covered EGaIn-based FTEGs. Moreover, the prepared FTEG has an excellent flexibility (>1500 bends) and output power stability (>30 days). At high humidity and high temperature, the prepared FTEG maintains good performance. These results demonstrate that the prepared FTEGs can be used as a stable and environmentally friendly energy supply for wearable devices.

The Lower Cambrian Niutitang Formation in the Northern Guizhou harbors abundant organic-rich mud shale, constituting the most significant marine shale gas reservoir in Guizhou. In this article, the reservoir characteristics of Lower Cambrian Niutitang Formation in Northern Guizhou are analyzed in terms of lithology, mineralogy, organic geochemistry, pore structure, gas content and continuous thickness of shale, and the exploration potential of shale gas in this area is evaluated. The results indicate that the content of brittle minerals in the shale of well QX1 is 65.29% to 95.22% (average of 82.10%). The total organic carbon (TOC) content ranges from 2.06% to 12.10% (average of 5.64%). The organic matter maturity (Ro) within the range of 2.29–2.67%, and the kerogen type is identified as type I. The shale samples from the Niutitang Formation have high TOC content, suitable thermal maturity, and a favorable kerogen type, suggesting good gas generation potential. The results of scanning electron microscopy (SEM) show that intergranular pores, intragranular pores and microfractures are developed in the shale of well QX1, which can provide sufficient storage space for shale gas. The shale exhibits a continuous thickness of 105.66 m in the QX1 well, comprising a gas-bearing interval of 32.89 m at the top (with an effective continuous thickness of 18 m) and a hydrocarbon source rock layer of 75.78 m at the bottom. In comparison with other shale gas regions, Niutitang Formation shale in Northern Guizhou exhibits characteristics such as favorable gas generation conditions, greater storage conditions, excellent gas-bearing, strong frackability, and substantial continuous thickness, it has greater potential for shale gas exploration.

MADS-box is a key transcription factor regulating the transition to flowering and flower development. Lagerstroemia indica ‘Xiang Yun’ is a new cultivar of crape myrtle characterized by its non-fruiting nature. To study the molecular mechanism underlying the non-fruiting characteristics of ‘Xiang Yun’, 82 MADS-box genes were identified from the genome of L. indica. The physicochemical properties of these genes were examined using bioinformatics methods, and their expression as well as endogenous hormone levels at various stages of flower development were analyzed. The results showed that LiMADS genes were primarily classified into two types: type I and type II, with the majority being type II that contained an abundance of cis-acting elements in their promoters. By screening nine core proteins by predicted protein interactions and performing qRT-PCR analysis as well as in combination with transcriptome data, we found that the expression levels of most MADS genes involved in flower development were significantly lower in ‘Xiang Yun’ than in the wild type ‘Hong Ye’. Hormonal analysis indicated that ‘Xiang Yun’ had higher levels of iP, IPR, TZR, and zeatin during its early stages of flower development than ‘Hong Ye’, whereas the MeJA content was substantially lower at the late stage of flower development of ‘Hong Ye’. Finally, correlation analysis showed that JA, IAA, SA, and TZR were positively correlated with the expression levels of most type II genes. Based on these analyses, a working model for the non-fruiting ‘Xiang Yun’ was proposed. During the course of flower development, plant hormone response pathways may affect the expression of MADS genes, resulting in their low expression in flower development, which led to the abnormal development of the stamen and embryo sac and ultimately affected the fruiting process of ‘Xiang Yun’.

The aim of this study was to examine the characteristics and prognosis of patients with myelodysplastic syndrome (MDS) accompanied by TP53 abnormalities and explore potential prognostic factors and treatment responses. This retrospective analysis included 95 patients with MDS and TP53 abnormalities and 173 patients with MDS without TP53 abnormalities at the Fujian Medical University Union Hospital between January 2016 and June 2023. Among patients with TP53 abnormalities, 26 (27.4%) developed AML during the disease course, with a median transformation time of 5.7 months. Complex karyotypes were observed in 73.1% of patients, and the proportions of -5 or del(5q), -7 or del(7q), +8, and -20 or del(20q) were 81.8%, 54.5%, 30.7%, and 25.0%, respectively. These patients exhibited poor survival, with a median overall survival (OS) of 7.3 months, and had 1- and 2-year OS rates of 42.2% and 21.5%, respectively. The complete response rates for azacitidine monotherapy, venetoclax combined with azacitidine, decitabine monotherapy, and decitabine combined with low-dose chemotherapy were 9.1%, 41.7%, 37.5%, and 33.3%, respectively. Long-term survival was similar among the four treatment groups. Patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) had a median OS of 21.3 months, which trended to be longer than that of patients who did not undergo allo-HSCT (5.6 months; P = 0.1449). Patients with pulmonary infection at diagnosis experienced worse OS than those without pulmonary infection (2.3 months vs. 15.4 months; P < 0.0001). Moreover, 61.9% of patients with pulmonary infection had immune dysfunction, with a ratio of CD4+ to CD8+ T lymphocytes below two. Pulmonary infections and complex karyotypes were independent adverse prognostic factors for OS. In conclusion, TP53 abnormalities in patients with MDS were frequently accompanied by complex karyotypes, and treatments based on hypomethylating agents or venetoclax have limited efficacy. Pulmonary infections associated with immune dysfunction is associated with poor prognosis.

In recent years, with the development of spatial crowdsourcing technology, online car-hailing, as a typical spatiotemporal crowdsourcing task application scenario, has attracted widespread attention. Existing researches on spatial crowdsourcing are mainly based on the coordinate positions of user and worker roles to achieve task allocation with the goal of maximum matching number or lowest cost. However, they ignores the problem of the selection of the pick-up point which needs to be solved in the actual scene of online car booking. This problem needs to take into account the four-dimensional coordinate positions of users, workers, pick-up point and destination. Based on this, this study designs a pick-up point recommendation strategy based on user incentive mechanism. Firstly, a new four-dimensional crowdsourcing model is established, which is closer to the practical application of crowdsourcing problem. Secondly, taking cost optimization as the index, a user incentive mechanism is designed to encourage users to walk to the appropriate pick-up point within a certain distance. Thirdly, a concept of forward rate is proposed to reduce the computation time. Some key factors, such as the maximum walking distance limit of users and task cost, are considered as the recommendation index for measuring the pick-up point. Then, an effective pick-up point recommendation strategy is designed based on this index. Experiments show that the strategy proposed in this article can achieve reasonable recommendation for pick-up points and improve the efficiency of drivers and reduce the total trip cost of orders to the greatest extent.

Diagnostic delay in dementia is common in the U.S. Drivers of diagnostic delay are poorly understood, but appear related to misconceptions about dementia, stigma, concerns about autonomy, the nature of the diagnostic process, and provider-related factors. There is little quantitative evidence underlying cited risks and benefits of receiving a diagnosis around the time of dementia onset, including impacts on physical health, impacts on mental health, care partner interactions, costs of care, increased time for care planning, or earlier access to treatment. While various groups continue to push for reductions in diagnostic delay, realization of benefits and mitigation of harms will require new research on potential benefits and harms. Workforce and resource constraints, coupled with the expected growth in the number of persons living with dementia, may be a barrier to realization of potential benefits and mitigation of identified harms, which will require adequate access to providers, services, and supports.

ABSTRACT: The liver serves as the central organ for lipid metabolism, making it a crucial component of chicken physiology. However, the intricate regulation of lipid absorption, synthesis, decomposition, and transport within the liver is influenced by various factors, such as environmental conditions, diet, and genetics. Recent research has suggested that numerous functional genes and transcription factors play a pivotal role in liver metabolism via different molecular mechanisms. In this study, we examined the transcriptomes of both healthy and fatty chicken livers to better understand the role of functional genes in chicken liver fat metabolism. Our bioinformatics analysis of RNA-seq data revealed differential expression of SLCO1B3 in healthy liver and fatty liver, with lower ex-pression levels observed in fatty liver. To further investigate the potential role of SLCO1B3 in liver metabolism, we conducted in vitro experiments to knock down its expression in primary hepatocytes. Our results indicated that SLCO1B3 could suppress lipogenesis, hepatocyte apoptosis, and inflammation. These findings provide insight into the molecular mechanism of SLCO1B3 as a functional gene capable of regulating fat metabolism in chicken liver, and may contribute to ad-dressing the issue of fatty liver in chicken.

Abstract Heat stroke is a life‐threatening disease with high mortality and complications. Endothelial glycocalyx (EGCX) is essential for maintaining endothelial cell structure and function as well as preventing the adhesion of inflammatory cells. Potential relationship that underlies the imbalance in inflammation and coagulation remains elusive. Moreover, the role of EGCX in heat stroke‐induced organ injury remained unclear. Therefore, the current study aimed to illustrate if EGCX aggravates apoptosis, inflammation, and oxidative damage in human pulmonary microvascular endothelial cells (HPMEC). Heat stress and lipopolysaccharide (LPS) were employed to construct in vitro models to study the changes of glycocalyx structure and function, as well as levels of heparansulfate proteoglycan (HSPG), syndecan‐1 (SDC‐1), heparansulfate (HS), tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, Von Willebrand factor (vWF), endothelin‐1 (ET‐1), occludin, E‐selectin, vascular cell adhesion molecule‐1 (VCAM‐1), and reactive oxygen species (ROS). Here, we showed that heat stress and LPS devastated EGCX structure, activated EGCX degradation, and triggered oxidative damage and apoptosis in HPMEC. Stimulation of heat stress and LPS decreased expression of HSPG, increased levels of SDC‐1 and HS in culture supernatant, promoted the production and release of proinflammation cytokines (TNF‐α and IL‐6,) and coagulative factors (vWF and ET‐1) in HPMEC. Furthermore, Expressions of E‐selection, VCAM‐1, and ROS were upregulated, while that of occludin was downregulated. These changes could be deteriorated by heparanase, whereas they meliorated by unfractionated heparin. This study indicated that EGCX may contribute to apoptosis and heat stroke‐induced coagulopathy, and these effects may have been due to the decrease in the shedding of EGCX.

Background: POEMS syndrome is a rare and complex plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, high M protein levels, and skin changes. Understanding of POEMS syndrome has advanced rapidly since the 21st century. This study aims to summarize and evaluate the research status of POEMS syndrome in the past 23 years through a bibliometric and visualization analysis, and identify research focuses and emerging hotspots for the future. Methods: POEMS syndrome-related articles published between January 1, 2000, and March 8, 2023, were systematically retrieved from the Web of Science Core Collection. Data processing and visualization analysis were carried out using a combination of R software, HistCite, VOSviewer, and CiteSpace. Results: Since entering the 21st century, 3677 authors from 1125 institutions in 68 countries/regions have published 830 original and review articles on POEMS syndrome in 408 journals so far, among which the USA, Japan, and China published the most articles, and Mayo Clinic, Udice French Research Universities, and Peking Union Medical College listed the top three most prolific institutions. However, collaborative research across countries and groups in the study of POEMS syndrome remain significantly limited. Angela Dispenzieri ranked first in POEMS syndrome research from every aspect of authors, producing the most papers and contributing the most-cited article, followed by Satoshi Kuwabara and Sonoko Misawa. Internal medicine was the most productive journal on POEMS syndrome. ''endothelial growth factor'' was the keyword with the highest occurrence except for ''POEMS syndrome'', and ''bevacizumab'', ''lenalidomide'', ''dexamethasone'', and ''management'' were recognized as emerging topics. Conclusion: This study utilized bibliometric and visualization analysis to systematically summarize the research of POEMS syndrome in the first two decades of the 21st century, offering a data-based and objective perspective on the field of POEMS syndrome and guiding researchers in the identification of novel research directions.

IntroductionUntil now, the mechanism underlying the impact of topping on hormone regulation in tobacco plants remains unclear, and most studies investigating the hormone signaling pathways in plants rely on genes or transcriptional pathways.MethodsThis study examines the regulatory mechanisms of hormones in the roots and leaves of tobacco plants with and without topping at the protein level.ResultsThe results demonstrate that, compared with non-topped plants, topping leads to a decrease in the levels of IAA (auxin), ABA (abscisic acid), and GA (gibberellin) hormones in the leaves, whereas the content of the JA (jasmonic acid) hormone increases. Furthermore, in the roots, topping results in an increase in the levels of IAA, ABA, and JA hormones, along with a decrease in GA content. In the leaves, a total of 258 significantly different proteins were identified before and after topping, with 128 proteins upregulated and 130 proteins downregulated. In the roots, there were 439 proteins with significantly different quantities before and after topping, consisting of 211 upregulated proteins and 228 downregulated proteins. Notably, these proteins were closely associated with the metabolic and biosynthetic pathways of secondary metabolites, as indicated by functional categorization.ConclusionsWhen integrating the hormone changes and the proteomics results, it is evident that topping leads to increased metabolic activity and enhanced hormone synthesis in the root system. This research provides a theoretical foundation for further investigations into the regulation and signaling mechanisms of hormones at the protein level before and after topping in plants.

Background Lung cancer (LC) is the most prevalent cancer with a poor prognosis. Semaphorin4A (Sema4A) is important in many physiological and pathological processes. This study aimed to explore the role and mechanism of Sema4A in LC. Methods Firstly, Sema4A expression was analyzed by the available dataset and detected in human normal bronchial epithelial cell line (HBE) and LC cell line (NCI-H460). Then, LC cells were transfected with Sema4A siRNA, and the cells were stimulated by PlexinB1, PlexinB2, PlexinD1 blocking antibodies, IgG antibody, BAY 11-7082 (an inhibitor for NF-κB pathway) and Sema4A-Fc protein, alone or in combination. After transfection, PlexinB1 mRNA expression was analyzed. Next, the biological functions, including proliferative, migratory, invasive abilities and viability of the cells were detected by colony formation, scratch, Transwell and MTT assays, respectively. NF-κB, Stat3 and MAPK protein expressions were determined by western blot. Furthermore, the secretion of IL-6 in LC cells was tested by ELISA. Results Sema4A was highly expressed in LC tissues and cells, could activate the NF-κB pathway and upregulate PlexinB1 mRNA expression. Furthermore, we observed that Sema4A knockdown suppressed the biological functions of NCI-H460 cells, while Sema4A-Fc protein reversed the situation. However, Sema4A-induced biological functions and activation in the NF-κB pathway were inhibited by PlexinB1 blocking antibody. Consistently, Sema4A promoted IL-6 production, which was down-regulated by PlexinB1 blocking antibody and BAY 11-7082. Conclusions Sema4A may facilitate LC development via the activation of the NF-κB pathway mediated by PlexinB1, suggesting that Sema4A would be a novel therapeutic target for LC treatment.

Tuberculous meningitis (TBM) poses a diagnostic challenge, particularly impacting vulnerable populations such as infants and those with untreated HIV. Given the diagnostic intricacies of TBM, there’s a pressing need for rapid and reliable diagnostic tools. This review scrutinizes the efficacy of up-and-coming technologies like machine learning in transforming TBM diagnostics and management. Advanced diagnostic technologies like targeted gene sequencing, real-time polymerase chain reaction (RT-PCR), miRNA assays, and metagenomic next-generation sequencing (mNGS) offer promising avenues for early TBM detection. The capabilities of these technologies are further augmented when paired with mass spectrometry, metabolomics, and proteomics, enriching the pool of disease-specific biomarkers. Machine learning algorithms, adept at sifting through voluminous datasets like medical imaging, genomic profiles, and patient histories, are increasingly revealing nuanced disease pathways, thereby elevating diagnostic accuracy and guiding treatment strategies. While these burgeoning technologies offer hope for more precise TBM diagnosis, hurdles remain in terms of their clinical implementation. Future endeavors should zero in on the validation of these tools through prospective studies, critically evaluating their limitations, and outlining protocols for seamless incorporation into established healthcare frameworks. Through this review, we aim to present an exhaustive snapshot of emerging diagnostic modalities in TBM, the current standing of machine learning in meningitis diagnostics, and the challenges and future prospects of converging these domains.

Magnetic soft robots featuring untethered actuation and high mechanical compliance have promising applications ranging from bionics to biomedicine. However, their fixed magnetization profiles pose a challenge for adaptive shape transformation in unpredictable environments and dynamic tasks. Herein, a reprogrammable magnetic soft composite is reported by encapsulating magnetic neodymium–iron–boron microparticles with low melting alloy (LMA) and embedding them into the elastomer. Utilizing the phase transition of the LMA, the magnetic microparticles can be reoriented under an external magnetic field and they can be immobilized through LMA solidification, allowing the robot to obtain a new magnetization profile corresponding to its temporary shape. By changing the LMA composition, the robot with multiple programming temperatures can be fabricated and its local magnetization profiles can be selectively programmed in different temperature ranges. A bioinspired crawler with multimode locomotion, a reconfigurable robotic gripper capable of adaptable grasping, and reconfigurable electronic circuits are also demonstrated. This work may pave the way for the next‐generation magnetic soft robots and reconfigurable devices.

To further study the sedimentary environment of the black mudstone in the early Carboniferous Dawuba Formation in the Middle and Upper Yangtze regions and support regional shale gas exploration and related research, the major and trace elements of the Dawuba Formation in Well CY1, located in deep water shelf facies, were tested and analyzed. The results show that the study area contains mainly continental margin deposits affected by hydrothermal deposition, and they are rich in organic matter and have high primary productivity. The parent rocks are mainly acidic rocks, such as felsic igneous rocks, granites and some sedimentary rocks. And the provenance is mainly provided by acidic igneous rocks of the Jiangnan Paleouplift. An ICV

The widespread use of antibiotics in animal and human medication has raised global concerns over environmental contamination caused by antibiotic residues. This research investigated the occurrence of 12 kinds of antibiotics belonging to three groups, sulfonamides (SAs), tetracyclines (TCs), and fluoroquinolones (FQs), in chicken manure and the surrounding soil from different chicken farms in Hangzhou, South China, were detected in the samples via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and the contamination characteristics of each type of antibiotic and the correlations between each antibiotic and environmental factors were analyzed to identify the key influencing factors. An ecological risk assessment of antibiotics in the soil environment was conducted using the risk quotient (RQ) method to analyze the potential hazard level. The results indicated that: the total concentration of FQs was much higher than those of SAs and TCs in chicken manures and the soil samples. The mean concentration of FQs (39.17 μg·kg–1), TCs (34.37 μg·kg–1), and SAs (20.24 μg·kg–1) in chicken manure were significantly higher than those in the soil samples. Ciprofloxacin (CIP) was the main antibiotics detected in manure (19.42 μg·kg–1) and the soils samples (near soil: 18.42 μg·kg–1, far soil: 10.29 μg·kg–1), followed by enrofloxacin (ENR), tetracycline (TC), and ofloxacin (OFL). The redundancy analysis (RDA) showed that moisture content (MS), total organic carbon (TOC) and total nitrogen (TN) had a greater influence on the antibiotic concentration in the soil samples. Basis on the calculated risk quotient (RQs) values, the risk assessment indicated Sulfamerazine (SD) and Sulfamethoxazole (SMX) in soil posed a high risk, while trimethoprim (TMP), TC, CIP, and OFL in soils posed a medium or low risk. This research provides control and environmental monitoring data about chicken farms and scientific information that can be used to alleviate antibiotics pollution.

This study investigated the changes in major bioactive compounds and 5-hydroxymethyl furfural (5-HMF) in coffee beans during the roasting process. A Kinetics model was employed to simulate these changes and investigated the thermostability, and the Pearson correlation analysis was applied to indicate the relationship between bioactive compounds and 5-HMF. The research found that three Caffeoylquinic acids (3-CQA, 5-CQA, 4-CQA), and 5-HMF followed a dynamic pattern of increase in the early stage of the roasting process and decrease afterward, which was described by the combination of zero-order and first-order kinetics model. All fitting models fit well and the rate constant (k) of all models follows the Arrhenius law. Therefore, to obtain a higher concentration of bioactive compounds and lower levels of 5-HMF, light or medium roasted coffee beans are recommended. The Pearson correlation analysis indicated that the high levels of 3-CQA, 4-CQA, and caffeine may correspond to higher levels of 5-HMF after roasting.

As harvesting at the right time is crucial to ensuring the best quality and maximizing the yield of tobacco leaves, great attention has been paid to the research of “harvest maturity”. Fresh tobacco leaves can be manually categorized into four maturity stages, including immature, pseudomature, mature, and hypermature, according to the leaf tissue structure and color. To improve the discriminative accuracy, convenience, and automation of maturity levels, a tobacco leaf maturity discriminative method based on machine vision and deep learning was developed and integrated into a system based on the mobile terminal. In this method, the chromatic features and texture features can be automatically extracted from the acquired digital image of tobacco leaf by convolutional neural networks (CNNs). Experimental results of an independent test set consisting of 480 tobacco leaf samples demonstrated that the proposed system was able to classify the maturity stage of tobacco leaf efficiently and accurately. The system's ability to run on mobile devices, like smartphones, makes it easier to accurately collect mature tobacco leaves and reduces subjectivity compared to the current visual identification approach. Moreover, this system can provide a picking date recommendation to tobacco growers.

Background: To survey the unmet medical needs associated with atrium thrombus screening in Chinese patients with atrial fibrillation (AF) who underwent transesophageal echocardiography (TEE) for planned radio-frequency catheter ablation (RFCA). Methods: This cross-sectional survey study interviewed 300 patients who underwent their first TEE for planned RFCA. The surveyed information included patients' anxiety, oropharynx pain and discomfort, time expense, and patient satisfaction related to TEE examination. Patient preference for a new atrium thrombus screening technology, hospital length of stay (LOS) of RFCA, and hospital costs of RFCA in these surveyed patients were collected as well. Descriptive statistical methods were used to summarize the collected survey information. Results: Of the 300 interviewed patients, 36.3% reported anxiety before TEE examination, 58.6% reported oropharynx pain related to TEE, and 76.2% reported oropharynx discomforts, mainly including foreign body sensation (54.3%), dry heaves (33.8%), nausea (31.9%), and bleeding (22.9%). Even though 62.3% were satisfied with TEE, 84.3% preferred a new technology to replace TEE. Conducting outpatient TEE took more wait time (4.4 days vs. 0.1 days, p = 0.016) but led to significantly shorter hospital LOS (3.8 days vs. 6.4 days, p

For 2D piston pump the churning torque of its cam guide rails at high speed is one of the main sources of mechanical efficiency loss. To conveniently calculate the churning torque and also provide guidance for future optimization of churning torque reduction, an accurate analytical model of constant acceleration and constant deceleration cam guide rail assembly of the stacked-rollers 2D piston pump is established, where the whole churning torque is divided into the peripheral churning torque, the pushing flow churning torque, and the end face churning torque. Then the analytical model is verified by CFD simulation preliminarily. Analytical modeling shows that at 16,000 rpm, the churning torque reaches about 0.826 N m, where the peripheral churning torque, the pushing flow churning torque, and the end face churning torque account for about 55.4%, 37.3%, and 7.3% of the total torque respectively, indicating that the structural parameters related to the pushing flow torque should be optimized with first priority at high rotational speed. Finally, the churning torque at 1000–16,000 rpm was experimentally measured and the influence of oil temperature was considered. The experimental results are in good agreement with the results of analytical modeling and CFD simulation, thus verifying the correctness of the proposed analytical model.

Objective: Infection with Helicobacter pylori (H. pylori) may increase atherosclerosis, which can lead to carotid plaque formation. Our study examined the relationship between H. pylori infection and carotid plaque formation, and its underlying mechanisms. Methods: A total of 36,470 people who underwent physical examination in Taizhou Hospital Health Examination Center from June 2017 to June 2022 were included in this study. All people participated in the urease test, neck ultrasound, blood pressure detection, anthropometric measurement and biochemical laboratory examination. In addition, the GSE27411 and GSE28829 datasets in the Gene Expression Omnibus (GEO) database were used to analyze the mechanism of H. pylori infection and atherosclerosis progression. Results: H. pylori infection, sex, age, blood lipids, blood pressure, fasting blood glucose, glycated hemoglobin and body mass index were risk factors for carotid plaque formation. An independent risk factor was still evident in the multivariate logistic regression analysis, indicating H. pylori infection. Furthermore, after weighted gene coexpression network analysis (WGCNA), we discovered 555 genes linked to both H. pylori infection and the advancement of atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed a strong correlation between these genes and immunity, infection, and immune disorders. SsGSEA analysis showed that H. pylori infection and atherosclerosis included changes in the immune microenvironment. Finally, three genes MS4A6A, ADAMDEC1 and AQP9 were identified to be involved in the formation of atherosclerosis after H. pylori infection. Conclusion: Our research affirms that H. pylori is a unique contributor to the formation of carotid plaque, examines the immune microenvironment associated with H. pylori infection and advanced carotid atherosclerosis, and offers fresh perspectives on how H. pylori infection leads to atherosclerosis.

Objectives: Cognitive impairment in schizophrenia patients with auditory hallucinations is more prominent compared to those without. Our study aimed to investigate the cognitive improvement effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) in schizophrenia with auditory hallucinations. Methods: A total of 60 schizophrenic patients with auditory hallucinations in this study were randomly assigned to sham or active group. Both groups received 10 Hz or sham rTMS targeted in left DLPFC for 20 sessions. The Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucination Rating Scale (AHRS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Udvalg for Kliniske Under-sogelser (UKU) side effect scale were used to measure psychiatric symptoms, auditory hallucinations, cognition, and side reaction, respectively. Results: Our results indicated that the active group experienced greater improvements in RBANS-total score (P = 0.043) and immediate memory subscale score (P = 0.001). Additionally, the PANSS-total score, negative and positive subscale score were obviously lower in the active group compared to the sham group (all P

Biochar is a versatile, carbon-rich, organic material that can effectively immobilize Cd in the soil. In this study, peanut shell biochar (SP), maize straw biochar (MS), and bamboo straw biochar (BS) were applied in different proportions to evaluate their effects on the remediation of Cd-contaminated farmland soil and plant growth. The results revealed that both single and mixed applications of biochar substantially increased corn biomass and chlorophyll content compared to the unamended control treatment, while the malondialdehyde (MDA) and proline contents were largely unaffected. The bamboo straw block biochar with maize straw biochar at a mass ratio of 2:1 (DBM) significantly increased the dry total biomass of maize (+107.24% compared to the unamended soil). SP application has highly increased the SPAD value. PB with BS application at a mass ratio of 1:1 (MSB) significantly decreased the soluble sugar content (+21.81% compared to the unamended control soil). Soil pH was increased by the application of biochar alone and in combination with feedstocks. The soil content of Fe/Mn oxide-bound (OX) and exchangeable-bound Cd (EX) was decreased, whereas that of carbonate-bound Cd (CA), residue-bound Cd (RE), and organic-bound Cd (OM) contents increased. The Cd content in corn grains under MSB and SP application was markedly reduced by 42.62% and 31.48%, respectively, compared to the unamended control soil. Overall, MSB and SP applications were effective in improving soil quality and crop growth.

BackgroundFluid loading is an essential component of treatment for reducing the incidence of post-spinal anesthesia hypotension and is necessary to maintain intravascular volume, perfuse tissues, and control spinal anesthesia hypotension after sympathetic blockade. We performed a randomized sequential allocation dose-finding study to compare the effects of 10 mL/kg crystalloid and 6% hydroxyethyl starch (130/0.4) co-load on the ED90 of prophylactic norepinephrine infusion for preventing post-spinal anesthesia hypotension during cesarean delivery.MethodsEighty patients were randomly allocated to receive either a 10 mL/kg crystalloid (Crystalloid Group, n = 40) or 6% hydroxyethyl starch (130/0.4) (Colloid Group, n = 40) co-load combined with prophylactic norepinephrine infusion during spinal anesthesia for cesarean delivery. The first patient received an initial prophylactic norepinephrine infusion rate of 0.025 μg/kg/min. Subsequent patients received a 0.005 μg/kg/min gradient dose of prophylactic norepinephrine. This dose was administered as a gradient based on its effectiveness for preventing post-spinal anesthesia hypotension (defined as SBP

As an effective soil amendment, biochars require a comprehensive ecological evaluation before they can be widely used in agriculture because endogenous contaminants, such as environmentally persistent free radicals (EPFRs), certainly pose an ecological risk to soil invertebrates. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to investigate the neurotoxicity of two rice straw biochars pyrolyzed at 500 and 700 °C. After 24 h exposure to unwashed biochar, washed biochar, and leaching fluids (supernatants), the neurobehavioral parameters of C. elegans were determined in a liquid toxicity test. The results showed that the washed 700 °C biochar particles significantly impaired locomotion and prolonged the defecation interval at a biochar concentration of 4 g·well−1, while the unwashed biochar and supernatants caused no apparent impairment. Supporting this, electron paramagnetic resonance (EPR) results showed that the intensity of EPFRs in unwashed 700 °C biochar was stronger than that of the corresponding washed particles. This indicates that, in the liquid test, the EPR signal alone is not indicative of particle toxicity. The accessibility and activity of the EPFRs should be considered. Dissolved organic matter (DOM) was observed in the leaching fluids. The neurotoxic activity of the washed biochar was alleviated after the re-addition of leaching fluids to the washed biochar, suggesting that the dissolved organic materials modulate the reactivity of the EPFRs in the liquid phase. This study suggests that the leaching process may increase the risk of biochar when used in the field environment.

Abstract Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.

2D metallenes have spurred considerable interests in heterogeneous catalytic reactions. Here the authors report an efficient galvanic replacement strategy to construct Pd metallenes mediated by Nb2C MXenes for boosting alkynes semihydrogenation.

Abstract Multidrug resistance is a major challenge in treating advanced hepatocellular carcinoma (HCC). Although recent studies have reported that the multidrug resistance phenotype is associated with abnormal DNA methylation in cancer cells, the epigenetic mechanism underlying multidrug resistance remains unknown. Here, we reported that the level of 5-hydroxymethylcytosine (5-hmC) in human HCC tissues was significantly lower than that in adjacent liver tissues, and reduced 5-hmC significantly correlated with malignant phenotypes, including poor differentiation and microvascular invasion; additionally, loss of 5-hmC was related to chemotherapy resistance in post-transplantation HCC patients. Further, the 5-hmC level was regulated by ten-eleven translocation 2 (TET2), and the reduction of TET2 in HCC contributes to chemotherapy resistance through histone acetyltransferase P300/CBP-associated factor (PCAF) inhibition and AKT signaling hyperactivation. In conclusion, loss of 5-hmC induces chemotherapy resistance through PCAF/AKT axis and is a promising chemosensitivity prediction biomarker and therapeutic target for HCC patients.

Abstract Ethnopharmacological relevance Sepsis is a systemic inflammatory response syndrome caused by an infection in the body, and accompanying acute kidney injury (AKI) is a common complication of sepsis. It is associated with increased mortality and morbidity. Forsythia Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a commonly used traditional Chinese medicine. Aims of the study This study aimed to elucidate the protective effect of Forsythiaside A (FTA) on sepsis-induced AKI by downregulating inflammatory and apoptotic responses, and exploring its underlying mechanism. Methods Septic AKI was induced through intraperitoneal injection of LPS (10 mg/kg) using male C57BL/6 mice and pretreated with FTA or control saline. First, we assessed the degree of renal injury by creatinine, blood urea nitrogen measurement, and HE staining of renal tissue; secondly, the inflammation and apoptosis were measured byELISA, qPCR, and TUNEL immunofluorescence; finally, the mechanism was explored by computer molecular docking and Western blot. Results Our data showed that FTA markedly attenuated pathological kidney injuries, alleviated the elevation of serum BUN and Creatinine, suggesting the renal protective effect of FTA. Notably, FTA significantly inhibited the renal expression of proinflammatory cytokine IL-1β, IL-6, and TNF-α both at protein and mRNA levels and attenuated cell apoptosis in the kidney, as measured by caspase-3 immunoblot and TUNEL assay, indicating its anti-Inflammation and antiapoptotic properties. Mechanistically, administration of LPS resulted in robust endoplasmic reticulum (ER) stress responses in the kidney, evidenced by glucose-regulated protein 78(GRP78) upregulation, protein kinase RNA–like endoplasmic reticulum kinase (PERK) activation, eukaryotic initiation factor 2 alpha (elF2α) phosphorylation and C/EBP homologous protein (CHOP) overexpression, which could be significantly blocked by FTA pretreatment. Dynamic simulation and molecular docking were performed to provide further insight. Conclusions Collectively, our data suggest that FTA ameliorates sepsis-induced acute kidney injury via its anti-inflammation and antiapoptotic properties by regulating PERK signaling dependent ER stress responses.

The use of video surveillance to monitor interrogation behavior can effectively maintain judicial civility in the context of law enforcement cases. However, analyzing and reviewing law enforcement videos can be a time-consuming and resource-intensive process, particularly in the manual identification of interrogation violations. This work is dedicated to the development of an intelligent recognition system for interrogation violations by using a spatio-temporal attention fusion SlowFast Network. To address the issue of feature information underutilization in the slow path of the traditional SlowFast, a slow-to-fast path is incorporated into the original SlowFast to enhance learning. The model fuses the attention of spatial and temporal channels, replacing the traditional convolution module with this new approach. The proposed model was evaluated using the publicly available UCF101 action recognition dataset, resulting in a 1.52% improvement in Top-1 recognition accuracy compared to the traditional SlowFast. Based on two custom interrogation misconduct datasets, the proposed model was evaluated, achieving a recognition rate of 99.16% for interrogation misconduct. This demonstrates its effectiveness in identifying misconduct behaviors inside interrogation rooms. Compared to some advanced behavior recognition models, the proposed model demonstrates strong competitiveness in identifying misconduct during interrogations.

Owing to the nature of wireless channels, wireless transmission is vulnerable to attacks by adversaries; therefore, security has always been a critical issue in wireless networks. In this context, intelligent reflecting surfaces (IRS), as an emerging and promising technology, synergize with physical layer security (PLS), offering novel avenues to enhance privacy and resistance against interference in wireless communication. This paper investigates a cooperative jamming communication model assisted by IRS. Under the constraints of minimum safe rate and inaccurate channel state information (CSI), a deep reinforcement learning (DRL)-based framework is proposed to jointly optimize the BS transmitting beamforming power distribution and IRS phase shift matrix to maximize the system energy efficiency. We first formulate an anti-jamming communication optimization problem as a Markov decision process (MDP) framework and then design a DRL-based algorithm, in which the joint design is obtained through trial-and-error interactions with the environment by observing predefined rewards in the context of continuous state and action to generate an optimal policy. The simulation results show that when the number of IRS components is increased from 20 to 100, the proposed scheme can improve energy efficiency by 40.1%, which is better than other schemes.

Pedestrian detection is the use of computer vision technology to identify and accurately locate pedestrians in image or video data, which has a strong use value. This technology can be used as the research basis for visual tasks such as person re-identification, human pose estimation and behavior analysis, and can also be applied to industrial fields such as intelligent security, automatic driving and human-computer interaction. However, the problems of low image resolution, blurred appearance, large scale difference of pedestrians, occluded pedestrians and complex background still bring great challenges to the detection performance. To solve these problems, this paper proposes a high-performance pedestrian detection network dedicated to difficult conditions: DCPDN. Firstly, we design an optimized super-resolution reconstruction network to preprocess the image to alleviate the performance damage caused by low-resolution and blurred images. Then, to solve the multi-scale problem in pedestrian detection, we propose a weighted cross-scale feature fusion module, which adopts a hierarchical detection strategy to deal with pedestrian objects of different scales while fully fusing feature maps of different levels. Finally, to solve the occlusion problem that has plagued pedestrian detection for a long time, we design an occlusion processing module based on graph convolutional network, which can effectively use the correlation information between different parts of the human body and promote the feature expression of occluded objects. On the CityPersons dataset, the ${MR}^{-2}$ of the detector is reduced by 6.9%, 19.2%, 8.9%, 1.9%, 3.6% and 14.2%, respectively, corresponding to different partition subsets of R, HO, A, L, M and S. On the Caltech dataset, corresponding to different divisions of R, HO, A, L and S, the ${MR}^{-2}$ of the detector is reduced by 9.9%, 15.8%, 16.3%, 6.8% and 25.8%, respectively. The experimental results show that the performance improvement of the detector is significant on both severe occlusion (HO) and small scale (S) subsets. After testing, the algorithm has strong robustness to occluded pedestrians, and can be easily embedded in other detection frameworks. Our DCPDN is able to compete with the state of the art methods and is especially effective when dealing with the pedestrian detection problem under difficult conditions.

Abstract Poly‐ADP‐ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA‐deficient tumors. However, over 40% of BRCA‐deficient patients fail to respond to PARPi. Here, we report that thioparib, a next‐generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi‐sensitive and ‐resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1‐dependent DNA damage and replication stress, causing S‐phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR‐mediated DNA repair while increasing RAD51 foci formation. Notably, the on‐target inhibition of PARP7 by thioparib‐activated STING/TBK1‐dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome‐scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next‐generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier‐generation PARPi.

The increasing demand for wireless Internet of Things (IoT) calls for power efficient RF energy harvesting approach. The current dominant single-band RF energy harvesting front-end system restricts itself to a single frequency, which is at the risk of ineffective operation when the harvesting frequency is unavailable. This paper reviews and explores the alternative approach of a multiband RF energy-harvesting front-end system. It covers all essential circuitry of a multiband RF energy harvesting front-end system, starting from the recent RF surveys which investigate the typical, usable, and high-strength RF input, to the overview of the state-of-the-art antenna, impedance matching network (IMN), and RF-DC rectifier. The recent advancement of the multiple RF input harvesting abilities, reflection loss minimization, and performance improvement are comprehensively reviewed for different operating conditions, and this review also presents the advantages and disadvantages of the different circuit architecture combinations for multiband RF energy harvesting front-end systems. In summary, this review aims to fill the research gap in the further advancement of multiband RF energy harvesting towards enhancing its performance through optimal circuit integration of the front-end system.

Abstract The prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in patients with hepatocellular carcinoma (HCC) remains controversial. This meta-analysis aims to evaluate the prognostic role of AAPR in patients with HCC. The databases of Web of Science, Embase, Cochrane Library and PubMed were comprehensively searched from inception to April 25, 2022. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated with Stata 16.0 software for the assessment of the relationship between AAPR and overall survival (OS) as well as recurrence-free survival (RFS) in patients with HCC. A total of 2634 patients from 12 cohorts were included in this meta-analysis. The pooled results showed that lower AAPR predicted poorer OS (HR 2.02, 95% CI 1.78–2.30). Similarly, pooled results demonstrated that lower AAPR also predicted poorer RFS (HR 1.88, 95% CI 1.37–2.57). The heterogeneity for RFS by multivariate analytic results and the publication bias for OS existed, however, the subgroup analysis, meta-regression analysis as well as adjustment using trim-and-fill analysis confirmed an association between AAPR and OS as well as RFS. This meta-analysis proves that lower AAPR in patients with HCC predicted inferior survival outcomes, and AAPR might be a promising indicator for the prognosis of HCC.

Abstract Background There were controversies for the association between computed tomography (CT)‐determined low skeletal muscle mass (SMM) and overall survival (OS) in gastric cancer (GC). In this study, we investigated whether cachexia could be a potential confounding variable for this issue. Methods We retrospectively collected the patients of GC in our institution between July 2016 and January 2021. Preoperative SMM was determined by analyzing the skeletal muscle index of L3 with abdominal CT, and the cut‐offs for low SMM were defined as

Abstract Background Oral administration offered a painless way and improved compliance for diabetics. However, the emerging GLP-1 analog peptide drugs for diabetes primarily rely on the injection route, and the development of oral dosage forms was hampered by the low oral bioavailability due to the structural vulnerability to digestive enzymes and molecule impermeability in the gastrointestinal tract. Results In this study, the non-covalent interaction between cholic acid (CA) and liraglutide (LIRA) was found and theoretically explained by molecular docking simulation. Formation of this physical complex of liraglutide and cholic acid (LIRA/CA Complex) reduced the self-aggregation of LIRA and accelerated intestinal epithelium penetration. By the anti-solvent method, LIRA/CA Complex was loaded into zein/rhamnolipids nanoparticles (LIRA/CA@Zein/RLs) with a loading efficiency of 76.8%. LIRA was protected from fast enzymatic degradation by the hydrophobic zein component. Meanwhile, Rhamnolipids, a glycolipid with surface activity, promoted endocytosis while also stabilizing the nanoparticles. The two components worked synergistically to ensure the delivery of LIRA/CA Complex to intestinal villi and improved oral absorption without disrupting tight junctions. LIRA/CA@Zein/RLs demonstrated a considerable intestinal epithelium absorption in mouse gastrointestinal section and a retention in vivo over 24 h, resulting in a significant and long-lasting hypoglycemic effect in Type 2 diabetes mice. Conclusion This study provided a promising oral delivery approach for LIRA and exhibited the potential for further translation into clinical application.

Abstract Background Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the “drug-active ingredient-disease-target-pathway” was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. Results The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. Conclusions The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Abstract Histone deacetylase (HDAC) is a kind of protease that modifies histone to regulate gene expression, and is usually abnormally activated in tumors. The approved pan-HDAC inhibitors have demonstrated clinical benefits for patients in some hematologic malignancies. Only limited therapeutic success in breast cancer has been observed in clinical trials. In this study, we declare that pan-HDAC inhibitors targeting NEDD9-FAK pathway exacerbate breast cancer metastasis in preclinical models, which may severely impede their clinical success. NEDD9 is not an oncogene, however, it has been demonstrated recently that there are high level or activity changes of NEDD9 in a variety of cancer, including leukemia, colon cancer, and breast cancer. Mechanistically, pan-HDAC inhibitors enhance H3K9 acetylation at the nedd9 gene promoter via inhibition of HDAC4 activity, thus increase NEDD9 expression, and then activate FAK phosphorylation. The realization that pan-HDAC inhibitors can alter the natural history of breast cancer by increasing invasion warrants clinical attention. In addition, although NEDD9 has been reported to have a hand in breast cancer metastasis, it has not received much attention, and no therapeutic strategies have been developed. Notably, we demonstrate that FAK inhibitors can reverse breast cancer metastasis induced by upregulation of NEDD9 via pan-HDAC inhibitors, which may offer a potential combination therapy for breast cancer.