Search

ObjectiveJianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth.Methods300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF.ResultsJPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration.ConclusionThese findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration.

Plant-based meat analogs have become an important topic in recent years. To scientifically understand the research situation of plant-based meat analogs, we analyzed 2,595 publications from January 2000 to October 2023 by bibliometric method based on the PubMed database. The results showed a gradual rise in the number of annual publications, with the fastest growth rate of 58.5% in 2021. The country with the most publications was the United States (685, 24.87%), followed by China (242, 8.79%) and the United Kingdom (196, 7.12%). The University of Helsinki, Texas A&M University and the University of California were core research institutions. Popular and important journals were mainly Foods, Nutrients, Meat Science, Food Research International, and Critical Reviews in Food Science and Nutrition. Current research topics focused on alternative proteins and their functional and nutritional characteristics, as well as sustainable development. The research interests have gradually expanded from quality characteristics to nutritional characteristics. Further improving the quality, controlling natural toxin contamination, as well as systematically investigating the effects on health were future research trends. The effects of plant-based meat analogs on metabolic pathways and diseases were important clues in the study of nutritional health. This bibliometric analysis comprehensively and quantitatively presents the research landscape and hotspots, and further suggests future research directions. These findings can benefit researchers in selecting appropriate journals and finding potential collaborators to achieve in-depth research in this field.

Currently, HgCdTe detectors are advancing towards very long wavelengths and room temperature operation. However, as operating temperatures and illumination intensity increase, the performance of these detectors deteriorates, evidenced by increased dark current, reduced responsivity and detectivity, and enhanced saturation effects. These limitations significantly hinder the application of detectors for strong illumination scenarios at room temperature. In this study, we utilize compositional gradients and array electrode designs to make better trade-offs among dark current, responsivity, and saturation characteristics of HgCdTe photovoltaic detectors under mid-wave and long-wave infrared conditions. We elucidate the underlying mechanisms from the perspectives of the responsive region and the non-photosensitive area, as well as carrier motion and recombination processes. The results indicate that increasing compositional gradients are beneficial for reducing dark current, while decreasing compositional gradients are advantageous for improving responsivity. Moreover, detectors with array electrodes design achieve a peak responsivity of 1.5 A/W under 200 W/cm2 (∼1.8 mW) at room temperature, which is three times higher than the pre-optimized structure. Additionally, the peak detectivity increased by more than 20%. These research findings provide guidance for the design of future HgCdTe detectors operating under strong injection levels and at various temperatures.

In recent years, there has been a growing interest in photovoltaic detectors based on mercury cadmium telluride (Hg1-xCdxTe), owing to their exceptional photoelectric properties. To provide the physical insights into the modulation effects of Cd composition x on Hg1-xCdxTe under strong injection conditions, specifically for MWIR HgCdTe detectors, we conduct the numerical simulations to investigate the coupling effects of optical and electrical fields on detector performance. The Hg1-xCdxTe detectors based on three kinds of coupling directions, namely inverse field (IF), vertical field (VF), and parallel field (PF), are compared in terms of responsivity and saturation threshold to account for the electric field contributions deriving from the compositional gradient and the applied bias voltage under front illumination (FI) and back illumination (BI). The simulations considering the modulation effects suggest that the detector exhibits better photoelectric response characteristics under FI and a higher saturation threshold for the BI case. The IF structure has the best current response at illumination intensities below 20 W/cm2, with the peak responsivity of the nonlinear model exceeding 2.8 A/W. The VF structure has the best current response at illumination intensities above 20 W/cm2 and exhibits the best saturation characteristics, with its saturation threshold consistently above 15 W/cm2, while the PF structure with nonlinear increasing (nInc) compositional gradient exhibits excellent linearity of response under conditions of high illumination intensity. The simulation methods help design and optimize the detectors with the physical understanding according to the specific requirements.

Salmonella and their biofilm formation are the primary bacterial causes of foodborne outbreaks and cross-contamination. The objective of the study was to investigate the potential of Salmonella phages as an alternative technology for biofilm removal. In this work, 21 Salmonella phages were isolated from a chicken farm and slaughter plant and the phage (CW1) with the broadest spectrum was characterized. Complete genome sequence analysis revealed that the genomes of phage CW1 is composed of 41763 bp with 58 open reading frames (ORFs) and a holin-endolysin system and it does not encode any virulence or lysogeny. A phage cocktail consisted of CW1 (with the broadest spectrum of 70.49 %) and CW11, M4 and M10 (with a high lytic activity of more than 67.11 %) was established. Treatment with the cocktail reduced the cells in the developing biofilm and mature biofilm by 0.79 lg(CFU/cm2) and 0.4 lg(CFU/cm2), respectively. More dead cells and scattered extracellular polymeric substances (EPS) were observed by confocal laser scanning microscopy and scanning electron microscopy. Raman analysis found that carbohydrates and proteins were the identification receptors for scattered EPS. This finding suggests that this phage cocktail has potential applications for the sterilization of Salmonella biofilm during meat processing.

Land degradation is a major impediment to achieving sustainable development. However, there is currently no harmonized global map of land degradation status and hotspots. This paper aims to obtain the status and hotspots map of global land degradation by multiple methods and indicators to give essential references for land degradation neutrality. The results show that there are significant differences in the distribution and degree of land degradation between the different methods and indicators. Validation through observation points reveals that most of the methods and indicators can reflect land degradation in arid and semi-arid areas, while there are suitable methods or indicators in tropical and high-latitude areas. The degree of degradation has a large difference after overlay analysis, which shows that there are shortcomings of different methods and indicators for monitoring the degree of land degradation. However, the overlay of land degradation extent displays a high consistency, reflecting the current state of global land degradation to a certain extent. These areas with high overlay value can be recognized as hotspots of land degradation. It is also found there are consistent water-energy change characteristics in the hotspot area, such as increased land surface temperature and air temperature and decreased soil moisture and precipitation. These results conclude that studies on the degree of land degradation need to be considered in an integrated manner about the regional background. The combination of multiple methods and indicators is recommended for land degradation extent studies in large areas. Comparison of different methods and indicators is important guidance for global land degradation research. Accelerating ecological monitoring and restoration of land degradation hotspots is the first step towards land degradation neutrality.

ABSTRACTSalmonella Enteritidis is a foodborne enteric pathogen that infects humans and animals, utilizing complex survival strategies. Bacterial small RNA (sRNA) plays an important role in these strategies. However, the virulence regulatory network of S. Enteritidis remains largely incomplete and knowledge of gut virulence mechanisms of sRNAs is limited. Here, we characterized the function of a previously identified Salmonella adhesive-associated sRNA (SaaS) in the intestinal pathogenesis of S. Enteritidis. We found that SaaS promoted bacterial colonization in both cecum and colon of a BALB/c mouse model; it was preferentially expressed in colon. Moreover, our results showed that SaaS enhanced damage to mucosal barrier by affecting expressions of antimicrobial products, decreasing the number of goblet cells, suppressing mucin gene expression, and eventually reducing thickness of mucus layer; it further breached below physical barrier by strengthening invasion into epithelial cells in Caco-2 cell model as well as decreasing tight junction expressions. High throughput 16S rRNA gene sequencing revealed that SaaS also altered gut homeostasis by depleting beneficial gut microbiota while increasing harmful ones. Furthermore, by employing ELISA and western blot analysis, we demonstrated that SaaS regulated intestinal inflammation through sequential activation P38-JNK-ERK MAPK signaling pathway, which enabled immune escape at primary infection stage but strengthened pathogenesis at later stage, respectively. These findings suggest that SaaS plays an essential role in the virulence of S. Enteritidis and reveals its biological role in intestinal pathogenesis.

Process variations (PV), including global variation (GV) and local variation (LV), have become one of the major issues in advanced technologies, which is crucial for circuit performance and yield. However, developing a mature and physics-based model is challenging and time-consuming. Thus, in this work, we propose a machine learning (ML) based method for device modeling with PV and implement the corresponding circuit simulation, which is demonstrated on advanced Nanosheet FETs (NSFET). Verified by TCAD simulations, the artificial neural network (ANN)-based ML algorithm enables to capture PV, e.g., dimension and work function variations (WFV), with high accuracy and improved efficiency. For GV, the ANN surrogated NSFET-based ring oscillator (RO) simulation results show that the larger width (Wsh) or height (Hsh) of the Nanosheet leads to the higher RO frequency and lower circuit delay. For LV, the respective impacts of grain size and WF on circuit performance can be distinguished. The proposed workflow, from ANN model training to circuit simulation based on the generated Verilog-A model, is fully automatic, promising to shorten the procedure of device modeling and accelerate the development of advanced technologies.

Background: The high incidence and mortality rates of colorectal cancer (CRC) are a severe challenge in China. In patients with stage III and high-risk stage II CRC after radical resection and postoperative adjuvant chemoradiotherapy, 40–60% experience recurrence and metastasis. Several years of clinical practice have shown that traditional Chinese medicine, including Jianpi Huatan granule (JHG), effectively prevents stage III and high-risk stage II CRC recurrence and metastasis after radical resection and postoperative standard adjuvant chemotherapy. However, high-level systematic plans and evidence-based medicine are lacking in this regard. Therefore, this randomised control trial aimes to determine the efficacy of JHG in reducing stage III and high-risk stage II CRC metastasis and recurrence after radical resection and postoperative standard adjuvant chemotherapy.Methods: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. Three hundred and fifty patients with stage III or high-risk stage II CRC who completed adjuvant chemotherapy after radical resection will be recruited from eight medical centres in China and randomly assigned to test (n = 175) and control (n = 175) groups at a ratio of 1:1. The test group will receive oral JHG for 3 months, whereas the control group will receive oral placebo for 3 months. The primary outcomes will be the disease-free survival and 1-, 2-, and 3-years metastasis and recurrence rates, whereas the secondary outcomes will be quality of life and circulating tumour cells. The patients will be followed-up monthly during treatment and every 3–6 months thereafter until recurrence, metastasis, death, or the end of the study.Trial registration: This trial was registered at ClinicalTrials.gov (NCT03716063).

Down's syndrome (DS) is one of the most commonly known disorders with multiple congenital disabilities. Besides severe cognitive impairment and intellectual disability, individuals with DS also exhibit additional phenotypes of variable penetrance and severity, with one or more comorbid conditions, including Alzheimer's disease, congenital heart disease, or leukemia. Various vital genes and regulatory networks had been studied to reveal the pathogenesis of the disease. Nevertheless, very few studies have examined alternative splicing. Alternative splicing (AS) is a regulatory mechanism of gene expression when making one multi-exon protein-coding gene produce more than one unique mature mRNA. We employed the GeneChip Human Transcriptome Array 2.0 (HTA 2.0) for the global gene analysis with hiPSCs from DS and healthy individuals. Examining differentially expressed genes (DEGs) in these groups and focusing on specific transcripts with AS, 466 up-regulated and 722 down-regulated genes with AS events were identified. These genes were significantly enriched in biological processes, such as cell adhesion, cardiac muscle contraction, and immune response, through gene ontology (GO) analysis of DEGs. Candidate genes, such as FN1 were further explored for potentially playing a key role in DS. This study provides important insights into the potential role that AS plays in DS.

Wild birds play an important role in the emergence, evolution, and spread of zoonotic avian influenza viruses (AIVs). However, there are few studies on the cross-species transmission of the H3N8 AIV originating from wild birds. In this study, we investigated the transmissibility and pathogenicity of two H3N8 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds, GZA1 and XJ47, to mammals. The HA genes of both strains belonged to Eurasian isolates, while the other genes were derived from a variety of other subtypes of AIVs. Both strains can infect specific-pathogen-free (SPF) chickens, BALB/c mice, and guinea pigs. The XJ47 strain spread horizontally in SPF chickens and guinea pigs. The GZA1 strain did not spread horizontally but caused higher weight loss and mild lung inflammation in mice. P12-GZA1- and P12-XJ47-adapted strains obtained after 12 passages in the lung of mice showed enhanced pathogenicity in mice, which led to obvious clinical symptoms, lung inflammation, and 100% death. Both adapted strains have the reported mutation T97I in the PA, and the reported mutation D701N in PB2 has been found in the P12-GZA1-adapted strain. This study provides an important scientific basis for the continuous monitoring of wild AIVs and the mechanism underlying AIV cross-species transmission.

Background: This study aimed to prepare monoclonal antibodies (mAbs) with high immunoreactivity, sensitivity, and specificity for the chelate (Cr(III)-EDTA) of trivalent chromium ion (Cr(III)) and ethylenediamine tetraacetic acid (EDTA). Further, the study established an indirect competitive enzyme-linked immunosorbent assay (icELISA) for detecting the total chromium content in food, feed, and environmental samples. Methods: Hapten Cr(III)-iEDTA was synthesized by chelating Cr(III) with isothiocyanatebenzyl-EDTA (iEDTA). Immunogen Cr(III)-iEDTA-BSA formed by chelating Cr(III)-iEDTA with bovine serum albumin (BSA), and coating antigen Cr(III)-iEDTA-OVA formed by chelating Cr(III)-iEDTA with ovalbumin (OVA) were prepared using the isothiocyanate method and identified by ultraviolet spectra (UV) and inductively coupled plasma optical emission spectrometry (ICP-OES). Balb/c mice were immunized with the Cr(III)-iEDTA-BSA, and the anti Cr(III)-EDTA mAb cell lines were screened by cell fusion. The Cr(III)-EDTA mAbs were prepared by induced ascites in vivo, and their immunological characteristics were assessed. Results: The immunogen Cr(III)-iEDTA-BSA was successfully synthesized, and the molecular binding ratio of Cr(III) to BSA was 15.48:1. Three hybridoma cell lines 2A3, 2A11, and 3D9 were screened, among which 2A3 was the best cell line. The 2A3 secreted antibody was stable after six passages, the affinity constant (Ka) was 2.69 × 109 L/mol, its 50% inhibition concentration (IC50) of Cr(III)-EDTA was 8.64 μg/L, and it had no cross-reactivity (CR%) with other heavy metal ion chelates except for a slight CR with Fe(III)-EDTA (1.12%). An icELISA detection method for Cr(III)-EDTA was established, with a limit of detection (LOD) of 1.0 μg/L and a working range of 1.13 to 66.30 μg/L. The average spiked recovery intra-assay rates were 90% to 109.5%, while the average recovery inter-assay rates were 90.4% to 97.2%. The intra-and inter-assay coefficient of variations (CVs) were 11.5% to 12.6% and 11.1% to 12.7%, respectively. The preliminary application of the icELISA and the comparison with ICP-OES showed that the coincidence rate of the two methods was 100%, and the correlation coefficient was 0.987. Conclusions: The study successfully established an icELISA method that meets the requirements for detecting the Cr(III)-EDTA chelate content in food, feed, and environmental samples, based on Cr(III)-EDTA mAb, and carried out its preliminary practical application.

Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein signaling, which was proposed to contribute to memory retention impairment in rats. Here, we first demonstrated that propofol perfusion could inhibit forskolin induced LTP in the rat hippocampal CA1 slices. Propofol also reduced the level of cAMP, which could be reversed by non-selective PDE inhibitor IBMX. We further discovered that propofol could increase both PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region. Furthermore, pretreatment of rolipram, a PDE4 inhibitor, rescued propofol induced inhibition of CA1 LTP and the impairment of hippocampus-dependent memory formation in rats. Thus, our results suggest that reduced levels of cAMP by increasing PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region plays an important role in the propofol-induced amnesia.

This research was conducted to compare chemical and microbiological properties during aerobic composting (AC) and vermicomposting (VC) of green waste. Relative to AC, VC significantly decreased the pH and lignin and cellulose contents, and significantly increased the electrical conductivity and total N and available P contents. For AC, BIrii41_norank (order Myxococcales) was the major bacterial genus at 30 d and again became dominant genus from 90-150 d, with relative abundances of 2.88% and 4.77-5.19%, respectively; at 45 d and 60 d, the dominant bacterial genus was Nitrosomonadaceae_uncultured (order Nitrosomonadales) with relative abundances of 2.83-7.17%. For VC, the dominant bacterial genus was BIrii41_norank (except at 45 d), which accounted for 2.11-7.96% of the total reads. The dominant fungal class was Sordariomycetes in AC (relative abundances 39.2-80.6%) and VC (relative abundances 42.1-69.5%). The abundances of microbial taxa and therefore the bacterial and fungal community structures differed between VC and AC. The quality of the green waste compost product was higher with VC than with AC. These results will also help to achieve further composting technology breakthroughs in reducing the composting time and improving compost quality.

Cement emulsified asphalt mixture (CEAM) is widely used in asphalt pavement for its environmental virtues. However, a CEAM layer can influence fatigue performance of asphalt pavement because of higher air voids of CEAM in contrast to hot mix asphalt (HMA). Therefore, it is common to use HMA and CEAM structure combinations for improving the fatigue performance. In this work, three different thickness structure combinations of HMA (AC-10) and CEAM (AC-16) were designed, in which HMA and CEAM were used as top layer and bottom layer, respectively. The fatigue performance of the three combinations was studied. The fatigue equations of the combinations were established and the rational combination was recommended. The distributions of the internal voids in the combinations were studied with X-ray computed tomography (X-ray CT); and the correlation between the fatigue life and the void ratios were analyzed. Artificial neural network (ANN) was employed to predict the fatigue life of each combination. The results show that the fatigue life of the combinations is inversely proportional to the stress ratio level and environment temperature. The optimal combination is the structure with 40 mm HMA and 40 mm CEAM. The internal void ratio of CEAM is higher than that of HMA. A thinner HMA and thicker CEAM structure can result in higher void ratios and lower fatigue life of the combinations. The prediction results of ANN are similar to the experimental results. The obtained results can potentially guide the design of cement emulsified asphalt pavement structures.