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Background: Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies. Methods: Using consensus clustering, patients in The Cancer Genome Atlas (TCGA) with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-β signaling pathway-related genes, and differences in survival, molecular, and immunological TME characteristics and drug sensitivity were examined in each subtype. Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation (LASSO) regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus (GEO) dataset. A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy. Results: Two TGF-β subtypes were identified, with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy. Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype. After completing signature construction, patients with colon cancer were categorized into high- and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature. The risk score exhibited superior predictive performance relative to age, gender, and stage, as evidenced by its AUC of 0.686. Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME, suggesting that these patients had better responses to immunotherapy. Conclusions: Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-β signaling pathway-related genes. The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer, with potential utility for screening individuals for immunotherapy.

Mesoderm induction is a crucial step for vascular cell specification, vascular development and vasculogenesis. However, the cellular and molecular mechanisms underlying mesoderm induction remain elusive. In the present study, a chemically-defined differentiation protocol was used to induce mesoderm formation and generate functional vascular cells including smooth muscle cells (SMCs) and endothelial cells (ECs) from human induced pluripotent stem cells (hiPSCs). Zebrafish larvae were used to detect an in vivo function of interleukin 10 (IL10) in mesoderm formation and vascular development. A three dimensional approach was used to create hiPSC-derived blood vessel organoid (BVO) and explore a potential impact of IL10 on BVO formation. A murine model hind limb ischemia was applied to investigate a therapeutic potential of hiPSC-derived cells treated with or without IL10 during differentiation. We found that IL10 was significantly and specifically up-regulated during mesoderm stage of vascular differentiation. IL10 addition in mesoderm induction media dramatically increased mesoderm induction and vascular cell generation from hiPSCs, whereas an opposite effect was observed with IL10 inhibition. Mechanistic studies revealed that IL10 promotes mesoderm formation and vascular cell differentiation by activating signal transducer and activator of transcription 3 signal pathway. Functional studies with an in vivo model system confirmed that knockdown of IL10 using morpholino antisense oligonucleotides in zebrafish larvae caused defective mesoderm formation, angiogenic sprouting and vascular development. Additionally, our data also show IL10 promotes blood vessel organoid development and enhances vasculogenesis and angiogenesis. Importantly, we demonstrate that IL10 treatment during mesoderm induction stage enhances blood flow perfusion recovery and increases vasculogenesis and therapeutic angiogenesis after hind limb ischemia. Our data, therefore, demonstrate a regulatory role for IL10 in mesoderm formation from hiPSCs and during zebrafish vascular development, providing novel insights into mesoderm induction and vascular cell specifications.

A rotary vibration-assisted polishing device (RVAPD) is designed to enhance polishing force by converting PZT’s linear motion into the rotary motion of a central platform via a flexible mechanism, improving material surface quality. The RVAPD is optimized, simulated, and tested to meet high-frequency and large-amplitude non-resonant vibration polishing requirements. Its structure, designed using theoretical models and finite element software, offers a wide range of polishing parameters. Performance parameters are validated through open-loop tests, confirming effectiveness in polishing experiments. The lever mechanism and Hoeckens connection enhance vibration parameters and motion efficiency, reducing surface flaws in SiC and improving uniformity. Adjusting the RVAPD structure and using the proposed method significantly improve SiC surface quality.

Trifolium repens L. (white clover) and Lolium perenne L. (ryegrass) are green manures widely used in conservation tillage systems worldwide. Eleusine indica L. (goosegrass) is a globally recognized noxious weed. Herein, we investigated the effects of aqueous extracts, decomposed liquids, and different straw-to-soil ratios on the germination and growth of goosegrass. The results showed that high concentrations (≥ 30%) of aqueous extracts or decomposed liquids of both green manures significantly inhibited germination-related parameters of goosegrass. The strongest inhibitory effect was observed for the 7-day decomposition treatment, and white clover’s inhibitory effect was greater than ryegrass’s. A pot experiment showed that non-photochemical quenching, catalase, and peroxidase activity levels of goosegrass leaves were significantly increased. At the same time, the net photosynthetic rate significantly decreased. Seedling growth was inhibited when the straw-to-soil ratio was greater than 3:100. The ryegrass treatments inhibited goosegrass seedlings more than the white clover treatments. This study demonstrated the inhibitory potential of white clover and ryegrass straw return on seed germination and seedling growth of goosegrass. The study has also helped to identify weed-resistant substances in these green manures so that their weed-control properties can be used more effectively and herbicide usage can be reduced.

BackgroundThere are discrepancies of olfactory impairment between Alzheimer’s disease (AD) and other neurodegenerative disorders. Olfactory deficits may be a potential marker for early and differential diagnosis of AD. We aimed to assess olfactory functions in patients with AD and other neurodegenerative disorders, to further evaluate the smell tests using subgroup analysis, and to explore moderating factors affecting olfactory performance.MethodsCross-sectional studies relating to olfactory assessment for both AD and other neurodegenerative disorders published before 27 July 2022 in English, were searched on PubMed, Embase and Cochrane. After literature screening and quality assessment, meta-analyses were conducted using stata14.0 software.ResultsForty-two articles involving 12 smell tests that evaluated 2,569 AD patients were included. It was revealed that smell tests could distinguish AD from mild cognitive impairment (MCI), Lewy body disease (LBD), depression, and vascular dementia (VaD), but not from diseases such as frontotemporal dementia (FTD). Our finding indicated that in discriminating AD from MCI, the University of Pennsylvania Smell Identification Test (UPSIT) was most frequently used (95%CI: −1.12 to −0.89), while the Brief Smell Identification Test (B-SIT), was the most widely used method in AD vs. LBD group. Further subgroup analyses indicated that the methods of smell test used contributed to the heterogeneity in olfactory threshold and discrimination scores in group AD vs. MCI. While the moderating variables including age, MMSE scores, education years in AD vs. LBD, were account for heterogeneity across studies.ConclusionOur finding suggests smell tests have potential value in early differential diagnosis of AD. UPSIT and its simplified variant, B-SIT, are widely used methods in the analyses.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID = 357970 (PROSPERO, registration number CRD42022357970).

Aim of the study: This study aims to identify the effects of Nuanxinkang (NXK) on inflammation and pyroptosis post-MI and understand the underlying mechanisms. Materials and methods: Left Anterior Descending (LAD) coronary artery ligation was used to induce MI in mice. NXK or Captopril were orally administered 3 days after surgery for 4 weeks. Cardiac function, as well as infarct size, was detected by echocardiography, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Hematoxylin and Eosin (H&E) staining. Inflammatory mediators were measured by flow cytometry, real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF). Pyroptosis-related protein expressions were determined through Western blot (WB). Intracellular Ca2+ measurements were conducted in bone marrow derived macrophages (BMDM) to detect calcium influx. Molecular docking (MD) was applied to define the candidate ingredients in NXK that regulate Piezo1. Results: NXK increased the ratio of heart or lung and body weight in mice post-MI. TTC and H&E staining infarct size and myocardial damage. The results obtained through echocardiography suggest that NXK remarkably enhanced heart function. Immunofluorescence of F4/80 and flow cytometry results demonstrated that NXK suppressed inflammatory infiltration. Molecular docking showed that Piezo1 had correlation with NXK. Intracellular Ca2+ measurements suggest that NXK inhibit Yoda1-evoked Piezo1 activation. Furthermore, NXK treatment significantly suppressed Piezo1-mediated pyroptosis in vivo and in vitro. Conclusions: The present study indicates that NXK may prevent ventricular remodeling post-MI through regulation of the Piezo1-mediated pyroptosis. Furthermore, the study provides a potential strategy for attenuating NLRP3-inflmmasome activation in the context of ventricular remodeling post-MI using NXK.

Manganese toxicity is a major obstacle to agriculture in acid soils. Dark pericarp disease (DPD) is a newly spread physiological disorder induced by excess Mn in litchi, leading to undesirable fruit appearance and substantial economic loss. In this work, broadcast of alkaline soil conditioner in winter, followed by foliar sprays of ascorbic acid and sulfur solution at fruit development, was adopted to examine the effect of these combinations on DPD alleviation in a litchi orchard, with DPD morbidities of 70~85% in recent ten years. The combination of soil conditioner broadcast and foliar water spray was used as the control. At harvest, DPD incidence was significantly decreased by sulfur spray (3.3 ± 1.0%) and slightly reduced by ascorbic acid spray (10.7 ± 8.0%) compared to the control (12.9 ± 7.6%). Soil pH and available Mn were significantly increased and reduced by the soil conditioner broadcast. Sulfur spray significantly inhibited Mn uptake but enhanced the accumulation of Mg, Ca, sugars and cyanidin-3-rutinoside in the pericarp, leading to improved fruit pigmentation. Antioxidase activities were regulated to resist Mn stress by sulfur spray. The spray of ascorbic acid could not mitigate DPD as expected, probably due to the dose used. Conclusively, this study provides a practicable approach to mitigate Mn phytoavailability in acid soils.

Persimmon wine has various nutritional elements and high commercial potential. However, the high content of methanol, which is derived from the fruit’s pectin, always hinders persimmon wine production. To reduce the methanol level in the wine, the effects of persimmon cultivar, starter, pectinase, and pretreatment methods were investigated via single-factor and orthogonal experiments. The persimmon cultivar ‘MaoKui’ was finally used throughout the study owing to its lowest pectin concentration (24.5 g/kg). The best treatment conditions against the persimmon pulp were pectinase (0.04 g/kg) at 30 °C for 4 h, then boiled at 115 °C for 15 min before fermentation started. The optimized fermentation conditions for wine production were pectinase (0.03 g/kg), 250 mg/kg starter (BO213 and SPARK with equal amounts), at 28 °C for 6 d. The obtained wine had 77.7 mg/L methanol and a 68.4% raw juice yield. The fruit wine had 111.4 mg/L methanol and a 90.6 sensory evaluation score. Forty-nine volatile aromas were identified. Ethyl acetate content was the highest, followed by 3-methyl-1-butanol, 2,3-butanediol, and lactate ethyl ester. The persimmon wine had a unique style with transparent color, elegant aroma, and pure taste.

Abstract This study aimed to construct a ferroptosis-related lncRNA signature to probe the prognosis and immune infiltration of HCC patients. The Cancer Genome Atlas (TCGA) database was randomly divided into two parts, with two-thirds training and one-third testing sets. Univariate, multivariate, and least absolute selection operator (LASSO) Cox regression analyses were performed to establish a ferroptosis-related lncRNA signature. The prognostic signature was constructed by 6 ferroptosis-related lncRNAs (PCAT6, MKLN1-AS, POLH-AS1, LINC00942, AL031985.3, LINC00942) shows a promising clinical prediction value in patients with HCC. Patients with high-risk score indicated a poorer prognosis than patients with low-risk score were shown in the training set (p

BackgroundHepatectomy is the recommended option for radical treatment of BCLC stage A/B hepatocellular carcinoma (HCC) that has progressed beyond the Milan criteria. This study evaluated the efficacy and safety of preoperative neoadjuvant transcatheter arterial chemoembolization (TACE) for these patients.MethodsIn this prospective, randomized, open-label clinical study, BCLC stage A/B HCC patients beyond the Milan criteria were randomly assigned (1:1) to receive either neoadjuvant TACE prior to hepatectomy (NT group) or hepatectomy alone (OP group). The primary outcome was overall survival (OS), while the secondary outcomes were progression-free survival (PFS) and adverse events (AEs).ResultsOf 249 patients screened, 164 meeting the inclusion criteria were randomly assigned to either the NT group (n = 82) or OP group (n = 82) and completed follow-up requirements. Overall survival was significantly greater in the NT group compared to the OP group at 1 year (97.2% vs. 82.4%), two years (88.4% vs. 60.4%), and three years (71.6% vs. 45.7%) (p = 0.0011) post-treatment. Similarly, PFS was significantly longer in the NT group than the OP group at 1 year (60.1% vs. 39.9%), 2 years (53.4% vs. 24.5%), and 3 years (42.2% vs. 24.5%) (p = 0.0003). No patients reported adverse events of grade 3 or above in either group.ConclusionsNeoadjuvant TACE prolongs the survival of BCLC stage A/B HCC patients beyond the Milan criteria without increasing severe adverse events frequency.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200055618.

Astragalus sinicus L. (milk vetch), a versatile plant that has a soil-enriching effect as green manure, is widely planted in the temperate zone of China. In previous experiments, milk vetch incorporated into the soil as green manure showed potential for goosegrass control. However, “what exactly happens at the chemical level?” and “what are the compounds that are potentially responsible for the phytotoxic effects observed during those previous assays?” In a recent study, in vitro phytotoxicity bioassays and chemical analyses of milk vetch decomposition leachates were carried out to explore the relationship between the temporal phytotoxic effects and the dynamics of chemical composition. For that, milk vetch decomposition leachates with a decay time of 12 h, 9 days, 12 days, 15 days, and 18 days were analyzed for organic compounds by liquid chromatography. The main results were as follows: (1) three compounds with goosegrass suppression potential produced during the decomposed process, i.e., 4-ethylphenol, N-acrylimorpholine, and allyl isothiocyanate. 2-Hydroxyethyl acrylate was present in the 12-h decomposition leachates but was at its highest concentration of 127.1 µg ml−1 at 15 days. (2) The cultures were configured according to the four concentrations of goosegrass-resistant active substances measured in the 15-day decomposition leachate and, as with the 15-day decomposition leachate, the mixture cultures inhibited 100% of goosegrass germination at the high concentrations (≥ 30%), which suggests that these substances have goosegrass suppression potential. (3) The high total phenolic content (302.8–532.3 mg L−1), the total flavonoid content (8.4–72.1 mg L−1), and the reducing activity of the decomposition leachates for different decay times may explain why the incorporation of milk vetch into the soil did not lead to peroxidation of goosegrass in the previous study. (4) Finally, the changes in acid fraction and total content (1.9–4.2 mg ml−1) for different decay times explain the variations in pH of the decomposition leachates, which, when discussed in conjunction with previous studies, may lead to changes in soil nutrient effectiveness and consequently affect crop growth. This study can provide a reference for green weed control research.

Astragalus sinicus L. (milk vetch), one of the most widespread green manure species, is widely planted in the temperate zone. Eleusine indica L. (goosegrass), a serious annual weed in the world, has evolved resistance to some non-selective herbicides. The use of milk vetch as green manure for weed control in paddy fields was proposed. Aqueous extracts of milk vetch are known to exert a different level of phytotoxicity on weeds and crops. Phytotoxic substances contained in green manure were released into the soil by leaching at the initial stage and decomposition at the later stage after the return of green manure. Considering the need for searching new sustainable strategies for weed control, a question arises: “if milk vetch could be applied in goosegrass control, which stage is the most important to control goosegrass after milk vetch returned to the field, and at the same time, will the subsequent crop, corn (Zea mays L.), be affected by the side effects from milk vetch phytotoxicity?” In this study, the potential of milk vetch for goosegrass control was approached by repeated laboratory experiments, which include the aqueous extract experiment, decomposed experiment, and pot experiment. The effects of milk vetch returning to the field on maize were simulated by a pot experiment. The extract of milk vetch could significantly inhibit the germination of goosegrass at 2% concentration, and the inhibition enhanced with the increase of concentration. In the decomposed liquid experiment, decay time within 15 days, with the increase of decay days or concentration, goosegrass inhibition effect of decomposed liquid was enhanced. When decay time was more than 15 days, the inhibition ability of the decomposed liquid to goosegrass decreased. According to the RI accumulated value, aqueous extract and decomposed liquid have a “hormesis effect” on the germination and growth of goosegrass. Pot experiment proved that the addition of 1–10% (w/w) of milk vetch significantly reduced the germination and growth of goosegrass. On the contrary, the comprehensive analysis showed that the participation of milk vetch was conducive to the growth of corn. Our results constitute evidence that the incorporation of milk vetch into the soil could be a feasible practice to reduce weed infarctions in the corn-based cropping system.

Abstract Osteoporosis is a condition of the skeleton that mainly results from estrogen deficiency. Periostin is a matricellular component in bone that is involved in osteoblast differentiation. However, how Periostin promotes osteogenesis remains largely unknown. Here, we isolated bone marrow skeletal stem cells (BMSCs) derived from an ovariectomy (OVX)-induced osteoporosis rat model and the effects of periostin on BMSCs derived from OVX rats (OVX-BMSCs) were assessed. Overexpression of periostin enhanced alkaline phosphatase (ALP) and alizarin red staining in OVX-BMSCs as well as the osteogenic genes OCN, BSP and Runx2. ILK is a downstream effector of signals from the extracellular matrix and participates in bone homeostasis. Overexpression of periostin also increased expression of protein levels for ILK, as well as the downstream targets pAkt and pGSK3β. Suppression of ILK or Akt partially suppressed the enhancement of osteogenic ability induced by periostin overexpression in OVX-BMSCs. Thus, periostin may promote the osteogenic ability of OVX-BMSCs through actions on the ILK/Akt/GSK3β axis.

Piezo1, a mechanosensitive Ca2+-permeable non-selective cationic ion channel protein, is involved in a wide range of biological processes and plays crucial roles in vascular development. However, the pharmacology of this protein is in its infancy. Yoda1, the first specific chemical activator of Piezo1 channels, can activate Piezo1 in absence of mechanical stimulation. Hence, we sought to identify inhibitors of Yoda1 from Traditional Chinese Medicine (TCM). Intracellular Ca2+ measurements were conducted in human umbilical vein endothelial cells (HUVECs), HEK 293T cells overexpressing TRPC5 and TRPM2 channels, as well as in CHO K1 cells overexpressing TRPV4 channels. We identified tubeimoside I (TBMS1) as a strong inhibitor of the Yoda1 response and demonstrated its selectivity for the Piezo1 channels. Similarly, Yoda1-induced inhibitory results were obtained in Piezo1 wild-type overexpressed cells, murine liver endothelial cells (MLECs), and macrophages. The physiological responses of TBMS1 were identified by isometric tension, which can inhibit Yoda1 relaxation of aortic rings. Our results demonstrated that TBMS1 can effectively antagonize Yoda1 induced Piezo1 channel activation. This study sheds light on the existence of Yoda1 inhibitors and improves the understanding of vascular pharmacology through Piezo1 channels.

White clover (Trifolium repens L.) and ryegrass (Lolium multiflorum L.) are widely used cover crops. This experiment investigated the potential of white clover (WC), ryegrass (RG), and fallow (FL) to inhibit the growth of weeds and the effect of their residue return to the field on subsequent crops in a cover crop-corn rotation system. Furthermore, we designed pot experiments to guide the scientific application of WC and RG. The results showed that the FL treatment had the highest mean weed biomass in two years (11.99 t ha−1) and the RG treatment recorded the lowest mean weed biomass in two years (2.04 t ha−1) as its early growth rate and aerial root cover. The combination of rotary tillage (RT) and WC recorded the highest total corn yield in two years (20.20 t ha−1) and an increase of 2.84% in the two-year average biomass of weeds compared to RT-FL. Compared to RT-FL, RT-RG treatments inhibited weed invasion by an average of 73%, but corn yield was reduced by 3.25%. Straw and soil ratios above 6:100 for RG resulted in stunted corn growth, including a reduction in fresh weight and chlorophyll content, and impaired photosynthesis, but this effect was not evident in WC treatment. From an ecological point of view, this study recommends RT-RG as a pre-crop for corn to reduce herbicide use.

The adaptability of traffic lights in the control of vehicle traffic heavily affects the trafficability of vehicles and the travel efficiency of traffic participants in busy urban areas. Existing studies mainly have focused on the presence of traffic lights, but rarely evaluate the impact of traffic lights by analyzing traffic data, thus there is no solution for practicably and precisely self-regulating traffic lights. To address these issues, we propose a low-cost and fast traffic signal detection and impact assessment framework, which detects traffic lights from GPS trajectories and intersection features in a supervised way, and analyzes the impact range and time of traffic lights from intersection track data segments. The experimental results show that our approach gains the best AUC value of 0.95 under the ROC standard classification and indicates that the impact pattern of traffic lights at intersections is high related to the travel rule of traffic participants.