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Despite advances in technology and treatment, colorectal cancer (CRC) remains a primary cause of cancer death worldwide, causing nearly 694,000 deaths annually with a high mortality among metastatic cases. Therefore, there is urgency to develop effective strategies to control metastasis or restrain its initiating stage and epithelial-mesenchymal transition (EMT). Activation of Notch1 is noted to positively induce cancer cell growth when inducing EMT. Curcumin is a polyphenol with anticancer activity, which works by activating various molecular pathways in cancer cells. Herein, we established curcumin-Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Cur-NPs) and investigated their physicochemical properties in CRC to provide a novel insight into treatment of CRC. Cur-NPs were established by emulsion solvent evaporation. CRC cells (HCT116, HT29) were co-cultured with 0, 1, 2.5, 5, and 10 μM Cur-NPs, respectively. After treatment, clone formation assay determined CRC cell viability, migration and invasion, whilst Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assessed cell apoptosis. Besides, EMT markers levels in each group were detected to evaluate the impact of Cur-NPs on the EMT process. The transmission electron microscopy (TEM) pictures depicted classical features of Cur-NPs, with encapsulation efficiency of Cur-NPs 70.685±2.597%, and drug loading rate of 2.831±0.108%. The CRC cells absorbed the Cur-NPs within 30 min, and the absorption was as early as 10 min, while fluorescence reached climax at 30 min. The advent of Cur-NPs at different concentration greatly suppressed CRC cell viability and hindered their clone formation in HCT116 and HT29 cells, but elevated apoptotic rate of cancer cells with concentration of Cur-NPs proportional to the rate, while the apoptosis of normal colorectal epithelial cells was not affected. 10 μM Cur-NPs group had the highest apoptosis rate and poorest invasion and migration ability. Moreover, upon treatment with Cur-NPs, E-cadherin expression increased, but the proteins in the Notch pathway declined dramatically. Cur-NPs suppressed CRC cell progression through regulating the Notch signaling pathway and decelerating the EMT process of CRC cells.

Photoinduced tandem cyclization of alkynes with phenylsulfinic acids has been accomplished, which gives a mild strategy for the preparation of sulfone-substituted seven-membered N-heterocycles. A variety of scaled-up experiments, further transformations, and mechanistic studies were also operated in the follow-up work.

The oxidation of anode carbon fuel directly affects the electrochemical performance of molten hydroxide direct carbon fuel cell (MHDCFC). In general, the anode carbon fuel can be oxidized at higher temperature, thus the direct carbon fuel cell (DCFC) can show a great electrochemical performance. In this study, rare earth oxide (La2O3, CeO2, Pr6O11) were prepared by the method of precipitation. Activated carbon was prepared by pretreatment of lignite. Rare earth oxide and activated carbon were mixed as anode carbon fuel, and rare earth oxide were used to catalyze the electrochemical oxidation of anode carbon fuel. The results show that CeO2 has better electrocatalytic activity compared with La2O3 and Pr6O11 in the MHDCFC. The electrochemical test results show that the current density (at 0.4V) increases from 81.02 to 112.90 mA/cm2 and the maximum power density increases from 34.78 to 47.05 mW/cm2 at 450 °C, when the mass fraction of CeO2 is increased from 0 to 40%. When the mass fraction of CeO2 is 30%, the current density (82.55 mA/cm2 at 0.4V) at 400 °C is higher than that (81.02 mA/cm2 at 0.4V) without CeO2 at 450 °C. The electrochemical oxidation mechanism of CeO2 catalyzed anode carbon fuel is discussed.

To ensure long-term food production in a changing world, it is critical to identify field management practices that increase crop yields and maintain soil health. Additionally, sustainable agriculture needs to provide experimental evidence to support the use of traditional agricultural practices. In this study, a 20-year investigation of the effects of different combinations of fertilizer types (control, chemical fertilizer, organic fertilizer, and bio-fertilizer) and fertilization amount (conventional dosages and high dosages) on wheat yield and soil health, including soil enzyme activity and microbial biomass, soil microbial diversity, and crop yield. Our long-term study indicates that the use of high dosages of bio-fertilizer can increase the fertilizer yield contribution rate by a minimum of 76.7% compared to other management combinations. Furthermore, this practice can improve soil biological quality, including the concentration of soil microbial biomass carbon, promote bacterial biodiversity, and enhance the soil health index. The effect of high dosages fertilizer was greater than that of conventional dosages fertilizer. The highest soil health index was 0.88 in high dosage bio-fertilizer, and the lowest was 0.12 in chemical fertilizer. In summary, these results suggested that the use of bio-fertilizer can help maintain soil health and crop productivity in the long term.

Purpose Patients with lung cancer often develop negative psychology, particularly anxiety and depression, which often leads to reduced quality of life, shorter survival time and increased mortality. The main aim of this study was to explore whether anxiety and depression contribute to a greater risk of irAEs in patients treated with combined ICIs.Methods A total of 317 lung cancer patients receiving combined immunotherapy were included in the Cancer Hospital of Harbin Medical University from September 2018 to May 2022. The Hospital Anxiety and Depression Scale (HADS) was used to measure the anxiety and depression of patients prior to treatment with the combined ICIs. The irAEs were assessed 1–3 days after each immunotherapy treatment and recorded according to the Common Terminology Criteria for Adverse Events version 5.0. Cardinality tests, univariate and multivariate logistic regression models were used to identify risk factors for the occurrence of irAEs.Results The prevalence of anxiety and depressive states before patients received the combined ICIs was 36.6% and 37.5% respectively. Multivariate logistic regression analysis showed that anxiety (P Conclusion We demonstrate that patients' anxiety and depressive states prior to receiving combined ICI therapy do increase the probability of irAEs and have a high chance of leading to more irAEs in patients.

The farnesoid X receptor (FXR) regulates inflammation and immune responses in a subset of immune-mediated diseases. We previously reported that FXR expression promotes tumor cell proliferation in non–small cell lung cancer (NSCLC). Here we study the relevance of FXR to the immune microenvironment of NSCLC. We found an inverse correlation between FXR and PD-L1 expression in a cohort of 408 NSCLC specimens; from this, we identified a subgroup of FXRhighPD-L1low patients. We showed that FXR downregulates PD-L1 via transrepression and other mechanisms in NSCLC. Cocultured with FXRhighPD-L1low NSCLC cell lines, effector function and proliferation of CD8+ T cell in vitro are repressed. We also detected downregulation of PD-L1 in FXR-overexpressing Lewis lung carcinoma (LLC) mouse syngeneic models, indicating an FXRhighPD-L1low subtype in which FXR suppresses tumor-infiltrating immune cells. Anti–PD-1 therapy was effective against FXRhighPD-L1low mouse LLC tumors. Altogether, our findings demonstrate an immunosuppressive role for FXR in the FXRhighPD-L1low NSCLC subtype and provide translational insights into therapeutic response in PD-L1low NSCLC patients treated with anti–PD-1. We recommend FXRhighPD-L1low as a biomarker to predict responsiveness to anti–PD-1 immunotherapy.

Supplementary Table 1, Supplementary Figures 1-7

Pyroptosis has been reported to improve the immunosuppressive tumor microenvironment and may be a strategy to enhance osteosarcoma treatment. The extent to which modulation of mitochondria could induce tumor pyroptosis to enhance immunotherapy has not been characterized. We synthesized a mitochondria-targeting polymer micelle (OPDEA-PDCA), in which poly[2-(

The sustainable production of crops faces increasing challenges from global climate change and human activities, which leads to increasing instances of many abiotic stressors to plants. Among the abiotic stressors, drought, salinity and excessive levels of toxic metals cause reductions in global agricultural productivity and serious health risks for humans. Cytokinins (CKs) are key phytohormones functioning in both normal development and stress responses in plants. Here, we summarize the molecular mechanisms on the biosynthesis, metabolism, transport and signaling transduction pathways of CKs. CKs act as negative regulators of both root system architecture plasticity and root sodium exclusion in response to salt stress. The functions of CKs in mineral-toxicity tolerance and their detoxification in plants are reviewed. Comparative genomic analyses were performed to trace the origin, evolution and diversification of the critical regulatory networks linking CK signaling and abiotic stress. We found that the production of CKs and their derivatives, pathways of signal transduction and drought-response root growth regulation are evolutionarily conserved in land plants. In addition, the mechanisms of CK-mediated sodium exclusion under salt stress are suggested for further investigations. In summary, we propose that the manipulation of CK levels and their signaling pathways is important for plant abiotic stress and is, therefore, a potential strategy for meeting the increasing demand for global food production under changing climatic conditions.

The processing method of Camellia oleifera fruit used in the industry was investigated, that is, fresh C. oleifera fruit was shelled in the drying equipment first and then the remaining C. oleifera seeds returned until the target moisture content (about 10% d.b.) was reached. The variable-temperature drying of C. oleifera seeds was investigated for the first time and the drying process was optimized and compared with constant-temperature drying. Two independent variables, including hot air drying temperature and air velocity, were studied by central composite design. The responses were drying time and quality of Camellia oil, including acid value and peroxide value. Results showed that the optimal constant-temperature drying conditions were drying at a temperature of 60.5°C and air velocity of 2.1 m/s. Under this condition, the total drying time was 607 min, and the acid and peroxide values were 1.72 mg/g and 0.12 g/100 g, respectively. The optimal variable-temperature drying conditions were drying at a constant air velocity of 2 m/s and a drying temperature of 55°C for 67 min, then 60°C for 213 min, and finally 65°C for 297 min. Under these conditions, the acid value was 1.75 mg/g and the peroxide value was 0.1 g/100 g. The optimal variable-temperature drying efficiency was 16.7% higher than that of constant-temperature drying when the optimization objective of drying time, acid value and peroxide value was 2:1:1.

With the development of oil and gas resources gradually extending to the deep sea, the blockage of gas hydrate is attracting more and more attention. How to inhibit hydrate blockage efficiently and economically in oil and gas gathering transportation pipelines and ensure the safe operation has become a hot and difficult point in the field of oil and gas gathering and transportation research. At present, the research on the safe flow of gas hydrate is still in the exploratory stage, and applying swirl flow to hydrate risk control technology has a great engineering application value. A systematic experimental study on the safe flow of gas hydrate in a swirl flow system is carried out herein. The experimental results show the following: (1) The laws of gas hydrate flow, transport, deposition, and pipe plugging under various experimental conditions of the swirl flow system are obtained, the safe flow region of hydrate under the swirl flow system in the pipeline is obtained, and the safe flow boundary of hydrate is expanded. (2) Beginning with the theoretical analysis of the safe flow of gas hydrate in a pipeline, the flow characteristics of gas hydrate in the flow system are described; the special flow form of swirl flow has a great influence on the safe flow law of hydrate. (3) The growth and coalescence mechanisms of spiral hydrate in two mainstream systems of separated flow and dispersed flow are explored and researched. The critical tangential velocity of flow is taken as the standard of criterion.

In this paper, the impact and mechanism of natural water constituents (humic acid, nitrate, iron and chloride ions) on the photodegradation of bisphenol A (BPA) was investigated in aqueous media under simulated UV light irradiation. Results suggested that the contributions of ·OH, 1O2, O2.− and BPA* to BPA photodegradation in pure water were 13.4%, 7.7%, 22.9% and 47.9%, respectively, indicating that direct photodegradation other than self-sensitized photodegradation was the main reaction pathway. Furthermore, the presence of humic acid (HA), nitrate, iron and chloride ions showed different impacts on BPA photodegradation. NO- 3 and NO- 2 both showed inhibitory effect but due to different ROS (reactive oxidization species). In the presence of HA, it was light-screening-induced direct photolysis not quenching effect dominated over the inhibited BPA photodegradation. The photodegradation of BPA was significantly enhanced by the addition of iron because iron-assisted indirect photolysis controlled the degradation process through promoting the production of ·OH and H2O2. Chloride had a dual effect on BPA photodegradation depending on the different concentration levels. Additionally, a simple linear model revealed that the interaction of these factors also significantly impacted BPA photodegradation. In natural water, the decreased photolytic rate of BPA was mainly attributed to triple-excited dissolved organic matter (3DOM*) and indirect photolysis was the primary transformation pathway of BPA. Finally, the detection of photolysis products including nitrate and chlorinated products suggested the possibility of increasing ecological risk of BPA photodegradation.

SUMMARY OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of crisaborole ointment in the treatment of vulvar leukoplakia. METHODS: A prospective, randomized controlled clinical trial was conducted, and a total of 100 patients with vulvar leukoplakia were divided into the observation group (n=50) treated with crisaborole ointment and the control group (n=50) treated with vitamin E. The symptom improvement and vulvar leukoplakia score after 2 weeks of treatment were analyzed, and the clinical efficacy of vulvar leukoplakia was evaluated by referring to the Guidelines for Clinical Research of New Drugs of Traditional Chinese Medicine (2018 Edition). RESULTS: After 2 weeks of treatment, the overall score of lesions in the observation group decreased, and the total treatment efficiency of patients in the observation group was 92% (46/50), which was significantly higher than that of 52% (26/50) in the control group P

Background Over the last two decades, global continuous efforts have been devoted to improving nursing research capacity. However, it is currently at a low to medium level in China and the training measures still have shortcomings such as lack of theoretical guidance, single content, short time and poor learning effect. To design a training programme about research capacity based on the ADDIE(analysis, design, development, implementation, and evaluation, ADDIE) model and the tutor system for clinical nurses and evaluate its effect through before-and-after control. Methods A quasi-experimental, one-group, self-control, and pretest-posttest design study. From July 2020 to June 2021, forty-five clinical nurses from a hospital were enrolled and underwent the training programme based on ADDIE model, which included five stages. By special scales, the nurses’ levels of research capacity, self-efficacy and professional values were evaluated on a six months of theory training, a six months of practice training, and a follow-up six months after the training. Finally, forty nurses completed this study. SPSS25.0 software was used for analysis. Results The score of research capacity before training was 43.42 ± 22.50. The total scores of research capacity and its all dimensions, total scores of general self-efficacy and nurses professional values differed significantly in before, immediately after training and six months after training (P P

In this paper, the covalent organic polymer of enaminone was modified by thiourea, and the covalent organic polymer of thiourea (CTOP) was synthesized by simple solvothermal method. At 25 ℃, the adsorption capacity of the polymer for trivalent gold ion is 2372.7 mg/g. In the mixed aqueous solution of divalent cadmium ion, trivalent gold ion, divalent copper ion, divalent cobalt ion and divalent nickel ion, CTOP can only adsorb trivalent gold ion, which indicates that CTOP has high selective adsorption performance for trivalent gold ion. In addition, CTOP material still maintains high adsorption performance after five adsorption cycles, which proves that the adsorption material has good reusability. According to the experimental results of adsorption kinetics and thermodynamics, the adsorption process of CTOP for trivalent gold ions conforms to the quasi second order adsorption model and Langmuir adsorption model, that is, the adsorption process of CTOP for trivalent gold ions is single-layer chemical adsorption. CTOP not only has strong adsorption and selectivity to Au (Ⅲ), but also has good reusability. Therefore, it is an ideal environmental functional material, which can be used to separate and enrich trivalent gold ions in wastewater.

Quercetin regulates the balance of osteoclastogenic differentiation mediated by NLRP3 inflammasome activation, delaying the progression of wear particles-induced osteolysis.

Celiac disease is a multisystem immune based disorder, caused by an immune-mediated reaction to ingested gluten with increasing prevalence in the USA. Celiac disease can cause a wide variety of symptoms, including gastrointestinal symptoms (diarrhea, abdominal distention, or abdominal pain), which may affect absorption of many nutritional components. All patients with celiac disease should remain on a strict and lifelong gluten-free diet, which are often low in certain trace elements such as zinc. On the other hand, zinc and copper as the essential trace elements have been hypothesized to help maintain optimum function of the immune system. Then, this study aims to examine the association between celiac disease seropositivity and serum zinc and copper levels. A nationally representative sample from National Health and Nutrition Examination Survey (2011-2014) was analyzed. Celiac disease seropositivity was determined using the tissue transglutaminase IgA antibody test (IgA-TTG). Multivariable linear regression models were performed with celiac disease seropositivity as a predictor and serum zinc and copper levels as outcome. The present study included 4732 participants (1398 children aged 6-19 years and 3334 adults aged ≥ 20 years). The weighted prevalence of celiac disease seropositivity was higher (11.6/1000) among children aged 6-19 years compared to that (6.3/1000) among adults aged ≥ 20 years. In the stratified analysis by age, the multivariable linear regression analysis revealed that among children aged 6-19 years, celiac disease seropositivity was associated with 5.32 (95% CI, - 9.71 to - 0.92) μg/dL lower serum zinc level, but not associated with serum copper level. However, the association between celiac disease seropositivity and serum zinc level was not statistically significant among adults aged 20 years or older. Future prospective studies are warranted to confirm these findings.

Context Light therapy is a non-pharmacological therapy that is currently being studied in cancer-related symptoms and is certificated as a low-risk intervention by FDA. Cancer-related fatigue (CRF) is the most common symptom reported by cancer patients. Objective To examine the effectiveness of light therapy for CRF in cancer patients through a systematic review and meta-analysis. Methods We conducted a systematic review of four electronic databases targeted randomized clinical trials evaluating light therapy for CRF (CRD42020215446), from inception to May 2021. The primary outcome was changes of CRF scores; secondary outcomes included depression, sleep, and quality of life (QoL). We quantitatively pooled outcomes using meta-analysis with random-effects models and assessed methodological bias. Results We identified thirteen RCTs representing 551 cancer patients, encompassing breast (n = 5), ovarian or endometrial (n = 1), multiple myeloma (n = 1), lung (n = 1), or combined (n = 5) cancers. The comparison groups included dim light (n = 12) and waiting list (n = 1). Duration of intervention ranged from 1 to 12 weeks. Light intensities ranged from 417.9 to 12,000 lux. Light therapy was associated with a significant improvement in CRF (SMD = 0.45, P = 0.007), depression (SMD = -0.26, P = 0.03) and sleep difficulty (SMD = -2.46, P = 0.0006); a statistically non-significant trend was observed for QoL (SMD = 0.33, P = 0.09). Funnel plots for CRF suggest not significant publication bias. Conclusion Light therapy could be a feasible and effective option for improving CRF in cancer patients. Larger sample, rigor trials design and a standard protocol of intervention are needed to draw more conclusive conclusions.

Objectives : The purpose of this study was to screen for depressive symptoms in a large sample of Chinese population, and explore the effects of demographic and lifestyle factors on depressive symptoms based on the brain maturity. Method : Adults from 8 health management centers in 6 provinces completed an online health self-report questionnaire. Finally, a total of 76223 valid questionnaires were collected. Result : A total of 76223 participants were included in this study, including 44167 (57.9%) males and 32056 (42.1%) females. The percentage of clinically relevant depressive symptoms among young, early mature and late mature participants was 13.5%, 18.5% and 27.3%, respectively. Among young participants, being female was a risk factor for depressive symptoms, while having a bachelor's or graduate degree, being married, smoking, and moderate alcohol consumption were protective factors. And among early mature participants, female, married and other marital status, BMI of 24-27.9 were risk factors, post-graduate education or above, smoking, moderate alcohol consumption and meeting exercise standard were protective factors. Among late mature participants, Compared with junior high school, all other degrees were protective factors, as was meeting physical activity standards, excessive alcohol consumption was a risk factor. Conclusion : This study analyzed the association among young, early mature and late mature participants respectively, and proposed strategies for improving healthy lifestyle of Chinese people. Our findings support the need for individualized recommendations to improve mental health based on brain maturity.

Two oxidative degradation impurities of sugammadex sodium have been successfully synthesized under stress conditions and isolated by preparative high performance liquid chromatography, which would be extremely difficult to prepare stochiometrically by conventional methods due to their structural complexity. Characteristic fragmentation pattern observed by mass spectrometry for sugammadex series compounds helped distinguish the two regioisomeric di-sulfoxide impurities. Confirmed by nuclear magnetic resonance analysis, Impurity I was identified as ortho-disulfoxide sugammadex and Impurity II as meta-disulfoxide sugammadex. It is the first time detailed structures of these two impurities are reported. Additionally, HPLC analysis also indicated the observance of these two impurities in long-term stored sugammadex sodium finished pharmaceutical product but absence in three pilot batches of sugammadex sodium drug substance which met ICH requirements. The compounded analysis technique has proven to be successful and reliable, and we hope that it could be well applied to structure identification for other sugammadex impurities and will be beneficial for other researchers focusing on this field.

A copper-catalyzed [4+1] cycloannulation of 2-aminochalcones with ethyl 2-diazo-2-phenylacetate has been developed in this paper, along with migration of ester group, which provided a simple and effective method for the synthesis of various indole heterocyclic compounds. This strategy displayed a wide range of substrates and good tolerance of functional groups. Mechanistic studies show that the reaction is performed step by step, includes the carbine N-H insertion, intramolecular hydroxaldehyde-type condensation and 1,2-acyl migration.

Photoinduced tandem cyclization of alkynes with NH4SCN was developed for the synthesis of various SCN-containing seven-membered N-heterocycles.