Health-driven mechanism of organic food consumption: A structural equation modelling approach.

The COVID-19 pandemic seriously threatened human survival and development. It has also highlighted the significant correlation between ecological and public health. After three years of the COVID pandemic, Chinese consumers have become more aware of the importance of health. Especially in the Internet era, consumers' purchasing methods and health awareness have been changed. Consumers can buy nutritious and organic foods. To understand the impact of consumer psychology and health beliefs on the willingness to purchase organic food in the post-pandemic period, this study uses organic beef as an example and extracts key variables from three basic theories. The three basic theories include the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and the Norm Activation Model (NAM), respectively. Specifically, perceived susceptibility and severity are combined to form a health belief variable that can drive organic food purchasing. In contrast, perceived benefit, moral norms, self-efficiency, and controllability are introduced as mediating variables to construct the health driving factors of organic beef purchasing. Structural equation modeling (SEM) and mediation effect tests are used to analyse 539 samples. Meanwhile, paths and mechanisms between health concern and other variables are explored. The results show that health concern is an important driving factor. Health concern can significantly promote the formation of willingness to purchase organic beef. Mediation effect tests suggest that health concern can indirectly affect the willingness to purchase organic beef through perceived benefit, moral norms, and controllability, but the mediation effect of self-efficiency is not significant. This study provides important references for government regulation and certification of organic foods as well as for enterprises'organic food marketing strategies.

Clinical value of ankle flexion and extension exercises combined with a psychological intervention in knee osteoarthritis.

BACKGROUND: Considering the limited effectiveness of clinical interventions for knee osteoarthritis (KOA), it is necessary to continue to explore appropriate and effective treatment strategies to improve the condition of KOA patients. AIM: To clarify the influence of ankle flexion and extension exercises combined with a psychological intervention on the psychological status and activities of daily living (ADLs) of patients with KOA. METHODS: The research participants were 116 KOA patients admitted to The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine between May 2019 and May 2022, including 54 patients receiving routine treatment, care and psychological intervention (control group) and 62 patients additionally treated with ankle flexion and extension exercises (research group). The two groups were comparatively analyzed in terms of psychological status (Self-rating Anxiety/Depression Scale, SDS/SAS), ADLs, knee joint function (Lysholm Knee Scoring Scale), pain (Visual Analog Scale, VAS), fatigue (Multidimensional Fatigue Inventory, MFI), and quality of life (QoL; Short-Form 36 Item Health Survey, SF-36). RESULTS: After evaluation, it was found that the postinterventional SDS, SAS, VAS, and MFI scores in the research group were significantly reduced compared with the baseline (before the intervention) values and those of the control group, while the postinterventional Lysholm, ADL and SF-36 scores were markedly elevated. CONCLUSION: Therefore, ankle flexion and extension exercises are highly effective in easing negative psychological status, enhancing ADLs, daily living ability, knee joint function and QoL, and relieving pain and fatigue in KOA patients, thus warranting clinical promotion.

Gold nanoclusters Cys-Au NCs as selective fluorescent probes for "on-off-on" detection of Fe3+ and ascorbic acid.

Gold nanoclusters exhibit attractive properties owing to their excellent biocompatibility and strong photostability in the biomedical domain. In this research, cysteine-protected fluorescent gold nanoclusters (Cys-Au NCs) were synthesized via decomposing Au(i)-thiolate complexes for the detection of Fe3+ and ascorbic acid in a bidirectional "on-off-on" mode. Meanwhile, the detailed characterization confirmed that the mean particle size of the prepared fluorescent probe was 2.43 nm and showed a fluorescence quantum yield of 3.31%. In addition, our results indicate that the fluorescence probe for ferric ions exhibited a broad detection scope ranging from 0.1 to 2000 µM and excellent selectivity. The as-prepared Cys-Au NCs/Fe3+ was demonstrated to be an ultrasensitive and selective nanoprobe for the detection of ascorbic acid. This study indicated that the "on-off-on" fluorescent probes Cys-Au NCs held a promising application for the bidirectional detection of Fe3+ and ascorbic acid. Furthermore, our novel "on-off-on" fluorescent probes provided insight into the rational design of thiolate-protected gold nanoclusters for biochemical analysis of high selectivity and sensitivity.

Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance.

The tumor microenvironment (TME) represents a milieu enabling cancer cells to develop malignant properties, while concerted interactions between cancer and stromal cells frequently shape an "activated/reprogramed" niche to accelerate pathological progression. Here we report that a soluble factor epiregulin (EREG) is produced by senescent stromal cells, which non-cell-autonomously develop the senescence-associated secretory phenotype (SASP) upon DNA damage. Genotoxicity triggers EREG expression by engaging NF-κB and C/EBP, a process supported by elevated chromatin accessibility and increased histone acetylation. Stromal EREG reprograms the expression profile of recipient neoplastic cells in a paracrine manner, causing upregulation of MARCHF4, a membrane-bound E3 ubiquitin ligase involved in malignant progression, specifically drug resistance. A combinational strategy that empowers EREG-specific targeting in treatment-damaged TME significantly promotes cancer therapeutic efficacy in preclinical trials, achieving response indices superior to those of solely targeting cancer cells. In clinical oncology, EREG is expressed in tumor stroma and handily measurable in circulating blood of cancer patients post-chemotherapy. This study establishes EREG as both a targetable SASP factor and a new noninvasive biomarker of treatment-damaged TME, thus disclosing its substantial value in translational medicine.

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH4/I2 system.

An economical and versatile protocol for the one-pot synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with NaBH4/I2 in THF at reflux temperature is described. This method used no special catalyst and various monomethylamines can be easily obtained in moderate to good yields from a wide range of raw materials including amines (primary amines and secondary amines), carboxylic acids and isocyanates. Besides, an interesting reduction selectivity was observed. Exploration of the reaction process shows that it undergoes a two-step pathway via a formamide intermediate and the reduction of the formamide intermediate to monomethylamine as the rate-determining step. This work can contribute significantly expanding the applications of N-substituted carbonylimidazoles.

High Dimensional Similarity Search With Satellite System Graph: Efficiency, Scalability, and Unindexed Query Compatibility.

Approximate nearest neighbor search (ANNS) in high-dimensional space is essential in database and information retrieval. Recently, there has been a surge of interest in exploring efficient graph-based indices for the ANNS problem. Among them, navigating spreading-out graph (NSG) provides fine theoretical analysis and achieves state-of-the-art performance. However, we find there are several limitations with NSG: 1) NSG has no theoretical guarantee on nearest neighbor search when the query is not indexed in the database; and 2) NSG is too sparse which harms the search performance. In addition, NSG suffers from high indexing complexity. To address above problems, we propose the satellite system graphs (SSG) and a practical variant NSSG. Specifically, we propose a novel pruning strategy to produce SSGs from the complete graph. SSGs define a new family of MSNETs in which the out-edges of each node are distributed evenly in all directions. Each node in the graph builds effective connections to its neighborhood omnidirectionally, whereupon we derive SSG's excellent theoretical properties for both indexed and unindexed queries. We can adaptively adjust the sparsity of an SSG with a hyper-parameter to optimize the search performance. Further, NSSG is proposed to reduce the indexing complexity of the SSG for large-scale applications. Both theoretical and extensive experimental analysis are provided to demonstrate the strengths of the proposed approach over the existing representative algorithms. Our code has been released at https://github.com/ZJULearning/SSG.

Overexpression of BIRC6 driven by EGF-JNK-HECTD1 signaling is a potential therapeutic target for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. The lack of targeted therapies and poor patient outcome have fostered efforts to discover new molecular targets to treat patients with TNBC. Here, we showed that baculoviral IAP repeat containing 6 (BIRC6) is overexpressed and positively correlated with epidermal growth factor (EGF) receptor (EGFR) in TNBC cells and tissues and that BIRC6 overexpression is associated with poor patient survival. Mechanistic studies revealed that BIRC6 stability is increased by EGF-JNK signaling, which prevents ubiquitination and degradation of BIRC6 mediated by the E3 ubiquitin ligase HECTD1. BIRC6 in turn decreases SMAC expression by inducing the ubiquitin-proteasome pathway, thereby antagonizing apoptosis and promoting the proliferation, colony formation, tumorsphere formation, and tumor growth capacity of TNBC cells. Therapeutically, the PEGylated cationic lipid nanoparticle (pCLN)-assisted delivery of BIRC6 small interfering RNA (siRNA) efficiently silences BIRC6 expression in TNBC cells, thus suppressing TNBC cell growth in vitro and in vivo, and its antitumor activity is significantly superior to that of the EGFR inhibitor gefitinib. Our findings identify an important regulatory mechanism of BIRC6 overexpression and provide a potential therapeutic option for treating TNBC.

Brca2 deficiency drives gastrointestinal tumor formation and is selectively inhibited by mitomycin C.

BRCA2 is crucial for repairing DNA double-strand breaks with high fidelity, and loss of BRCA2 increases the risks of developing breast and ovarian cancers. Herein, we show that BRCA2 is inactively mutated in 10% of gastric and 7% of colorectal adenocarcinomas, and that this inactivation is significantly correlated with microsatellite instability. Villin-driven Brca2 depletion promotes mouse gastrointestinal tumor formation when genome instability is increased. Whole-genome screening data showed that these BRCA2 monoallelic and biallelic mutant tumors were selectively inhibited by mitomycin C. Mechanistically, mitomycin C provoked double-strand breaks in cancer cells that often recruit wild-type BRCA2 for repair; the failure to repair double-strand breaks caused cell-cycle arrest at the S phase and p53-mediated cell apoptosis of BRCA2 monoallelic and biallelic mutant tumor cells. Our study unveils the role of BRCA2 loss in the development of gastrointestinal tumors and provides a potential therapeutic strategy to eliminate BRCA2 monoallelic and biallelic mutant tumors through mitomycin C.

MYC predetermines the sensitivity of gastrointestinal cancer to antifolate drugs through regulating TYMS transcription.

BACKGROUND: Thymidylate synthase (TYMS) is a successful chemotherapeutic target for anticancer therapy. Numerous TYMS inhibitors have been developed and used for treating gastrointestinal cancer now, but they have limited clinical benefits due to the prevalent unresponsiveness and toxicity. It is urgent to identify a predictive biomarker to guide the precise clinical use of TYMS inhibitors. METHODS: Genome-scale CRISPR-Cas9 knockout screening was performed to identify potential therapeutic targets for treating gastrointestinal tumours as well as key regulators of raltitrexed (RTX) sensitivity. Cell-based functional assays were used to investigate how MYC regulates TYMS transcription. Cancer patient data were used to verify the correlation between drug response and MYC and/or TYMS mRNA levels. Finally, the role of NIPBL inactivation in gastrointestinal cancer was evaluated in vitro and in vivo. FINDINGS: TYMS is essential for maintaining the viability of gastrointestinal cancer cells, and is selectively inhibited by RTX. Mechanistically, MYC presets gastrointestinal cancer sensitivity to RTX through upregulating TYMS transcription, supported by TCGA data showing that complete response cases to TYMS inhibitors had significantly higher MYC and TYMS mRNA levels than those of progressive diseases. NIPBL inactivation decreases the therapeutic responses of gastrointestinal cancer to RTX through blocking MYC. INTERPRETATION: Our study unveils a mechanism of how TYMS is transcriptionally regulated by MYC, and provides rationales for the precise use of TYMS inhibitors in the clinic. FUNDING: This work was financially supported by grants of NKRDP (2016YFC1302400), STCSM (16JC1406200), NSFC (81872890, 81322034, 81372346) and CAS (QYZDB-SSW-SMC034, XDA12020210).