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Yeast, identified as a microorganism, boasts a considerable protein content, positioning yeast protein as a highly promising alternative in the quest for sustainable protein sources. The primary aim of this study is to evaluate the protein quality of yeast protein and compare it with animal proteins (whey concentrate/isolate proteins) and plant proteins (soy, wheat, pea proteins). Notably, yeast protein exhibits the highest ratio of indispensable/dispensable amino acids (IAAs/DAAs, 0.91). However, in both in vivo and in vitro digestion experiments, yeast protein demonstrated lower true protein digestibility (TPD) and true ileal digestibility (TID) compared to other proteins. Despite this, the yeast protein's amino acid score (AAS, 1.37 for >3 years), protein digestibility-corrected amino acid score (PDCAAS, 100 % for >3 years), and digestibility-corrected amino acid score (DIAAS, 82.42 % for >3 years) of yeast protein surpassed those of plant proteins, yet remained lower than animal proteins primarily due to its lower digestibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: Anesthetic drugs play a vital role during surgery, however, due to individual differences and complex physiological mechanisms, the prediction of anesthetic drug dosage has always been a challenging problem. In this study, we propose a model for predicting the dosage of anesthetic drugs based on deep learning to help anesthesiologists better control their dosage during surgical procedures., Methods: We design a model based on the artificial neural network to predict the dosage of preoperative anesthetic, and use the SELU activation function and the loss function for weighted regularization to solve the problem of unbalanced sample. Moreover, we design a CNN-based model for the prior extraction of intraoperative features by using a 7 × 1 convolution kernel to enhance the receptive field, and combine maximum pooling and average pooling to extract key features while eliminating noise. A predictive model based on the LSTM network is designed to predict the intraoperative dosage of the anesthetic, and the bidirectional propagation-based LSTM network is used to improve the ability to learn the trend of changes in the physiological states of the patient during surgery. An attention module is added before the connection layer to appropriately attend to areas containing prominent features., Results: The results of experiments showed that the proposed method reduced values of the MAPE to 15.83% and 12.25% compared with the traditional method in predictions of the preoperative and intraoperative doses of the anesthetic, respectively, and increased the values of R 2 to 0.887 and 0.915, respectively., Conclusion: The intelligent anesthesia prediction algorithm designed in this study can effectively predict the dosage of anesthetic drugs needed by patients, assist clinical judgment of anesthetic drug dose, and assist the anesthesiologists to ensure the smooth progress of the operation., Competing Interests: The authors have no conflicts of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

The identification of key points in the human body is vital for sports rehabilitation, medical diagnosis, human-computer interaction, and related fields. Currently, depth cameras provide more precise depth information on these crucial points. However, human motion can lead to variations in the positions of these key points. While the Mediapipe algorithm demonstrates effective anti-shake capabilities for these points, its accuracy can be easily affected by changes in lighting conditions. To address these challenges, this study proposes an illumination-adaptive algorithm for detecting human key points through the fusion of multi-source information. By integrating key point data from the depth camera and Mediapipe, an illumination change model is established to simulate environmental lighting variations. Subsequently, the fitting function of the relationship between lighting conditions and adaptive weights is solved to achieve lighting adaptation for human key point detection. Experimental verification and similarity analysis with benchmark data yielded R2 results of 0.96 and 0.93, and cosine similarity results of 0.92 and 0.90. With a threshold range of 8, the joint accuracy rates for the two rehabilitation actions were found to be 89% and 88%. The experimental results demonstrate the stability of the proposed method in detecting key points in the human body under changing illumination conditions, its anti-shake ability for human movement, and its high detection accuracy. This method shows promise for applications in human-computer interaction, sports rehabilitation, and virtual reality.

Scope: To assess the associations of dietary protein intake from different sources during pregnancy with maternal and umbilical cord plasma amino acid levels., Methods and Results: The study includes 216 pregnant women and 39 newborns from the Tongji Birth Cohort in Wuhan, China. The study examines the levels of 21 amino acids in maternal and cord plasma samples using ultra-performance liquid chromatography with tandem mass spectrometry. A significant positive relationship is observed between dietary protein intake from refined grains and maternal plasma cysteine levels. Dietary protein intake from dairy products is positively associated with maternal plasma levels of sulfur amino acid (mainly cystine), but negatively associated with maternal plasma levels of glutamic acid. In addition, the study observes that pre-pregnancy body mass index and parity may be potential determinants of maternal plasma amino acid levels, whereas a history of passive smoking during pregnancy is an important factor influencing cord plasma amino acid levels., Conclusions: These findings suggest that dietary protein intakes from specific sources during pregnancy may affect maternal plasma levels of amino acids., (© 2024 Wiley‐VCH GmbH.)

Objective: This study aims to assess the effectiveness of traditional Chinese exercise therapy in alleviating pain, improving sleep quality, and reducing symptoms of anxiety and depression among fibromyalgia patients., Methods: We conducted a comprehensive search across various databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge, VIP database, and Wanfang, to identify randomized controlled trials (RCTs) examining the impact of Traditional Chinese Exercise (TCE) interventions on fibromyalgia. Two independent authors extracted data from the selected studies based on predefined inclusion and exclusion criteria. Meta-analyses were performed using RevMan 5.3., Results: The analysis encompassed 15 RCTs, comprising 936 participants. The meta-analysis revealed that TCE significantly surpassed the control group in reducing pain scores for fibromyalgia patients, as evidenced by improvements in FIQ [MD = -3.30, 95% CI (- 5.37, - 0.69), z = 2.53, p = 0.01] and VAS [MD = -1.87, 95% CI (- 2.12, - 1.61), z = 6.98, p < 0.00001]. Additionally, TCE demonstrated notable enhancements in sleep quality (PSQI) [MD = -2.23, 95% CI (- 2.86, - 1.61), z = 6.98, p < 0.0001], as well as in alleviating symptoms of anxiety and depression [MD = - 0.59, 95% CI (- 0.80, - 0.39), z = 5.63, p < 0.0001]., Conclusion: Traditional Chinese Exercise (TCE) exhibits significant efficacy in ameliorating pain, enhancing sleep quality, and alleviating symptoms of anxiety and depression in fibromyalgia patients., (© 2024. The Author(s).)

The metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague-Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8 h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture., (© 2023 John Wiley & Sons Ltd.)

Mercury is one heavy metal toxin that could cause severe health impairments. Mercury exposure has become a global environmental issue. Mercury chloride (HgCl 2 ) is one of mercury's main chemical forms, but it lacks detailed hepatotoxicity data. The present study aimed to investigate the mechanism of hepatotoxicity induced by HgCl 2 through proteomics and network toxicology at the animal and cellular levels. HgCl 2 showed apparent hepatotoxicity after being administrated with C57BL/6 mice (16 mg/kg.bw, oral once a day, 28 days) and HepG2 cells (100 μmol/L, 12 h). Otherwise, oxidative stress, mitochondrial dysfunction and inflammatory infiltration play an important role in HgCl 2 -induced hepatotoxicity. The differentially expressed proteins (DEPs) after HgCl 2 treatment and enriched pathways were obtained through proteomics and network toxicology. Western blot and qRT-PCR results showed acyl-CoA thioesterase 1 (ACOT1), acyl-CoA synthetase short chain family member 3 (ACSS3), epidermal growth factor receptor (EGFR), apolipoprotein B (APOB), signal transducer and activator of transcription 3 (STAT3), alanine--glyoxylate aminotransferase (AGXT), cytochrome P450 3A5 (CYP3A5), CYP2E1 and CYP1A2 may be the major biomarkers for HgCl 2 -induced hepatotoxicity, which involved chemical carcinogenesis, fatty acid metabolism, CYPs-mediated metabolism, GSH metabolism and others. Therefore, this study can provide scientific evidence for the biomarkers and mechanism of HgCl 2 -induced hepatotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Liping Hao reports financial support was provided by Ministry of Science and Technology of the People's Republic of China., (Copyright © 2023. Published by Elsevier Ltd.)

A novel vardenafil analogue was identified in dietary supplement as an adulterant in herbal formulations. The structure of this analogue was elucidated using HRMS, NMR after extraction from the pulverized powder. It was named morphardenafil as a morpholine ring has replaced the N -ethyl piperazine ring in vardenafil. A tablet of this dietary supplement contained about 50 mg of unspecified morphardenafil, which is 2.5 - 20-times the prescriptive dosage of Levetra, the commercial formulation of the vardenafil monohydrochloride salt in the market and probably places unwary consumers at risk for potentially serious adverse effects or drug-drug interaction (DDI)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2023 The Authors.)

Background: Although endoscopic screening for esophageal cancer has been performed in high-risk areas in China for decades, there is limited and inconsistent evidence regarding the starting age for individuals participating in screening. The aim of this study is to investigate the optimal starting age of esophageal cancer screening., Methods: This study is based on a multicenter prospective cohort consisting 338,017 permanent residents aged 40-69 years in six high-risk areas of esophageal cancer in China. The participation rate, detection rate, hazard ratios (HRs), cumulative incidence and mortality and number needed to screen (NNS) were calculated in each age group. Screening burden, benefit and risk were compared among screening strategies with different initiation ages to explore the optimal starting age for population-based screening in high-risk areas., Results: Individuals aged 50-69 had a higher participation rate, a higher detection rate and improved screening effectiveness than those aged 40-49. The endoscopic screening had no significant effect on reducing the incidence of esophageal cancer in individuals under 55 and mortality in individuals under 45. Increasing the starting age to 50 years reduced the screening demand and NNS by 40% and 55%, and resulted in 12% of detectable positive cases, 16% of preventable incident cases, and 14% of preventable deaths being missed., Conclusions: Postponing the starting age of endoscopic screening to 50 years might yield a more-favorable balance between screening benefit and burden in high- risk areas with limited resources., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Hepatic steatosis is a common pathological change of liver that manifests as abnormal lipid accumulation. Epidemiological findings support that diseases such as obesity, diabetes, and hyperlipidemia are mostly accompanied by the development of hepatic steatosis. By screening the disease targets of several traditional Chinese medicines (TCMs) with lipid-reducing effects (hawthorn, semen cassiae, etc .) through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we found that peroxisome-activated receptor gamma (PPAR-γ) is involved in regulating several lipid metabolism-related signaling pathways. Further experiments confirmed that PPAR-γ was correlated with aggravated endoplasmic reticulum (ER) stress in overnutrition-induced hepatic steatosis. The stimulation of hepatocytes by abnormal lipid metabolism signals causes an imbalance in ER homeostasis, which subsequently exacerbates hepatocyte lipid abnormalities. The inhibition of glucose regulatory protein 78 (GRP78, a master regulator of ER homeostasis) was effective in reducing hepatocyte PPAR-γ and lipid synthesis levels. In fact, the hawthorn/semen cassiae treatment effectively downregulated hepatocyte ER stress in high-fat-diet fed rats and reduced the PPAR-γ expression as well as related lipid synthesis. Herein, we confirmed that TCMs characterized by natural lipid-lowering effectively target hepatic PPAR-γ and GRP78, improve ER stress, and have a protective effect against obesity-related hepatic steatosis.

The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine-producing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (H 1 R)-Ca 2+ -NF-κB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of H 1 R using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Nutrition and health knowledge play a crucial role in promoting healthy dietary behaviors, and have been found to be related to sociodemographic characteristics. However, the existing evidence is limited and inconsistent. We aimed to evaluate the awareness level of nutrition and health knowledge and its influencing factors among Wuhan residents, and to provide scientific basis for carrying out targeted nutrition education programmes., Methods: By stratified random sampling, residents aged 18-64 in Wuhan were selected for self-administered questionnaire survey. We adopted the structured questionnaire to investigate respondents' sociodemographic characteristics, nutrition and health knowledge, and the way to acquire knowledge. Among them, nutrition and health knowledge includes the following four parts: dietary guidelines recommendations, food and nutrients, nutrition and disease prevention, and nutrition skills. Chi-square tests were used to analyze the associations between total awareness rate and sociodemographic characteristics. Multiple linear regression models were used to analyze the influencing factors of nutrition and health awareness., Results: A total of 33,436 valid questionnaires were obtained, with a response rate of 97.8%. The total awareness rate was 20.4%, with the highest in nutrition and disease prevention (72.7%) and the lowest in nutrition skills (46.3%). Responders aged 35-44 (23.3%), females (22.8%), educational workers (24.8%), obtaining a master's degree or above (34.1%), living in downtown area (23.1%), and without a history of chronic disease (24.6%) were more likely to have higher awareness rates (all p < 0.001). The multiple linear regression models showed that age, gender, education level, occupation, residential address, and the history of chronic disease were the potential factors affecting individual nutrition awareness., Conclusion: The total awareness rate of nutrition and health knowledge among Wuhan residents was not optimistic. Besides, our findings suggested that sociodemographic characteristics are closely related to nutrition awareness, which may provide important clues for carried out nutrition education campaigns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Wang, Shi, Wang, Liu, Guo, Tan, Yang, Wu and Hao.)

Dimethylarsenic acid is a natural organic arsenic in seafood and one of the important metabolites of inorganic arsenic, which is generally considered to have low or no toxicity. However, due to the controversy of the toxicity of organic arsenic, the food safety standard of organic arsenic has not been established until now, and the effects of organic arsenic on chronic toxicity and the overall metabolic level of animals are rarely reported. In our study, 64 female C57BL/6 mice were exposed to different concentrations of dimethylarsenic acid with water intake. Fifteen metabolites in serum were detected to be altered with the increase of arsenic concentration and exposure time. Dimethylarsenic acid exposure significantly affected the overall metabolic level of mice, and the related effects were not recovered shortly after the suspension of arsenic intake. Although arsenic was excreted largely in urine and feces, continued dimethylarsenic acid exposure could still lead to arsenic accumulation in the liver and kidneys and cause mild nephritis in mice., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Kinases are attractive therapeutic targets since they are commonly altered in cancers. Here, to identify kinases of potential therapeutic interest in HCC, a quantitative kinomic study of tumour and adjacent non-tumour liver tissues was performed using a chemical proteomics approach. In total, 124 kinases were found differentially expressed and they were distributed over all nine kinase groups. Exploration of The Cancer Genome Atlas (TCGA) data showed that the dysregulation of 45 kinases was correlated with poor prognosis in HCC patients. We then tested 11 inhibitors targeting 12 crucial protein kinases alone or in combination for their ability to inhibit cell growth in Hep3B and PLC/PRF/5 cell lines. Six inhibitors significantly reduced viability in both cell lines. Combination inhibition of polo-like kinase 1 (PLK1) and casein kinase 1 epsilon (CSNK1E) significantly induced growth arrest in both cell lines synergistically. In summary, our analysis presents the most complete view of kinome reprogramming in HCC and provides novel insight into crucial kinases in HCC and potential therapeutic targets for HCC treatment. Moreover, the identification of hundreds of differentially expressed kinases forms a rich resource for novel drug targets or diagnostic biomarker discovery. Data are available via ProteomeXchange (identifier PXD023806)., (© 2021 Wiley-VCH GmbH.)

Background: Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease., Methods: We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40-69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram., Results: We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: "Healthy", "Western", "Lower consumers-combination", "Medium consumers-combination" and "Higher consumers-combination" patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into "Asymptomatic", "Mild symptoms" and "Overt symptoms" classes based on health-related symptoms reported by the participants. Compared to the "Healthy" pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the "Asymptomatic". The nomograms reflect the good predictive ability of the model., Conclusion: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation., (© 2022. The Author(s).)

With the acceleration of industrialization, environmental arsenic pollution is threatening human health. However, by the time clinical symptoms appear, arsenic toxicity has usually caused irreversible damage to the body, so it is important to establish a rapid and accurate screening method for early arsenic exposure. In this work, 32 female C57BL/6 mice were exposed to different concentrations of inorganic arsenic in drinking water for a week. By analyzing the changes in serum, more than 20 compounds were detected to increase or decrease with the increase of arsenic intake. The abnormal increase in inosine, xanthine, xanthosine, and hypoxanthine and the abnormal purine pathway were found at the same time. Dimethylarsenic acid, an important inorganic arsenic metabolite in the body, was also found in serum. Combined with statistical analysis, early arsenic exposure can be easily and quickly detected, and the potential health risks of short-term exposure can be revealed simultaneously., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions., Methods: We performed an endoscopic examination of 44,857 individuals aged 40-69 years from five high incidence regions of China in 2017-2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors., Results: We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52-3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03-3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05-1.37) was essential risk factor of LGIN., Conclusions: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC., (© 2021. The Author(s).)

Low levels of reactive oxygen species (ROS) are crucial for maintaining cancer stem cells (CSCs) and their ability to resist therapy, but the ROS regulatory mechanisms in CSCs remains to be explored. Here, we discover that prohibitin (PHB) specifically regulates mitochondrial ROS production in glioma stem-like cells (GSCs) and facilitates GSC radiotherapeutic resistance. We find that PHB is upregulated in GSCs and is associated with malignant gliomas progression and poor prognosis. PHB binds to peroxiredoxin3 (PRDX3), a mitochondrion-specific peroxidase, and stabilizes PRDX3 protein through the ubiquitin-proteasome pathway. Knockout of PHB dramatically elevates ROS levels, thereby inhibiting GSC self-renewal. Importantly, deletion or pharmacological inhibition of PHB potently slows tumor growth and sensitizes tumors to radiotherapy, thus providing significant survival benefits in GSC-derived orthotopic tumors and glioblastoma patient-derived xenografts. These results reveal a selective role of PHB in mitochondrial ROS regulation in GSCs and suggest that targeting PHB improves radiotherapeutic efficacy in glioblastoma.

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 μM and 32 μM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.

Objectives: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China., Design: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group., Results: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively., Conclusion: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Type I interferons (IFNs) are known to mediate antineoplastic effects during tumor progression. Type I IFNs can be produced by multiple cell types in the tumor microenvironment; however, the molecular mechanisms by which tumor cells evade the inhibition of immune microenvironment remain unknown. Here we demonstrate that glioma stem-like cells (GSCs) evade type I IFN suppression through downregulation of STAT1 to initiate tumor growth under inhospitable conditions. The downregulation of STAT1 is mediated by MBD3, an epigenetic regulator. MBD3 is preferentially expressed in GSCs and recruits NuRD complex to STAT1 promoter to suppress STAT1 expression by histone deacetylation. Importantly, STAT1 overexpression or MBD3 depletion induces p21 transcription, resensitizes GSCs to IFN suppression, attenuates GSC tumor growth, and prolongs animal survival. Our findings demonstrate that inactivation of STAT1 signaling by MBD3/NuRD provides GSCs with a survival advantage to escape type I IFN suppression, suggesting that targeting MBD3 may represent a promising therapeutic opportunity to compromise GSC tumorigenic potential., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Zhan et al.)

Glioblastoma (GBM) is an incurable primary brain tumor that is highly resistant to current treatments. Glioma stem-like cells (GSCs) are an aggressive population of glioma cells that not only initiate malignant growth, but also promote therapeutic resistance. Thus, targeting GSCs is critical for improving GBM treatment and ensuring complete eradication of the tumor. Here, we show that NT5DC2 (5'-Nucleotidase Domain Containing 2), a functionally unknown protein, plays a crucial role in GSC tumor initiation via upregulating Fyn expression. NT5DC2 is preferentially expressed in GSCs relative to the non-stem tumor cells. Knockdown of NT5DC2 significantly inhibits the GSC tumorsphere formation and cell viability in vitro, and tumorigenesis in vivo, thus, prolonging animal survival. Moreover, disruption of NT5DC2 in GSCs markedly reduces the expression of Fyn, a Src family proto-oncogene that has been implicated in the regulation of GBM progression. Importantly, the expression of NT5DC2 strongly correlated with increased aggression of human gliomas, but not that of other brain tumors. Taken together, our results uncover the function of NT5DC2 in GSC maintenance and highlight NT5DC2 as a promising therapeutic target for GBM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA-induced autoinflammatory responses in an Aicardi-Goutières syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases.

The lack of early diagnostic maneuvers and effective pharmacotherapy for osteoarthritis (OA) is predominantly attributed to current limited understanding of its pathogenesis. In the present study, the alteration of synovial fluid (SF) proteome in OA were analyzed using SWATH‑mass spectrometry (SWATH‑MS) to further elucidate the pathogenesis of OA. SF samples were collected from 10 OA and 10 rheumatoid arthritis (RA) patients undergoing arthroplasty and 10 patients undergoing arthroscopy for traumatic arthritis (meniscus injury without cartilage lesion). According to the Kellgren‑Lawrence (KL) radiographic grading criteria, all the OA and RA patients were classified as KL grade 4. SWATH‑MS was applied to identify differentially expressed proteins specifically regulated in OA. Differentially expressed proteins identified by SWATH‑MS were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. Proteins of interest were quantified by enzyme‑linked immunosorbent assay (ELISA) following identification. With the use of SWATH‑MS, 131 proteins were identified to be differentially expressed in OA, of which 93 corresponded to upregulation and 38 to downregulation. Complement C1r was the most significantly upregulated protein in OA. Twenty‑eight out of the 131 proteins were specifically regulated in OA, of which 17 were upregulated and 11 were downregulated. Dickkopf‑related protein 2 (DKK2) was one of the proteins specifically upregulated in OA. Furthermore, KEGG pathway annotation indicated that differentially expressed proteins in OA were enriched in complement and coagulation cascades. ELISA indicated that OA severity was positively correlated with the levels of complement C1r (r=0.549; P<0.001) and DKK2 (r=0.79; P<0.001) in the SF. The results indicate that complement and coagulation cascades are involved in the pathogenesis of OA. Differentially expressed proteins, including complement C1r and DKK2 may be used as potential biomarkers or drug targets, which may facilitate with intervention of OA.

Curcumin is a polyphenol extracted from turmeric, which that belongs to the Zingiberaceae family. Curcumin has numerous effects, including anti-inflammatory, antitumor, anti-oxidative and antimicrobial effects. However, the effects of curcumin on human breast cancer cells remain largely unknown. The aim of the present study was to investigate the anticancer effects and the mechanisms by which curcumin affects breast cancer cells. The anticancer effect of curcumin on cell viability and cytotoxicity on human breast cancer MCF-7 cells was analyzed using 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide and lactate dehydrogenase assays, respectively. Cell apoptosis of MCF-7 cells was detected using flow cytometry, 4',6-diamidino-2-phenylindolestaining assay and caspase-3/9 activity kits. Reverse transcription-quantitative polymerase chain reaction was used to analyze microRNA-21 (miR-21) expression in MCF-7 cells. The protein expression of phosphatase and tensin homolog (PTEN) and phospho-protein kinase B (pAkt) was determined by western blot analysis. miR-21 was transfected into MCF-7 cells and the anticancer effect of curcumin on cell viability and the expression of PTEN and pAkt was analyzed. The present results demonstrated that curcumin inhibited cell viability and induced cytotoxicity of MCF-7 cells in a concentration- and time-dependent manner, by inducing apoptosis and increasing caspase-3/9 activities. In addition, curcumin downregulated miR-21 expression in MCF-7 cells by upregulating the PTEN/Akt signaling pathway. The present study has for the first time, to the best of our knowledge, revealed the anticancer effect of curcumin in suppressing breast cancer cell growth, and has elucidated that the miR-21/PTEN/Akt signaling pathway is a key mechanism for the anticancer effects of curcumin.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and understanding its molecular pathogenesis is pivotal to managing this disease. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is an optimal proteomic strategy to seek crucial proteins involved in HCC development and progression. In this study, a quantitative proteomic study of tumour and adjacent non-tumour liver tissues was performed using a SWATH-MS strategy. In total, 4,216 proteins were reliably quantified, and 338 were differentially expressed, with 191 proteins up-regulated and 147 down-regulated in HCC tissues compared with adjacent non-tumourous tissues. Functional analysis revealed distinct pathway enrichment of up- and down-regulated proteins. The most significantly down-regulated proteins were involved in metabolic pathways. Notably, our study revealed sophisticated metabolic reprogramming in HCC, including alteration of the pentose phosphate pathway; serine, glycine and sarcosine biosynthesis/metabolism; glycolysis; gluconeogenesis; fatty acid biosynthesis; and fatty acid β-oxidation. Twenty-seven metabolic enzymes, including PCK2, PDH and G6PD, were significantly changed in this study. To our knowledge, this study presents the most complete view of tissue-specific metabolic reprogramming in HCC, identifying hundreds of differentially expressed proteins, which together form a rich resource for novel drug targets or diagnostic biomarker discovery.

Background: This meta-analysis aimed to determine whether exercise interventions were effective in preventing fall-related fractures in older people. The treatment effects on rate of falls, leg strength and balance were also examined., Methods: An electronic database search was conducted in PubMed, EMBASE, the Cochrane library and PEDro up to 1 September 2015. Randomized controlled trials (RCTs) that conducted exercise interventions and reported fall-related fracture data in older people were included. The primary outcome was the treatment effects on fall-related fractures determined by relative risk (RR) and 95% confidence interval (CI). The treatment effects on falls, leg strength and balance were also reported using rate ratio (RaR) with 95% CI and standardized mean difference (SMD) with 95% CI, respectively. Random effects models were used for meta-analysis., Results: Fifteen studies including 3136 participants met the inclusion criteria. Exercise had a beneficial effect on reduction of fall-related fractures, with pooled estimates of RR 0.604 (95% CI 0.453 - 0.840, P  = 0.003, I 2  = 0%). The rate of falls (RaR 0.856, 95% CI 0.778 - 0.941, P  = 0.001, I 2  = 45%) and leg strength (SMD 0.613, 95% CI 0.119 - 1.107, P  = 0.015, I 2  = 76.7%) were also potentially affected by exercise interventions. These only had a marginally beneficial effect on balance (SMD 0.468, 95% CI -0.011 - 0.947, P  = 0.055, I 2  = 93.6%)., Conclusions: Our findings implied that exercise interventions were effective in preventing fall-related fractures and reducing risk factors of fall-related fractures in older people., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Objective: To explore the factors affecting the successful rate of nano-carbon in sentinel lymph node biopsy.
, Methods: A total of 270 patients with breast cancer, who were treated in First Affilitated Hospital of Henan University of Science and Technology from January 2013 to March 2015, were chosen and given sentinel lymph node biopsy (SLN) with nano-carbon, and the influencial factors were examined by logistic analysis.
, Results: Successful rate of biopsy, accuracy, sensitivity and false negative rate was 92.2%, 97.6%, 93.1% and 6.8%, respectively. Age, primary tumor lesions, body mass index, axillary lymph node status, number of SLN and pathological grade were the factors affetcing successful biopsy (all P<0.05), and body mass index, age, and number of SLN were three independent factors affecting the successful rate of biopsy (all P<0.05). The history of biopsy, tumor location, affected sides, injection sites and chemotherapy showed little effect on the successful rate of biopsy (all P> 0.05).
, Conclusion: Nano-carbon tracer method is a reliable method in sentinel lymph node biopsy. The body mass index, age, and number of lymph node metastasis greatly impact the successful rate of biopsy.

Aim: The study aimed to investigate cellular expression of IL-17 by CD4+ T-cells in osteoporotic postmenopausal women., Methods: We enrolled 25 postmenopausal women with osteoporosis (PostMO) and 25 postmenopausal women with normal bone mineral density measurements (PostM) to examine the production of IL-17, tumor necrosis factor α (TNFα) and receptor activator of nuclear factor x03BA;-B ligand (RANKL) by CD4+ T-cells and IL-17, RORx03B3;t, TNFα and RANKL mRNA levels in CD4+ T-cells. Circulating concentrations of IL-17 along with IL-6, TNFα, RANKL and osteoprotegerin (OPG) were also determined., Results: Osteoporotic postmenopausal women had higher serum concentrations of IL-17 (3.7 ± 1.3 vs. 2.5 ± 1.1 ng/ml, p = 0.042), IL-6 (158 ± 56 vs. 105 ± 39 pg/ml, p = 0.044), TNFα (138 ± 41 vs. 74 ± 11 pg/ml, p < 0.001) and OPG (1.7 ± 0.4 vs. 1.3 ± 0.4 ng/ml, p = 0.039) than healthy controls. The IL-17-producing CD4+ T-cells were higher in the PostMO group than in the PostM group (7.1 ± 2.4 vs. 4.9 ± 1.4%, p = 0.0015). Additionally, osteoporotic postmenopausal women had greater mRNA levels of IL-17 (3.5 ± 2.9 vs. 1.2 ± 1.0%, p = 0.019) and RORx03B3;t (5.7 ± 2.5 vs. 2.2 ± 1.0%, p < 0.001) in CD4+ T-cells than in healthy controls., Conclusions: Our findings implied that the upregulated production of IL-17 may play an important role in regulating bone loss in osteoporotic postmenopausal women., (© 2016 S. Karger AG, Basel.)

Objective: To evaluate the prognosis of cervical intraepithelial neoplasia grade 1 (CIN1) at different follow-up time points in Chinese women and the relationship with high-risk human papillomavirus (HR-HPV) infection., Methods: Biopsy-confirmed CIN1 women were followed up from cervical cancer screening cohorts established during 1999 to 2008 in Xiangyuan county, Yangcheng county, Qinxian county and Wuxiang county, Shanxi Province.In each follow-up visit, participants were examined by visual inspection with acetic acid, liquid-based cytology and HR-HPV DNA testing. Those with any positive results received colposcope and biopsies. The cumulative incidence rates of CIN grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+), regression rates and persistent rates were calculated using pathological findings as a gold standard. The risks of progression related with HR-HPV were evaluated stratified by baseline and follow-up HR-HPV status., Results: A total of 228, 224, 261 and 105 CIN1 women received the 1-year, 2-year, 6-year and 11-year follow-up exams, respectively. The cumulative incidence rate of CIN2+ among baseline HR-HPV positive women was 4.8% (6/126), 10.7% (16/150), 16.9% (29/172) and 35% (19/55) in the above follow-up visits, respectively, and their risk of progression was 2.7(95%CI:0.3-22.0), 2.9 (95%CI:0.7-12.1), 12.0 (95%CI:1.7-86.2) and 30.6 (95%CI:1.9-493.5) times higher than baseline HR-HPV negative women. Moreover, the cumulative incidence of CIN2+ among women with positive HR-HPV both at baseline and follow-up visit was 11% (6/55), 14% (6/42), 17% (10/60) and 50% (13/26) in the above follow-up visits, respectively.No new CIN2+ cases were found among those with negative HR-HPV both at baseline and follow-up visits., Conclusion: Given that CIN1 progression is related to HR-HPV infection, different follow-up intervals and strategies for CIN1 should be taken according to HR-HPV infection status.