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Background: In this study, we analyzed the potential active components, related crucial targets and possible signaling pathway mechanisms of Alpiniae Oxyphyllae Fructus and Saposhnikoviae Radix (AOF-SR) herb pairs in the treatment of diabetic kidney disease (DKD) using network pharmacology and verification experiments. Methods: The active compounds and potential targets of AOF-SR were derived from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, The Encyclopedia of Traditional Chinese Medicine, and PubChem databases, and the potential therapeutic targets of DKD were derived from the OMIM, Drugbank, and DisGeNET databases. The "compounds-diseases-targets" network was constructed using Cytoscape 3.6.0. ClusterMaker functionality in Cytoscape is being used to screen important targets for AOF-SR treatment of DKD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of important targets were performed using DAVID database. In addition, according to the predicted results of network pharmacology, HK-2 cells were used to construct DKD model for verification experiment. HK-2 cells were divided into control group, high glucose (HG) group and AOF-SR (HG + AOF-SR) group to detect survival rate and expression of key proteins in NF-B and PI3K/Akt signaling pathways. Results: A total of 38 compounds were selected from AOF-SR, of which 23 were Alpiniae Oxyphyllae Fructus and 15 were Saposhnikoviae Radix. Through enrichment analysis of 82 important targets, 88 signaling pathways were identified; some of these pathways, such as the NF-B, PI3K-Akt, IL-17, and JAK/STAT signaling pathways, regulate the pathological process of DKD. In verification experiment, the HK-2 cells survival rate was higher in the HG + AOF-SR group than in the HG group (P < 0.05). Moreover, western blotting results showed that the expression levels of NF-B, p-PI3K, and p-Akt in HG + AOF-SR group were significantly lower than those in HG group (P < 0.05). Conclusion: Overall, this study revealed the active compounds, important targets and possible mechanisms of AOF-SR treatment for DKD, and conducted preliminary verification experiments on its correctness, provided novel insights into the treatment of DKD by AOF-SR. [ABSTRACT FROM AUTHOR]

Abstract The formation of a nano-apatite surface layer is frequently considered a measure of bioactivity, especially for non-phosphate bioceramics. In the present study, strontium-doped calcium sulfate, (Ca,Sr)SO4, was used to verify the feasibility of this measure. The (Ca,Sr)SO4 specimen was prepared by mixing 10% SrSO4 by weight with 90% CaSO4·½H2O powder by weight. A solid solution of (Ca,7.6%Sr)SO4 was then produced by heating the powder mixture at 1100 °C for 1 h. The resulting (Ca,Sr)SO4 specimen was readily degradable in phosphate solution. A newly formed surface layer in the form of flakes was formed within one day of specimen immersion in phosphate solution. Structural and microstructure–compositional analyses indicated that the flakes were composed of octacalcium phosphate (OCP) crystals. An amorphous interface containing OCP nanocrystals was found between the newly formed surface layer and the remaining (Ca,Sr)SO4 specimen. The specimen was also implanted into a rat distal femur bone defect. In addition to new bone, fibrous tissue and inflammatory cells were found to interlace the (Ca,Sr)SO4 specimen. The present study indicated that a more comprehensive evaluation is needed to assess the bioactivity of non-phosphate bioceramics. The newly formed surface layer on the (Ca,Sr)SO4 specimen after soaking in phosphate solution for 28 days.

ObjectivesTo investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy.MethodsWe conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00–11:00 AM) with evening radiotherapy (7:00–9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy.ResultsThe total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups.ConclusionThe radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy.Clinical Trial Registrationhttp://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

Deep Neural Networks (DNNs) have achieved remarkable progress in various real-world applications, especially when abundant training data are provided. However, data isolation has become a serious problem currently. Existing works build privacy-preserving DNN models from either algorithmic perspective or cryptographic perspective. The former mainly splits the DNN computation graph between data holders or between data holders and server, which demonstrates good scalability but suffers from accuracy loss and potential privacy risks. In contrast, the latter leverages time-consuming cryptographic techniques, which has strong privacy guarantee but poor scalability. In this article, we propose SPNN—a Scalable and Privacy-preserving deep Neural Network learning framework, from an algorithmic-cryptographic co-perspective. From algorithmic perspective, we split the computation graph of DNN models into two parts, i.e., the private-data-related computations that are performed by data holders and the rest heavy computations that are delegated to a semi-honest server with high computation ability. From cryptographic perspective, we propose using two types of cryptographic techniques, i.e., secret sharing and homomorphic encryption, for the isolated data holders to conduct private-data-related computations privately and cooperatively. Furthermore, we implement SPNN in a decentralized setting and introduce user-friendly APIs. Experimental results conducted on real-world datasets demonstrate the superiority of our proposed SPNN. [ABSTRACT FROM AUTHOR]

AimThe study (PROSPERO: CRD42021240905) aims to reveal the relationships among red meat, serum lipids and inflammatory biomarkers.Methods and resultsPubMed, EMBASE and the Cochrane databases were explored through December 2021 to identify 574 studies about red meat and serum lipids markers including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP) or hypersensitive-CRP (hs-CRP). Finally, 20 randomized controlled trials (RCTs) involving 1001 people were included, red meat and serum lipid markers and their relevant information was extracted. The pooled standard mean difference (SMD) was obtained by applying a random-effects model, and subgroup analyses and meta-regression were employed to explain the heterogeneity. Compared with white meat or grain diets, the gross results showed that the consumption of red meat increased serum lipid concentrations like TG (0.29 mmol/L, 95% CI 0.14, 0.44,P

Strontium (Sr) ions are known for its role on increasing bone mineral density. However, a high dosage through mouth may cause many side effects. An alternative to provide a low but steady release at the location of bone defect is therefore explored. In the present study, various amounts of strontium sulfate (SrSO4) were dissolved into calcium sulfate (CaSO4) at elevated temperatures. The release of Sr ions from the (Ca,Sr)SO4 solid solution into various aqueous solutions was then measured. Through the control of Sr content in (Ca,Sr)SO4, the Sr amount releasing into the aqueous solutions could be tailored. After implanting a solid solution into distal femur in rat, a low release of Sr into blood was confirmed.

Young adults (YA) who report viewing pro-tobacco and cannabis marketing are at increased risk for using tobacco and cannabis. However, there is a growing diversity of tobacco and cannabis products on the market, as well as methods for marketing them. Prevalence of, and sociodemographic differences in, YA’s recall of various types of tobacco and cannabis marketing is not well-characterized. Data were from a cohort of YA (mean age: 19.8) from Southern California in 2019. Respondents were asked whether they recalled having seen two types of marketing (online advertisements and portrayals of product use in TV/movies) for 5 tobacco and 3 cannabis products among never-users of tobacco (N = 954) and cannabis (N = 1,046), respectively. Sociodemographic differences in marketing recall were subsequently assessed. Among tobacco-naïve respondents, 31.3% and 49.3% recalled seeing online advertisements and tobacco use in TV/movies, respectively. Among cannabis-naïve respondents, 18.7% and 31.0% recalled seeing online advertisements and cannabis use in TV/movies, respectively. Overall, respondents recalled seeing tobacco and cannabis products on TV/movies at higher rates than seeing online advertisements, with the exception of electronic cigarettes, for which online advertisements were seen at higher rates. Women (vs. men) had higher odds of seeing tobacco (aOR = 1.9) and cannabis use in TV/movies (aOR = 1.4) and cannabis marketing online (aOR = 1.4). LGB (vs. straight) respondents had higher odds of seeing cannabis marketing online (aOR = 1.7). Efforts to regulate exposure to tobacco and cannabis marketing among young women and LGB people merit further consideration.

Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer. TNBC does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. Cytotoxic chemotherapy and surgery are the current therapeutic strategies for TNBC patients, but the chemoresistance of TNBC limits the efficiency of this strategy and shortens the lifespan of patients. The exploration of targeted therapy is ongoing in TNBC research. The aim of the present study was to identify the mechanism underlying acquired resistance in TNBC through the exploration of the relationship between the expression of USP7 and of ABCB1. We found that ubiquitin specific protease 7 (USP7) is a potential therapeutic target for overcoming the chemoresistance of TNBC. USP7 overexpression increased the chemoresistance of TNBC, while the knockdown of USP7 effectively increased the chemosensitivity of chemoresistant TNBC. A USP7 inhibitor effectively induced apoptosis and suppressed metastasis in chemoresistant TNBC. We further clarified that USP7 is a specific deubiquitinating enzyme for ABCB1 that plays an essential role in drug resistance. USP7 directly interacted with ABCB1 and regulated its stability. We concluded that USP7 promotes the chemoresistance of TNBC by stabilizing the ABCB1 protein.

Many smokers reported using Electronic Nicotine Delivery System (ENDS, e.g., electronic cigarettes or e-cigarettes) to quit cigarette smoking. Previous studies suggested that daily ENDS use may promote cigarette smoking cessation. We assessed variations in the prevalence of daily ENDS use among adult smokers by demographics and implications for cigarette smoking disparities. Data were from a nationally representative sample of US adults who participated in the 2014–2015 Tobacco Use Supplement to the Current Population Survey (n = 163,920). Participants reported socio-demographics, current cigarette smoking, current ENDS use, and past-year cigarette smoking cessation attempts. We estimated the prevalence of current cigarette smoking in the full sample by socio-demographics. We also estimated the prevalence of daily ENDS use among current smokers (n = 23,232) and those who attempted to quit smoking in the past year (n = 9,341) by socio-demographics. Multivariable logistic regression models were used to assess associations between daily ENDS use and socio-demographics. Prevalence of daily ENDS use was low: 1–6% among current smokers and 2–9% among those who made a past-year quit attempt, across socio-demographics. Hispanic (Adjusted odds ratio [AOR] = 0.45, 95% confidence interval [CI] = 0.29–0.69) and non-Hispanic black smokers (AOR = 0.38, 95% CI = 0.23–0.61) were less likely than non-Hispanic white smokers to use ENDS daily. Similar associations were observed among current smokers who made a past-year quit attempt (p

IntroductionGiven JUUL e-cigarettes' potential for smoking cessation and its drastically increased sales in the U.S., more evidence is needed to understand the antecedents of JUUL use among adult cigarette smokers. This study assessed the relationships between awareness sources, perceptions about using JUUL, and JUUL use behavior.MethodsIn an online study with adult smokers who were aware of JUUL e-cigarettes (n = 341), respondents reported their sources for learning about JUUL, perceptions of using JUUL versus Vuse (a competitor brand), and ever and past-30-day (current) JUUL use. Multivariable logistic regressions were used to examine the associations between awareness sources, perceptions, and JUUL use, adjusting for covariates.ResultsLearning about JUUL through internet ads was associated with positive perceptions about JUUL compared to Vuse, including JUUL was more fun to use (AOR = 2.04, 95% CI = 1.21, 3.42) and tastier (AOR = 1.96, 95% CI = 1.19, 3.22). Perceiving JUUL as being tastier (AOR = 2.07, 95% CI = 1.23, 3.49), more helpful for quitting smoking (AOR = 2.07, 95% CI = 1.22, 3.53), and cooler (AOR = 2.07, 95% CI = 1.21, 3.56) than Vuse was associated with ever using JUUL. Only perceiving JUUL as being tastier (AOR = 1.98, 95% CI = 1.10, 3.59) than Vuse was associated with current use of JUUL.DiscussionAdult smokers may be more likely to focus on the sensory and social experience of using JUUL rather than JUUL's smoking cessation benefits. These positive perceptions are likely to be influenced by internet ads in general instead of JUUL's official marketing outlets. They are also more likely to sustain JUUL use than JUUL's perceived smoking cessation benefits.

The interplay between defense and counterdefense systems of bacteria and bacteriophages has been driving the evolution of both organisms, leading to their great genetic diversity. Restriction-modification systems are well-studied defense mechanisms of bacteria, while phages have evolved covalent modifications as a counterdefense mechanism to protect their genomes against restriction. Here, we present evidence that these genome modifications might also have been selected to counter, broadly, the CRISPR-Cas systems, an adaptive bacterial defense mechanism. We found that the phage T4 genome modified by cytosine hydroxymethylation and glucosylation (ghmC) exhibits various degrees of resistance to the type V CRISPR-Cas12a system, producing orders of magnitude more progeny than the T4(C) mutant, which contains unmodified cytosines. Furthermore, the progeny accumulated CRISPR escape mutations, allowing rapid evolution of mutant phages under CRISPR pressure. A synergistic effect on phage restriction was observed when two CRISPR-Cas12a complexes were targeted to independent sites on the phage genome, another potential countermechanism by bacteria to more effectively defend themselves against modified phages. These studies suggest that the defense-counterdefense mechanisms exhibited by bacteria and phages, while affording protection against one another, also provide evolutionary benefits for both. [ABSTRACT FROM AUTHOR]

BACKGROUND:There is an increased need to understand how e-cigarette flavors may contribute to e-cigarette uptake and use among youth. We examined the relationship between perceived ease of flavored e-cigarette use and e-cigarette use susceptibility and progression among a nationally representative sample of U.S. youth never tobacco users. METHODS:The wave 1 (2013-2014) and wave 2 (2014-2015) surveys of PATH Study were used. Youth never tobacco users (ages 12-17) who reported whether flavored e-cigarettes were easier to use than unflavored e-cigarettes at wave 1 (n = 6,983) were included in the study. Multivariable logistic regressions were used to examine the associations between perceived ease of using flavored e-cigarettes (wave 1) and e-cigarette use outcomes including e-cigarette use susceptibility (wave 1) and e-cigarette initiation and past-30-day use (wave 2). RESULTS:Overall, 21.2% of the sample perceived flavored e-cigarettes easier to use than unflavored e-cigarettes; and 28.9% of the sample were susceptible to using e-cigarettes at wave 1, and 7.5% and 2.0% initiated e-cigarettes and used e-cigarettes in the past 30 days at wave 2, respectively. Among those who perceived flavored e-cigarettes easier to use, 41.0% were susceptible to using e-cigarettes at wave 1, and 10.6% and 3.4% initiated and used e-cigarettes in the past 30 days at wave 2, respectively. Perceiving flavored e-cigarettes as easier to use than unflavored e-cigarettes at wave 1 was positively associated with e-cigarette use susceptibility at wave 1 (AOR = 1.43, CI = 1.21, 1.69), and e-cigarette initiation (AOR = 1.32, CI = 1.12, 1.67) and past-30-day use (AOR = 1.25, CI = 1.10, 2.47) at wave 2. CONCLUSIONS:Perceiving flavored e-cigarettes as easier to use than unflavored e-cigarettes may lead to e-cigarette use progression among youth never tobacco users. Determining the factors (including e-cigarette marketing and specific e-cigarette flavors) that lead to perceived ease of using flavored e-cigarettes would inform efforts to prevent and curb youth e-cigarette use.

Introduction Tobacco use in India is a major health concern; however, little is known about the influence of tobacco-related social and environmental cues on tobacco use. This study uses ecological momentary assessment (EMA) to examine real-time tobacco use and exposure to social and environmental cues. Material and Methods In Hyderabad and Kolkata, participants were recruited, and an EMA application was installed on their mobile phones. Momentary prompts (MP) were randomly used to collect real-time information and end-of-day (EOD) prompts gathered retrospective information on daily basis. Besides personal tobacco use, the surveys asked about exposure to social (e.g., presence of others using tobacco) and environmental cues (e.g., visual and olfactory stimuli). Using the data aggregation approach, bivariate and multivariate analyses were performed to examine the association of tobacco use and cue exposure. Moderating roles of participants’ socio-demographic characteristics were also tested to gain an in-depth understanding of the relationship. Results Among the 205 participants, around a third (MP, 33.7 %; EOD, 37.6 %) used tobacco at least once during the study period. Tobacco-related social and environmental cues related were commonly reported. In the bivariate models, tobacco use was associated with gender, age, and all the examined social and environmental cues except for seeing restrictions on tobacco use. In the multivariate models, tobacco use was associated with age, gender, seeing others using tobacco, and seeing restrictions on tobacco use. Seeing others in one’s immediate group using tobacco was the strongest predictor of tobacco use in both MP and EOD assessments. Gender and age did not moderate the relationship between cue exposure and tobacco use, although males reported higher tobacco use and cue exposure in general. Conclusions This research provides data on the ubiquity of social and environmental tobacco cues in India. The EMA approach was feasible and informative. Future cessation interventions and advocacy efforts should address the high prevalence of tobacco use and exposure to pro-tobacco use cues especially among Indian males. Health education campaigns for promoting tobacco use restrictions in private places as well as changing the norms of tobacco use in social settings are recommended.

Ferroptosis is a newly described type of programmed cell death and intensively related to both maintaining homeostasis and the development of diseases, especially cancers. Inducing ferroptosis leads to mitochondrial dysfunction and toxic lipid peroxidation in cells, which plays a pivotal role in suppressing cancer growth and progression. Here, we reviewed the existing studies about the molecular mechanisms of ferroptosis involved in different antitumor treatments, such as chemotherapy, targeted therapy, radiotherapy, and immunotherapy. We focused in particular on the distinct combinatorial therapeutic effects such as the synergistic sensitization effect and the drug-resistance reversal achieved when using ferroptosis inducers with conventional cancer therapy. Finally, we discussed the challenges and opportunities in clinical applications of ferroptosis. The application of nanotechnolgy and other novel technologies may provide a new direction in ferroptosis-driven cancer therapies., (Copyright © 2020 Wu, Yu, Luo, Cen, Qiu, Zhang and Hu.)