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Liver fibrosis is the common consequence of almost all liver diseases and has become an urgent clinical problem without efficient therapies. Recent evidence has shown that hepatocytes-derived extracellular vesicles (EVs) play important roles in liver pathophysiology, but little is known about the role of damaged hepatocytes-derived EVs in hepatic stellate cell (HSC) activation and following fibrosis. Tetramethylpyrazine (TMP) from Ligusticum wallichii Franchat exhibits a broad spectrum of biological activities including liver protection. In this study, we investigated whether TMP exerted liver-protective action through regulating EV-dependent intercellular communication between hepatocytes and HSCs. Chronic liver injury was induced in mice by CCl

Proposed mechanism by which KF-8 improves oxidative stress tolerance and lifespan in Caenorhabditis elegans. ↑: Upregulated; ↓: downregulated. Red arrows: Role of aging, H2O2 and juglone. Green arrows: Role of KF-8.

Silylated MXene/BC aerogels demonstrate great potential for practical applications, considering the simultaneous realization of high electrical conductivity, superior hydrophobicity, and excellent reversible compressibility.

A template strategy is developed for the precision synthesis of biologically important “complex coacervates-in-dodecyl atmosphere” ultrathin lamellae possessing exceptional shape-preservation and charge-tolerance properties.

In this paper, a gray-box dynamic modeling approach for direct-expansion cooling systems is presented. The overall approach incorporates a multi-stage training procedure that consists of 1) identification of component sub-models from quasi-steady-state performance data, 2) system model integration with estimation of refrigerant charge and 3) fine tuning of thermal capacitances of the evaporator and condenser to capture the system dynamic responses. Compared to traditional physics-based models, the proposed modeling approach has advantages including reduced engineering efforts in the model development phase, improved computational efficiency and enhanced prediction accuracy. The modeling method was validated using a 3-ton variable-speed heat pump and proved to be capable of accurately predicting the system transient behaviors over a wide range of operating conditions. The established dynamic model was then applied for control stability analysis, with a specific goal of determining a proper control execution time step. The case study results showed that the stable control execution time step could change significantly, from 3 sec to 19 sec, as the operating conditions and control settings vary, and a proper selection of the execution time step is critical to ensure stable and reliable operations.

Under the background of the rapid development of information technology, people’s data and information security problems are becoming increasingly serious. Data and information can be leaked in daily Internet access or communications. When doing data sharing, the security mechanism of the data sharing platform should be analyzed. This article aims to study how to analyze the security mechanism of cloud computing-based data sharing platforms in the Internet of Things era. This article presented an attribute-based encryption (ABE) algorithm, a detailed interpretation of the attribute-based encryption algorithm, and analyzed security problems in data sharing in cloud computing. The experimental results showed that the ABE algorithm takes an average of 11 s with five trials, while the other two methods take 51.8 and 31.6 s. ABEs take less time for different encryption numbers under the same data than the other two methods and are more efficient than the other two methods. Thus, attribute-based encryption algorithms should have more advantages.

The present study aimed to explore the effect of subliminal priming on team trust and the mechanism through the mediating role of perceived trustworthiness. A total of 144 participants were asked to complete a lexical decision task that was embedded with the “trust” or “suspicion” Chinese words as the subliminal stimuli. Then, they played a public good game and evaluated the perceived trustworthiness of the team. The results of the study showed that subliminal stimuli had a significant effect on team trust [β = –0.99, 95% CI = (−1.64, −0.33)]. Perceived trustworthiness was found to have a significant mediating effect between the priming condition and team trust [β = −0.35, 95% CI = (−0.72, −0.02)]. The current study revealed the underlying mechanism through which subliminal priming techniques influence team trust and informed efforts by altering perceived trustworthiness.

With the outbreak of the COVID-19 pandemic, artificial intelligence (AI) has been widely used in fields such as medical treatment, while the threat of artificial intelligence has also received extensive attention. However, this topic has been only limitedly explored in China. To provide a measurement tool for AI threat research in China, this study aimed to examine the validity and reliability of the Threats of Artificial Intelligence Scale (TAI) in two Chinese samples of adults (N1 = 654, N2 = 1483). Results of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) suggested that the one-factor model of TAI as the best fitting model. Furthermore, the Chinese TAI was significantly related to Positive and Negative Affect Scale and Self-Rating Anxiety Scale, proving good criterion-related validity of the Chinese TAI. In sum, this study suggested the Chinese version of the TAI as a reliable and effective tool in assessing AI threat in the Chinese context. Limitations and future directions are discussed.

BACKGROUND: Several reports are available regarding the treatment decision regret of patients receiving conventional treatments for localized prostate cancer (PCa); yet data on patients undergoing focal therapy (FT) are sparse. OBJECTIVE: To evaluate the treatment decision satisfaction and regret among patients who underwent FT for PCa with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). DESIGN, SETTING, AND PARTICIPANTS: We identified consecutive patients who underwent HIFU or CRYO FT as the primary treatment for localized PCa at three US institutions. A survey with validated questionnaires, including the five-question Decision Regret Scale (DRS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5), was mailed to the patients. The regret score was calculated based on the five items of the DRS, and regret was defined as a DRS score of >25. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression models were applied to assess the predictors of treatment decision regret. RESULTS AND LIMITATIONS: Of 236 patients, 143 (61%) responded to the survey. Baseline characteristics were similar between responders and nonresponders. During a median (interquartile range) follow-up of 43 (26–68) mo, the treatment decision regret rate was 19.6%. On a multivariable analysis, higher prostate-specific antigen (PSA) at nadir after FT (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.1–2, p = 0.009), presence of PCa on follow-up biopsy (OR 3.98, 95% CI 1.5–10.6, p = 0.006), higher post-FT IPSS (OR 1.18, 95% CI 1.01–1.37, p = 0.03), and newly diagnosed impotence (OR 6.67, 95% CI 1.57–27, p = 0.03) were independent predictors of treatment regret. The type of energy treatment (HIFU/CRYO) was not a predictor of regret/satisfaction. Limitations include retrospective abstraction. CONCLUSIONS: FT for localized PCa is well accepted by the patients, with a low regret rate. Higher PSA at nadir, presence of cancer on follow-up biopsy, bothersome postoperative urinary symptoms, and impotence after FT were independent predictors of treatment decision regret. PATIENT SUMMARY: In this report, we looked at the factors affecting satisfaction and regret in patients with prostate cancer undergoing focal therapy. We found that focal therapy is well accepted by the patients, while presence of cancer on follow-up biopsy as well as bothersome urinary symptoms and sexual dysfunction can predict treatment decision regret.

The reactive oxygen species (ROS) signal regulates stress-induced leaf abscission in cassava. The relationship between the function of the cassava transcription factor bHLH gene and low temperature-induced leaf abscission is still unclear. Here, we report that MebHLH18, a transcription factor, involved in regulating low temperature-induced leaf abscission in cassava. The expression of the MebHLH18 gene was significantly related to low temperature-induced leaf abscission and POD level. Under low temperatures, the levels of ROS scavengers in different cassava genotypes were significantly different in the low temperature-induced leaf abscission process. Cassava gene transformation showed that MebHLH18 overexpression significantly decreased the low temperature-induced leaf abscission rate. Simultaneously, interference expression increased the rate of leaf abscission under the same conditions. ROS analysis showed a connection between the decrease in the low temperature-induced leaf abscission rate caused by MebHLH18 expression and the increase in antioxidant activity. A Genome-wide association studies analysis showed a relationship between the natural variation of the promoter region of MebHLH18 and low temperature-induced leaf abscission. Furthermore, studies showed that the change in MebHLH18 expression was caused by a single nucleotide polymorphism variation in the promoter region upstream of the gene. The high expression of MebHLH18 led to a significant increase in POD activity. The increased POD activity decreased the accumulation of ROS at low temperatures and the rate of leaf abscission. It indicates that the natural variation in the promoter region of MebHLH18 increases antioxidant levels under low temperatures and slows down low temperature-induced leaf abscission.

Bile salt hydrolase (BSH) in Bacteroides is considered a potential drug target for obesity-related metabolic diseases, but its involvement in colon tumorigenesis has not been explored. BSH-expressing Bacteroides is found at high abundance in the stools of colorectal cancer (CRC) patients with overweight and in the feces of a high-fat diet (HFD)-induced CRC mouse model. Colonization of B. fragilis 638R, a strain with low BSH activity, overexpressing a recombinant bsh gene from B. fragilis NCTC9343 strain, results in increased unconjugated bile acids in the colon and accelerated progression of CRC under HFD treatment. In the presence of high BSH activity, the resultant elevation of unconjugated deoxycholic acid and lithocholic acid activates the G-protein-coupled bile acid receptor, resulting in increased β-catenin-regulated chemokine (C-C motif) ligand 28 (CCL28) expression in colon tumors. Activation of the β-catenin/CCL28 axis leads to elevated intra-tumoral immunosuppressive CD25+FOXP3+ Treg cells. Blockade of the β-catenin/CCL28 axis releases the immunosuppression to enhance the intra-tumoral anti-tumor response, which decreases CRC progression under HFD treatment. Pharmacological inhibition of BSH reduces HFD-accelerated CRC progression, coincident with suppression of the β-catenin/CCL28 pathway. These findings provide insights into the pro-carcinogenetic role of Bacteroides in obesity-related CRC progression and characterize BSH as a potential target for CRC prevention and treatment.

BACKGROUND An increasing trend of pancreatic cancer (PC) in young adults has emerged in some countries. OBJECTIVE This study aimed to describe global trends of PC in young adults and to explore the impact of exposure to risk factors during youth. METHODS Global and national data on PC incidence, disability-adjusted life-years, attributive mortality, and summary exposure values of risk factors were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) of incidence and mortality were estimated. Additionally, generalized additive models were applied to explore the non-linear associations between the levels and changes in the Human Development Index (HDI) and AAPC. RESULTS Global PC incidence increased in various periods from 1990–2019, particularly in adults aged < 45 years from 2010–2019, with an average increase rate of 0.69% per year (95% CI: 0.35–1.03). The AAPC of early-onset PC incidence from 2010–2019 was negatively correlated with HDI levels both in 2010 and 2019, and positively correlated with HDI acceleration. Significant increases in early-onset PC incidence were observed over this period in 32 of 88 countries, primarily in South America, North America, Oceania, and Africa. Early-onset PC mortality attributed to high body mass index (BMI) and fasting plasma glucose (FPG) increased, while that attributed to tobacco use declined. CONCLUSIONS An increasing trend has emerged in the global incidence and burden of early-onset PC over the last decades, which may partly be attributed to global epidemics of high BMI and FPG.

Currently, tumor immunotherapy is becoming a new revolution in tumor treatment. Generated from tumor cell lysate or irradiated tumor cells, the whole tumor antigen-based vaccines have the possibility to enhance antitumor immune response without survival from immune surveillance in personalized immunotherapy. Here, polydopamine nanoparticles (PDA NPs) after self-polymerization were covalently coated with tumor cell lysate (TCL) to form PDA@CL. Engineered salmonella (EnS) wrapped with PDA@CL (EnS@PDA@CL) was targeted the localization in the tumor site by intravenous administration. EnS@PDA@CL delivered autologous antigen-containing nanoparticles to tumor hypoxia regions through blood circulation. The PDA@CL particles promoted the maturation of dendritic cells, thus eliciting the infiltration of whole tumor antigens specific cytotoxic T lymphocytes, significantly triggering antitumor immunity. The tumor regression in the Panc02 mice confirmed the therapeutic potential of EnS@PDA@CL in clinical personalized immunotherapy. This article is protected by copyright. All rights reserved.

BACKGROUND Background: Since more HIV-infected people are living longer, it is crucial to monitor the number of non-AIDS-related events, especially liver diseases. Liver-related deaths in HIV-infected patients occur more often in comparison with the general population. The CD4/CD8 ratio is considered an emerging biomarker for non-AIDS-related events. However, the current research was rarely designed to investigate the connection between the CD4/CD8 ratio and certain types of non-AIDS-related events, particularly liver damage. OBJECTIVE Objective: The aim of this study was to determine whether the CD4/CD8 ratio was associated with the development of liver damage in a large cohort of HIV-infected patients receiving antiretroviral treatment (ART) and to evaluate the efficacy of three antiretroviral drugs in normalizing the CD4/CD8 ratio and lowering the incidence of liver damage among this population. METHODS Methods: An observational cohort study was conducted among HIV-infected adults receiving ART from 2004 to 2020 in Guangxi, China. Propensity score matching, multivariable Cox proportional hazard and Fine-Gray competing risk regression models were constructed to determine the relationship of CD4/CD8 ratio normalization with liver damage. RESULTS Results: The incidence of liver damage was 20.12% among 2,440 eligible individuals during a median of four person-years of follow-up. Patients whose CD4/CD8 ratio did not normalize to 1.0 had a higher liver damage incidence than patients whose CD4/CD8 ratio normalized (adjusted HR = 7.90, 95% CI 4.39–14.21, P < 0.001; sub-distribution HR = 6.80, 95% CI 3.83–12.11, P < 0.001), similar to the PSM analysis (aHR = 6.94, 95% CI 3.41–14.12, P < 0.001; sHR = 5.67, 95% CI 2.74–11.73, P< 0.001). The Efavirdine-based regimen required the least time to normalize the CD4/CD8 ratio (71 months IQR 49–88) and had a lower prevalence of liver damage (4.18 /100 person-years). CONCLUSIONS Conclusions: Normalization of the CD4/CD8 ratio was associated with a decreased risk of liver damage in HIV-infected patients receiving ART, providing further evidence that the CD4/CD8 ratio might be utilized to identify people at risk of non-AIDS-related diseases. Efavirdine-based regimen was a recommended option for normalizing the CD4/CD8 ratio and reducing the risk of liver damage.

Background Magnesium chelatase plays an important role in photosynthesis, but only a few subunits have been functionally characterized in cassava. Results Herein, MeChlD was successfully cloned and characterized. MeChlD encodes a magnesium chelatase subunit D, which has ATPase and vWA conservative domains. MeChlD was highly expressed in the leaves. Subcellular localization suggested that MeChlD:GFP was a chloroplast-localized protein. Furthermore, the yeast two-hybrid system and BiFC analysis indicated that MeChlD interacts with MeChlM and MePrxQ, respectively. VIGS-induce silencing of MeChlD resulted in significantly decreased chlorophyll content and reduction the expression of photosynthesis-related nuclear genes. Furthermore, the storage root numbers, fresh weight and the total starch content in cassava storage roots of VIGS-MeChlD plants was significantly reduced. Conclusion Taken together, MeChlD located at the chloroplast is not only required for chlorophyll biosynthesis and photosynthesis, but also affecting the starch accumulation in cassava. This study expands our understanding of the biological functions of ChlD proteins.

Women with polycystic ovarian syndrome (PCOS) are more likely to have non-alcoholic fatty liver disease (NAFLD) than non-PCOS women; however, the exact mechanism underlying this trend is unknown. The receptor activator of NF-κB ligand (RANKL) is strongly involved in bone metabolism and has multiple functions. Recent studies suggest that RANKL is implicated in hepatic insulin resistance (IR), which is the highest risk factor for NAFLD. This study aimed to assess the role of RANKL in NAFLD in Chinese women with PCOS. A cross-sectional observational study was conducted on women newly diagnosed with PCOS, which included 146 patients with NAFLD and 142 patients without NAFLD. Sex hormones, glucose, insulin, and lipids were measured, and anthropometric data were collected. The concentration of serum total RANKL was measured using commercial ELISA kits. PCOS patients with NAFLD had a significantly higher mean age, body mass index (BMI), waist circumference (WC), and worsened metabolic profile than non-NAFLD subjects. The concentrations of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol increased with the RANKL tertile (p for trend = 0.023, 0.026, and 0.035, respectively). A significantly positive association was found between RANKL (per SD change) and the risks of NAFLD (OR = 1.545, 95% CI = 1.086–2.199) after adjusting for confounders, including demographic factors, metabolic markers, and sex hormones. Subgroup multivariate logistic analyses stratified by age, BMI, and WC showed the same tendency. In addition, the positive association between RANKL and NAFLD seemed more prominent in lean patients with a BMI < 24 kg/m2 (OR = 1.70, 95% CI = 1.06–2.75) when compared to overweight/obesity subjects. Therefore, this study suggests that RANKL is positively associated with the increased risk of NAFLD in Chinese women with PCOS, independent of metabolic and reproductive factors.

Background The aim of the study was to investigate the relationship between sarcopenia and both clinical and functional outcome scores following total knee arthroplasty (TKA) performed for patients over 65 years of age. Methods We assessed patient demographics, preoperative health status, postoperative Knee Society Clinical (KSS-C) and Function (KSS-F) subscores, and perioperative complications for 180 patients with sarcopenia and 345 comparatively healthy patients at a mean of 12.0 months after surgery. Multivariate logistic regression analysis was performed to define whether sarcopenia was an independent risk factor for lower KSS-F and KSS-C subscores and peroperative complication rates. Patients with sarcopenia had lower mean body mass index, preoperative albumin, and preoperative hemoglobin levels (p Results Compared with the healthy control group, patients with sarcopenia had lower KSS-C (83.0 vs. 88.2, p Conclusion Patients with sarcopenia present with generally poorer preoperative health and this appears to be associated with lower patient-reported clinical and functional outcome scores. Complication rates were higher among patients with sarcopenia who were still determined to have adequate health status to support TKA. Most complications were limited and could be managed with supportive treatment.

The pharmacokinetics (PK) of several drugs including antimicrobials might be highly altered during extracorporeal membrane oxygenation (ECMO) therapy. We present the change of voriconazole (VRC) PK during ECMO in a critically ill patient who received intravenous VRC at a maintenance dose of 200 mg every 12 h for empirical antifungal therapy. Two PK profiles were drawn before and after the initiation of ECMO therapy. Though the trough levels (both

OBJECTIVE To investigate the incidence, risk factors, and natural history of parastomal hernia. MATERIALS AND METHODS We reviewed the records of patients who underwent radical cystectomy and ileal conduit from 2007 to 2020. Patients who had available follow-up CT imaging were included in this study. All CT scans were re-reviewed for detection of parastomal hernia per Moreno-Matias classification. Patients who developed hernia were followed up and classified into stable or progressive (defined as radiologic upgrading and/or need for surgical intervention). Multivariable cox regression was performed to identify independent predictors of hernia development and progression. RESULTS A total of 361 patients were included in this study. The incidence of radiologic parastomal hernia was 30%, graded as I (56.5%), II (12%), and III (31.5%). Median (IQR) time to radiologic hernia was 8 (5-15) months. During the median (IQR) follow-up of 27 (13-47) months in 108 patients with a hernia, 26% progressed. Median (IQR) time to progression was 12 (6-21) months. On multivariable analysis, female gender (HR 1.86), diabetes (HR 1.81), chronic obstructive pulmonary disease (HR 1.78), and higher body mass index (HR 1.07 for each unit) were independent predictors for radiologic parastomal hernia development. No significant factor was found to be associated with hernia progression. CONCLUSION The incidence of radiologic parastomal hernia following radical cystectomy and ileal conduit is 30%; a quarter of whom progress in a median time of 12 months. Female gender, diabetes, chronic obstructive pulmonary disease, and high body mass index are independent predictors for radiologic hernia development.

Utilization of renewable energy resources, such as solar and wind, has seen rapid growth on the power grid worldwide. To mitigate the adverse impact of these volatile generation on the reliability of the power grid, fast balancing services are increasingly procured by system operators from various resources, such as flexible air-conditioning and space heating loads. Recent work of the authors has demonstrated technical feasibility and various benefits of using variable-speed vapor compression equipment for two fast load balancing services, namely frequency regulation and solar photovoltaic power smoothing. A major control issue was also identified in prior experimental tests: the drastic changes of the compressor speed for fast load balancing have caused severe superheat regulation issues including oscillations and even wet compression. To this end, a gain-scheduled feedforward and proportional integral (PI) controller is proposed and presented in this paper, which uses the real-time compressor speed in determining compensating control actuation of the expansion valve to mitigate the disturbance effect. Both simulation and experimental validations of the proposed control strategy were carried out with a 3-ton variable-speed heat pump. Test results have shown that the proposed controller is effective in improving the superheat regulation performance for three load balancing scenarios, i.e., compressor speed step changes, frequency regulation and photovoltaic smoothing. The demonstrated performance gains include fast post-disturbance recovery of the superheat with the settling time shortened by 63% to 83%, complete avoidance of wet compression and enhanced transient energy efficiency.

Chitosan-based materials have attracted considerable attention owing to their inherent biodegradability, biocompatibility, and antimicrobial properties. However, the establishment of a scalable technology for the fabrication of high-strength and high-toughness chitosan films remains a major challenge. Herein, a new route for the fabrication of high-strength and high-toughness chitosan films mediated by a unique hydrated chitosan crystal structure is reported, using an aqueous KOH/urea solution as a solvent and an aqueous KCl solution as a neutralization bath. The KCl concentration, neutralization temperature, and neutralization time significantly affect the self-assembly and lateral aggregation of chitosan chains and the microstructure and morphology of the chitosan hydrogels and films. Furthermore, stretching orientation endows the chitosan films with a high tensile strength, Young’s modulus, and work of fracture of 579 ± 52 MPa, 18.8 ± 1.5 GPa, and 26.7 ± 6.9 MJ m−3, respectively. To the best of our knowledge, the chitosan films developed in this study are the first example of extremely high-strength and high-toughness chitosan films. We believe that our findings will be useful for the fabrication of polysaccharide-based films with excellent mechanical properties and in broader applications in the fields of biomedicine, flexible bioelectronics, water treatment, and food packaging.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. China, Europe and northern America account for more than half of the new CRC cases and associated deaths globally. This review summarizes the current status and temporal trends of CRC in China, Europe, and northern America. The potential primary preventive strategies and latest advances in CRC screening techniques and programs are discussed. Recently, the incidence and mortality of CRC in some European and northern American countries have decreased; conversely, CRC incidence and mortality continue to increase in China. The overall 5-year relative survival rate for CRC is similar between these regions, but there is considerable heterogeneity among European countries. Implementing population-based CRC screening programs can effectively address the growing disease burden. The effectiveness of nationwide CRC screening programs in these regions has been limited by relatively low coverage and participation rate. The deployment of state-of-the-art techniques and precise risk-adapted screening strategies incorporating effective risk prediction models and screening techniques may boost screening effectiveness. Our review provides novel foundations for the development and optimization of CRC preventive strategies.

This study aimed to evaluate role of nano-sized zinc (Zn) on lactation performance, health status, and mammary permeability of lactating dairy cows. Thirty multiparous dairy cows with similar days in milk (158 ± 43.2) and body weight (694 ± 60.5 kg) were chosen based on parity and milk production and were randomly assigned to 3 treatment groups: basal diet (control, 69.6 mg/kg of Zn adequate in Zn requirement), basal diet additional Zn-methionine (Zn-Met, providing 40 mg/kg of Zn), and basal diet additional nano-sized Zn oxide (nZnO, providing 40 mg/kg of Zn). The study lasted for 10 wk, with the first 2 wk as adaptation. Feed intake, milk yield and the related variables, and plasma variables were determined every other week. Blood hematological profiles were determined in the 8th week of the study. We found that feed intake, milk yield, and milk composition were similar across the 3 groups. The nZnO- and Zn-Met-fed cows had greater milk Zn concentrations in the milk (3.89 mg/L (Zn-Met) and 3.93 mg/L (nZnO)) and plasma (1.25 mg/L (Zn-Met) and 1.29 mg/L (nZnO)) than the control cows (3.79 mg/L in milk and 1.21 mg/L in plasma). The nZnO-fed cows had higher Zn concentrations in plasma but not in milk compared to Zn-Met-fed cows. The Zn appearance in milk was greater in nZnO-fed (area under curve during the first 4 h post-feeding for milk Zn: 16.1 mg/L) and Zn-Met-fed cows (15.7 mg/L) than in control cows (15.0 mg/L). During the first 4 h post-feeding, milk to blood Zn ratio was greater in nZnO-fed animals but lower in Zn-Met-fed cows compared with control cows. Oxidative stress-related variables in plasma, blood hematological profiles, and mammary permeability related variables were not different across treatments. In summary, lactation performance, Zn concentrations in milk and plasma, hematological profiles, mammary permeability were similar in cows fed nZnO and Zn-Met. We therefore suggested that nZnO feeding can improve Zn bioavailability without impairing lactation performance, health status, and mammary gland permeability in dairy cows.

Purpose The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on atrial fibrillation (AF) in rats. Methods A rat AF model was established by angiotensin-II (Ang-II) induction, to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-β/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-Ⅱ-induced atrial fibrosis, to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-β/Smad3 pathway at the cellular level. Results The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-β/Smad3 pathway, and LOX increasedsignificantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to TGF-βSmad3 pathway. Conclusion EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-β/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.

Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers’ attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.

This research proposes an optimization technique for an integrated energy system that includes an accurate prediction model and various energy storage forms to increase load forecast accuracy and coordinated control of various energies in the current integrated energy system. An artificial neural network is utilized to create an accurate short-term load forecasting model to effectively predict user demand. The 0–1 mixed integer linear programming approach is used to analyze the optimal control strategy for multiple energy systems with storage, cold energy, heat energy, and electricity to solve the problem of optimal coordination. Simultaneously, a precise load forecasting method and an optimal scheduling strategy for multienergy systems are proposed. The equipment scheduling plan of the integrated energy system of gas, heat, cold, and electricity is proposed after researching the operation characteristics and energy use process of the equipment in the combined power supply system. A system economic operation model is created with profit maximization in mind, while also taking into account energy coordination between energy and the power grid. The rationality of the algorithm and model is verified by analyzing the real data of a distributed energy station in Wuhan for two years.

Small molecule(SM) drugs can affect the expression of miRNAs, which plays crucial roles in many important biological processes. The chemical structure and clinical information of small molecule can simultaneously incorporate information such as anatomical distribution, therapeutic effects and structural characteristics. It is necessary to develop a novel model that incorporates small molecule chemical structure and clinical information to reveal the unknown small molecule-miRNA associations. In this study, we developed a new framework based on non-negative matrix factorization, called SMANMF, to discover the potential small molecules-miRNAs associations. First, the functional similarity of two miRNAs can be obtained by computing the overlap of the target gene sets in which the miRNAs interact together, and we integrated two types of small molecule similarities, including chemical similarity and clinical similarity. Then, we utilized a non-negative matrix factorization model to discover the unknown relationship between small molecules and miRNAs. The evaluation results indicate that our model can achieve superior prediction performance compared with previous approaches in 5-fold cross-validation. At the same time, the results of case studies also reveal that the SMANMF model has good predictive performance for predicting the potential association between small molecules and miRNAs.

STUDY OBJECTIVES This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN Prospective pharmacokinetics study. SETTING The intensive care unit in a tertiary-care medical center. PATIENTS A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.

Two novel D–π–π–A prototype organic fluorescent compounds, namely (E)-2-(3-([1,1′-biphenyl]-4-yl)-1-(naphthalen-2-yl)allylidene)malononitrile (3-BNM) and (E)-2-(1-([1,1′-biphenyl]-4-yl)-3-(naphthalen-2-yl)allylidene)malononitrile (1-BNM) were synthesized to examine the isomeric effect on their structures and photophysical properties. The results indicated that 3-BNM and 1-BNM display different crystal packing and optical properties, because of the differences in substitution position. 3-BNM molecules packed into a 2D layer structure, while a 2D layer structure was formed in 1-BNM. Compared to that of 1-BNM, red-shifted emissions were observed in the crystal and dilute solution of 3-BNM. The structure–property relationship of the two isomers showed that it is the differences in electronic structures that lead to their different emission behaviors. The obvious isomeric effect indicated that subtle manipulation of substitution position is indeed a feasible and efficient way for tuning the structures and photophysical properties of D–π–π–A prototype organic fluorescent materials.

Two novel organic fluorescent isomers with D-π-π-A prototype structure, namely, (E)-2-[3-([1,1'-biphenyl]-4-yl)-1-(6-methoxynaphthalen-2-yl)allylidene]malononitrile and (E)-2-[1-([1,1'-biphenyl]-4-yl)-3-(6-methoxynaphthalen-2-yl)allylidene]malononitrile, were synthesized. Due to the exchange of naphthalene and biphenyl moieties on each side of conjugated bridge (C = C(CN)2)-conjugated bridge (C = C) group, two compounds are organic fluorescent isomers, and display different molecular stacking mode and photophysical property. Molecules of (E)-2-[3-([1,1'-biphenyl]-4-yl)-1-(6-methoxynaphthalen-2-yl)allylidene]malononitrile are packed with H-aggregation, while (E)-2-[1-([1,1'-biphenyl]-4-yl)-3-(6-methoxynaphthalen-2-yl)allylidene]malononitrile has a J-aggregation. Both of two compounds show solvatochromism and tunable aggregation-induced enhanced emission property.

Content moderation is an essential part of online community health and governance. While much of extant research is centered on what happens to the content, moderation also involves the management of violators. This study focuses on how moderators (mods) make decisions about their actions after the violation takes place but before the sanction by examining how they "profile" the violators. Through observations and interviews with volunteer mods on Twitch, we found that mods engage in a complex process of collaborative evidence collection and profile violators into different categories to decide the type and extent of punishment. Mods consider violators' characteristics as well as behavioral history and violation context before taking moderation action. The main purpose of the profiling was to avoid excessive punishment and aim to integrate violators more into the community. We discuss the contributions of profiling to moderation practice and suggest design mechanisms to facilitate mods' profiling processes.

BACKGROUND For mycophenolic acid (MPA), therapeutic drug monitoring is an essential tool for dosage optimization in transplant recipients and autoimmune diseases. In China, a new commercial kit using an immunochromatographic assay (FICA) with a point-of-care testing system was approved for therapeutic drug monitoring of MPA. However, corroboration between FICA and clinically used assays remains unknown. The authors evaluated MPA concentrations in heart transplant recipients obtained by FICA, high-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS), and enzyme-multiplied immunoassay technique (EMIT). METHODS Nine heart transplant recipients administered a single mycophenolate mofetil (MMF) dose, and 4 administered multiple MMF doses were enrolled. MPA samples were collected before administration, and after 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours, and assessed by 2 immunoassays (EMIT and FICA) and LC-MS/MS. Consistency between methods was evaluated using Passing-Bablok regression and Bland-Altman analysis. RESULTS For Passing-Bablok regression between FICA and LC-MS/MS, FICA = 0.784 LC-MS/MS + 0.360 (95% CI slope: 0.739 to 0.829, 95% CI intercept: 0.174-0.545). Regardless of a significant observed correlation coefficient (R2 = 0.9126), statistical analyses revealed a significant difference between FICA and the reference LC-MS/MS method. The mean absolute bias was 0.69 mcg/mL between FICA and LC-MS/MS. Bland-Altman plots showed a mean bias of -0.23 mcg/mL (±1.96 SD, -2.19 to 1.72 mcg/mL) and average relative bias of 14.73% (±1.96 SD, -67.91% to 97.37%) between FICA and LC-MS/MS. Unsatisfactory consistency was observed between EMIT and LC-MS/MS, and FICA and EMIT. Differences between pharmacokinetic parameters after a single or 7 days of MMF administration, by LC-MS/MS and FICA, were not statistically significant. CONCLUSIONS The consistency of the new FICA using a point-of-care testing device with LC-MS/MS and EMIT was inadequate, and the accuracy of EMIT and LC-MS/MS was inappropriate. Clinicians should be informed when switching MPA detection methods to avoid misleading results.