Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS.

RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.

Comparative Analysis of Droplet-Based Ultra-High-Throughput Single-Cell RNA-Seq Systems.

Since its establishment in 2009, single-cell RNA sequencing (RNA-seq) has been a major driver behind progress in biomedical research. In developmental biology and stem cell studies, the ability to profile single cells confers particular benefits. Although most studies still focus on individual tissues or organs, the recent development of ultra-high-throughput single-cell RNA-seq has demonstrated potential power in characterizing more complex systems or even the entire body. However, although multiple ultra-high-throughput single-cell RNA-seq systems have attracted attention, no systematic comparison of these systems has been performed. Here, with the same cell line and bioinformatics pipeline, we developed directly comparable datasets for each of three widely used droplet-based ultra-high-throughput single-cell RNA-seq systems, inDrop, Drop-seq, and 10X Genomics Chromium. Although each system is capable of profiling single-cell transcriptomes, their detailed comparison revealed the distinguishing features and suitable applications for each system.

Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis.

Metastasis is a major cause of cancer therapy failure and mortality. However, targeting metastatic seeding and colonization remains a significant challenge. In this study, we identified NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, as being overexpressed in metastatic tumors. Our findings suggest that NSD2 overexpression enhances tumor metastasis both in vitro and in vivo. Further analysis revealed that NSD2 promotes tumor metastasis by activating Rac1 signaling. Mechanistically, NSD2 combines with and activates Tiam1 (T lymphoma invasion and metastasis 1) and promotes Rac1 signaling by methylating Tiam1 at K724. In vivo and in vitro studies revealed that Tiam1 K724 methylation could be a predictive factor for cancer prognosis and a potential target for metastasis inhibition. Furthermore, we have developed inhibitory peptide which was proved to inhibit tumor metastasis through blocking the interaction between NSD2 and Tiam1. Our results demonstrate that NSD2-methylated Tiam1 promotes Rac1 signaling and cancer metastasis. These results provide insights into the inhibition of tumor metastasis.

A New Surgical Assistance Aid for Mesiodens Extraction Based on the Ideal Approach.

BACKGROUND: To date, the classification of mesiodens has been based on the location, crown orientation, and morphology; however, there is no assistance aid focusing on choosing surgical approach. PURPOSE: This study aimed to introduce and evaluate a new surgical assistance aid for mesiodens extraction based on surgical approach. STUDY DESIGN, SETTING, SAMPLE: For the retrospective trial part of this study, case data from mesiodens patients who had surgery at the Affiliated Stomatological Hospital was collected, and a new surgical assistance aid was developed. A prospective randomized controlled trial was conducted on mesiodens patients who were seen in our department (patients with one mesiodens were included). PREDICTOR VARIABLE: The predictor variable was surgical approach either with or without the surgical assistance aid. Subjects were randomized to one of the two study groups. For subjects assigned to the group using the surgical assistance guide, the approach was selected according to the aid detailed in this study. For subjects assigned to the group without the surgical assistant aid, 2 residents chose an approach based on their judgment and review of relevant imaging and physical examination. MAIN OUTCOME VARIABLES: The preoperative evaluation time, operative time, and complications associated with surgery were recorded separately for the two groups. COVARIATES: The age and sex were also recorded. ANALYSES: Variables were analyzed using the independent t-test and χ2 test. The level of statistical significance is P < .05. RESULTS: In the retrospective trial part, a new surgical assistance aid for mesiodens extraction was developed based on the ideal surgical approach. In the prospective randomized controlled trial, the experimental group (n = 50) was statistically significant in preoperative evaluation time (4.51 ± 0.34 mins vs 5.43 ± 0.34 mins) and operative time (31.87 ± 5.57 mins vs 36.32 ± 5.28 mins) compared to the control group (n = 50) (P < .001). There was no significant intergroup difference in complications associated with surgery (P > .05). CONCLUSION AND RELEVANCE: The new surgical assistance aid developed in this study guides surgeons to ease the selection of surgical approaches and shorten the operative time.

Comparison of Characteristics and Outcomes Between Acute Ischemic Stroke Patients with Different Types of Heart Failure.

Acute ischemic stroke (AIS) can be complicated by heart failure involving preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), and whether or not the prognosis differs between the 2 types of patients remains unclear. We compared the clinical characteristics and outcomes of the 2 types of patients at 3 months after the stroke.We retrospectively analyzed patients who, between 1 January 2018 and 1 January 2021, experienced AIS that was complicated by HFrEF or HFpEF. All patients had been prospectively registered in the Chengdu Stroke Registry. Poor outcome was defined as a modified Rankin Scale (mRS) score of 2-6 at 3 months. Univariate and binary logistic regression was used to assess whether HFpEF was associated with a significantly worse prognosis than HFrEF.Among the final sample of 108 patients (60.2% men; mean age, 73.08 ± 10.82 years), 75 (69.4%) had HFpEF. Compared to HFrEF patients, those with HFpEF were older (P = 0.002), were more likely to have chronic kidney disease (P = 0.033), and were more likely to experience a poor outcome (P = 0.022). After adjustments, HFpEF was associated with significantly greater risk of poor outcome than HFrEF (OR 4.13, 95%CI 1.20-15.79, P = 0.029). However, rates of hemorrhagic transformation or mortality at 3 months after AIS did not differ significantly between the 2 types of heart failure (all P > 0.05).Patients with AIS involving HFpEF experience worse outcomes than those with HFrEF and therefore may require special monitoring and management. Our findings need to be verified in large prospective studies.

Transcriptome analysis of miRNAs during myoblasts adipogenic differentiation.

Intramuscular fat content is closely related to meat quality traits and has high heritability. miRNAs are a class of small non-coding RNA, which are highly conserved in animals and play important regulatory roles in adipogenesis. Therefore, they can be used as molecular markers for meat quality traits. Herein, we used in vitro model of myoblasts adipogenic differentiation to screen differential miRNAs by RNA-seq. A total of 71 differentially miRNAs were filtered, including 31 up-regulated miRNAs and 40 down-regulated miRNAs. Since, we selected 18 miRNAs for RT-qPCR validation, including some miRNAs likely miR-146a-5p, miR-210-3p, miR-199a, miR-224, and miR-214-3p that play important regulatory roles in adipogenesis. In addition, functional enrichment analysis results revealed that members of miRNA target genes were enriched into insulin signaling pathway and MAPK signaling pathway, which are closely related to adipogenesis. Taken together, these data will contribute to further investigate the function of miRNAs in intramuscular fat deposition. These differentially miRNAs can be developed as biomarkers for animal breeding.

MiR-424-5p targets HSP90AA1 to facilitate proliferation and restrain differentiation in skeletal muscle development.

MiR-424-5p was found to be a potential regulator in the proliferation, migration, and invasion of various cancer cells. However, the effects and functional mechanism of miR-424-5p in the process of myogenesis are still unclear. Previously, using microRNA (miRNA) sequencing and expression analysis, we discovered that miR-424-5p was expressed differentially in the different skeletal muscle growth periods of Xuhuai goats. We hypothesized that miR-424-5p might play an important role in skeletal muscle myogenesis. Then, we found that the proliferation ability of the mouse myoblast cell (C2C12 myoblast cell line) was significantly augmented, whereas the C2C12 differentiation was repressed after increasing the expression of miR-424-5p. Mechanistically, HSP90AA1 presented a close interrelation with miR-424-5p, which was predicted as a target gene in the progression of skeletal muscle myogenesis, using transcriptome sequencing, dual luciferase reporter gene detection, and qRT-PCR. The silencing of HSP90AA1 obviously increased C2C12 proliferation and diminished differentiation, which is consistent with the ability of miR-424-5p in C2C12. Altogether, our findings indicated the role of miR-424-5p as a novel potential regulator via HSP90AA1 during muscle myogenesis progression.

Sexual risk behaviours among factory workers in Shenzhen, China: a cross-sectional study.

BACKGROUND: Factory workers are a key population for HIV transmission in China, as they often engage in sexual risk behaviours. This study aims to evaluate sexual risk behaviours and associated factors among factory workers in Shenzhen, China. METHODS: A cross-sectional study was conducted by using multi-stage stratified cluster random sampling. Full-time workers aged ≥18years were eligible to participate in the study. A self-administered questionnaire was used to collect information. Univariate and multivariable logistic regression were applied to assess factors associated with sexual risk behaviours. RESULTS: A total of 2029 factory workers were included. Mean age was 37.2 (±4.4)years; 48.5% were men. Two-thirds (64.9%) had had vaginal intercourse. Their sexual risk behaviours included condomless sex with casual partners in the last sex episode (23.6%), multiple sex partners (11.5%) and engaging in commercial sex (8.4%), in the past year. Having HIV/AIDS knowledge (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.24-0.70) and using a condom at sexual debut (AOR 0.08, 95% CI 0.05-0.13) were factors associated with condomless sex with casual partners in the last sex episode. Males (AOR 3.03, 95% CI 1.96-4.69 and AOR 2.19, 95% CI 1.33-3.60), local workers (AOR 2.11, 95% CI 1.01-4.42 and AOR 3.42, 95% CI 1.63-7.21), being single (AOR 2.04, 95% CI 1.39-3.01 and AOR 2.49, 95% CI 1.61-3.87), having sexual debut aged Conclusions : Sexual risk behaviours were prevalent despite most participants having basic HIV/AIDS knowledge. Future workplace-based prevention programs should target factory workers and there should be a focus on enhanced sexual education to reduce HIV transmission in China.

CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice.

AIM: Renal tubular epithelial cell (RTEC) apoptosis is important in acute kidney injury (AKI). Calcium/calmodulin-dependent protein kinase II (CaMKII) plays an important role in cell apoptosis, but its potential role in AKI remains unknown. METHODS: Using co-immunoprecipitation, immunofluorescence, immunohistochemistry, western blotting, flow cytometry, and cell transfection, this study aimed to verify whether CaMKII is involved in RTEC apoptosis and to explore the underlying mechanism. RESULTS: We found that CaMKII was involved in RTEC apoptosis. In adriamycin-induced AKI mice, serum creatinine levels, cell apoptosis, CaMKII activity, and nuclear factor of activated T cells 2 (NFAT2) levels increased, whereas nuclear Yes-associated protein (YAP) expression decreased; inhibition of CaMKII activity reversed these changes. Phosphorylated CaMKII could bind to phosphorylated YAP in the cytoplasm and block it from entering the nucleus, thereby failing to inhibit NFAT2-mediated cell apoptosis. Sequestrated phosphorylated YAP in the RTEC cytoplasm was finally degraded by ubiquitination. CONCLUSION: CaMKII may regulate RTEC apoptosis through YAP/NFAT2 in AKI mice. CaMKII may be a potent molecular target for AKI treatment.

Identification of DNA aptamers that specifically targets EBV+ nasopharyngeal carcinoma via binding with EphA2/CD98hc complex.

Nasopharyngeal carcinoma (NPC) is one of the Epstein-Barr virus (EBV)-associated malignancies and has a distinct geographical distribution. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for biomarkers for early diagnosis and effective treatments. In this study, we developed DNA aptamers that specifically bind to EBV positive NPC cells by the Cell-SELEX procedure. We further identified the EphA2 (ephrin type-A receptor 2)/CD98hc (CD98 heavy chain) complex as the potential target of the aptamer EA-3 by combining aptamer-based separation and mass spectrometry analysis. Our results revealed for the first time that EphA2 colocalized with CD98hc at the plasma membrane and EphA2 coimmunoprecipitated with CD98hc, which may serve as a starting point for exploring the potential functions of the complex of EphA2 and CD98hc in NPCs. Here, we demonstrated that aptamers can be useful for the identification of protein complexes on the surface of cancer cells.

A model to predict adherence to antiretroviral therapy among people living with HIV.

OBJECTIVES: Suboptimal adherence to antiretroviral therapy (ART) dramatically hampers the achievement of the UNAIDS HIV treatment targets. This study aimed to develop a theory-informed predictive model for ART adherence based on data from Chinese. METHODS: A cross-sectional study was conducted in Shenzhen, China, in December 2020. Participants were recruited through snowball sampling, completing a survey that included sociodemographic characteristics, HIV clinical information, Information-Motivation-Behavioural Skills (IMB) constructs and adherence to ART. CD4 counts and HIV viral load were extracted from medical records. A model to predict ART adherence was developed from a multivariable logistic regression with significant predictors selected by Least Absolute Shrinkage and Selection Operator (LASSO) regression. To evaluate the performance of the model, we tested the discriminatory capacity using the concordance index (C-index) and calibration accuracy using the Hosmer and Lemeshow test. RESULTS: The average age of the 651 people living with HIV (PLHIV) in the training group was 34.1±8.4 years, with 20.1% reporting suboptimal adherence. The mean age of the 276 PLHIV in the validation group was 33.9±8.2 years, and the prevalence of poor adherence was 22.1%. The suboptimal adherence model incorporates five predictors: education level, alcohol use, side effects, objective abilities and self-efficacy. Constructed by those predictors, the model showed a C-index of 0.739 (95% CI 0.703 to 0.772) in internal validation, which was confirmed be 0.717 via bootstrapping validation and remained modest in temporal validation (C-index 0.676). The calibration capacity was acceptable both in the training and in the validation groups (p>0.05). CONCLUSIONS: Our model accurately estimates ART adherence behaviours. The prediction tool can help identify individuals at greater risk for poor adherence and guide tailored interventions to optimise adherence.

Monitoring the Thiol/Thiophenol Molecule-Modulated Plasmon-Mediated Silver Oxidation with Dark-Field Optical Microscopy.

Surface plasmon can trigger or accelerate many photochemical reactions, especially useful in energy and environmental industries. Recently, molecular adsorption has proven effective in modulating plasmon-mediated photochemistry, however the realized chemical reactions are limited and the underlying mechanism is still unclear. Herein, by using in situ dark-field optical microscopy, the plasmon-mediated oxidative etching of silver nanoparticles (Ag NPs), a typical hot-hole-driven reaction, is monitored continuously and quantitatively. The presence of thiol or thiophenol molecules is found essential in the silver oxidation. In addition, the rate of silver oxidation is modulated by the choice of different thiol or thiophenol molecules. Compared with the molecules having electron donating groups, the ones having electron accepting groups accelerate the silver oxidation dramatically. The thiol/thiophenol modulation is attributed to the modulation of the charge separation between the Ag NPs and the adsorbed thiol or thiophenol molecules. This work demonstrates the great potential of molecular adsorption in modulating the plasmon-mediated photochemistry, which will pave a new way for developing highly efficient plasmonic photocatalysts.

The association between entrapment and depression among migrant workers in China: a social rank theory based study.

BACKGROUND: Migrant workers are a group susceptible for depression evolution due to occupational maladaptive triggers. The social rank theory illustrates the pathology process from defensive adaptation to depression, pointing out the early prevention of depression by discovering entrapment. This study aims to reveal the relationship between migrant workers' entrapment and depressive symptoms. METHODS: A total of 1805 migrant workers in Shenzhen were recruited by stratified multi-stage sampling. Sample's demographic, behavioral and psychosocial characteristics were described and analyzed to reveal the relationship between entrapment and depressive symptoms. The Receiver Operator Characteristic was performed to find the optimal cut-off point of Entrapment Scale for predicting depressive symptoms. RESULTS: In the binary logistic regression of sociodemographic variables, migrant workers who were married (univariate odds ratio (ORu) = 0.69, 95% Confidence Interval (CI) = 0.56-0.84), owned 1 or 2 children (ORu = 0.71, 95% CI = 0.58-0.86), had been working over 10 years (ORu = 0.71, 95% CI = 0.54-0.95), earned > 4999 yuan per month (ORu = 0.68, 95% CI = 0.47-0.99; multivariate odds ratio (ORm) = 0.57, 95% CI = 0.38-0.87) or with low risks of alcohol use disorders (ORu = 0.51, 95% CI = 0.34-0.75) had lower risks of depressive symptoms. After adjusted the aforementioned significant sociodemographic variables, migrant workers with severer entrapment were more likely to have depressive symptoms (adjusted odds ratio (ORa) = 1.13, 95% CI = 1.12-1.15). Besides, the study proved the reliability and validity of the Chinese version Entrapment Scale, preferring a two-dimensional structure, and 11 was the optimal cut-off value of this scale for predicting depressive symptoms among migrant workers. CONCLUSIONS: This result indicates the potential value of entrapment according to the social rank theory on facilitating early prevention of migrant works' depression and the application value of Entrapment Scale for effectively measuring mental status among migrant workers.

Temperature adaptations of the thermophilic snail Echinolittorina malaccana: insights from metabolomic analysis.

The periwinkle snail Echinolittorina malaccana, for which the upper lethal temperature is near 55°C, is one of the most heat-tolerant eukaryotes known. We conducted a multi-level investigation - including cardiac physiology, enzyme activity, and targeted and untargeted metabolomic analyses - that elucidated a spectrum of adaptations to extreme heat in this organism. All systems examined showed heat intensity-dependent responses. Under moderate heat stress (37-45°C), the snail depressed cardiac activity and entered a state of metabolic depression. The global metabolomic and enzymatic analyses revealed production of metabolites characteristic of oxygen-independent pathways of ATP generation (lactate and succinate) in the depressed metabolic state, which suggests that anaerobic metabolism was the main energy supply pathway under heat stress (37-52°C). The metabolomic analyses also revealed alterations in glycerophospholipid metabolism under extreme heat stress (52°C), which likely reflected adaptive changes to maintain membrane structure. Small-molecular-mass organic osmolytes (glycine betaine, choline and carnitine) showed complex changes in concentration that were consistent with a role of these protein-stabilizing solutes in protection of the proteome under heat stress. This thermophilic species can thus deploy a wide array of adaptive strategies to acclimatize to extremely high temperatures.

Cyclic Peptides from the Soft Coral-Derived Fungus Aspergillus sclerotiorum SCSIO 41031.

Three novel cyclic hexapeptides, sclerotides C-E (1-3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus sclerotiorum SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey's method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (4) exhibited acetylcholinesterase inhibitory activity with an IC50 value of 15.6 µM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC50 value of 10.1 µM.

Behavioral Intention to Receive a COVID-19 Vaccination Among Chinese Factory Workers: Cross-sectional Online Survey.

BACKGROUND: COVID-19 vaccines will become available in China soon. Understanding communities' responses to the forthcoming COVID-19 vaccines is important. We applied the theory of planned behavior as the theoretical framework. OBJECTIVE: This study investigates the prevalence of and factors associated with behavioral intention to receive self-financed or free COVID-19 vaccinations among Chinese factory workers who resumed work during the pandemic. We examined the effects of factors including sociodemographics, perceptions related to COVID-19 vaccination, exposure to information about COVID-19 vaccination through social media, and COVID-19 preventive measures implemented by individuals and factories. METHODS: Participants were full-time employees 18 years or older who worked in factories in Shenzhen. Factory workers in Shenzhen are required to receive a physical examination annually. Eligible workers attending six physical examination sites were invited to complete a survey on September 1-7, 2020. Out of 2653 eligible factory workers, 2053 (77.4%) completed the online survey. Multivariate two-level logistic regression models and ordinal logistic regression models were fitted. RESULTS: The prevalence of behavioral intention to receive a COVID-19 vaccination was 66.6% (n=1368, conditional on 80% vaccine efficacy and market rate) and 80.6% (n=1655, conditional on 80% vaccine efficacy and free vaccines). After adjusting for significant background characteristics, positive attitudes toward COVID-19 vaccination (adjusted odds ratio [AOR] 1.20, 95% CI 1.15-1.25 and AOR 1.24, 95% CI 1.19-1.30), perceived support from significant others for getting a COVID-19 vaccination (AOR 1.43, 95% CI 1.32-1.55 and AOR 1.37, 95% CI 1.25-1.50), and perceived behavioral control to get a COVID-19 vaccination (AOR 1.51, 95% CI 1.32-1.73 and AOR 1.28, 95% CI 1.09-1.51) were positively associated with both dependent variables (conditional on 80% vaccine efficacy and market rate or free vaccines, respectively). Regarding social media influence, higher frequency of exposure to positive information related to COVID-19 vaccination was associated with a higher intention to receive a COVID-19 vaccination at market rate (AOR 1.53, 95% CI 1.39-1.70) or a free vaccination (AOR 1.52, 95% CI 1.35-1.71). Higher self-reported compliance with wearing a face mask in the workplace (AOR 1.27, 95% CI 1.02-1.58 and AOR 1.67, 95% CI 1.24-2.27) and other public spaces (AOR 1.80, 95% CI 1.42-2.29 and AOR 1.34, 95% CI 1.01-1.77), hand hygiene (AOR 1.21, 95% CI 1.00-1.47 and AOR 1.52, 95% CI 1.19-1.93), and avoiding social gatherings (AOR 1.22, 95% CI 1.01-1.47 and AOR 1.55, 95% CI 1.23-1.95) and crowded places (AOR 1.24, 95% CI 1.02-1.51 and AOR 1.73, 95% CI 1.37-2.18) were also positively associated with both dependent variables. The number of COVID-19 preventive measures implemented by the factory was positively associated with the intention to receive a COVID-19 vaccination under both scenarios (AOR 1.08, 95% CI 1.04-1.12 and AOR 1.06, 95% CI 1.01-1.11). CONCLUSIONS: Factory workers in China reported a high behavioral intention to receive a COVID-19 vaccination. The theory of planned behavior is a useful framework to guide the development of future campaigns promoting COVID-19 vaccination.

Chemical, physical and physiological quality attributes of fruit and vegetables induced by cold plasma treatment: Mechanisms and application advances.

In recent years, applications of cold plasma treatments have shown high efficiency in sterilization of fresh fruit and vegetables. With encouraging results, development of this technique focuses on influences of cold plasma on the quality attributes of these fresh produce. More studies found that the quality attributes are maintained in an acceptable range or can even be improved under certain plasma treatment conditions. This review provides an overview of the multiple effects of cold plasma on the fresh produce, in terms of physical, chemical and physiological aspects. Besides, the possible mechanisms of how plasma influences these quality attributes is elaborated, which is useful for further modification and improvement of the plasma technology, so that quality enhancement and shelf life extension can be achieved. Future trends in the development of cold plasma technology are also presented. Cold plasma treatment is a potential technology for treating fresh fruit and vegetables to enhance their quality and extend their shelf life. However, knowledge of the effects of cold plasma on the quality changes of fresh fruit and vegetables is still limited. Therefore, there is a need for future studies to understand the mechanisms of plasma effects on controlling the interactions between plasma and food products in order to realize the early adoption of the technology to the food industry.

The role of acetylation sites in the regulation of p53 activity.

As a "genomic guardian", p53 mainly functions as a transcription factor that regulates downstream targets responsible for cell fate control, and the activity of p53 is tightly regulated by a complex network that include an abundance of post-translational modifications. Notably, acetylation of p53 at many positions has been demonstrated to play a major role in accurate p53 regulation and cell fate determination. However, no evidence has been provided to compare the effect of acetylation at different sites on p53 regulation. Here, we constructed six acetylation-defective p53 mutants that lysine was substituted by arginine at residues 120, 164, 305, 320, 370/372/373 or 381/382/386, respectively, and determined their effects on p53 activity systematically. Our results showed that all six mutants exhibited diminished transactivation ability and selective regulation of target genes expression through distinct mechanisms. Specifically, lysine 370/372/373 and 381/382/386 mutations decreased p53 stability, and lysine 305 mutation reduced p53 phosphorylation level at serine 15, while lysine 120 and 164 mutations decreased p53 acetylation level at lysine 382. Collectively, these data indicate that acetylation of p53 at different sites has diverse regulatory effects on p53 transcriptional activity through different mechanisms.

Efficacy of HIV interventions among factory workers in low- and middle-income countries: a systematic review.

BACKGROUND: Factory workers in low- and middle-income countries (LMICs) are vulnerable to HIV transmission. Interventions are needed to prevent HIV in this population. We systematically reviewed published literature on the efficacy of various HIV interventions in reducing stigma, risk behaviors and HIV transmission among factory workers. METHODS: A systematic review was performed using predefined inclusion and exclusion criteria. Four databases (PubMed, PsycINFO, Scopus and EMBASE) were searched for relevant publications between January 1, 1990 and December 31, 2018. Two independent reviewers assessed the methodological quality of studies. RESULTS: Thirteen articles were included, with 2 randomized controlled trials and 11 cohort studies. Five interventions and their combinations were summarized. Educational intervention increased condom use and reduced the use of recreational drugs and alcohol before sex. Community intervention that proactively provide HIV counselling and testing (HCT) services could increase the detection rate of HIV and other sexually transmitted diseases (STDs). Lottery intervention increased HCT uptake and decreased HIV public stigma. Education combined with community intervention reduced the proportion of workers with casual sex and enhanced HIV knowledge. Peer education combined with community intervention increased the proportion of workers who were willing to take their partners to HCT. Policy intervention combined with peer education enhanced HIV knowledge, perceived condom accessibility and condom use with regular partners. CONCLUSIONS: Various interventions improved HIV knowledge, decreased HIV stigma and reduced HIV-related risk behaviors among factory workers in LMICs. The combination of multiple interventions tended to achieve better efficacy than a single intervention. Persistent combination interventions are essential to address HIV in this population.

[The Effect of Interference of NLRP3 with shRNA on AGEs-induced Inflammatory Response in Myocardial Cell].

OBJECTIVE: This study aims to explore the effect of silence of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome on advanced glycation end products (AGEs)-induced myocardial injury. METHODS: The myocardial injury model was indued by AGEs. NLRP3 was silenced by shRNA. H9c2 cells were divided into four groups: H9c2 (control group); AGEs group; AGEs+sh-Ctrl group; AGEs+sh-NLRP3 group. The latter two groups of cells will first shRNA control (sh-Ctrl) and shRNA-NLRP3 (sh-NLRP3) plasmids were transfected into H9c2 cells, the last 3 cells were then treated for 24 h with 100 mg/L AGEs, establishment of H9c2 damage model, control cells were treated with solvent for 24 h; Apoptosis was measured by Hoechst33258 staining. The levels of interleukin (IL)-6, IL-18 and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). The protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-3, Caspase-9, nuclear factor κB (NF-κB) P65 and p-P65 were tested by Western blot. The nuclear NF-κB P65 levels were detected by immunofluorescent staining. RESULTS: The expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs group and AGEs+sh-Ctrl group was higher than control group ( P<0.05). Compared with AGEs group, the expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs+sh-NLRP3 group was decreased ( P<0.05). Compared with control group, the apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs group and AGEs+sh-Ctrl group were elevated ( P<0.05). The apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs+sh-NLRP3 group were lower than those of AGEs group ( P<0.05). The phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs group and AGEs+sh-Ctrl group were higher than control group ( P<0.05). Compared with AGEs group, the phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs+sh-NLRP3 group were reduced ( P<0.05). Conlusion Silencing of NLRP3 inflammasome alleviates AGEs-induced apoptosis and inflammatory response in myocardial cell via inhibiting NF-κB P65 activation.