Urinary protein changes during the short-term growth and development of rats.

Can the urine proteome reflect short-term changes in the growth and development of animals? Do short-term developmental effects on urinary protein need to be considered when performing urine marker studies using model animals with faster growing periods? In this study, urine samples were collected from 10 Wistar rats aged 6-8 weeks 3 and 6 days apart. The results showed that the urine proteome could sensitively reflect short-term growth and development in rats. For example, comparing the urine proteome of Day 0 and Day 6, 195 differential proteins were identified after screening (FC ≥ 1.5 or ≤ 0.67, P < 0.05), and verified by randomization, the average number of randomly generated differential proteins was 17.99. At least 90.77 % of the differential proteins were not randomly generated. This finding demonstrates that the differential proteins identified in the samples collected at different time points were not randomly generated. A large number of biological processes and pathways related to growth and development were enriched, which shows that the urine proteome reflects the short-term growth and development of rats, and provides a means for in-depth and meticulous study of growth and development. Moreover, an interfering factor in animal experiments using 6- to 8-week-old rats to construct models was identified. The results of this study demonstrated that there were differences in the urinary proteome in rats aged 6-8 weeks only 3-6 days apart, which suggests that the sensitivity of urinary proteomics is high and shows the sensitive and precise response of the urinary proteome to body changes.

Seroprevalence of Anti-SARS-CoV-2 Remained Extremely Low in Taiwan Until the Vaccination Program Was Implemented.

Background: The Taiwanese government made a concerted effort to contain a coronavirus disease 2019 (COVID-19) nosocomial outbreak of variant B.1.429, shortly before universal vaccination program implementation. This study aimed to investigate seroprevalence in the highest-risk regions. Methods: Between January and February 2021, we retrieved 10 000 repository serum samples from blood donors to examine for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) and spike (S) antigens. A positive result was confirmed if anti-N and anti-S antibodies were positive. Overall, 2000 donors residing in the highest-risk district and donating blood in January 2021 were further examined for SARS-CoV-2 RNA. We estimated seroprevalence and compared the epidemic curve between confirmed COVID-19 cases and blood donors with positive antibodies or viral RNA. Results: Twenty-one cases with COVID-19 were confirmed in the nosocomial cluster, with an incidence of 1.27/100 000 in the COVID-affected districts. Among 4888 close contacts of the nosocomial cases, 20 (0.4%) became confirmed cases during isolation. Anti-SARS-CoV-2 was detected in 2 of the 10000 blood donors, showing a seroprevalence of 2/10000 (95% CI, 0.55-7.29). None of the 2000 donors who underwent tests for SARS-CoV-2 RNA were positive. The SARS-CoV-2 infection epidemic curve was observed sporadically in blood donors compared with the nosocomial cluster. Conclusions: In early 2021, an extremely low anti-SARS-CoV-2 seroprevalence among blood donors was observed. Epidemic control measures through precise close contact tracing, testing, and isolation effectively contained SARS-CoV-2 transmission before universal vaccination program implementation.

Preparation and characterization of monoclonal antibodies against porcine gasdermin D protein.

Pyroptosis is a newly discovered type of pro-inflammatory programmed cell death that plays a vital role in various processes such as inflammations, immune responses, and pathogen infections. As one of the main executioners of pyroptosis, gasdermin D (GSDMD) is a membrane pore-forming protein that typically exists in a self-inhibitory state. Once activated, GSDMD will be cleaved into an N-terminal fragment with pore-forming activity, becoming the key indicator of pyroptosis activation, and a C-terminal fragment. Although commercial antibodies against human and murine GSDMD proteins are currently available, their reactivity with porcine GSDMD (pGSDMD) is poor, which limits research on the biological functions of pGSDMD and pyroptosis in pigs in vivo and in vitro. Here, five monoclonal antibodies (mAbs) were prepared by immunizing BALB/c mice with procaryotically expressed full-length pGSDMD, all of which did not cross react with human and murine GSDMD proteins. Epitope mapping demonstrated that 15H6 recognizes amino acids (aa) at positions 28-34 of pGSDMD (LQTSDRF), 19H3 recognizes 257-260aa (PPQF), 23H10 and 27A10 recognize 78-82aa (GPFYF), and 25E2 recognizes 429-435aa (PPTLLGS). The affinity constant and isotype of 15H6, 19H3, 23H10, 27A10, and 25E2 mAbs were determined to be 1.32 × 10-9, 3.66 × 10-9, 9.04 × 10-9, 1.83 × 10-9, and 8.00 × 10-8 mol/L and IgG1/κ, IgG2a/κ, IgG2a/κ, IgG1/κ, and IgG1/κ, respectively. Heavy- and light-chain variable regions sequencing showed that the heavy-chain complementarity-determining region (CDR) sequences of all five mAbs are completely different, while the light-chain CDR sequences of the four mAbs that recognize the N-terminus of pGSDMD are identical. Our prepared mAbs provide valuable materials for studying pGSDMD function and pyroptosis. KEY POINTS: • A total of five mouse anti-pGSDMD mAbs were prepared, of which four recognize the N-terminus of pGSDMD and one recognize its C-terminus. • The main performance parameters of the five mAbs, including epitope, antibody titer, affinity constant, isotype, and heavy- and light-chain CDR, were characterized. • All five mAbs specifically recognize pGSDMD protein and do not cross react with human and murine GSDMD proteins.

SLC25A21 downregulation promotes KRAS-mutant colorectal cancer progression by increasing glutamine anaplerosis.

Emerging evidence shows that KRAS-mutant colorectal cancer (CRC) depends on glutamine (Gln) for survival and progression, indicating that targeting Gln metabolism may be a promising therapeutic strategy for KRAS-mutant CRC. However, the precise mechanism by which Gln metabolism reprogramming promotes and coordinates KRAS-mutant CRC progression remains to be fully investigated. Here, we discovered that solute carrier 25 member 21 (SLC25A21) expression was downregulated in KRAS-mutant CRC, and that SLC25A21 downregulation was correlated with poor survival of KRAS-mutant CRC patients. SLC25A21 depletion selectively accelerated the growth, invasion, migration, and metastasis of KRAS-mutant CRC cells in vitro and in vivo, and inhibited Gln-derived α-ketoglutarate (α-KG) efflux from mitochondria, thereby potentiating Gln replenishment, accompanied by increased GTP availability for persistent KRAS activation in KRAS-mutant CRC. The restoration of SLC25A21 expression impaired the KRAS-mutation-mediated resistance to cetuximab in KRAS-mutant CRC. Moreover, the arrested α-KG efflux that occurred in response to SLC25A21 depletion inhibited the activity of α-KG-dependent DNA demethylases, resulting in a further decrease in SLC25A21 expression. Our studies demonstrate that SLC25A21 plays a significant role as a tumor suppressor in KRAS-mutant CRC by antagonizing Gln-dependent anaplerosis to limit GTP availability for KRAS activation, which suggests potential alternative therapeutic strategies for KRAS-mutant CRC.

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia.

Objectives: This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. Methods: This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4-5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. Results: A total of 75 MG patients with insomnia were included in this study. After 4-5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Conclusion: Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment.

"They have their own people": Emotional connections, community belonging, and Chinese gay, bisexual and other men who have sex with men (GBMSM) college students' needs for sexual health support.

Gay, bisexual and other men who have sex with men (GBMSM) college students in China have unique sexual health challenges, including a higher risk of HIV infection, stigma and discrimination against LGBTQ (lesbian, gay, bisexual, transgender, and queer) population, and limited access to LGBTQ-affirmative sexual health support. Nonetheless, previous research or policymaking has rarely addressed the students' needs for sexual health support from their perspectives. This study aims to explore GBMSM college students' perceptions and attitudes to current sexual health resources, the challenges they encounter, and their expectations to acquiring LGBTQ-affirmative sexual health information and services. The exploration was carried out through field visits and in-depth interviews with 26 GBMSM college students and eight relevant stakeholders in five cities in China. Qualitative thematic analysis was applied to the interview transcripts and fieldwork memos. Four themes emerged around the preference and needs of GBMSM students in dealing with their sexual health challenges: the association between tackling sexual health challenges and entering LGBTQ communities, the roles of emotional attachment in shaping the preference for HIV-related care and support, the desired modes of acquiring sexual health support, and the current unmet service needs. We discovered that the information-and-care-seeking behaviors of GBMSM college students are highly influenced by and connected to their participation in online and in-person LGBTQ communities. Due to the overall stigmatizing sociocultural environment of LGBTQ in China, GBMSM college students tend to rely on LGBTQ communities, seeking trust and a sense of belongingness for tackling their sexual health challenges. Conventional school-based sexual health educational programs, which often apply top-down, stigma-and-fear-based, and non-LGBTQ-inclusive teaching strategies, rarely help GBMSM college students to solve sexual health problems in real life. GBMSM college students are eager to have LGBTQ-affirmative "health managers" who can understand their emotional experiences and interpersonal contexts and assist them with sexual health issues. However, such support is generally perceived as limited by the students. Our study highlights these unmet needs of the GBMSM students and emphasizes the importance of developing future LGBTQ-affirmative sexual health programs among Chinese GBMSM college students and young GBMSM in general.

A nitric oxide-catalytically generating carboxymethyl chitosan/sodium alginate hydrogel coating mimicking endothelium function for improving the biocompatibility.

Thanks to their outstanding mechanical properties and corrosion resistance in physiological environments, titanium and its alloys are broadly explored in the field of intravascular devices. However, the biocompatibility is insufficient, causing thrombus formation and even implantation failure. In this study, inspired by the functions of endothelial glycocalyx and the NO-releasing of endothelial cells (ECs), a biomimetic coating (TNTA-Se) with three-dimensional gel-like structures and NO-catalytically generating ability was constructed on the titanium surface. To this end, the titanium alloy was firstly anodized and then annealed to form nanotube structures imitating the three-dimensional villous of glycocalyx, followed by the preparation of the Cu2+-loaded polydopamine intermediate layer for the immobilization of carboxymethyl chitosan and sodium alginate to form the hydrogel structure. Finally, an organoselenium compound (selenocystamine) as an active catalyst was covalently immobilized on the surface to develop a bioactive coating mimicking endothelial function with NO-generating activity. The surface morphologies and chemical structures of the biomimetic coating were characterized by scanning electron microscopy (SEM), energy dispersion X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and the results indicated that the NO-catalytically generating hydrogel coating was successfully constructed. The results of water contact angle and protein adsorption suggested that the TNTA-Se coating exhibited excellent hydrophilicity, the promotion of bovine serum albumin (BSA) adsorption while the inhibition of fibrinogen (FIB) adsorption. Upon the addition of NO donor S-nitroso glutathione (GSNO) and reducing agent glutathione (GSH), the surface (TNTA-NO) displayed excellent blood compatibility and cytocompatibility to ECs. Compared with other surfaces, the TNTA-NO coating can not only further promote BSA adsorption and inhibit the adhesion and activation of platelets as well as hemolysis, but also significantly enhance ECs adhesion and proliferation and up-regulate VEGF and NO expression of ECs. The current study demonstrated that the NO-catalytically generating hydrogel coating on the titanium alloy can mimic the glycocalyx structure and endothelium function to catalyze a large number of NO donors in human blood to produce NO, and thus simultaneously enhance the surface hemocompatibility and endothelialization, representing a promising strategy for long-term cardiovascular implants of titanium-based devices.

SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation.

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

A new soft tissue constructed with chitosan for wound dressings-incorporating nanoparticles for medical and nursing therapeutic efficacy.

The skin, being the largest organ in the human body, plays a vital role in shielding internal organs from external physical and chemical factors. However, skin damage caused by various factors such as injuries, surgeries, diabetes, or burns can lead to wounds that diminish the skin's protective function. Monitoring essential physiological parameters like temperature, moisture, and pH is crucial to facilitate antibiotic treatment, remote physician monitoring, patient comfort, cost reduction, and prevention of hospital-acquired infections. To this end, innovative wound coverings made of biological materials like gelatin, carboxymethyl chitosan, and titanium nanoparticles have been developed, mainly for hospital and pediatric applications. These wound coverings come equipped with sensors to monitor temperature, pH, and moisture and are suitable for pediatric hospitals where children experience difficulty in wound healing due to their sensitive skin. The temperature monitoring feature allows physicians to accurately assess the wound's temperature, detect potential infections, and take prompt actions. These wound coverings can significantly enhance wound treatment for patients, as real-time monitoring of physiological parameters enables informed decision-making by physicians, leading to better therapeutic outcomes. Furthermore, the use of these wound coverings can minimize the risk of hospital-acquired infections. Their adaptability and flexibility make them ideal for various wound types and sizes, ensuring patient comfort and compliance with the treatment plan. In conclusion, the development of innovative and flexible wound coverings using biological materials and equipped with sensors represents a significant breakthrough in wound management. The use of these wound coverings has the potential to revolutionize wound care and improve patient outcomes, particularly in pediatric hospitals where wound healing is often challenging.

Fabrication of CO-releasing surface to enhance the blood compatibility and endothelialization of TiO2 nanotubes on titanium surface.

Although the construction of nanotube arrays with the micro-nano structures on the titanium surfaces has demonstrated a great promise in the field of blood-contacting materials and devices, the limited surface hemocompatibility and delayed endothelial healing should be further improved. Carbon monoxide (CO) gas signaling molecule within the physiological concentrations has excellent anticoagulation and the ability to promote endothelial growth, exhibiting the great potential for the blood-contact biomaterials, especially the cardiovascular devices. In this study, the regular titanium dioxide nanotube arrays were firstly prepared in situ on the titanium surface by anodic oxidation, followed by the immobilization of the complex of sodium alginate/carboxymethyl chitosan (SA/CS) on the self-assembled modified nanotube surface, the CO-releasing molecule (CORM-401) was finally grafted onto the surface to create a CO-releasing bioactive surface to enhance the biocompatibility. The results of scanning electron microscopy (SEM), X-ray energy dispersion spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) revealed that the CO-releasing molecules were successfully immobilized on the surface. The modified nanotube arrays not only exhibited excellent hydrophilicity but also could slowly release CO gas molecules, and the amount of CO release increased when cysteine was added. Furthermore, the nanotube array can promote albumin adsorption while inhibit fibrinogen adsorption to some extent, demonstrating its selective albumin adsorption; although this effect was somewhat reduced by the introduction of CORM-401, it can be significantly enhanced by the catalytic release of CO. The results of hemocompatibility and endothelial cell growth behaviors showed that, as compared with the CORM-401 modified sample, although the SA/CS-modified sample had better biocompatibility, in the case of cysteine-catalyzed CO release, the released CO could not only reduce the platelet adhesion and activation as well as hemolysis rate, but also promote endothelial cell adhesion and proliferation as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression. As a result, the research of the present study demonstrated that the releasing CO from TiO2 nanotubes can simultaneously enhance the surface hemocompatibility and endothelialization, which could open a new route to enhance the biocompatibility of the blood-contacting materials and devices, such as the artificial heart valve and cardiovascular stents.

"Live a normal life": Constructions of resilience among people in mixed HIV status relationships in Canada.

Positive Plus One is a mixed-methods study of long-term mixed HIV-serostatus relationships in Canada (2016-19). Qualitative interviews with 51 participants (10 women, 41 men, including 27 HIV-positive and 24 HIV-negative partners) were analyzed using inductive thematic analysis to examine notions of relationship resilience in the context of emerging HIV social campaigns. Relationship resilience meant finding ways to build and enact life as a normal couple, that is, a couple not noticeably affected by HIV, linked to the partner with HIV maintaining viral suppression and achieving "undetectable = untransmittable" (U = U). Regardless of serostatus, participants with material resources, social networks, and specialized care were better able to construct resilience for HIV-related challenges within their relationships. Compared to heterosexual couples and those facing socioeconomic adversity, gay and bisexual couples were easier able to disclose, and access capital, networks and resources supporting resilience. We conclude that important pathways of constructing, shaping, and maintaining resilience were influenced by the timing of HIV diagnosis in the relationship, access to HIV-related information and services, disclosure, stigma and social acceptance.

Changes in the urinary proteome of rats after short-term intake of magnesium L-threonate(MgT).

Introduction: Magnesium (Mg) is an important mineral in living organisms. Magnesium has multiple functions in the human body, wherein it plays an important therapeutic and preventive role in a variety of diseases. Methods: Urine samples of rats before and after gavage of magnesium L-threonate (MgT) were collected, and the urinary proteome was identified using the LC-MS/MS technique and analyzed using various databases. Results and discussion: The results illustrated that the urinary proteome of rats was significantly altered after short-term intake of magnesium supplements and that the differential proteins and the biological functions were related to magnesium. This study innovatively establishes a method to study nutrients from the perspective of urine proteomics. This work demonstrates that the urinary proteome is capable of reflecting the effects of nutrient intake on the organism in a more systematic and comprehensive manner and has the potential to provide clues for clinical nutrition research and practice.

Construction of Mussel-Inspired Dopamine-Zn2+ Coating on Titanium Oxide Nanotubes to Improve Hemocompatibility, Cytocompatibility, and Antibacterial Activity.

Zinc ions (Zn2+) are a highly potent bioactive factor with a broad spectrum of physiological functions. In situ continuous and controllable release of Zn2+ from the biomaterials can effectively improve the biocompatibility and antibacterial activity. In the present study, inspired by the adhesion and protein cross-linking in the mussel byssus, with the aim of improving the biocompatibility of titanium, a cost-effective one-step metal-catecholamine assembly strategy was developed to prepare a biomimetic dopamine-Zn2+ (DA-Zn2+) coating by immersing the titanium oxide nanotube (TNT) arrays on the titanium surface prepared by anodic oxidation into an aqueous solution containing dopamine (DA) and zinc ions (Zn2+). The DA-Zn2+ coatings with the different zinc contents exhibited excellent hydrophilicity. Due to the continuous release of zinc ions from the DA-Zn2+ coating, the coated titanium oxide nanotubes displayed excellent hemocompatibility characterized by platelet adhesion and activation and hemolysis assay. Moreover, the DA-Zn2+-coated samples exhibited an excellent ability to enhance endothelial cell (EC) adhesion and proliferation. In addition, the DA-Zn2+ coating can also enhance the antibacterial activity of the nanotubes. Therefore, long-term in situ Zn2+-releasing coating of the present study could serve as the bio-surfaces for long-term prevention of thrombosis, improvement of cytocompatibility to endothelial cells, and antibacterial activity. Due to the easy operation and strong binding ability of the polydopamine on various complicated shapes, the method of the present study can be further applied to other blood contact biomaterials or implantable medical devices to improve the biocompatibility.

Prediction of atherosclerosis using machine learning based on operations research.

BACKGROUND: Atherosclerosis is one of the major reasons for cardiovascular disease including coronary heart disease, cerebral infarction and peripheral vascular disease. Atherosclerosis has no obvious symptoms in its early stages, so the key to the treatment of atherosclerosis is early intervention of risk factors. Machine learning methods have been used to predict atherosclerosis, but the presence of strong causal relationships between features can lead to extremely high levels of information redundancy, which can affect the effectiveness of prediction systems. OBJECTIVE: We aim to combine statistical analysis and machine learning methods to reduce information redundancy and further improve the accuracy of disease diagnosis. METHODS: We cleaned and collated the relevant data obtained from the retrospective study at Affiliated Hospital of Nanjing University of Chinese Medicine through data analysis. First, some features that with too many missing values are filtered out of the 34 features, leaving 25 features. 49% of the samples were categorized as the atherosclerosis risk group while the rest 51% as the control group without atherosclerosis risk under the guidance of relevant experts. We compared the prediction results of a single indicator that had been medically proven to be highly correlated with atherosclerosis with the prediction results of multiple features to fully demonstrate the effect of feature information redundancy on the prediction results. Then the features that could distinguish whether have atherosclerosis risk or not were retained by statistical tests, leaving 20 features. To reduce the information redundancy between features, after drawing inspiration from graph theory, machine learning combined with optimal correlation distances was then used to screen out 15 significant features, and the prediction models were evaluated under the 15 features. Finally, the information of the 5 screened-out non-significant features was fully utilized by ensemble learning to improve the prediction superiority for atherosclerosis. RESULTS: Area Under the Receiver Operating Characteristic (ROC) Curve (AUC), which is used to measure the predictive performance of the model, was 0.84035 and Kolmogorov-Smirnov (KS) value was 0.646. After feature selection model based on optimal correlation distance, the AUC value was 0.88268 and the KS value was 0.688, both of which were improved by about 0.04. Finally, after ensemble learning, the AUC value of the model was further improved by 0.01369 to 0.89637. CONCLUSIONS: The optimal distance feature screening model proposed in this paper improves the performance of atherosclerosis prediction models in terms of both prediction accuracy and AUC metrics. Code and models are available at https://github.com/Cesartwothousands/Prediction-of-Atherosclerosis.

Dual pharmaceutical citizenship: Exploring biomedicalization in the daily lives of mixed HIV-serostatus couples in Canada.

Positive Plus One is the first large-scale mixed methods study of mixed HIV serostatus couples in Canada. We aimed to understand how biomedicalization i.e., a social process of commodification and expansion of the jurisdiction of medicine over health, influenced the everyday relationships of these couples. We completed 51 semi-structured interviews among a purposive sample of HIV-positive (n = 27) and HIV-negative (n = 24) partners in current or past mixed-serostatus relationships. Participants were recruited after completing an online survey where they consented to be re-contacted for qualitative interviews. Participants represented a diversity of sexual orientations, gender identities, and other sociodemographic characteristics. Drawing on inductive thematic analysis to identify patterns within couples, across serostatus and sexual orientations, we argue that everyday lives of mixed-serostatus couples were shaped by biomedical knowledge and enacted through routine adherence to obtain and maintain viral load undetectability. Our findings illustrated the importance of learning biomedical knowledge for mixed-serostatus couples in this study, the empowering influence of undetectable = untransmittable (UU) discourse, and its role in rendering HIV mundane through routine ART adherence. We introduce the concept of 'dual pharmaceutical citizenship' to underscore a process by which particular biopolitical and biomedical expectations are fulfilled in mixed-serostatus relationships. These findings have implications for people who do not readily accept or have access to biomedical knowledge, particularly when treatment-as-prevention frames a "right" and "wrong" approach to HIV management. Future studies should focus on couples where at least one partner does not readily accept or have access to biomedical knowledge.

Synthesis of Star 6-Arm Polyethylene Glycol-Heparin Copolymer to Construct Anticorrosive and Biocompatible Coating on Magnesium Alloy Surface.

Magnesium alloy has become a research hotspot of the degradable vascular stent materials due to its biodegradability and excellent mechanical properties. However, its rapid degradation rate after implantation and the limited biocompatibility restrict its application in clinic. Constructing a multifunctional bioactive polymer coating on the magnesium alloys represents one of the popular and effective approaches to simultaneously improve the corrosion resistance and biocompatibility. In the present study, the copolymer of 6-arm polyethylene glycol and heparin (PEG-Hep) was successfully synthesized and then immobilized on the surface of chitosan (Chi)-modified magnesium alloy surface through electrostatic interaction to improve the corrosion resistance and biocompatibility. The results of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy showed that a dense and compact coating was created on the magnesium alloy surface. The coating displayed excellent hydrophilicity. At the same time, the as-prepared coating can significantly not only improve the corrosion potential, reduce the corrosion current and the pH changes of the immersion solution, but also keep a relatively intact surface morphology after immersing in simulated body fluid solution for 14 days, demonstrating that the coating can significantly improve the corrosion resistance of the magnesium alloy. Moreover, the magnesium alloy with PEG-Hep coating exhibited excellent hemocompatibility according to the results of the hemolysis rate and platelet adhesion and activation. In addition, the modified magnesium alloy had a good ability to promote the endothelial cell adhesion and proliferation. Therefore, the PEG-Hep multifunctional coating can be applied in the surface modification of the biodegradable magnesium alloy stent to simultaneously improve the corrosion resistance and biocompatibility.

Oleanolic Acid Induces Autophagy and Apoptosis via the AMPK-mTOR Signaling Pathway in Colon Cancer.

AIMS: The purpose of this study was to explore the biological functions of the mTOR and AMPK signaling pathways in colon cancer (CC). The potential molecular mechanisms by which oleanolic acid (OA) induces autophagy and apoptosis were also investigated. METHODS: The biological functions of mTOR were analyzed by GeneCards, the Search Tool for the Retrieval of Interacting Genes (STRING), and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to obtain prognostic and survival data of CC patients from the Gene Expression Omnibus (GEO) database. The effects of OA on the CC cell lines HCT-116 and SW-480 were analyzed by CCK-8, colony formation assay, and high-content system (HCS) array scan. The apoptosis rate of SW-480 and HCT-116 cells was detected by flow cytometry. The mRNA and protein expression levels in HCT-116 and SW-480 cells and NCM-460 normal colonic epithelial cells were detected by RT-PCR and Western blotting. RESULTS: mTOR was highly expressed in CC patients and acted as an oncogene. The AMPK signaling pathway mediated by mTOR predicted the poor prognosis of CC patients. OA effectively inhibited the proliferation and viability of CC cells. Furthermore, the apoptosis rate of CC cells was clearly increased following OA administration. Regarding the molecular mechanism of OA, the results indicated that mTOR and the antiapoptosis gene Bcl-2 were downregulated by OA. In addition, regulator genes of autophagy and apoptosis, including BAX, caspase-9, caspase-8, and caspase-3, were significantly upregulated by OA. Moreover, OA upregulated AMPK and its downstream proteins, including TSC2, BAX, Beclin 1, LC3B-II, and ULK1, to induce autophagy and apoptosis in CC cells. CONCLUSION: The findings from this study demonstrate that OA could effectively inhibit the proliferation and viability of CC cells. The anti-CC activity of OA is closely related to the activation of the AMPK-mTOR signaling pathway. Activation of AMPK and inhibition of mTOR are involved in the induction of autophagy and apoptosis by OA. OA induced autophagy and apoptosis mainly in an AMPK activation-dependent manner in CC cells.

Loading Gentamicin and Zn2+ on TiO2 Nanotubes to Improve Anticoagulation, Endothelial Cell Growth, and Antibacterial Activities.

Titanium and its alloys are widely used in blood-contacting implantable and interventional medical devices; however, their biocompatibility is still facing great challenges. In the present study, in order to improve the biocompatibility and antibacterial activities of titanium, TiO2 nanotubes were firstly in situ prepared on the titanium surface by anodization, followed by the introduction of polyacrylic acid (PAA) and gentamicin (GS) on the nanotube surface by layer-by-layer assembly, and finally, zinc ions were loaded on the surface to further improve the bioactivities. The nanotubes displayed excellent hydrophilicity and special nanotube-like structure, which can selectively promote the albumin adsorption, enhance the blood compatibility, and promote the growth of endothelial cells to some degree. After the introduction of PAA and GS, although the superhydrophilicity cannot be achieved, the results of platelet adhesion, cyclic guanosine monophosphate (cGMP) activity, hemolysis rate, and activated partial thromboplastin time (APTT) showed that the blood compatibility was improved, and the blood compatibility was further enhanced after zinc ion loading. On the other hand, the modified surface showed good cytocompatibility to endothelial cells. The introduction of PAA and zinc ions not only promoted the adhesion and proliferation of endothelial cells but also upregulated expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO). The slow and continuous release of GS and Zn2+ over 14 days can significantly improve the antibacterial properties. Therefore, the present study provides an effective method for the surface modification of titanium-based blood-contacting materials to simultaneously endow with good blood compatibility, endothelial growth behaviors, and antibacterial properties.

Incorporation of heparin/BMP2 complex on GOCS-modified magnesium alloy to synergistically improve corrosion resistance, anticoagulation, and osteogenesis.

The in vivo fast degradation and poor biocompatibility are two major challenges of the magnesium alloys in the field of artificial bone materials. In this study, graphene oxide (GO) was first functionalized by chitosan (GOCS) and then immobilized on the magnesium alloy surface, finally the complex of heparin and bone morphogenetic protein 2 was incorporated on the modified surface to synergistically improve the corrosion resistance, anticoagulation, and osteogenesis. Apart from an excellent hydrophilicity after the surface modification, a sustained heparin and BMP2 release over 14 days was achieved. The corrosion resistance of the modified magnesium alloy was significantly better than that of the control according to the results of electrochemical tests. Moreover, the corrosion rate was also significantly reduced in contrast to the control. The modified magnesium alloy not only had excellent anticoagulation, but also can significantly promote osteoblast adhesion and proliferation, upregulate the expression of alkaline phosphatase and osteocalcin, and enhance mineralization. Therefore, the method of the present study can be used to simultaneously improve the corrosion resistance and biocompatibility of the magnesium alloys targeted for the orthopedic applications.

In-situ fabrication of a spherical-shaped Zn-Al hydrotalcite with BiOCl and study on its enhanced photocatalytic mechanism for perfluorooctanoic acid removal performed with a response surface methodology.

Perfluorooctanoic acid (PFOA), a widely used compound, is harmful to the environment and human health. In this study, a facile one pot solvothermal method of integrating BiOCl with Zn-Al hydrotalcite to form spherical-shaped BiOCl/Zn-Al hydrotalcite (B-BHZA) sample is reported. The characteristics and main factors affecting photocatalytic PFOA and photocatalytic mechanism of BiOCl/Zn-Al hydrotalcite (B-BHZA) are systematically investigated. It is found that spherical-shaped B-BHZA possesses abundant defects and a larger surface area of 64.4 m2 g-1. The factors affecting photocatalytic removal PFOA (e.g., time, pH, initial concentration and dosage) are investigated by modeling the 3D surface response. The removal rate of PFOA is over 90 % in 6 h under UV light at an optimal pH of 2, an initial concentration of 500 µg/L and a dose of dosage 0.5 g/L. The main mechanism occurs by photo-generated h+ oxidation and synergistic effects from the photocatalysis process. Though investigating the intermediates of PFOA degradation and F-, a possibility was proposed that h+ initiated the rapidly decarboxylation of PFOA. The unstable perfluoroheptyl group is formatted and further conversed to short chain perfluorocarboxylic acid. This study provides a new insight for the preparation of highly efficient photocatalysts to the treatment of halogenated compounds in UV system.