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Abstract Introduction Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. Materials and methods In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. Results Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. Conclusions We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.

Abstract Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection.Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up.Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported.Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19.Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

Gas temperature is one of the critical parameters that affects the velocity, temperature of particle and the consequent coating quality in cold spray additive manufacturing. The accurate control of the gas temperature is of great importance to the stability of the gas heating efficiency, deposition efficiency, and microstructure of coatings. Therefore, a numerical model was established using ANSYS-FLUENT to study the influence of PID strategy and traditional switch control strategy on the precise temperature of cold spraying gas. Results showed that both the stable time and the overshoot of gas temperature were significantly optimized when the PID strategy was applied. Moreover, the influences of the three factors (proportional, integral and derivative) in PID strategy on the stable time and the overshoot of gas temperature were investigated using an orthogonal experiment. The experimental results showed that the stable time and the overshoot were mainly affected by the proportional parameter and the integral parameter, respectively. With the increase of the proportional parameter and the integral parameter, the stable time and the overshoot rate reduced, and the control accuracy of the gas temperature increased.

AbstractPhototherapy is a conventional antipsoriatic approach based on oxygen-relevant generation of oxidative stress to inhibit keratinocyte hyperproliferation. However, this therapy can be restricted due to local hypoxia in psoriatic lesions. The generation of alkyl radicals is oxygen-independent and suppresses hyperproliferation. Herein, we established alkyl radical-based therapy to treat psoriatic hyperplasia. Because alkyl radicals are short-lived compounds, we loaded 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) as a precursor of alkyl radicals into the chitosan nanogels to improve stability. The present study presented a topically applied nanogel that led to a pH-responsive network sensitive to skin pH. This pH responsiveness of the nanogels allowed fast alkyl radical release in the target site. The physicochemical properties of the prepared nanogels were determined through size, zeta potential, scanning electron microscopy, and absorption spectroscopy. The antipsoriatic activity was examined with keratinocyte- and animal-based studies. The nanogels displayed a smooth and spherical morphology with a hydrodynamic diameter of 215 nm. This size was largely increased as the environmental pH increased to 6. The nanogels heated at 44 °C produced alkyl radicals to induce keratinocyte death through the necrosis pathway. Bioimaging demonstrated that topically applied nanogels could deliver alkyl radicals into the epidermis. This targeting was accompanied by the accumulation of free radicals in the epidermis according to the 2′,7′-dichlorodihydrofluorescein diacetate assay. The imiquimod-stimulated psoriasiform animal model indicated a remarkable reduction in erythema, scaling, and overexpressed cytokines upon topical treatment of the nanogels. The transepidermal water loss of the psoriasiform skin was inhibited from 51.7 to 27.0 g/m2/h, suggesting barrier function recovery by the nanocarriers. The nanogels lowered hyperplasia by decreasing the epidermal thickness from 212 to 89 μm. The incorporation of 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) as a pH-sensitive fluorescence dye in the nanogels could be used to diagnose the severity of the psoriasiform plaque due to the stronger fluorescence of HPTS in skin with lower pH (psoriasiform skin pH = 4.4) than in healthy skin (pH = 4.9). It was possible to deliver the prepared nanogels into the epidermis to restrain hyperplasia without causing cutaneous irritation.

Objective To investigate whether endothelial nitric oxide synthase (eNOS) rs1799983, rs2070744, and rs61722009 gene polymorphisms are associated with pulmonary arterial hypertension (PAH) in South Fujian newborns with congenital heart disease (CHD). Methods Genotyping for the eNOS rs1799983, rs2070744, and rs61722009 polymorphisms was performed using Sanger sequencing in 50 newborns with PAH secondary to CHD [CHD PAH (+)], 52 newborns with CHD without PAH [CHD PAH (-)], and 60 healthy controls. Results The genotype and allele frequency distributions of eNOS rs1799983, rs2070744, and rs61722009 were similar between CHD and healthy controls (P > .05). The frequencies of the eNOS rs1799983 G/T allele were 85% and 15% in the CHD PAH (+) group and 96.15% and 3.85% in the CHD PAH (-) group, the frequency of the T allele was higher in the CHD PAH (+) group than in the CHD PAH (-) group(P

Recommender systems are devoted to find and automatically recommend valuable information and services for users from massive data,which can effectively solve the information overload problem,and become an important information technology in the era of big data.However,the problems of data sparsity,cold start,and interpretability are still the key technical difficulties that limit the wide application of the recommender systems.Reinforcement learning is an interactive learning technique,which can dynamically model user preferences by interacting with users and obtaining feedback to capture their interest drift in real time,and can better solve the classical key issues faced by traditional recommender systems.Nowadays,reinforcement lear-ning has become a hot research topic in the field of recommendation systems.From the perspective of survey,this paper first analyzes the improvement ideas of reinforcement learning for recommender systems based on a brief review of recommender systems and reinforcement learning.Then,the paper makes a general overview and summary of reinforcement learning based recommender systems in recent years,and further summarizes the research situation of traditional reinforcement learning based recommendation and deep reinforcement learning based recommendation respectively.Furthermore,the paper summarizes the frontiers of reinforcement learning based recommendation research topic in recent years and its application.Finally,the future development trend and application of reinforcement learning in recommender systems are analyzed.

AbstractDuring the past decade, team work emerged as an important research area in business management, focusing on the enterprise. However, publications on course learning team are very few. In China, team-learning course practice is one popular and important teaching and learning reform in high schools. In this study, we examine the team-learning course practices from the pedagogical perspective of learning performance. We want to know: Can the team communication, team trust influence the college students’ course learning team’s performance? If do, to what degree do they affect team learning? How can the useful practices be enhanced further? We drew theory from organizational learning and team working literatures to carry on our investigation. The data was collected using a set of questionnaires distributed to six different colleges in China in 2021. We got 404 copies valid, and the data were analyzed using SEM. Results showed the communication frequency, the feedback degree and the learning degree all have a significant positive influence on team performance. Team cognitive trust, institutional trust, arithmetic trust and relational trust also have a significant positive effect on learning performance; yet the degree of these influences differs sharply. The teams’ performance is influenced by team communication and team trust. We recommend enhancement of the course reform practice by team communication and team trust. Teachers who had put team-learning model into practice yet had little confidence in its efficiency can use this to help them to guide the course learning team in a better way.

Abstract Background Losing a child to death is one of the most stressful life events experienced in adulthood. The aim of the current study is to investigate parental risk of seeking treatment for major depression disorders (MDD) after a child’s death and to explore whether such connection may operate differentially by parents’ prior medical condition. Methods We studied a retrospective cohort of 7245 parents (2987 mothers and 4258 fathers) identified in the National Health Insurance Research Database of Taiwan (NHIRD) who had lost a child with age between 1 and 12 years. For comparison, the parents of 1:4 birth year- and gender-matched non-deceased children were retrieved (16,512 mothers and 17,753 fathers). Gender-specific Cox regression analyses were performed to estimate risk. Results Nearly 5.0% and 2.4% of bereaved mothers and fathers sought treatment for MDD within three years after a child’s death, significantly higher than 0.8% and 0.5% in the non-bereaved parents. With covariate adjustment, the hazard ratio (HR) for maternal and paternal seeking treatment for MDD was estimated 4.71 (95% confidence interval [CI]: 3.35–6.64) and 1.93 (95% CI: 1.27–2.95), respectively. The increased risk of MDD varied by prior disease history; specifically, the increased risk of seeking treatment for MDD was especially prominent for those without chronic physical condition (CPC) (e.g., mothers with CPC: aHR = 2.38, 95% CI: 1.56–3.65 vs. no CPC: aHR = 9.55, 95% CI: 6.17–14.79). Conclusions After the death of a child, parental elevated risk of MDD was especially prominent for the women and those without prior medical condition. Effective strategies addressing bereavement may require family-based, integrated physical and mental healthcare and even extended counseling service.