Psychometric evaluation of Suicide Management Competency Scale for nursing students: A cross-sectional study.

Suicide management skills are essential for nursing students, as they are often the initial healthcare contact for individuals at risk of suicide. Recognising signs of suicidal ideation and behaviour is critical for initiating timely interventions. This study aimed to develop and access the psychometric evaluation of the Suicide Management Competency Scale (SMCS) for nursing students. A first draft of the SMCS was initially developed following literature and focus group, and a scale containing 28 items was constructed. We recruited 216 participants from two nursing schools. Construct validity was evaluated with exploratory factor analysis (EFA). Internal consistency reliability was determined with Cronbach's alpha, and test-retest reliability was examined with intra-class correlation. After four rounds of EFA and item analysis, we reduced the number of items to 16. We deleted 12 items, including 4 items for communalities less than 0.40, 3 items for cross-loading, 3 items for factor loading less than 0.40, and 2 items for low corrected item-total correlation. The final 16-item SMCS resulted in three subscales, which explained 55.813% of the total variance: emotional challenges in suicide risk assessment, delivering suicide interventions, and suicide risk nursing competence and confidence. Cronbach's alpha was 0.854 for the total score and 0.748 to 0.847 for the subscales. The newly developed SMCS was found to have good reliability and validity, suggesting that this scale could be used to evaluate nursing students' perceived competency in managing suicide, which might help cultivate competence in nurses' ability to effectively manage and prevent suicide, thus contributing to saving lives.

Dual-task training in older adults with cognitive impairment: A meta-analysis and trial sequential analysis of randomized controlled trials.

OBJECTIVE: To determine the effects of simultaneous dual-task training on cognitive function, physical function, and depression in older adults with mild cognitive impairment or dementia. METHODS: Comprehensive database searches were conducted in PubMed, Embase, the Cochrane Library, CINAHL, Ovid-Medline, Web of Science, and Scopus up to December 2022. Randomized controlled trials were included to assess the efficacy of simultaneous dual-task training for older adults with mild cognitive impairment or dementia. The analysis utilized Comprehensive Meta-Analysis version 3.0, presenting Hedges' g and the corresponding 95 % confidence interval (CI) for the pooled effect size and, applying a random-effects model. The I2 and Cochran's Q tests were employed to evaluate heterogeneity. The Cochrane Risk of Bias 2.0 tool was employed to assess study quality. The Copenhagen Trial Unit (version 0.9.5.10 Beta) was employed for trial sequential analysis, providing a rigorous methodology for evaluating cumulative evidence from multiple studies. RESULTS: Of the 1676 studies identified, 20 studies involving 1477 older adults with cognitive impairment were included. Dual-task training significantly enhanced global cognition (0.477, 95 % CI: 0.282 to 0.671), executive function (-0.310, 95 % CI: -0.586 to -0.035), working memory (0.714, 95 % CI: 0.072 to 1.355), gait (0.418, 95 % CI: 0.252 to 0.583), physical activity (0.586, 95 % CI: 0.012 to 1.16), and depression (-0.703, 95 % CI: -1.253 to -0.153). Trial sequential analyses revealed the robustness of this meta-analysis, which was based on a sufficient sample size from the included studies. Moreover, dual-task training demonstrated beneficial effects on global cognition, executive function, working memory, and gait. CONCLUSIONS: Dual-task training improved cognition, physical function, and depression among older adults with cognitive impairment. Accordingly, dual-task training should be considered a clinical nonpharmacological intervention for older adults with mild cognitive impairment or dementia. Nevertheless, the trial sequential analysis results were consistent with those of the pairwise meta-analysis but only global cognition reached significance by crossing the trial sequential analysis boundary. Future studies with higher-quality designs and larger sample sizes are required to obtain more conclusive results regarding other outcomes. REGISTRATION: PROSPERO CRD42023418598.

Chemo-photothermal therapy of chitosan/gold nanorod clusters for antibacterial treatment against the infection of planktonic and biofilm MRSA.

Bacterial infections trigger inflammation and impede the closure of skin wounds. The misuse of antibiotics exacerbates skin infections by generating multidrug-resistant bacteria. In this study, we developed chemo-photothermal therapy (chemo-PTT) based on near-infrared (NIR)-irradiated chitosan/gold nanorod (GNR) clusters as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents. The nanocomposites exhibited an average size of 223 nm with a surface charge of 36 mV. These plasmonic nanocomposites demonstrated on-demand and rapid hyperthermal action under NIR. The combined effect of positive charge and PTT by NIR-irradiated nanocomposites resulted in a remarkable inhibition rate of 96 % against planktonic MRSA, indicating a synergistic activity compared to chitosan nanoparticles or GNR alone. The nanocomposites easily penetrated the biofilm matrix. The combination of chemical and photothermal treatments by NIR-stimulated clusters significantly damaged the biofilm structure, eradicating MRSA inside the biomass. NIR-irradiated chitosan/GNR clusters increased the skin temperature of mice by 13 °C. The plasmonic nanocomposites induced negligible skin irritation in vivo. In summary, this novel nanosystem demonstrated potent antibacterial effects against planktonic and biofilm MRSA, showcasing the possible efficacy in treating skin infections.

Long stem revision versus short stem revision with plate osteosynthesis for Vancouver type B2 periprosthetic femoral fracture: a comparative study of eighty five cases.

PURPOSE: Periprosthetic femoral fractures (PPFs) around the hip are challenging complications in orthopaedic surgery, particularly Vancouver type B2 (VTB2) fractures. The surgical management of these fractures is crucial and depends on various factors. Cementless short taper stem with plate osteosynthesis is an alternative surgical technique. This study aims to compare the outcomes of this surgical technique with revision arthroplasty (RA) with long stem in the treatment of VTB2 PPFs. METHODS: This retrospective study was conducted in a single medical institute from February 2010 to May 2019. Patients who had received either total hip arthroplasty or bipolar hemiarthroplasty and subsequently developed a VTB2 PPF were included; patients who sustained intra-operative fractures or received a cemented stem previously were excluded from the analysis. The patients were divided into two groups: group I received RA with cementless long stem, while group II underwent RA with cementless short taper stem with plate osteosynthesis. Demographic data, radiographic and functional outcomes, and complications were analyzed between the two groups. RESULTS: A total of 85 patients diagnosed with VTB2 PPFs were included in the study. There were no significant differences between the two groups in terms of demographic data, including age, gender, mean follow-up times, estimated blood loss, and operative times. The radiographic results showed that there was no significant difference in the incidence of subsidence and implant stability between the two groups. However, group II tended to have less subsidence and periprosthetic osteolysis. Patients in group II had significantly better functional scores (mean Harris hip score: post-operative: 60.2 in group I and 66.7 in group ii; last follow-up: 77.4 in group 1 and 83.2 in group II (both p < 0.05)). There were no significant differences in the overall complication rate, including infection, dislocation, re-fracture, and revision surgery, between the two groups. CONCLUSIONS: Both surgical techniques, cementless long stem and cementless short taper stem with plate osteosynthesis, are effective in the treatment of Vancouver B2 PPFs, with no significant differences in outcomes or complications. However, patients in cementless short taper stem with plate osteosynthesis had better functional scores at both post-operative and the last follow-up.

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19.

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.

RNA-Based Antipsoriatic Gene Therapy: An Updated Review Focusing on Evidence from Animal Models.

Psoriasis presents as a complex genetic skin disorder, characterized by the interaction between infiltrated immune cells and keratinocytes. Substantial progress has been made in understanding the molecular mechanisms of both coding and non-coding genes, which has positively impacted clinical treatment approaches. Despite extensive research into the genetic aspects of psoriasis pathogenesis, fully grasping its epigenetic component remains a challenging endeavor. In response to the pressing demand for innovative treatments to alleviate inflammatory skin disorders, various novel strategies are under consideration. These include gene therapy employing antisense nucleotides, silencing RNA complexes, stem cell therapy, and antibody-based therapy. There is a pressing requirement for a psoriasis-like animal model that replicates human psoriasis to facilitate early preclinical evaluations of these novel treatments. The authors conduct a comprehensive review of various gene therapy in different psoriasis-like animal models utilized in psoriasis research. The animals included in the list underwent skin treatments such as imiquimod application, as well as genetic and biologic injections, and the results of these interventions are detailed. Animal models play a crucial role in translating drug discoveries from the laboratory to clinical practice, and these models aid in improving the reproducibility and clinical applicability of preclinical data. Numerous animal models with characteristics similar to those of human psoriasis have proven to be useful in understanding the development of psoriasis. In this review, the article focuses on RNA-based gene therapy exploration in different types of psoriasis-like animal models to improve the treatment of psoriasis.

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1.

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.

The anti-inflammatory activity of flavonoids and alkaloids from Sophora flavescens alleviates psoriasiform lesions: Prenylation and methoxylation beneficially enhance bioactivity and skin targeting.

The herb Sophora flavescens displays anti-inflammatory activity and can provide a source of antipsoriatic medications. We aimed to evaluate whether S. flavescens extracts and compounds can relieve psoriasiform inflammation. The ability of flavonoids (maackiain, sophoraflavanone G, leachianone A) and alkaloids (matrine, oxymatrine) isolated from S. flavescens to inhibit production of cytokine/chemokines was examined in keratinocytes and macrophages. Physicochemical properties and skin absorption were determined by in silico molecular modeling and the in vitro permeation test (IVPT) to establish the structure-permeation relationship (SPR). The ethyl acetate extract exhibited higher inhibition of interleukin (IL)-6, IL-8, and CXCL1 production in tumor necrosis factor-α-stimulated keratinocytes compared to the ethanol and water extracts. The flavonoids demonstrated higher cytokine/chemokine inhibition than alkaloids, with the prenylated flavanones (sophoraflavanone G, leachianone A) led to the highest suppression. Flavonoids exerted anti-inflammatory effects via the extracellular signal-regulated kinase, p38, activator protein-1, and nuclear factor-κB signaling pathways. In the IVPT, prenylation of the flavanone skeleton significantly promoted skin absorption from 0.01 to 0.22 nmol/mg (sophoraflavanone G vs. eriodictyol). Further methoxylation of a prenylated flavanone (leachianone A) elevated skin absorption to 2.65 nmol/mg. Topical leachianone A reduced the epidermal thickness in IMQ-treated mice by 47%, and inhibited cutaneous scaling and cytokine/chemokine overexpression at comparable levels to a commercial betamethasone product. Thus, prenylation and methoxylation of S. flavescens flavanones may enable the design of novel antipsoriatic agents.

Laparoscopic repair of perineal hernia and unilateral inguinal hernia after rectal cancer surgery: A case report.

INTRODUCTION: Perineal hernia (PH) is a rare complication that can occur after abdominoperineal resection for rectal cancer. Laparoscopic repair of PHs has gained increasing popularity compared to open approaches due to advantages such as superior visualization, decreased invasiveness, and faster recovery. This case report highlights the successful use of laparoscopic tension-free mesh repair for concurrent perineal and inguinal hernias after rectal cancer surgery. CASE DESCRIPTION: A 51-year-old man underwent laparoscopic-assisted abdominoperineal resection for rectal cancer. About 2 months postoperatively, he developed reducible masses in the perineal and left groin regions, associated with urinary symptoms and sensation of prolapse. Physical exam revealed protruding masses that enlarged with Valsalva. Pelvic CT confirmed PH and left inguinal hernia. INTERVENTIONS: Laparoscopic tension-free repair of the PH and inguinal hernia was performed on this patient. The repair was completed by the steps of adhesion separation, mesh placement, and fixation. OUTCOMES: The 98-minute surgery was successful without complications. The patient recovered well, ambulating on postoperative day 2 and getting discharged on day 6. CONCLUSION: This case demonstrates that laparoscopic tension-free repair with mesh is an effective approach for treating PH and concurrent inguinal hernia following rectal cancer surgery, resulting in successful outcomes and low recurrence rates. The laparoscopic technique provides benefits of minimal invasiveness and rapid recovery.

Facile adipocyte uptake and liver/adipose tissue delivery of conjugated linoleic acid-loaded tocol nanocarriers for a synergistic anti-adipogenesis effect.

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.

First-principles study of phase transition in theα-In2Se3/metal heterostructures.

With the discovery of two-dimensional (2D) ferroelectric materials such as CuInP2S6andα-In2Se3, the ferroelectric field effect transistors (Fe-FETs) based on these materials have entered a rapid-development period. The metal/semiconductor contact is an unavoidable topic in the construction of devices. In this paper, heterostructuresα-In2Se3/metals (Pd, Pt, Cu, Ag and Au) are discussed. According to different stacking types, the structures and energy of 160 heterostructures are calculated and compared. Whenα-In2Se3contacts with the Pd, Pt and Cu, theα-In2Se3may transforms intoß-In2Se3. This phenomenon has hardly been mentioned or analyzed in previous reports. Contacting with the Au and Ag, theα-In2Se3maintains the original structure. The internal physical mechanism of phase transition is explained from the binding energy and the charge transfer. The paper provides sufficient theoretical support for research and development of the Fe-FETs based onα-In2Se3.

Neutrophil-targeted combinatorial nanosystems for suppressing bacteremia-associated hyperinflammation and MRSA infection to improve survival rates.

There is currently no specific and effective treatment for bacteremia-mediated sepsis. Hence, this study engineered a combinatorial nanosystem containing neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles to enable the dual mitigation of bacteremia-associated inflammation and methicillin-resistant Staphylococcus aureus (MRSA) infection. The targeted nanoparticles were developed by conjugating anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibody fragment on the nanoparticulate surface. The particle size and zeta potential of the as-prepared nanosystem were about 200 nm and -25 mV, respectively. The antibody-conjugated nanoparticles showed a three-fold increase in neutrophil internalization compared to the unfunctionalized nanoparticles. As a selective phosphodiesterase (PDE) 4 inhibitor, the roflumilast in the nanocarriers largely inhibited cytokine/chemokine release from the activated neutrophils. The fusidic acid-loaded nanocarriers were vital to eliminate biofilm MRSA colony by 3 log units. The nanoparticles drastically decreased the intracellular bacterial count compared to the free antibiotic. The in vivo mouse bioimaging demonstrated prolonged retention of the nanosystem in the circulation with limited organ distribution and liver metabolism. In the mouse bacteremia model, the multifunctional nanosystem produced a 1‒2 log reduction of MRSA burden in peripheral organs and blood. The functionalized nanosystem arrested the cytokine/chemokine overexpression greater than the unfunctionalized nanocarriers and free drugs. The combinatory nanosystem also extended the median survival time from 50 to 103 h. No toxicity from the nanoformulation was found based on histology and serum biochemistry. Furthermore, our data proved that the active neutrophil targeting by the versatile nanosystem efficiently alleviated MRSA infection and organ dysfunction caused by bacteremia. STATEMENT OF SIGNIFICANCE: Bacteremia-mediated sepsis poses a significant challenge in clinical practice, as there is currently no specific and effective treatment available. In our study, we have developed a novel combinatorial nanosystem to address this issue. Our nanosystem consists of neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles, enabling the simultaneous mitigation of bacteremia-associated inflammation and MRSA infection. Our nanosystem demonstrated the decreased neutrophil activation, effective inhibition of cytokine release, elimination of MRSA biofilm colonies, and reduced intracellular bacterial counts. In vivo experiments showed prolonged circulation, limited organ distribution, and increased survival rates in a mouse bacteremia model. Importantly, our nanosystem exhibited no toxicity based on comprehensive assessments.

Skin delivery of synthetic benzoyl pterostilbenes suppresses atopic dermatitis-like inflammation through the inhibition of keratinocyte and macrophage activation.

Atopic dermatitis (AD) is one of the most common skin autoimmune diseases needing continuous anti-inflammatory management. Pterostilbene is reported to exhibit anti-inflammatory activity with higher bioavailability and stability than its parent compound, resveratrol. In this study, a series of synthetic pterostilbene analogs were designed by the hybridization of pterostilbene with chalcones or benzoyl chloride. Seventeen analogs derived from pterostilbene were synthesized with differences in the positions of hydroxyl, methoxyl, or fluoro moieties. These compounds were screened by the inhibitory effect on the overexpressed Th2-associated cytokines/chemokines in the activated human keratinocytes (HaCaT). The anti-IL-5 and anti-CCL5 activity of these compounds led to the identification of three effective compounds: 3a ((E)- 4-(3,5-dimethoxystyryl)phenyl benzoate), 3d ((E)- 4-(3,5-dimethoxystyryl)phenyl 2-methoxybenzoate), and 3g ((E)- 4-(3,5-dimethoxystyryl)phenyl 2-fluorobenzoate). These benzoyl pterostilbenes also significantly decreased Th1/Th17-associated proinflammatory mediators in the activated macrophages (differentiated THP-1). The result showed that the conditioned medium of benzoyl pterostilbene-treated macrophages reduced the phosphorylated STAT3 in the keratinocytes, indicating the blockade of crosstalk between resident and immune cells. Compounds 3d and 3g generally showed greater skin absorption than 3a. The flux of 3g across barrier-defective skins mimicking the AD skin was 3-fold higher than that of across intact skin. The dinitrochlorobenzene (DNCB)-induced AD mouse model manifested that topical delivery with 3g improved the pathological signs through inhibiting cytokines/chemokines (IL-5, TNF-α, CCL17, and CCL22) and macrophage recruitment. The epidermal thickness was reduced from 76 to 55 µm after topical 3g delivery. The therapeutic activity of 3g was comparable to that of tacrolimus (TAC) used as a positive control. The benzoyl pterostilbenes attenuated the inflammation via the MAPK and c-Jun signaling. Furthermore, this study provided experimental evidence of benzoyl pterostilbene analogs for therapeutic potential on AD.

[Craving in Substance Addiction: A Concept Analysis].

Craving in the context of substance addiction is considered an important predictor of substance addictive disorders and relapse risk. Behavior therapy, mindfulness, and exercise may be employed clinically to alleviate cravings. However, many scholars have offered various interpretations of craving in substance addiction. Despite these definitions sharing some overlapping elements, a consensus has yet to be reached. Although many studies have presented the effects of and interventions for craving to alleviate substance addiction, this issue has rarely been explored in the clinical nursing context, resulting in a lack of understanding of the concept of craving in substance addiction among nursing professionals. Therefore, based on the conceptual analysis approach proposed by Walker and Avant (2019), a conceptual analysis of craving in substance addiction was conducted in this study by interpreting and defining the characteristics, pre-factors, consequences, and effects of craving in substance addiction using examples of typical, borderline, related, and contrary cases. The findings are intended to help nurses gain a more comprehensive understanding of craving in substance addiction and become more familiar with cases requiring clinical care.

Association between metal exposure from e-cigarette components and toxicity endpoints: A literature review.

Electronic cigarette is often promoted and perceived as an 'healthy' alternative compared to conventional cigarettes. However, growing body of evidence indicate the possible adverse health effect associated with e-cigarette. Here we reviewed the literature with a focus on metal exposure in relation to e-cigarette use and related toxicity endpoints. Twenty-nine studies were identified for full text screening after applying the screening criteria of which 5 in vitro studies and 11 epidemiological studies were included for data extraction. Cr, Cu, Ni, Sn are the most found metal in all studies. In vitro, metal from e-cigarette (liquid or aerosols) induced cytotoxicity, oxidative stress, genotoxicity and pro-inflammatory responses. It was observed that the presence of nicotine can influence metal-induced in vitro toxicity. Based on epidemiological studies, the metal burden in e-cigarette users showed to be elevated in different populations (including e.g. NHANES). However, most often such studies were limited by the missing user characteristics, and information of other potential sources of metal exposure. In general, metals from e-cigarette use can be associated with toxicity endpoints but to uncover the metal related hazard of e-cigarette in users, more detailed data on metals in vapors and e-liquids; user habits and user demographics are needed.

Topically applied pH-responsive nanogels for alkyl radical-based therapy against psoriasiform hyperplasia.

Phototherapy 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.

Proteinase K/Retinoic Acid-Loaded Cationic Liposomes as Multifunctional Anti-Acne Therapy to Disorganize Biofilm and Regulate Keratinocyte Proliferation.

Background: Simultaneous anti-Cutibacterium acnes and anti-inflammatory actions are highly beneficial in treating acne vulgaris. In this study, we present novel anti-acne nanovesicles based on liposomes loaded with proteinase K (PK), retinoic acid (RA), and soyaethyl morpholinium ethosulfate (SME) to achieve an effective and safe treatment. Materials and Methods: This study examined in vitro planktonic and biofilm C. acnes elimination, as well as the keratinocyte proliferation suppression by liposomes. The multifunctional liposomes for treating C. acnes in mice were also evaluated. Results: We acquired multifunctional liposomes with a size of 71 nm and zeta potential of 31 mV. The antimicrobial activity of SME was enhanced after liposomal encapsulation according to the reduction of minimum bactericidal concentration (MBC) by 6-fold. The multifunctional liposomes exhibited a synergistically inhibitory effect on biofilm C. acnes colonization compared with the liposomes containing PK or those containing SME individually. The adhesive bacterial colony in the microplate was lessened by 62% after multifunctional liposome intervention. All liposomal formulations tested here demonstrated no cytotoxicity against the normal keratinocytes but inhibited C. acnes-stimulated cell hyperproliferation. The in vitro scratch assay indicated that the liposomal RA-but not free RA-restrained keratinocyte migration. The animal study showed that free RA combined with SME and multifunctional nanovesicles had a similar effect on diminishing C. acnes colonies in the skin. On the other hand, liposomes exhibited superior performance in recovering the impaired skin barrier function than the free control. We also found that RA-loaded nanovesicles had greater skin tolerability than free RA. Conclusion: The cationic liposomes containing dual PK and RA represented a potential treatment to arrest bacterial infection and associated inflammation in acne.

Dynamic Resource Allocation for Network Slicing with Multi-Tenants in 5G Two-Tier Networks.

Virtualization is a core 5G network technology which helps telecom companies significantly reduce capital expenditure and operating expenses by deploying multiple services on the same hardware infrastructure. However, providing QoS-guaranteed services for multi-tenants poses a significant challenge due to multi-tenant service diversity. Network slicing has been proposed as a means of addressing this problem by isolating computing and communication resources for the different tenants of different services. However, optimizing the allocation of the network and computation resources across multiple network slices is a critical but extremely difficult problem. Accordingly, this study proposes two heuristic algorithms, namely Minimum Cost Resource Allocation (MCRA) and Fast Latency Decrease Resource Allocation (FLDRA), to perform dynamic path routing and resource allocation for multi-tenant network slices in a two-tier architecture. The simulation results show that both algorithms significantly outperform the Upper-tier First with Latency-bounded Overprovisioning Prevention (UFLOP) algorithm proposed in previous work. Furthermore, the MCRA algorithm achieves a higher resource utilization than the FLDRA algorithm.

Correction: Fang et al. In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity. Nutrients 2019, 11, 530.

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OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS: The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.