pH- and Matrix Metalloproteinase-Responsive Multifunctional Bilayer Microneedles Platform for Treatment of Tinea Pedis.

Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans. They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by T. mentagrophytes. Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.

Genomic epidemiology of hypervirulent carbapenem-resistant Klebsiella pneumoniae at Jinshan local hospital, Shanghai, during 2014-2018.

BACKGROUND: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) triggered a significant public health challenge. This study explored the prevalence trends and key genetic characteristics of Hv-CRKP in one Shanghai suburbs hospital during 2014-2018. METHODS: During five years, Hv-CRKP strains identified from 2579 CRKP by specific PCR, were subjected to performed short- and long-read sequencing technology; epidemiological characteristics, antimicrobial-resistance genes (ARGs), virulence determinants, detailed plasmid profiles and conjugation efficiency were comprehensively investigated. RESULTS: 155 Hv-CRKP and 31 non-Hv-CRKP strains were sequenced. Hv-CRKP strains exhibited significant resistance to six common antibiotic classes (>92%). ST11 steadily increased and became the most prevalent ST (85.2%), followed by ST15 (8.5%), ST65 (2.6%), ST23 (1.9%), and ST86 (0.6%). ST11-KL64 (65.2%) rapidly increased from 0 in 2014 to 93.9% in 2018. blaKPC-2 was the primary carbapenemase gene (97.4%). Other ARGs switched from aac(3)-IId to aadA2 in aminoglycoside and from sul1 to sul2 in sulfanilamide. The time-dated phylogenetic tree was divided into four independent evolutionary clades. Clade 1 and 3 strains were mostly limited in the ICU, whereas Clade 2 strains were distributed among multiple departments. Compared to ybt14 in ICEKp12 in Clade 1, Clade 3 strains harbored ybt9 in ICEKp3 and blaCTX-M-65. Hv-CRKP infected more wards than non-Hv-CRKP and showed greater transmission capacity. Three plasmids containing crucial carbapenemase genes demonstrated their early transmission across China. CONCLUSION: The Hv-CRKP ST11-KL64 has rapidly replaced ST11-KL47 and emerged as the predominant epidemic subtype in various hospital wards, highlighting the importance of conducting comprehensive early surveillance for Hv-CRKP, especially in respiratory infections.

Combination of intraoperative indocyanine green video-angiography FLOW 800 and computed tomography perfusion to assess the risk of cerebral hyperperfusion syndrome in chronic internal carotid artery occlusion patients after revascularization surgery.

Background and purpose: To study the changes of corticocerebral hemodynamics in surgical area and postoperative hyperperfusion syndrome in patients with chronic internal carotid artery occlusion (CICAO) by intraoperative indocyanine green videoangiography (ICGA)-FLOW 800 and CT perfusion after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery. Methods: From October 2019 to January 2021, 77 patients diagnosed with CICAO underwent direct bypass surgery at Huadong hospital (affiliated with Fudan University) were enrolled. Regions of interest (ROIs) at STA, proximal MCA (PMCA), distal MCA (DMCA), cortical blood capillary (CBC), and cortical vein (CV) were identified after anastomosis by ICGV-FLOW 800 including peak fluorescence intensity (PFI), time to peak (TTP), and area under the time curve (AUC) of fluorescence intensity. All patients underwent perfusion-weighted CT before bypass surgery and those patients with HPS were verified by CTP after bypass. Results: 14 patients with HPS were verified by perfusion-weighted CT after bypass. In HPS group, the AUCTTP of DMCA was significantly larger (T = -3.301, p = 0.004) and TTP of CBC was shorter (T = -2.929, p = 0.005) than patients in non-HPS group. The larger AUCTTP of DMCA (OR = 3.024, 95%CI 1.390-6.578, p = 0.0050) was an independent risk factor by further multivariate logistic regression analysis. Conclusion: The hemodynamic changes of cortical vessels during STA-MCA bypass surgery could be recorded accurately by ICGV-FLOW 800. Furthermore, the increased AUCTTP of DMCA and shorter TTP of CBC may be potential risk factors of HPS.

Public perceived risks and benefits of carbon capture, utilization, and storage (CCUS): Scale development and validation.

As a critical technology to mitigate climate change, the large-scale implementation of carbon capture, utilization, and storage (CCUS) depends on both technological advancement and public acceptance, which is significantly influenced by the perceived risks and benefits. Existing studies, however, have yet to reach a consensus regarding the measurement of CCUS in these two aspects. To fill this gap, this paper develops and validates new scales based on four studies. Specifically, Study 1 generates the initial item pool based on a literature review and semi-structured interviews, and then invites experts to examine the content validity of these items; Study 2 identifies the dimensions and assesses the reliability and validity of the measures through an exploratory and confirmatory factor analysis; Study 3 conducts a one-way ANOVA to test known-group validity; and Study 4 employed structural equation modeling to evaluate the nomological validity. The results demonstrate the internal consistency, reliability, and construct validity of the new scales developed to measure CCUS. This study provides a valuable tool for investigating public perceptions of CCUS and can help policymakers develop future publicity strategies.

Identification of fibroblast-related genes based on single-cell and machine learning to predict the prognosis and endocrine metabolism of pancreatic cancer.

Background: Single-cell sequencing technology has become an indispensable tool in tumor mechanism and heterogeneity studies. Pancreatic adenocarcinoma (PAAD) lacks early specific symptoms, and comprehensive bioinformatics analysis for PAAD contributes to the developmental mechanisms. Methods: We performed dimensionality reduction analysis on the single-cell sequencing data GSE165399 of PAAD to obtain the specific cell clusters. We then obtained cell cluster-associated gene modules by weighted co-expression network analysis and identified tumorigenesis-associated cell clusters and gene modules in PAAD by trajectory analysis. Tumor-associated genes of PAAD were intersected with cell cluster marker genes and within the signature module to obtain genes associated with PAAD occurrence to construct a prognostic risk assessment tool by the COX model. The performance of the model was assessed by the Kaplan-Meier (K-M) curve and the receiver operating characteristic (ROC) curve. The score of endocrine pathways was assessed by ssGSEA analysis. Results: The PAAD single-cell dataset GSE165399 was filtered and downscaled, and finally, 17 cell subgroups were filtered and 17 cell clusters were labeled. WGCNA analysis revealed that the brown module was most associated with tumorigenesis. Among them, the brown module was significantly associated with C11 and C14 cell clusters. C11 and C14 cell clusters belonged to fibroblast and circulating fetal cells, respectively, and trajectory analysis showed low heterogeneity for fibroblast and extremely high heterogeneity for circulating fetal cells. Next, through differential analysis, we found that genes within the C11 cluster were highly associated with tumorigenesis. Finally, we constructed the RiskScore system, and K-M curves and ROC curves revealed that RiskScore possessed objective clinical prognostic potential and demonstrated consistent robustness in multiple datasets. The low-risk group presented a higher endocrine metabolism and lower immune infiltrate state. Conclusion: We identified prognostic models consisting of APOL1, BHLHE40, CLMP, GNG12, LOX, LY6E, MYL12B, RND3, SOX4, and RiskScore showed promising clinical value. RiskScore possibly carries a credible clinical prognostic potential for PAAD.

Unveiling the efficient state of Pd catalyst for robust electrocatalytic hydrodechlorination.

The application of electrochemical hydrodechlorination has been impeded due to the low utilization and activity of Pd catalyst. Herein, a series of Pd catalysts were prepared via the controllable evolution of Zn state during the pyrolysis of ZIF-8 nanosheet. Various forms of Pd with different chemical surroundings were generated upon the combined use of galvanic displacement and ion exchange process. Electrocatalytic hydrodechlorination of 4-chlorophenol was performed and the electrocatalytic hydrodechlorination efficiency of Pd/CN reaches 100% within 3 h at extra low Pd concentration. The coexistence of zero-valent Pd (Pd0) and nitrogen coordinated Pd (Pd-N) was verified by XAFS which provide multiple active sites for focusing on adsorbing H* and cracking C-Cl respectively. The synergetic effect between different chemical state of Pd for efficient hydrodechlorination of chloroaromatics and scheme for dexterous preparation of Pd based electrocatalyst are proposed and discussed.

A cell transmembrane peptide chimeric M(27-39)-HTPP targeted therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, with a growing incidence and death rate worldwide. The aims and challenges of treating HCC include targeting the tumor, entering the tumor tissue, inhibiting the spread and growth of tumor cells. M27-39 is a small peptide isolated from the antimicrobial peptide Musca domestica cecropin (MDC), whereas HTPP is a liver-targeting, cell-penetrating peptide obtained from the circumsporozoite protein (CSP) of Plasmodium parasites. In this study, M27-39 was modified by HTPP to form M(27-39)-HTPP, which targeted tumor penetration to treat HCC. Here, we revealed that M(27-39)-HTPP had a good ability to target and penetrate the tumor, effectively limit the proliferation, migration, and invasion, and induce the apoptosis in HCC. Notably, M(27-39)-HTPP demonstrated good biosecurity when administered at therapeutic doses. Accordingly, M(27-39)-HTPP could be used as a new, safe, and efficient therapeutic peptide for HCC.

A novel antimicrobial peptide M1-8 targets the lysosomal pathway to inhibit autolysosome formation and promote apoptosis in liver cancer cells.

Lysosomes, a central regulator of autophagy, play a critical role in tumour growth. Lysosomal protease cathepsin D can initiate apoptosis when released from lysosomes into the cytosol. In this study, we observed that Musca domestica cecropin (Mdc) 1-8 (M1-8), a small anti-tumour peptide derived from Mdc, inhibits hepatoma cell growth by blocking autophagy-lysosome fusion. This effect is likely achieved by targeting lysosomes to activate lysosomal protease D. Additionally, we examined whether lysosomal content and cathepsin D release were involved in M1-8-induced apoptosis. After exposure to M1-8, human hepatoma HepG2 cells rapidly co-localized with lysosomes, disrupted lysosomal integrity, caused leakage of lysosomal protease cathepsin D, caspase activation and mitochondrial membrane potential changes; and promoted cell apoptosis. Interestingly, in M1-8-treated HepG2 cells, autophagic protein content increased and the lysosome-autophagosome fusion was inhibited, suggesting that M1-8 can cause apoptosis through autophagy and lysosomes. This result indicates that a small accumulation of autophagy and autolysosome inhibition in cells can cause cell death. Taken together, these data suggest a novel insight into the regulatory mechanisms of M1-8 in autophagy and lysosomes, which may facilitate the development of M1-8 as a potential cancer therapeutic agent.

Influence of continuous positive airway pressure on lipid profiles of obstructive sleep apnea: A systematic review and meta-analysis.

BACKGROUND: To investigate the influence of continuous positive airway pressure (CPAP) on lipid profiles of the patients with obstructive sleep apnea (OSA) in this meta-analysis. METHODS: Relevant studies reporting the correlation between CPAP and lipid profiles of OSA patients were searched in Pubmed, Cochrane Library and Embase before January 1, 2021. Data of eligible studies were extracted and analyzed using the fixed-effect or random-effect model. Standard mean difference (SMD) and 95% confidence interval (95% CI) were calculated to assess such influence. Subgroup analysis based on CPAP duration was further performed. STATA 12.0 was used in this meta-analysis. RESULTS: A total of 12 independent randomized controlled studies involved 1129 OSA patients were recruited in this meta-analysis. The analyzed lipid profiles included total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL). CPAP was not correlated to TC (SMD = -0.07, 95% CI = -0.33 to 0.19), TG (SMD = -0.01, 95% CI = -0.19 to 0.17), LDL (SMD = -0.01, 95% CI = -0.23 to 0.21) and HDL (SMD = 0.10, 95% CI = -0.03 to 0.22) in OSA patients. Moreover, CPAP duration (=12 weeks; >12 weeks; <12 weeks) also did not influence lipid profiles of OSA patients as well. CONCLUSIONS: Regardless of the treatment in CPAP duration, it doses does not influence lipid profiles of OSA patients, including TC, TG, LDL and HDL. The results are inconsistent with previous findings, which should be further validated in the multi-center, long-term randomized controlled trials.

Mitochondria-targeting folic acid-modified nanoplatform based on mesoporous carbon and a bioactive peptide for improved colorectal cancer treatment.

Oral colon-targeted drug delivery systems (OCDDs) are designed to deliver the therapeutic agents to colonic disease sites to improve the effectiveness of drug treatment, increase bioavailability, and reduce systemic side effects and are beneficial for the treatment of colorectal cancer (CRC) and inflammatory bowel disease (IBD). However, concerns about the biosafety of OCDDs are increasing, and changes in the physiological environment of the gastrointestinal tract can affect the therapeutic efficacy of the drug. Herein, we report about an orally administered colon-accumulating mitochondria-targeted drug delivery nanoplatform (M27-39@FA-MCNs), which was synthesized using the small peptide, M27-39, and folic acid (FA)-modified mesoporous carbon nanoparticles (FA-MCNs). The phenolic resin polymerized with phloroglucinol and formaldehyde (PF) was used for fabricating MCNs using a one-step soft-template method. Folic acid (FA) can be covalently combined with chitosan-modified MCNs to obtain FA-MCNs. The M27-39@FA-MCNs were stable with a spherical morphology and an average diameter of 129 nm. The cumulative release rate of M27-39@FA-MCNs in the artificial gastric fluid (pH = 1.2) and intestinal fluid (pH = 6.8) for 6 h was 87.77%. This nanoplatform maintains the advantages of both FA and MCNs to improve the bioactivity of M27-39 with high drug accumulation in colorectal tumor tissues and the ease of excretion, thus ameliorating its biosafety and targetability. Furthermore, M27-39@FA-MCNs induced tumor-cell apoptosis and inhibited tumor growth by disrupting mitochondrial energy metabolism and regulating the mitochondrial apoptosis signaling pathway and immune inflammatory response. Thus, such a mitochondria-targeting FA-modified nanoplatform based on mesoporous carbon and a bioactive peptide may provide a precise strategy for CRC treatment. STATEMENT OF SIGNIFICANCE: In this study, we constructed an orally administered colon-accumulating mitochondria-targeted drug delivery nanoplatform (M27-39@FA-MCNs), which was synthesized using the small peptide (M27-39) and folic acid-modified mesoporous carbon nanoparticles (FA-MCNs). M27-39@FA-MCNs increased the targeting ability of M27-39 toward mitochondria and colon based on the properties of FA-MCNs; they also increased M27-39 accumulation and residence time in colon tumors. Oral administration of M27-39@FA-MCNs remarkably alleviated colorectal cancer (CRC) by targeting tumor cell mitochondria and interfering with the mitochondrial energy metabolism process, and inducing apoptosis related P53/Caspase-3 mitochondrial pathway activation. Therefore, M27-39@FA-MCNs may provide a safe and precise therapeutic strategy for CRC.

Dissemination of Multiple Drug-Resistant Shigella flexneri 2a Isolates Among Pediatric Outpatients in Urumqi, China.

Multiple drug-resistant (MDR) Shigella isolates have been reported worldwide. Between May 2017 and September 2018, 55 Shigella flexneri 2a isolates were collected from 3322 stool samples of 0-10-year-old outpatients with diarrhea at the Children's Hospital of Urumqi, China. All isolates were characterized using serotyping, antimicrobial susceptibility testing, and whole-genome sequencing. A total of 54 of 55 (98.2%) isolates exhibited MDR phenotypes and had accumulated multiple resistance determinants, particularly of fluoroquinolones and cephalosporins preferred for shigellosis treatment: point mutations in quinolone resistance-determining regions (QRDRs) of topoisomerases (GyrA (S83L, D87N) and ParC (S80I) [n = 9]; GyrA (S83L) and ParC (S80I) [n = 45]) and acquisition of qnrS1 (n = 3) and blaCTX-M (n = 8). Over 70% of isolates acquired two point mutations of GyrA (S83L) and ParC (S80I) in QRDRs and 11 highly resistant isolates accumulated three point mutations in QRDRs or acquired qnrS1. Four S. flexneri 2a isolates from three single-nucleotide polymorphism clusters exhibited coresistance to ciprofloxacin, cefotaxime, or azithromycin (AZM), which are used as first- and second-line shigellosis treatment antimicrobials in clinics. Our data indicated that fluoroquinolones should be terminated in shigellosis treatment for outpatients in Urumqi. The transferable antimicrobial resistance determinants have been identified for third-generation cephalosporins and AZM. Novel strategies are urgently required for developing empirical medication to reduce the antimicrobial selective pressure and prevent dissemination of MDR S. flexneri 2a isolates.

Comparative proteomic analysis of Leptospira interrogans serogroup Icterohaemorrhagiae human vaccine strain and epidemic isolate from China.

Leptospira interrogans serogroup Icterohaemorrhagiae is the predominant pathogen causing leptospirosis in China and is still used as the vaccine strain for the current human inactivated vaccine. Unlike the clade ST17, which is distributed worldwide, ST1 is the most prevalent in serogroup Icterohaemorrhagiae in China. To further characterize leptospiral pathogens, isobaric tags for relative and absolute quantitation and parallel reaction monitoring were used to analyze differences at the proteomic level between serogroup Icterohaemorrhagiae vaccine strain 56001 (ST1) and circulating isolate 200502 (ST17) from different periods. Two hundred and eighty-one proteins were differentially expressed between the circulating isolate and vaccine strain, of which 166 were upregulated (> 1.2-fold change, P < 0.05) and 115 (< 0.8-fold change, P < 0.05) were downregulated. Function prediction revealed that nine upregulated proteins were outer membrane proteins, including several known immunogenic and/or virulence-related proteins, such as ompL1, LipL71, and LipL41. Furthermore, important expression differences in carbohydrate, amino acid, and energy metabolism and transport proteins were identified between both strains from different clusters, suggesting that these differences may reflect metabolic diversity and the potential of the pathogens to adapt to different environments. In summary, our findings provide insights into a better understanding of the component strains of the Chinese human leptospirosis vaccine at the proteomic level. Additionally, these data facilitate evaluating the mechanisms by which pathogenic Leptospira species adapt to the host environment.

Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-||(4,5-dimethylthiazol-2-yl)-2,|5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.

Characteristics of childhood-onset systemic lupus erythematosus in pregnancy and its association with pregnancy outcomes: a retrospective comparative cohort study.

BACKGROUND: Disease situations are more aggressive in patients with childhood-onset systemic lupus erythematosus (cSLE) than in those with adult-onset SLE (aSLE). However, information on pregnant women with cSLE and its association with pregnancy outcomes is limited. This study aimed to compare pregnancies in patients with cSLE vs. aSLE, and further analyse the characteristics of cSLE in pregnant women and explore its association with adverse pregnancy outcomes. METHODS: Altogether, data of 167 pregnancies from 150 women, including 22 pregnancies with cSLE and 145 pregnancies with aSLE, were retrospectively analysed. Characteristics and disease activity were compared between the cSLE and aSLE groups during pregnancy. Associations between cSLE and the risk of active SLE (SLEPDAI > 4), active lupus nephritis (LN), and adverse pregnancy outcomes were analysed using logistic regression. RESULTS: The cSLE group had a higher incidence of active SLE (12/22 vs. 30/145, P = 0.001) and active LN (11/22 vs. 26/145, P = 0.001) than the aSLE group. In the multivariable analysis, cSLE was a risk factor for active SLE and active LN during pregnancy, with ORs of 4.742 (95%CI 1.678-13.405, P = 0.003) and 4.652 (95%CI 1.630-13.279, P = 0.004), respectively. No significant association between cSLE and the risk of composite adverse gestational outcomes was identified after sequentially adjusting pre-pregnancy characteristics and pregnancy factors (P > 0.05). CONCLUSION: Disease activity of women with cSLE in pregnancy was more aggressive than that of women with aSLE, which was similar to the characteristics of non-pregnant women with SLE. cSLE might have indirect effects on the risk of adverse pregnancy outcomes through LN and active disease. Therefore, closely monitoring patients with cSLE during pregnancy is crucial.

Impact of an acute geriatric outreach service to residential aged care facilities on hospital admissions.

INTRODUCTION: Residential aged care facility (RACF) residents frequently present to the emergency department (ED) and are often admitted to hospital. Some presentations and admissions may be avoidable. In 2013, Bankstown-Lidcombe Hospital introduced a subacute geriatric outreach service (SGOS), which had little impact on reducing ED presentations. In 2015, Bankstown-Lidcombe Hospital introduced an acute geriatric outreach service (AGOS), a geriatrician-led team that assesses and treats acutely unwell patients in RACFs. We aim to determine whether the AGOS reduces the risk of hospital admission for RACF residents. METHODS: Hospital admissions data from 2010 to 2019 were used to conduct an interrupted time series (ITS) analysis. AGOS activity data were also summarized. RESULTS: The average number of admissions from RACF per month declined from 42.8 during the SGOS period to 27.1 during the AGOS period. The difference of 15.7 admissions from RACF per month was statistically significant (95% CI 12.1-19.2; P < .001). After the introduction of the AGOS, the risk of admission to our geriatric department from RACFs was reduced by 36.1% (incidence rate ratio =0.64; 95% CI: 0.58-0.71; P < .001) compared to the SGOS period, adjusting for seasonality. DISCUSSION: The AGOS probably reduced the risk of hospital admission for RACF residents.

Development of an Aerobic Glycolysis Index for Predicting the Sorafenib Sensitivity and Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.

Colon tissue-accumulating mesoporous carbon nanoparticles loaded with Musca domestica cecropin for ulcerative colitis therapy.

Ulcerative colitis (UC) is a modern refractory disease with steadily increasing incidence worldwide that urgently requires effective and safe therapies. Therapeutic peptides delivered using nanocarriers have shown promising developments for the treatment of UC. We developed a novel colon-accumulating oral drug delivery nanoplatform consisting of Musca domestica cecropin (MDC) and mesoporous carbon nanoparticles (MCNs) and investigated its effects and mechanism of action for the treatment of UC. Methods: An optimized one-step soft templating method was developed to synthesize MCNs, into which MDC was loaded to fabricate MDC@MCNs. MCNs and MDC@MCNs were characterized by BET, XRD, and TEM. MDC and MDC@MCNs resistance to trypsin degradation was measured through Oxford cup antibacterial experiments using Salmonella typhimurium as the indicator. Uptake of MDC and MDC@MCNs by NCM460 cells was observed by fluorescence microscopy. The biocompatibility of MDC, MCNs, and MDC@MCNs was evaluated in three cell lines (NCM460, L02, and NIH3T3) and C57BL/6 mice. Dextran sulphate sodium was used to establish models of NCM460 cell injury and UC in mice. MTT assay, flow cytometry, and mitochondrial membrane potential assay were applied to determine the effects of MDC@MCNs on NCM460 cells injury. Additionally, a variety of biological methods such as H&E staining, TEM, ELISA, qPCR, Western blotting, and 16s rDNA sequencing were performed to explore the effects and underlying mechanism of MDC@MCN on UC in vivo. Colonic adhesion of MCNs was compared in normal and UC mice. The oral biodistributions of MDC and MDC@MCNs in the gastrointestinal tract of mice were also determined. Results: MDC@MCNs were successfully developed and exhibited excellent ability to resist destruction by trypsin and were taken up by NCM460 cells more readily than MDC. In vitro studies showed that MDC@MCNs better inhibited DSS-induced NCM460 cells damage with lower toxicity to L02 and NIH3T3 cells compared with MDC. In vivo results indicated that MDC@MCNs have good biocompatibility and significantly improved colonic injury in UC mice by effectively inhibiting inflammation and oxidative stress, maintaining colonic tight junctions, and regulating intestinal flora. Moreover, MDC@MCNs were strongly retained in the intestines, which was attributed to intestinal adhesion and aggregation of MCNs, serving as one of the important reasons for its enhanced efficacy after oral administration compared with MDC. Conclusion: MDC@MCNs alleviated DSS-induced UC by ameliorating colonic epithelial cells damage, inhibiting inflammation and oxidative stress, enhancing colonic tight junctions, and regulating intestinal flora. This colon-accumulating oral drug delivery nanoplatform may provide a novel and precise therapeutic strategy for UC.