A novel α,ß-unsaturated ketone inhibits leukemia cell growth as PARP1 inhibitor.

Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.

A Novel Quinazoline Derivative Prevents and Treats Arsenic-Induced Liver Injury by Regulating the Expression of RecQ Family Helicase.

Arsenic is a carcinogenic metalloid toxicant widely found in the natural environment. Acute or prolonged exposure to arsenic causes a series of damages to the organs, mainly the liver, such as hepatomegaly, liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Therefore, it is imperative to seek drugs to prevent arsenic-induced liver injury. Quinazolines are a class of nitrogen heterocyclic compounds with biological and pharmacological effects in vivo and in vitro. This study was designed to investigate the ameliorating effects of quinazoline derivatives on arsenic-induced liver injury and its molecular mechanism. We investigated the mechanism of the quinazoline derivative KZL-047 in preventing and ameliorating arsenic-induced liver injury in vitro by cell cycle and apoptosis. We performed real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blotting combined with molecular docking. In vivo, the experiments were performed to investigate the mechanism of KZL-047 in preventing and ameliorating arsenic-induced liver injury using arsenic-infected mice. Physiological and biochemical indices of liver function in mouse serum were measured, histopathological changes in liver tissue were observed, and immunohistochemical staining was used to detect changes in the expression of RecQ-family helicases in mouse liver tissue. The results of in vitro experiments showed that sodium arsenite (SA) inhibited the proliferation of L-02 cells, induced apoptosis, blocked the cell cycle at the G1 phase, and decreased the expression of RecQ family helicase; after KZL-047 treatment in arsenic-induced L-02 cells, the expression of RecQ family helicase was upregulated, and the apoptosis rate was slowed, leading to the restoration of the cell viability level. KZL-047 inhibited arsenic-induced oxidative stress, alleviated oxidative damage and lipid peroxidation in vivo, and ameliorated arsenic toxicity-induced liver injury. KZL-047 restored the expression of RecQ family helicase proteins, which is consistent with the results of in vitro studies. In summary, KZL-047 can be considered a potential candidate for the treatment of arsenic-induced liver injury.

Design, synthesis and bioevaluation of novel trifluoromethylquinoline derivatives as tubulin polymerization inhibitors.

Aim: A series of novel trifluoromethylquinoline derivatives were designed, synthesized and evaluated for antitumor activities. Methodology: All compounds were evaluated for antiproliferative activity against four human cancer cell lines. Results: Among them, 5a, 5m, 5o and 6b exhibited remarkable antiproliferative activities against all the tested cell lines at nanomolar concentrations. Mechanism of action studies demonstrated that 6b targeted the colchicine binding site, potentially inhibiting tubulin polymerization, and further studies indicated that 6b could arrest LNCaP cells in the G2/M phase and induce cell apoptosis. Molecular docking confirmed that 6b could bind to the colchicine binding site. Conclusion: Results suggested that 6b could serve as a promising lead compound for the development of novel tubulin polymerization inhibitors and cancer therapy.

Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity.

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC50) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents.

N-methylpiperazine-diepoxyovatodiolide ameliorates peritoneal fibrosis via suppressing TGF-ß/Smad and JAK/STAT signaling pathway.

Peritoneal fibrosis (PF) is the main cause of peritoneal ultrafiltration failure in patients undergoing long-term peritoneal dialysis (PD). Epithelial-mesenchymal transition (EMT) is the key pathogenesis of PF. However, currently, no specific treatments are available to suppress PF. N-methylpiperazine-diepoxyovatodiolide (NMPDOva) is a newly synthesized compound that involves a chemical modification of ovatodiolide. In this study, we aimed to explore the antifibrotic effects of NMPDOva in PD-related PF and underlying mechanisms. A mouse model of PD-related PF was established via daily intraperitoneal injection of 4.25% glucose PD fluid. In vitro studies were performed using the transforming growth factor-beta1 (TGF-ß1)-stimulated HMrSV5 cell line. Pathological changes were observed, and fibrotic markers were significantly elevated in the peritoneal membrane in mice model of PD-related PF. However, NMPDOva treatment significantly alleviated PD-related PF by decreasing the extracellular matrix accumulation. NMPDOva treatment decreased the expression of fibronectin, collagen Ⅰ, and alpha-smooth muscle actin (α-SMA) in mice with PD-related PF. Moreover, NMPDOva could alleviate TGF-ß1-induced EMT in HMrSV5 cells, inhibited phosphorylation and nuclear translocation of Smad2/3, and increased the expression of Smad7. Meanwhile, NMPDOva inhibited phosphorylation of JAK2 and STAT3. Collectively, these results indicated that NMPDOva prevents PD-related PF by inhibiting the TGF-ß1/Smad and JAK/STAT signaling pathway. Therefore, because of these antifibrotic effects, NMPDOva may be a promising therapeutic agent for PD-related PF.

A comparative study of tea polyphenols and its palmitic acid-modified derivatives: their effects on the microbial ecosystem and biogenic amines in Chinese sausage.

Control of biogenic amines (BAs) is important to guarantee the safety of sausage-like fermented meat products. This study investigated the influences of tea polyphenols (TP) and its lipophilic palmitic acid-modified derivatives, palmitoyl-TP (pTP) and palmitoyl-epigallocatechin gallate (pEGCG), on BAs and microbial ecosystem in Chinese sausages. TP, epigallocatechin gallate (EGCG), pTP, and pEGCG all reduced the formation of BAs and N-nitrosodimethylamine at 0.05% (g/g); yet, compared with TP and EGCG, the modified derivatives exhibited stronger action on BAs decreasing (P < 0.05), and pEGCG showed the highest effect (a reduction of total BAs from 376.22 to 168.98 mg/kg compared to control). The improved inhibitory effect of pTP and pEGCG should be attributed to their stronger dual-directional regulation of the bacterial and fungal communities during the natural fermentation of sausage. The modified pTP and pEGCG highly suppressed the growth of Staphylococcus, Candida, and Kurtzmaniella, all of which were positively correlated with BAs formation (all P < 0.05). However, pTP and pEGCG worked more effectively than the unmodified ones to promote Lactobacillus, Lactococcus, and Debaryomyces (all P < 0.05). The results above are significant for the application of palmitoyl-TP and similar TP derivatives in meat products in consideration of food safety. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05717-z.

Metabolic reprogramming of renal epithelial cells contributes to lithium-induced nephrogenic diabetes insipidus.

Lithium, mainstay treatment for bipolar disorder, frequently causes nephrogenic diabetes insipidus (NDI) and renal injury. However, the detailed mechanism remains unclear. Here we used the analysis of metabolomics and transcriptomics and metabolic intervention in a lithium-induced NDI model. Mice were treated with lithium chloride (40 mmol/kg chow) and rotenone (ROT, 100 ppm) in diet for 28 days. Transmission electron microscopy showed extensive mitochondrial structural abnormalities in whole nephron. ROT treatment markedly ameliorated lithium-induced NDI and mitochondrial structural abnormalities. Moreover, ROT attenuated the decrease of mitochondrial membrane potential in line with the upregulation of mitochondrial genes in kidney. Metabolomics and transcriptomics data demonstrated that lithium activated galactose metabolism, glycolysis, and amino sugar and nucleotide sugar metabolism. All these events were indicative of metabolic reprogramming in kidney cells. Importantly, ROT ameliorated metabolic reprogramming in NDI model. Based on transcriptomics analysis, we also found the activation of MAPK, mTOR and PI3K-Akt signaling pathways and impaired focal adhesion, ECM-receptor interaction and actin cytoskeleton in Li-NDI model were inhibited or attenuated by ROT treatment. Meanwhile, ROT administration inhibited the increase of Reactive Oxygen Species (ROS) in NDI kidneys along with enhanced SOD2 expression. Finally, we observed that ROT partially restored the reduced AQP2 and enhanced urinary sodium excretion along with the blockade of increased PGE2 output. Taken together, the current study demonstrates that mitochondrial abnormalities and metabolic reprogramming play a key role in lithium-induced NDI, as well as the dysregulated signaling pathways, thereby serving as a novel therapeutic target.

Development and validation of a clinical score combining the sequential organ failure assessment score with inflammation-based markers to predict outcome of patients with sepsis.

BACKGROUND: Whether combining the Sequential Organ Failure Assessment (SOFA) score at admission with inflammation-based markers can improve performance of prediction and risk stratification of patients with sepsis, compared to use of the SOFA score alone, remains unknown. METHODS: Data from septic patients included in the Medical Information Mart for Intensive Care database (MIMIC-IV) database were used for model development and internal validation. We developed a predictive nomogram model that included SOFA score, Charlson Comorbidity Index (CCI), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and mean corpuscular volume (MCV) values. The primary outcome was the performance of the risk score. RESULTS: Data from 4704 septic patients included in the database were used for the primary cohort and to build the model. The multivariate analyses included SOFA score, CCI, RDW, NLR, LMR, and MCV values. These values were used for nomogram model construction. The nomogram model showed good calibration, and had better discrimination in terms of area under the receiver operating characteristic (AUROC) curve results than use of the SOFA score alone (0.724 (95% CI: 0.705-0.743) vs. 0.585 (95% CI: 0.562-0.609), respectively; P<0.001). It also had better classification in terms of net reclassification improvement (20.5% (95% CI: 16.2%-24.7%; P<0.001)) and integrated discrimination improvement (6.0% (95% CI: 5.1%-6.8%; P<0.001)). The validation cohort results supported these findings. CONCLUSION: The results suggested that this simple-to-use nomogram model provided a relatively accurate risk of death prediction in patients with sepsis.

Targeting inhibition of prognosis-related lipid metabolism genes including CYP19A1 enhances immunotherapeutic response in colon cancer.

BACKGROUND: Lipid metabolic reprogramming in colon cancer shows a potential impact on tumor immune microenvironment and is associated with response to immunotherapy. Therefore, this study aimed to develop a lipid metabolism-related prognostic risk score (LMrisk) to provide new biomarkers and combination therapy strategies for colon cancer immunotherapy. METHODS: Differentially expressed lipid metabolism-related genes (LMGs) including cytochrome P450 (CYP) 19A1 were screened to construct LMrisk in TCGA colon cancer cohort. The LMrisk was then validated in three GEO datasets. The differences of immune cell infiltration and immunotherapy response between LMrisk subgroups were investigated via bioinformatic analysis. These results were comfirmed by in vitro coculture of colon cancer cells with peripheral blood mononuclear cells, human colon cancer tissue microarray analysis, multiplex immunofluorescence staining and mouse xenograft models of colon cancer. RESULTS: Six LMGs including CYP19A1, ALOXE3, FABP4, LRP2, SLCO1A2 and PPARGC1A were selected to establish the LMrisk. The LMrisk was positively correlated with the abundance of macrophages, carcinoma-associated fibroblasts (CAFs), endothelial cells and the levels of biomarkers for immunotherapeutic response including programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden and microsatellite instability, but negatively correlated with CD8+ T cell infiltration levels. CYP19A1 protein expression was an independent prognostic factor, and positively correlated with PD-L1 expression in human colon cancer tissues. Multiplex immunofluorescence analyses revealed that CYP19A1 protein expression was negatively correlated with CD8+ T cell infiltration, but positively correlated with the levels of tumor-associated macrophages, CAFs and endothelial cells. Importantly, CYP19A1 inhibition downregulated PD-L1, IL-6 and TGF-ß levels through GPR30-AKT signaling, thereby enhancing CD8+ T cell-mediated antitumor immune response in vitro co-culture studies. CYP19A1 inhibition by letrozole or siRNA strengthened the anti-tumor immune response of CD8+ T cells, induced normalization of tumor blood vessels, and enhanced the efficacy of anti-PD-1 therapy in orthotopic and subcutaneous mouse colon cancer models. CONCLUSION: A risk model based on lipid metabolism-related genes may predict prognosis and immunotherapeutic response in colon cancer. CYP19A1-catalyzed estrogen biosynthesis promotes vascular abnormality and inhibits CD8+ T cell function through the upregulation of PD-L1, IL-6 and TGF-ß via GPR30-AKT signaling. CYP19A1 inhibition combined with PD-1 blockade represents a promising therapeutic strategy for colon cancer immunotherapy.

Changes in N-nitrosamines, Residual Nitrites, Lipid Oxidation, Biogenic Amines, and Microbiota in Chinese Sausages Following Treatment with Tea Polyphenols and Their Palmitic Acid-modified Derivatives.

This study aimed to investigate the effects of tea polyphenol (TP), epigallocatechin gallate (EGCG), and their palmitic acid-modified derivatives palmitoyl-TP (pTP) and palmitoyl-EGCG (pEGCG) on the accumulation of N-nitrosamine and biogenic amines (BAs), residual nitrites, and lipid oxidation in Chinese sausages. The microorganisms, color, and texture properties of sausages were evaluated. TP, EGCG, pTP, or pEGCG significantly inhibited the accumulation of N-nitrosodimethylamine (NDMA) and BAs, residual nitrites, and lipid oxidation, but enhanced the redness, hardness, and chewiness of sausages. The concentration of NDMA in sausages was reduced by 58.11%, 63.51%, 36.49%, and 44.59%, respectively, after treatment with TP, EGCG, pTP, and pEGCG. Both EGCG and pEGCG exhibited excellent inhibitory effects on the predominant BAs, including putrescine, tyramine, cadaverine, histamine, and 2-phenylethylamine. Palmitoyl-EGCG was found to be the strongest inhibitor of lipid oxidation. Besides, the four antioxidants weakly affected the population of total aerobic bacteria and lactic acid bacteria but totally suppressed the growth of undesirable Enterobacteriaceae. The principal component and correlation analyses proved that BAs, nitrites, lipid oxidation, and microbiota were responsible for the formation of NDMA. The results indicated that palmitic acid-modified TPs and similar derivatives might serve as potential preservatives to improve the safety and quality of fermented meat products.

Risk factors associated with fasting during Ramadan among individuals with diabetes according to IDF-DAR risk score in Atbara city, Sudan: Cross-sectional hospital-based study.

BACKGROUND: Ramadan is a holy month for Muslims. The aim of this study was to assess risk associated with Ramadan fasting among Sudanese individuals with diabetes (high, moderate, and low risk) according to International Diabetes Federation in collaboration with Diabetes and Ramadan International alliance (IDF-DAR) Practical Guidelines 2021 risk score. METHODS: This was a cross-sectional hospital-based study recruited 300 individuals with diabetes (79% have type 2 diabetes) from diabetes centers in Atbara city, the River Nile state, Sudan. RESULTS: The risk score was distributed as low risk (13.7%), Moderate risk (24%), and High risk (62.3%). T-test showed a significant difference in mean risk score by gender, duration and type of diabetes (p values = 0.004, 0.000, & 0.000, respectively). One-way ANOVA revealed a statistically significant difference in the risk score by age groups (p = 0.000). Logistic regression revealed that the odds of being in the 41-60 years age group had lower probability to be categorized in the moderate risk group of fasting rather than low risk by 4.3 times than being in the age more than 60 years. (p = 0.008), the odds of being in the age group 41-60 years lower probability to be categorized in the high risk of fasting rather than low risk by 8 times than being in the age more than 60 years. (p = 0.000). CONCLUSION: The majority of patients in this study have a high risk for Ramadan fasting. IDF-DAR risk score is of great significance in assessing individuals with diabetes for Ramadan fasting.

Photothermal Hydrogels for Promoting Infected Wound Healing.

Photothermal therapies (PTT), with spatiotemporally controllable antibacterial capabilities without inducing resistance, have shown encouraging prospects in the field of infected wound treatments. As an important platform for PTT, photothermal hydrogels exhibit attractive advantages in the field of infected wound treatment due to their excellent biochemical properties and have been intensively explored in recent years. This review summarizes the progress of the photothermal hydrogels for promoting infected wound healing. Three major elements of photothermal hydrogels, i.e., photothermal materials, hydrogel matrix, and construction methods, are introduced. Furthermore, different strategies of photothermal hydrogels in the treatment of infected wounds are summarized. Finally, the challenges and prospects in the clinical treatment of photothermal hydrogels are discussed.

Improvement and regeneration of Co-B amorphous alloy nanowires for the selective hydrogenation of cinnamaldehyde.

One-dimensional Co-B amorphous alloy nanowires (NWs) were prepared using surfactant as a template and were treated with plasma to study the effect of different treatment times on the essential physical and chemical properties of the catalyst. The study showed that plasma with a certain amount of strength will not change the morphology and amorphous structure of the NWs within the chosen treatment time. It could, however, modify the electronic structure and active sites of the catalyst surface, increase its specific surface area and H2 adsorption capacity, and also improve the selective hydrogenation performance of cinnamaldehyde. Most of all, plasma treatment could also play an important role in the reuse of catalysts. After several recycling reactions, plasma treatment on Co-B amorphous alloy NWs could regenerate their high catalytic activity. This work provides a novel method for preserving the high catalytic activity and stability of amorphous alloy nanomaterials, as well as for increasing their reusability.

The need for psychological counseling in breast cancer patients before radiotherapy during the COVID-19 pandemic.

The aims of this study were to explore the need for psychological counseling in breast cancer patients before radiotherapy during the COVID-19 pandemic, to distinguish which type of psychological guidance they demanded and to investigate the related factors that could be associated with the need for psychological counseling. A total of 112 eligible patients diagnosed with stage I-IV breast cancer who had received surgery were included. The self-rating depression scale (SDS), self-rating anxiety scale (SAS), Pittsburgh sleep quality index (PSQI), cancer fatigue scale (CFS), and survey for the need for psychological counseling were completed for all subjects prior to radiotherapy. A total of 8.9% and 3.6% of patients suffered from depression and anxiety during the COVID-19 pandemic, respectively. The prevalence of sleep disturbance was 62.5%. Only 12.5% of the patients needed psychological counseling, especially for the type of tumor diagnosis and treatment rather than COVID-19-related protection. The higher the total CFS score was, the lower the need for psychological counseling in breast cancer patients during this pandemic (OR = 0.91, 95% CI = 0.84-0.98). Patients who received 7-8 chemotherapeutic cycles had 6.7 times the risk of needing psychological counseling when compared with those who received 1-6 chemotherapeutic cycles. Fewer breast cancer patients suffered from depression and anxiety before radiotherapy during the COVID-19 pandemic. However, a large number of patients complained of sleep disturbance and fatigue. The majority of patients did not need psychological counseling. More chemotherapeutic cycles or less fatigue could increase their risk of needing psychological counseling, especially for tumor diagnosis and treatment, but not COVID-19-related protection.

Policymakers' and patients' perspectives on breast cancer management in the Gaza Strip-Palestine: A qualitative study.

PURPOSE: This study aimed to explore the perspectives of policymakers and patients on breast cancer (BC) management in the Gaza Strip. METHODS: A descriptive qualitative study design was employed using semi-structured in-depth interviews with 13 policymakers and focus group discussions with 19 BC patients. The four criteria presented by Lincoln and Guba were used to evaluate the validity and reliability. Data were analysed using conventional content analysis approach. RESULTS: Three categories were generated from the qualitative data analysis: (1) limited human resources in the BC management, (2) inadequate institutional level service provision in the BC management, and (3) a lack of policy level support for the BC management. The current health services provided to Gazan BC patients are either fragmented or partially unavailable. The roles and responsibilities at the policy, system and individual levels were ambiguous. Policymakers attributed the fragmented BC services to the shortage of qualified healthcare professionals, inadequate training programmes for the staff, and lack of coordination among health institutions. Some patients expressed an insufficient knowledge about cancer screening tests, while others ignored screening for cultural reasons. CONCLUSION: Gaza's BC services are fragmented and not well-organised and they have received inadequate attention at the leadership and governance levels. The government in the Gaza Strip should strengthen its leadership to upgrade and develop the policies and strategies necessary for proper BC management, including an improved information system and cooperation with national and international institutions to secure funding for developing BC services and ensure medication availability.

Acute benign pleural effusion, a rare presentation of hepatitis A virus: a case report and review of the literature.

INTRODUCTION: Hepatitis A virus infections are mostly asymptomatic or mildly symptomatic, and generally this disease has a benign course and resolves spontaneously. However, intrahepatic and rarer extrahepatic manifestations can complicate typical cases of acute hepatitis. Pleural effusion is an extremely rare extrahepatic entity with 20 cases reported in literature. CASE PRESENTATION: We report herein a recent case of both pleural effusion and ascites accompanying hepatitis A infection in a 5-year-old middle eastern child, diagnosed using serological testing and imaging studies, who was treated with supportive management with full resolution after 2 weeks. In addition, we review available literature regarding hepatitis A virus associated with pleural effusion using PubMed and summarize all reported cases in a comprehensive table. RESULTS: Literature contains 20 reported cases of serology-confirmed hepatitis A virus presenting with pleural effusion, most in the pediatric population with average age at presentation of 9 years 8 months. The majority of reported patients had right-sided pleural effusion (50%) or bilateral effusion (45%), while only 5% presented with pleural effusion on the left side. Hepatomegaly and ascites occurred concurrently in 80% and 70% respectively. Supportive treatment without invasive procedures (except one chylothorax case) yielded complete recovery in 95% of cases, while only one case progressed to fulminant liver failure followed by death. CONCLUSION: Acute hepatitis A virus rarely presents with pleural effusion, usually following a benign course with spontaneous resolution in most patients. Pleural effusion does not change the prognosis or require any invasive treatment. Thus, further invasive procedures are not recommended and would only complicate this self-resolving benign condition.

Bioinspired Janus particles for hydrophobic modification of hydrogels with photothermal antibacterial capability.

Hydrogels have received considerable attention due to their biocompatibility and desirable physical characteristics. Nonetheless, due to their open structure, hydrogels are prone to dehydration in air, resulting in a loss in their elasticity and function. Herein, we report a facile yet effective method for the modification of hydrophobic hydrogel surfaces by using bioinspired amphiphilic Janus silica particles, which are obtained by modifying hydrophilic polydopamine and hydrophobic 1H,1H,2H,2H-perfluorodecanthiol on their two sides via a templating method. With the coating of amphiphilic Janus silica particles, the water contact angles of poly(ethylene imine)-polyacrylamide and polydopamine-polyacrylamide hydrogels significantly increase to 96° and 97°, respectively. Furthermore, we demonstrate that the hydrophobic modification of the hydrogels by Janus silica particles improves the water retention capability, and the overall mechanical properties of bulk hydrogels are not compromised. In addition, we show that hydrogels coated with Janus silica particles not only exhibit hydrophobic surfaces but also have photothermal antibacterial capabilities. Consequently, this study provides a facile method for the fabrication of hydrogels with hydrophobic surfaces, which could potentially be applied to biomedical materials.

Photonic Hydrogels for Synergistic Visual Bacterial Detection and On-Site Photothermal Disinfection.

Rapid and sensitive diagnostics in the early stage of bacterial infection and immediate treatment play critical roles in the control of infectious diseases. However, it remains challenging to develop integrated systems with both rapid detection of bacterial infection and timely on-demand disinfection ability. Herein, we demonstrate a photonic hydrogel platform integrating visual diagnosis and on-site photothermal disinfection by incorporating Fe3O4@C nanoparticles into a poly(hydroxyethyl methacrylate)-co-polyacrylamide (PHEMA-co-PAAm) matrix. In vitro experiments demonstrate that such a hydrogel can respond to pH variation caused by bacterial metabolism and generate the corresponding color changes to realize naked-eye observation. Meanwhile, its excellent photothermal conversion ability enables it to effectively kill bacteria by destroying cell membranes under near-infrared irradiation. Moreover, the pigskin infection wound model also verifies the bacterial detection performance and disinfection ability of the hydrogel in vivo. Our strategy demonstrates a new approach for visual diagnosis and treatment of bacterial infections.

Pornography Use Could Lead to Addiction and Was Associated With Reproductive Hormone Levels and Semen Quality: A Report From the MARHCS Study in China.

This study aimed to investigate the situations of pornography use among male college students of China, to explore the addiction possibility for pornography use, and to study the associations between pornography use and reproductive hormone levels and semen quality. Five hundred sixty-eight participants met the inclusion criteria and finished all of the questionnaires and hormone level and semen parameter examinations. A majority of participants (except one) had pornography use experience, 94.2% participants started pornography use before college, and 95.9% participants reported they had masturbation experience when using pornography. Early contact to pornography, frequent pornography use, high amount of time spending on pornography use, and frequent masturbation during pornography use were correlated with addiction trends. Earlier pornography use was found to be associated with lower serum prolactin (PRL), follicle-stimulating hormone (FSH), and progesterone (Prog), as well as lower sperm concentration and total sperm count. Higher frequency of pornography use was associated with lower serum estrogen (E2). In conclusion, pornography use was common among male college students in China. Early contact, high frequent use, and high frequency of masturbation during pornography use could lead to addiction trends and aberrant reproductive hormone levels and semen quality.

Synbiotic Therapy Prevents Nosocomial Infection in Critically Ill Adult Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Based on a Bayesian Framework.

Background: The efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition (EPN) and total parenteral nutrition (TPN) in preventing nosocomial infection (NI) in critically ill adults has been questioned. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) to evaluate and rank the effectiveness of these therapies on NI amongst critically ill adults. Methods: Four electronic databases were systematically searched up to June 30, 2019 for RCTs comparing the administration of probiotics, prebiotics, synbiotics, EPN and TPN in critically ill adults. The primary outcome was NI. The relative efficacy of all outcomes was determined by a Bayesian framework with random effects NMA. We estimated the odds ratio (OR) and mean difference (MD) and ranked the comparative effects of all regimens with the surface under the cumulative ranking probabilities. The study has been registered on PROSPERO (CRD42019147032). Results: Fifty-five RCTs (7,119 patients) were identified. Primary outcome showed that synbiotics had the best effect in preventing NI than EPN (OR 0.37; 95% CrI 0.22-0.61), probiotics followed (OR 0.52; 95% CrI 0.34-0.77), whereas TPN significantly increased NI (OR 2.29; 95% CrI 1.48-3.67). Subgroup analysis showed that TPN significantly increased NI in intensive care unit (ICU) patients (OR 1.57; 95% CrI 1.01-2.56) and severe acute pancreatitis (SAP) patients (OR 3.93; 95% CrI 1.74-9.15). Secondary outcomes showed that synbiotics were more effective in preventing hospital-acquired pneumonia (HAP) (OR 0.34; 95% CrI 0.11-0.85), catheter-related bloodstream infection (OR 0.08; 95% CrI 0.01-0.80), urinary tract infection (OR 0.27; 95% CrI 0.08-0.71) and sepsis (OR 0.34; 95% CrI 0.16-0.70) than EPN. Amongst the treatments, probiotics were most effective for shortening the mechanical ventilation duration (MD -3.93; 95% CrI -7.98 to -0.02), prebiotics were most effective for preventing diarrhea (OR 0.24; 95% CrI 0.05-0.94) and TPN was the least effective in shortening hospital length of stay (MD 4.23; 95% CrI 0.97-7.33). Conclusions: Amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. Take-Home Message: Nosocomial infection is a leading cause of mortality in critically ill patients in the ICU. However, the efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition and total parenteral nutrition in preventing nosocomial infection in critically ill adults has been questioned. The network meta-analysis provides evidence that amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. The results of this study will provide a new scientific basis and a new idea for the debate on the efficacy of synbiotics and other treatments in the improvement of prognosis in critically ill adult patients. Tweet: Synbiotic prevents nosocomial infection in critically ill adults, while total parenteral nutrition has the adverse curative.