Injectable hydrogels doped with PDA nanoparticles for photothermal bacterial inhibition and rapid wound healing in vitro.

The difficulty of wound healing due to skin defects has been a great challenge due to the complex inflammatory microenvironment. Delayed wound healing severely affects the quality of life of patients and represents a significant economic burden for public health systems worldwide. Therefore, there is an urgent need for the development of novel wound dressings that can efficiently resist drug-resistant bacteria and have superior wound repair capabilities in clinical applications. In this study, we designed an adhesive antimicrobial hydrogel dressing (GMH) based on methacrylic-anhydride-modified gelatin and oxidized hyaluronic acid formed by Schiff base and UV-induced double cross-linking for infected wound repair. By inserting PDA nanoparticles into the hydrogel (GMH/PDA), the hydrogel has the capability of photothermal conversion and exhibits good photothermal antimicrobial properties under near-infrared (NIR) light irradiation, which helps to reduce the inflammatory response and avoid bacterial infections during the wound healing process. In addition, GMH/PDA hydrogel exhibits excellent injectability, allowing the hydrogel dressings to be adapted to complex wound surfaces, making them promising candidates for wound therapy. In conclusion, the multifunctional injectable GMH/PDA hydrogel possesses high antimicrobial efficiency, antioxidant properties and good biocompatibility, making them promising candidates for the treatment of infected skin wounds.

Disulfidptosis-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in colon adenocarcinoma.

BACKGROUND: Disulfidptosis is independent of apoptosis, ferroptosis, and cuproptosis and is associated with cancer progression, treatment response, and prognosis. However, the predictive potential of disulfidptosis-associated lncRNAs in colon adenocarcinoma (COAD) and their features in the tumor immune microenvironment (TIME) require further elucidation. METHODS: RNA transcriptome, clinical information, and mutation data of COAD samples were obtained from the TCGA database. The risk model was first constructed by co-expression analysis of disulfidptosis genes and lncRNAs, and prognostic lncRNAs were screened using Cox regression, followed by least absolute shrinkage and selection operator analysis. Enrichment analyses were performed to explore the underlying biological functions and signaling of model-associated differentially expressed genes (MADEGs). Moreover, TIME of MADEGs was analyzed to assess the immunotherapy. Finally, the expression levels of the lncRNAs were verified by taking specimens of patients with COAD from the Affiliated Hospital of Qingdao University. RESULTS: We constructed a prognosis-related risk model based on four disulfidptosis-associated lncRNAs (ZEB1-AS1, SNHG16, SATB2-AS1, and ALMS1-IT1). By analyzing the survival of patients in the whole, training, and test groups, we found that patients with COAD in the low-risk group had better overall survival than those in the high-risk group. Validation of the model via Cox analysis and clinical indicators demonstrated that the model had a decent potential for predicting the prognosis of patients with COAD. Enrichment analyses revealed that the MADEGs were related to disulfidptosis-associated biological functions and cancer pathways. Furthermore, patients with COAD in the high-risk group had more positive responses to immune checkpoint inhibitors (ICIs) than those in the low-risk group, as confirmed by TIME analysis. ZEB1-AS1, SNHG16, and ALMS1-IT1 were expressed at higher levels in tumor samples than those in the corresponding paracancerous samples (p < 0.05), whereas SATB2-AS1 was upregulated in the paracancerous samples (p < 0.05). CONCLUSIONS: This signature may guide prognosis, molecular mechanisms, and treatment strategies, including ICIs and chemotherapy, in patients with COAD.

Seasonal variations in the composition and diversity of gut microbiota in white-lipped deer (Cervus albirostris).

The gut microbiota has key physiological functions in host adaptation, although little is known about the seasonal changes in the composition and diversity of the gut microbiota in deer. In this study, seasonal variations (grassy and withering season) in the gut microbiota of white-lipped deer (Cervus albirostris), which lives in alpine environments, were explored through 16S rRNA high-throughput sequencing based on sixteen fecal samples collected from Gansu Qilian Mountain National Nature Reserve in China. At the phylum level, Firmicutes, Bacteroidota, and Actinobacteriota dominated the grassy season, while Firmicutes, Proteobacteria, and Actinobacteriota dominated the withering season. At the genus level, Carnobacterium dominated the grassy season, while Arthrobacter and Acinetobacter dominated the withering season. Alpha diversity results (Shannon: P = 0.01, ACE: P = 0.00, Chao1: P = 0.00) indicated that there was a difference in the diversity and richness of the gut microbiota between the two seasons, with higher diversity in the grassy season than in the withering season. Beta diversity results further indicated that there was a significant difference in the community structure between the two seasons (P = 0.001). In summary, the composition, diversity, and community structure of the gut microbiota showed significant seasonal variations, which could be explained by variations in the seasonal food availability, composition, diversity, and nutrition due to phenological alternations. The results of this study indicate that the gut microbiota can adapt to changes in the environment and provide the scientific basis for health assessment of white-lipped deer.

Environmental and human health risk evaluation of heavy metals in ceramsites from municipal solid waste incineration fly ash.

Municipal solid waste incineration (MSWI) for power generation can reuse waste effectively, but it generates a large amount of fly ash enriched with heavy metals. If this fly ash cannot be treated properly, it can cause ecological damage and human health risk. According to the production of ceramsites from MSWI fly ash, an evaluation methodology is established, in which the influence of heavy metal stability on the environment is considered for the first time, and the health risks of heavy metals via different exposure pathways are distinguished. The results show that heavy metals in MSWI fly ash have moderate potential environmental risks to environment and have strong non-carcinogenic and carcinogenic risks both to children and adults. By contrast, heavy metals in ceramsites pose little risk to environment and human health. This paper explains some reasons of heavy metal content and leaching ratio change in ceramsite and also illustrates why stability is a concern through comparing the potential risk index method and the improved evaluation method. This evaluation system can be applied to different production processes of building materials using solid hazardous waste and provides a quantitative evaluation method for reducing environment and human health risks of heavy metals.

Integrated assessment of the environmental and economic effects of "coal-to-gas conversion" project in rural areas of northern China.

Northern China suffers from serious air pollution especially in winter, much of which derives from solid fuel used for domestic heating in rural areas. In order to reduce pollution emissions in the heating season, the Chinese government has introduced a "coal-to-gas conversion" policy, promoting a switch to natural gas which is much cleaner than the coal normally used for winter heating. The "coal-to-gas conversion" project will cover more than 1.8 billion m2 of heated built floor area and affect more than 12 million heat users in Beijing, Tianjin, Hebei, and the surrounding areas. Life cycle assessment and life cycle cost methods are applied to compare and analyze the environmental impact and economic cost of household energy usage for the whole year under 5 scenarios before and after "coal-to-gas conversion." In the three scenarios after "coal-to-gas conversion," the environmental impact decreases by around 50% while the total economic cost increases by around 80%. Particulate emissions responsible for air pollution are considerably reduced with accompanying benefits for human health, though significant, but reduced, impacts on freshwater and marine ecotoxicity remain. Improving thermal efficiency through natural gas utilization, implementing an energy-saving retrofit of rural housing, and promoting straw utilization yield benefits for people and the environment in rural areas of northern China.

ATP-induced cardioprotection against myocardial ischemia/reperfusion injury is mediated through the RISK pathway.

The aim of the present study was to examine the post-infarct acute effect of adenosine-5'-triphosphate (ATP) on myocardial infarction (MI) size as well as its precise molecular mechanism. Sixty New Zealand white male rabbits were exposed to 40 min of ischemia followed by 180 min of reperfusion. The rabbits were intravenously administered 3 mg/kg of ATP (ATP group) or saline (control group) immediately after reperfusion and maintained throughout the first 30 min. The wortmannin+ATP, PD-98059+ATP, and 5-hydroxydecanoic acid (5-HD) sodium salt+ATP groups were separately injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), and 5-HD (5 mg/kg) 5 min prior to ATP administration. MI size was calculated as the percentage of the risk area in the left ventricle. Myocardial apoptosis was determined using a TUNEL assay. Western blot analysis was performed to examine the levels of protein kinase B (Akt)/p-Akt and extracellular signal-regulated kinase (ERK)/p-ERK in the ischemic myocardium, 180 min after reperfusion. The infarct size was significantly smaller in the ATP group than in the control group (p<0.05). The infarct size-reducing effect of ATP was completely blocked by wortmannin, PD-98059 and 5-HD. Compared with the control group, cardiomyocyte apoptosis was significantly reduced in the ATP group, while this did not occur in the wortmannin+ATP, PD-98059+ATP and 5-HD+ATP groups. Western blot analysis revealed a higher myocardial expression of p-Akt and p-ERK 180 min following reperfusion in the ATP versus the control group. In conclusion, cardioprotection by postischemic ATP administration is mediated through activation of the reperfusion injury salvage kinase (RISK) pathway and opening of the mitochondrial ATP-dependent potassium channels.

Evaluation of Cranial and Cervical Arteries and Brain Tissue in Transient Ischemic Attack Patients with Magnetic Resonance Angiography and Diffusion-Weighted Imaging.

BACKGROUND: Magnetic resonance angiography (MRA) and diffusion-weighted imaging (DWI) have been widely used in the prediction of ischemic stroke; however, the differences of the 2 methods in detection the artery lesion differences between transient ischemic attack (TIA) and infarction patients have been long neglected. We performed the present study to investigate the differences between vessel characteristics detected by MRA and DWI in acute stroke and TIA patients. MATERIAL AND METHODS: We classified 110 subjects into 2 groups and all the patients underwent both MRA and DWI. The degree of stenosis of cranial and cervical arteries, the distribution of the stenosis, the development and changes of the vessels, and the DWI scanning results of the brain tissue were all analyzed. RESULTS: We detected a significant difference in the number and the degree of stenosis of cranial and cervical arteries among the 3 groups (P=0.006). Compared with health controls, patients with TIA and cerebral infraction had much more severe stenosis and occlusive arteries (P<0.05). However, no significant difference was detected between TIA and cerebral infraction patients (P=0.148). Moreover, a higher rate of unilateral vertebral artery dysplasia was found in the vertebrobasilar TIA patients. Higher lesion signals were also observed by DWI in TIA patients of internal carotid artery system (4/8, 50%). CONCLUSIONS: Vessel characteristics were not significantly different between TIA and infarction patients. Unilateral vertebral artery hypoplasia was a predisposing factor for vertebrobasilar TIA and ischemic focus in DWI detection was always caused by severe artery lesions.

Dynamical observation on biological progression of VX2 liver tumors to identify the optimal time for intervention in animal models.

PURPOSE: Based on practice guideline of "management of hepatocellular carcinoma (HCC): update" published by American Association for the Study of Liver Diseases (AASLD) and "Barcelona Clinic Liver Cancer staging system (BCLC)," this study investigated how to enroll the optimal VX2 liver tumor model for HCC researches by dynamically observing the biological progression of the tumor. MATERIALS: Thirty-two healthy New Zealand white rabbits were implanted VX2 liver tumor by cell suspension method (n=24) and tissue fragment method (n=8). All the rabbits underwent CT scans on day 7, 14, 21 and 28 after implantation to observe the size of the tumors, the time when metastases and ascites occurred and the survival time. Appropriate intervention times were estimated corresponding to different clinical HCC stages by using tumor diameter-time curve. RESULTS: The VX2 liver tumors grew rapidly within 28 days after implantation. And the tumors in the cell suspension group grew faster than those of the tissue fragment group. The appropriate intervention time corresponding to very early stage, early stage and intermediate stage were <11 days, 11-16.9 days and >16.9 days, respectively in the cell suspension group, and <19.9 days, 19.9-25.5 days and >25.5 days, respectively in the tissue fragment group. CONCLUSION: Preclinical animal research needs to improve on different levels to yield best predictions for human patients. Researchers should seek for an individualized proposal to select optimal VX2 liver tumor models for their experiments. This approach may lead to a more accurate determination of therapeutic outcomes.

[Current situation on the China infectious disease automated-alert and response system in Guangdong Province, China].

OBJECTIVE: To analyze the current situation on China Infectious Disease Automated-alert and Response System (CIDARS) in Guangdong province, China. METHODS: Early-warning signals and response time were analyzed by using three approaches of CIDARS. Positive rates of early-warning signals and error early-warning rates prior and after the adjustment,were compared. RESULTS: Totally, 114 585 early-warning signals appeared, with an average response time of 1.35 hours from April 21, 2008 to December 31, 2012. There were 12,394 early-warning signals in terms of fixed threshold method with a positive rate of 7.96%. 85 727 early-warning signals appeared under the mobile percentile method with a positive rate of 0.85%. There were 16,464 early-warning signals by using accumulation and control chart methods,with a positive rate of 1.82%. Results showed there was a positive correlation between the number of reported cases and the number of early-warning signals (r = 0.924, P < 0.01). The overall positive rate in Guangdong province increased from 1.48% to 2.14%, after the adjustment done by the Chinese Center for Disease Control and Prevention in 2010. The error early-warning rates regarding eight infectious diseases including hepatitis A, bacillary or amebic dysentery, both typhoid and paratyphoid fevers had reduced. CONCLUSION: The early-warning signal response appeared timely in CIDARS with good operation. However, despite the improvement on the efficacy of CIDARS, some functions and parameters of the systems still need to be adjusted.

[Expression and characterization of soluble recombinant Ulp1p with glutathione S-transferase tag in Escherichia coli].

The aim of the study is to obtain an efficient expression of recombinant ubiquitin-like specific protease 1 (Ulp1) by gene engineering. We cloned the Ulp1p, active fragment (403 aa-621 aa) of Ulp1, from Saccharomyces cerevisia, and subcloned into pGEX/Rosetta (DE3) to form an expression plasmid, pGEX-Ulp1p-His6. In order to enhance the solubility of GST-Ulp1p-His6, we purified the fusion protein GST-Ulp1p-His6 by either glutathione S-transferase agarose or Ni-NTA resin chromatography, the purity was up to 98%. We utilized the protein to cleave the SUMO fusions, and the specific activity of GST-Ulp1p-His6 was 1.375 x 10(4) U/mg. This study showed that the recombinant protein GST-Ulp1p-His6 displayed high specificity and activity.

[Diagnostic significance of combining telomerase activity with CYFRA21-1 level in differentiating malignant pleural effusion caused by lung cancer from benign pleural effusion].

UNLABELLED: BACKGROUND AND OBJECTIVE Telomerase and CYFRA21-1 may be positively expressed in malignant pleural effusion, but the sensitivity and specificity of single tumor marker were low. The aim of this study is to investigate the diagnostic value of combining determination of telomerase activity and CYFRA21-1 levels in differentiating benign from malignant pleural effusion caused by lung cancer. METHODS: 80 patients with malignant and 50 patients with benign pleural effusion were enrolled into this study. The telomerase activity in pleural effusion was tested by means of telomeric repeat amplification protocal-PCR-ELISA (TRAP-PCR-ELISA) and CYFRA21-1 levels were tested by the EIA method. All the results were analyzed by the statistical method. RESULTS: The levels of telomerase and CYFRA21-1 in malignant pleural effusion was significantly higher than that in benign one (t = 17.252 and t = 13.951, P < 0.001). The sensitivity of telomerase activity testing for diagnosing malignant pleural effusion was 71.3%; the specificity was 86.0% and the overall accuracy was 76.9%. The sensitivity of CYFRA 21-1 testing was 60.0%, the specificity was 78.0% and the overall accuracy was 66.9%. The sensitivity of the combined testing was 90.0%, the specificity was 76.0% and the overall accuracy was 86.9%. The sensitivity and the overall accuracy of combined testing were higher than those of telomerase and CYFRA21-1 testing single (chi2 = 9.002 and chi2 = 19.201, P < 0.01; chi2 = 4.389 and chi2 = 14.647, P < 0.05). CONCLUSION: The combined testing oftelomerase with CYFRA21-1 can increase the sensitivity and overall accuracy of differential diagnosis of benign and malignant pleural effusion diagnosis.