Ascorbic acid potentiates photodynamic inactivation mediated by octyl gallate and blue light for rapid eradication of planktonic bacteria and biofilms.

This study reported for the first time that Ascorbic acid (AA) could appreciably boost the efficiency of Octyl gallate (OG)-mediated photodynamic inactivation (PDI) on Escherichia coli and Staphylococcus aureus in planktonic and biofilm states. The combination of OG (0.075 mM) and AA (200 mM) with 420 nm blue light (212 mW/cm2) led to a >6 Log killing within only 5 min for E. coli and S. aureus and rapid eradication of biofilms. The mechanism of action appears to be the generation of highly toxic hydroxyl radicals (•OH) via photochemical pathways. OG was exposed to BL irradiation to generate various reactive oxygen radicals (ROS) and the addition of AA could transform singlet oxygen (1O2) into hydrogen peroxide (H2O2), which could further react with AA to generate enormous •OH. These ROS jeopardized bacteria and biofilms by nonspecifically attacking various biomacromolecules. Overall, this PDI strategy provides a powerful microbiological decontamination modality to guarantee safe food products.

UNVEILING THE PROTECTIVE MECHANISMS OF PUERARIN AGAINST ACUTE LUNG INJURY: A COMPREHENSIVE EXPLORATION OF THE ROLES AND MECHANISMS OF MST1/ERS SIGNALING.

ABSTRACT: Objectives: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). Methods: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through western blotting. Histological alterations and apoptosis were scrutinized using hematoxylin-eosin staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. Results: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. Conclusion: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.

Comparison of the effect between traditional conservation and nasointestinal tube placement in adhesive small bowel obstruction: A matched case-control study.

Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy. After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups. According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018). TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.

Ultraefficient OG-Mediated Photodynamic Inactivation Mechanism for Ablation of Bacteria and Biofilms in Water Augmented by Potassium Iodide under Blue Light Irradiation.

While photodynamic inactivation (PDI) has emerged as a novel sterilization strategy for drinking water treatment that recently attracted tremendous attention, its efficiency needs to be further improved. In this study, we aimed to clarify the ultraefficient mechanism by which potassium iodide (KI) potentiates octyl gallate (OG)-mediated PDI against bacteria and biofilms in water. When OG (0.15 mM) and bacteria were exposed to blue light (BL, 420 nm, 210 mW/cm2), complete sterilization (>7.5 Log cfu/mL of killing) was achieved by the addition of KI (250 mM) within only 5 min (63.9 J/cm2). In addition, at lower doses of OG (0.1 mM) with KI (100 mM), the biofilm was completely eradicated within 10 min (127.8 J/cm2). The KI-potentiated mechanism involves in situ rapid photogeneration of a multitude of reactive oxygen species, especially hydroxyl radicals (•OH), reactive iodine species, and new photocytocidal substances (quinone) by multiple photochemical pathways, which led to the destruction of cell membranes and membrane proteins, the cleavage of genomic DNA and extracellular DNA within biofilms, and the degradation of QS signaling molecules. This multitarget synergistic strategy provided new insights into the development of an environmentally friendly, safe, and ultraefficient photodynamic drinking water sterilization technology.

Comprehensively evaluate the short outcome of small bowel obstruction: A novel medical-economic score system.

BACKGROUND: Small bowel obstruction (SBO) still imposes a substantial burden on the health care system. Traditional evaluation systems for SBO outcomes only focus on a single element. The comprehensive evaluation of outcomes for patients with SBO remains poorly studied. Early intensive clinical care would effectively improve the short-term outcomes for SBO, however, the full spectrum of the potential risk status regarding the high complication-cost burden is undetermined. AIM: We aim to construct a novel system for the evaluation of SBO outcomes and the identification of potential risk status. METHODS: Patients who were diagnosed with SBO were enrolled and stratified into the simple SBO (SiBO) group and the strangulated SBO (StBO) group. A principal component (PC) analysis was applied for data simplification and the extraction of patient characteristics, followed by separation of the high PC score group and the low PC score group. We identified independent risk status on admission via a binary logistic regression and then constructed predictive models for worsened management outcomes. Receiver operating characteristic curves were drawn, and the areas under the curve (AUCs) were calculated to assess the effectiveness of the predictive models. RESULTS: Of the 281 patients, 45 patients (16.0%) were found to have StBO, whereas 236 patients (84.0%) had SiBO. Regarding standardized length of stay (LOS), total hospital cost and the presence of severe adverse events (SAEs), a novel principal component was extracted (PC score = 0.429 × LOS + 0.444 × total hospital cost + 0.291 × SAE). In the multivariate analysis, risk statuses related to poor results for SiBO patients, including a low lymphocyte to monocyte ratio (OR = 0.656), radiological features of a lack of small bowel feces signs (OR = 0.316) and mural thickening (OR = 1.338), were identified as risk factors. For the StBO group, higher BUN levels (OR = 1.478) and lower lymphocytes levels (OR = 0.071) were observed. The AUCs of the predictive models for poor outcomes were 0.715 (95%CI: 0.635-0.795) and 0.874 (95%CI: 0.762-0.986) for SiBO and StBO stratification, respectively. CONCLUSION: The novel PC indicator provided a comprehensive scoring system for evaluating SBO outcomes on the foundation of complication-cost burden. According to the relative risk factors, early tailored intervention would improve the short-term outcomes.

Dual-Stage Blue-Light-Guided Membrane and DNA-Targeted Photodynamic Inactivation Using Octyl Gallate for Ultraefficient Eradication of Planktonic Bacteria and Sessile Biofilms.

This study aimed to investigate the synergistic bactericidal activity and mechanism of dual-stage light-guided membrane and DNA-targeted photodynamic inactivation (PDI) by the combination of blue light (BL, 420 nm) and the food additive octyl gallate (OG) against Vibrio parahaemolyticus in planktonic and biofilm growth modes. While OG serves as an outstanding exogenous photosensitizer, the planktonic cells were not visibly detectable after the OG-mediated PDI treatment with 0.2 mM OG within 15 min (191.7 J/cm2), and its biofilm was nearly eradicated within 60 min (383.4 J/cm2). Gram-positive Staphylococcus aureus was more susceptible to the PDI than Gram-negative V. parahaemolyticus. The cellular wall and proteins, as well as DNA, were the vulnerable targets for PDI. The membrane integrity could be initially disrupted by OG bearing a hydrophilic head and a hydrophobic tail via transmembrane insertion. The enhancement of OG uptake due to the first-stage light-assisted photochemical internalization (PCI) promoted the accumulation of OG in cells. It further boosted the second-stage light irradiation of the photosensitizer-inducing massive cell death. Upon the second-stage BL irradiation, reactive oxygen species (ROS) generated through the OG-mediated PDI in situ could extensively deconstruct membranes, proteins, and DNA, as well as biofilms, while OG could be activated by BL to carry out photochemical reactions involving the formation of OG-bacterial membrane protein (BMP) covalent conjugates and the interactions with DNA. This dual-stage light-guided subcellular dual-targeted PDI strategy exhibits encouraging effects on the eradication of planktonic bacteria and sessile biofilms, which provides a new insight into the development of an ultraeffective antimicrobial and biofilm removing/reducing technique to improve microbiological safety in the food industry.

Discovery of novel DGAT1 inhibitors by combination of machine learning methods, pharmacophore model and 3D-QSAR model.

DGAT1 plays a crucial controlling role in triglyceride biosynthetic pathways, which makes it an attractive therapeutic target for obesity. Thus, development of DGAT1 inhibitors with novel chemical scaffolds is desired and important in the drug discovery. In this investigation, the multistep virtual screening methods, including machine learning methods and common feature pharmacophore model, were developed and used to identify novel DGAT1 inhibitors from BioDiversity database with 30,000 compounds. 531 compounds were predicted as DGAT1 inhibitors by combination of machine learning methods comprising of SVM, NB and RP models. Then, 12 agents were filtered from 531 compounds by using the common feature pharmacophore model. The 3D chemical structures of the 12 hits coordinated with surface charges and isosurface have been carefully analyzed by the established 3D-QSAR model. Finally, 8 compounds with desired properties were retained from the final hits and have been assigned to another research group to complete the follow-up compound synthesis and biologic evaluation.

[Spatial Distribution Characteristics and Pollution Evaluation of Heavy Metals in Arable Land Soil of China].

Soil is an important component of the terrestrial ecosystem and an indispensable natural resource in agricultural production. Understanding the spatial distribution characteristics and pollution levels of heavy metals in arable land soil is important to safeguard the agriculture ecosystem and human health. Based on the collected data of heavy metal concentrations in arable land soil in various administrative regions of China since 2002, first, we selected and removed the abnormal values, then obtained the spatial distribution of the provinces by the Kriging method, and discussed the spatial distribution characteristics of seven heavy metals (Cr, Cd, Pb, Zn, Cu, As, and Hg) in arable land soil. Finally, we adopted the geo-accumulation index to evaluate the pollution status of arable land soil. The results showed that the spatial distribution of heavy metals Cr, Pb, Cu, Zn, and As in arable land soil of China was obvious, while the spatial distribution of soil Cd and Hg was very similar. Furthermore, the concentration of arable land soil in south China was obviously higher than that in the north. The mean value of the results showed that heavy metals are enriched to different degrees in arable land soil of China, and the average soil heavy metal concentrations of arable land are higher in Hunan, Yunnan, Guizhou, Sichuan, Fujian, Guangxi, and Shanghai. The results of geo-accumulation index pollution evaluations showed that the pollution degree of the seven heavy metals was in the order Cd > Hg > Pb > Cu > Zn > As > Cr, among which the soil heavy metals in arable land soil had a higher enrichment degree in Fujian, Guangdong, Hainan, Zhejiang, Hunan, Shaanxi, Gansu, Henan, Chongqing, Shanxi, Tianjin, Inner Mongolia, and Anhui. In general, the geo-accumulation indexes of Cd and Hg in each administrative region are higher, whereas the average land accumulation indexes also indicate that Cd and Hg in arable land shows greater pollution specially. Results from this study provide valuable scientific basis for formulating effective arable land pollution control strategies in the future.

[Meta analysis of postoperative complications between laparoscopic resection and traditional open resection of mid-low rectal carcinoma].

OBJECTIVE: To conduct a meta-analysis of postoperative complications between laparoscopic resection (Group LR) and traditional open resection (Group OR) of mid-low rectal carcinoma. METHODS: Meta analysis was performed by two reviewers, who independently selected and extracted data retrieved from literatures and papers published in China Knowledge Resource Integrated Database (CNKI), Wangfang Data, Foreign Medical Journal Service (FMJS), PubMed, EMBASE and The Cochrane before August 2012 on comparison between two groups. The statistical analysis for research of complex standard was conducted through Revman 5.0. RESULTS: Thirteen clinical case-control studies with a total of 2733 cases were enrolled for analysis, including 1368 cases in Group LR and 1365 in Group OR. The result showed that, compared with Group OR, Group LR had lower overall rate of postoperative complication (OR=0.76, 95%CI:0.62-0.92, P<0.01), lower rate of postoperative intestinal obstruction (OR=0.53, 95%CI:0.35-0.80, P<0.01), lower rate of incision complications (OR=0.43, 95%CI:0.28-0.67, P<0.01), similar incidence of anastomotic bleeding and fistula, and similar incidence of bleeding in abdominal cavity and pelvic cavity (all P>0.05). CONCLUSIONS: The overall rate of postoperative complications of laparoscopic resection for mid-low rectal carcinoma is obviously lower than that of open resection. Laparoscope can be applied safely in the resection of mid-low rectal carcinoma.

[Improvement upon construction of tissue-engineered allogeneic cartilage molded with polyglycolic acid as the scaffold].

OBJECTIVE: To improve the method for constructing allogeneic molded cartilage by means of tissue engineering techniques. METHODS: The chondrocytes from the rib and articular cartilage of infant rabbits were harvested by type II collagenase digestion, followed by in vitro cell culture for 3 to 4 passages. The chondrocytes were then prepared into cell suspension and seeded onto C -and O -shaped pre-molded polyglycolic acid (PGA) scaffolds form chondrocyte-PGA composites, which were subsequently cultured in vitro for 7 to 10 d before implanted subcutaneously into adult rabbits. Improvement was made upon conventional shaping and implantation procedures. Morphological observation and cartilage regeneration assessment were conducted at different time points following the implantation, in comparison with the observation by conventional shaping and implantation methods. RESULTS: During in vitro cell culture, the rate of viable chondrocytes in the final cell suspension was (92+/-2)% after well-controlled prolongation of digestion trypsin, similar to the viable cell rate (93+/-2) % by traditional procedures (P>0.05). Gross observation found milk-white, newly generated cartilage which had good flexibility 4 weeks after implantation, and after 8 weeks and later, the cartilage took on the color of porcelain-white. Histological examination showed a few inflammatory cells around the newly generated immature cartilage 4 weeks after implantation, and the inflammation abated when the newly generated cartilage acquired similar histological properties to that of the original cartilage 8 weeks postoperatively and later. After 16 weeks, no blood vessel or capillaries were visible within the new cartilage. CONCLUSION: The chondrocyte viability is not affected when the cells are treated with well-controlled prolonged digestion with trypsin during in vitro cell culture. Improved PGA scaffolds shaping and the implantation procedure facilitate the regeneration of the cartilage after the implantation of the composites.