Green Preparation and Antibacterial Activity Evaluation of AgNPs-Blumea balsamifera Oil Nanoemulsion.

Bacterial infection is a thorny problem, and it is of great significance to developing green and efficient biological antibacterial agents that can replace antibiotics. This study aimed to rapidly prepare a new type of green antibacterial nanoemulsion containing silver nanoparticles in one step by using Blumea balsamifera oil (BBO) as an oil phase and tea saponin (TS) as a natural emulsifier and reducing agent. The optimum preparation conditions of the AgNPs@BBO-TS NE were determined, as well as its physicochemical properties and antibacterial activity in vitro being investigated. The results showed that the average particle size of the AgNPs@BBO-TS NE was 249.47 ± 6.23 nm, the PDI was 0.239 ± 0.003, and the zeta potential was -35.82 ± 4.26 mV. The produced AgNPs@BBO-TS NE showed good stability after centrifugation and 30-day storage. Moreover, the AgNPs@BBO-TS NE had an excellent antimicrobial effect on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These results demonstrated that the AgNPs@BBO-TS NE produced in this study can be used as an efficient and green antibacterial agent in the biomedical field.

Folic acid blocks ferroptosis induced by cerebral ischemia and reperfusion through regulating folate hydrolase transcriptional adaptive program.

Cerebral ischemia-reperfusion (I/R) injury is notably linked with folic acid (FA) deficiency. The aim of our investigation was to explore the effects and underlying mechanisms by which FA mitigates I/R, specifically through regulating the GCPII transcriptional adaptive program. Initially, we discovered that following cerebral I/R, levels of FA, methionine synthase (MTR), and methylenetetrahydrofolate reductase (MTHFR) were decreased, while GCPII expression was elevated. Secondly, administering FA could mitigate cognitive impairment and neuronal damage induced by I/R. Thirdly, the mechanism of FA supplementation involved suppressing the transcriptional factor Sp1, subsequently inhibiting GCPII transcription, reducing Glu content, obstructing cellular ferroptosis, and alleviating cerebral I/R injury. In summary, our data demonstrate that FA affords protection against cerebral I/R injury by inhibiting the GCPII transcriptional adaptive response. These findings unveil that targeting GCPII might be a viable therapeutic strategy for cerebral I/R.

A multisite dynamic synergistic oxygen evolution reaction mechanism of Fe-doped NiOOH: a first-principles study.

Changing the composition is an important way to regulate the electrocatalytic performance of the oxygen evolution reaction (OER) for metallic compounds. Clarifying the synergistic mechanism among different compositions is a key scientific problem to be solved urgently. Here, based on first-principles calculations, a Ni-O-Fe multisite dynamic synergistic reaction mechanism (MDSM) for the OER of Fe-doped NiOOH (NiFeOOH) has been discovered. Based on the MDSM, Fe/O/Ni are triggered as the active sites in turn, resulting in an overpotential of 0.33 V. The factors affecting the deprotonation, O-O coupling, and O2 desorption during the OER process are analyzed. The electron channels related to the magnetic states among Fe-O-Ni is revealed, which results in the decoupling between OER sites and the oxidation reaction sites. O-O coupling and O2 desorption are affected by ferromagnetic coupling and the instability of the lattice O during the OER process, respectively. The results give a comprehensive understanding of the active sites in NiFeOOH and provide a new perspective on the synergistic effects among different compositions in metal compounds during the OER process.

Effect of WiFi signal exposure in utero and early life on neurodevelopment and behaviors of rats.

The aim of this study is to examine the long-term effects of prenatal and early-life WIFI signal exposure on neurodevelopment and behaviors as well as biochemical alterations of Wistar rats. On the first day of pregnancy (E0), expectant rats were allocated into two groups: the control group (n = 12) and the WiFi-exposed group (WiFi group, n = 12). WiFi group was exposed to turn on WiFi for 24 h/day from E0 to postnatal day (PND) 42. The control group was exposed to turn-off WiFi at the same time. On PND7-42, we evaluated the development and behavior of the offspring, including body weight, pain threshold, and swimming ability, spatial learning, and memory among others. Also, levels of proteins involved in apoptosis were analyzed histologically in the hippocampus in response to oxidative stress. The results showed that WiFi signal exposure in utero and early life (1) increased the body weight of WiFi + M (WiFi + male) group; (2) no change in neuro-behavioral development was observed in WiFi group; (3) increased learning and memory function in WiFi + M group; (4) enhanced comparative levels of BDNF and p-CREB proteins in the hippocampus of WiFi + M group; (5) no neuronal loss or degeneration was detected, and neuronal numbers in hippocampal CA1 were no evidently differences in each group; (6) no change in the apoptosis-related proteins (caspase-3 and Bax) levels; and (7) no difference in GSH-PX and SOD activities in the hippocampus. Prenatal WiFi exposure has no effects on hippocampal CA1 neurons, oxidative equilibrium in brain, and neurodevelopment of rats. Some effects of prenatal WiFi exposure are sex dependent. Prenatal WiFi exposure increased the body weight, improved the spatial memory and learning function, and induced behavioral hyperactivity of male rats.

Effects of low-dose furosemide combined with aminophylline on the renal function in septic shock patients.

BACKGROUND: To investigate the effects of low-dose furosemide and aminophylline on the renal function in patients with septic shock. METHODS AND RESULTS: A total of 109 eligible septic shock patients in the intensive care unit were randomly divided into a control group (n = 55) and an intervention group (n = 54). The control group received normal saline, and the intervention group received low-dose furosemide (0.048 mg/kg.h-1) with aminophylline (0.3 mg/kg.h-1). The primary outcomes included the levels of serum creatinine (Scr), creatinine clearance rate (Ccr), blood urea nitrogen (BUN), glomerular filtration rate (GFR), and urine output on admission and on days 3, 7 and 14. The secondary outcomes were the sequential organ failure assessment (SOFA) scores, continuous renal replacement therapy (CRRT) time and intensive care unit (ICU) mortality, hospital mortality and 28-day mortality. There were no significant differences in the levels of Scr, Ccr, BUN, or GFR between the two groups, while the urine output was higher in the intervention group on days 3, 7, and 14. Compared with the control group, the SOFA scores, ICU mortality, hospital mortality and 28-day mortality were significantly lower in the intervention group on days 3, 7, and 14, the CRRT time was shorter, and the cumulative fluid balance was lower on days 3 and 7 in the intervention group. CONCLUSIONS: Although low-dose furosemide and aminophylline have fewer protective effects on the renal function in septic shock patients, they could reduce the CRRT time and improve the prognosis.

Genome-Wide Identification and Characterization of TCP Gene Family Members in Melastoma candidum.

It has been confirmed that the plant-specific Teosinte-branched 1/Cycloidea/Proliferating (TCP) gene family plays a pivotal role during plant growth and development. M. candidum is a native ornamental species and has a wide range of pharmacodynamic effects. However, there is still a lack of research on TCP's role in controlling M. candidum's development, abiotic stress responses and hormone metabolism. A comprehensive description of the TCP gene family in M. candidum is urgently needed. In this study, we used the HMMER search method in conjunction with the BLASTp method to identify the members of the TCP gene family, and a total of 35 TCP genes were identified. A domain analysis further confirmed that all 35 TCPs contained a TCP superfamily, a characteristic involved in dimerization and DNA binding that can be found in most genes from this gene family, suggesting that our identification was effective. As a result of the domain conservation analysis, the 35 TCP genes could be classified into two classes, TCP-P and TCP-C, based on the conservative regions of 55 and 59 amino acids, respectively. Gene-duplication analysis revealed that most TCP genes were present in duplication events that eventually led to TCP gene expansion in M. candidum. All the detected gene pairs had a Ka/Ks value of less than one, suggesting that purification selection is the most important factor that influences the evolution of TCP genes. Phylogenetic analysis of three species displayed the evolutionary relationship of TCP genes across different species and further confirmed our results. The real-time quantitative PCR (qRT-PCR) results showed that McTCP2a, McTCP7a, McTCP10, McTCP11, McTCP12a, McTCP13, McTCP16, McTCP17, McTCP18, McTCP20 and McTCP21 may be involved in leaf development; McTCP4a, McTCP1, McTCP14, McTCP17, McTCP18, McTCP20, McTCP22 and McTCP24 may be involved in flower development; and McTCP2a, McTCP3, McTCP5a, McTCP6, McTCP7a, McTCP9, McTCP11, McTCP14 and McTCP16 may be involved in seed development. Our results dissect the TCP gene family across the genome of M. candidum and provide valuable information for exploring TCP genes to promote molecular breeding and property improvement of M. candidum in the future.

Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disorder that causes airway obstruction and lung inflammation. The first-line treatment of COPD is the bronchodilators of ß2-agonists and antimuscarinic drugs, which can help control the airway obstruction, but the long-term use might render the drug tolerance. Bisphosphonates are widely used in osteoclast-mediated bone diseases treatment for decades. For drug repurposing, can delivery of a third generation of nitrogen-containing bisphosphonate, risedronate (RIS) ameliorate the progression of COPD? METHODS: COPD rats or mice models have been established through cigarette-smoking and elastase injection, and then the animals are received RIS treatment via nebulization. Lung deposition of RIS was primarily assessed by high-performance liquid chromatography (HPLC). The respiratory parameters of airway obstruction in COPD rats and mice were documented using plethysmography method and resistance-compliance system. RESULTS: High lung deposition and bioavailability of RIS was monitored with 88.8% of RIS input dose. We found that RIS could rescue the lung function decline of airspace enlargement and mean linear intercept in the COPD lung. RIS could curb the airway obstruction by suppressing 60% of the respiratory resistance and elevating the airway's dynamic compliance, tidal volume and mid-expiratory flow. As an inhibitor of farnesyl diphosphate synthase (FDPS), RIS suppresses FDPS-mediated RAS and RhoA prenylation to obstruct its membrane localization in airway smooth muscle cells (ASMCs), leading to the inhibition of downstream ERK-MLCK and ROCK1-MLCP pathway to cause ASMCs relaxation. Additionally, RIS nebulization impeded pro-inflammatory cell accumulation, particularly macrophages infiltration in alveolar parenchyma. The NF-κB, tumor necrosis factor-alpha, IL-1ß, IL-8, and IL-6 declined in microphages following RIS nebulization. Surprisingly, nebulization of RIS could overcome the tolerance of ß2-agonists in COPD-rats by increasing the expression of ß2 receptors. CONCLUSIONS: Nebulization of RIS could alleviate airway obstruction and lung inflammation in COPD, providing a novel strategy for treating COPD patients, even those with ß2-agonists tolerance.

A comparative evaluation of lasers and photodynamic therapy in the nonsurgical treatment of peri-implant diseases: A Bayesian network meta-analysis.

PURPOSE: We conducted this Bayesian network meta-analysis (NMA) to evaluate the safety and efficacy of different lasers and PDT compared to conventional mechanical debridement (CMD) for peri-implant treatment. METHODS: The Web of Science, Cochrane Library and PubMed databases were searched for randomized clinical trials (RCTs) assessing the clinical effectiveness of adjunctive PDT, different lasers, and CMD until January 1st, 2022. Clinical outcomes were the changes in pocket probing depth (PPD), marginal bone loss (MBL), and clinical attachment level (CAL). RESULTS: Twenty-three studies, including 4 types of lasers, were included. Compared to that with CMD alone, PPD reduction was significantly more efficient in the diode laser (LD)+CMD groups (MD, 0.53; 95%CI, 0.13-0.93) and the PDT+CMD groups (MD, 0.83; 95%CI, 0.32-1.34) than in the CMD group in the follow-up period. Moreover, PDT+CMD treatment also showed a significantly better marginal bone level gain (MD, 0.32; 95%CI, 0.06-0.57). No significant effect on ΔCAL was observed among the different treatment strategies. Despite no differences in PPD reduction, MBL and CAL gains were found among the adjunctive laser treatment groups, PDT+CMD had the highest ranking probability of the most effective treatment in these clinical indices of periodontitis. The certainty of evidence for all outcomes was judged as very low to moderate. CONCLUSIONS: Within the limits of this NMA, we found that adjunctive PDT achieved a small additional benefit on PPD reduction and MBL gain compared with CMD alone and had the highest probability of being ranked first on the changes in PPD, MBL and CAL. PDT+CMD may represent an alternative method for peri­implant treatment. Further high-quality RCTs are needed to assess the influence of potential confounders on the efficacy of lasers and PDT.

Enhancing interactions between cells and hierarchical micro/nanostructured TiO2films for efficient capture of circulating tumor cells.

Micro/nano hierarchical substrates with different micropillar spacings were designed and prepared for capture of tumor cells. The cell capture efficiency of hierarchical substrates with low-density micropillar arrays was similar to that of nanostructured substrate. Increasing the density of micopillars could significantly improve the capture efficiency. The maximum capture efficiency was achieved on the hierarchical substrate with micropillar spacings of 15µm, but further reducing the micropillar spacings did not increase the cell capture efficiency. It was also found that hierarchical substrates with appropriate spacing of micropillars appeared more favorable for cell attachment and spreading, and thus enhancing the cell-material interaction. These results suggested that optimizing the micropillar arrays, such as the spacing between adjacent micropillars, could give full play to the synergistic effect of hierarchical hybrid micro/nanostructures in the interaction with cells. This study may provide promising guidance to design and optimize micro/nano hierarchical structures of biointerfaces for biomedical application.

A gain-of-function NLRP3 3'-UTR polymorphism causes miR-146a-mediated suppression of NLRP3 expression and confers protection against sepsis progression.

Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1ß and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3'-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3'-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.

Circulating Neutrophil-Derived Microparticles Associated with the Prognosis of Patients with Sepsis.

INTRODUCTION: Because of its high morbidity and mortality, sepsis remains the leading cause of death in the ICU. Microparticles (MP) have been largely studied as potential diagnostic or prognostic markers in various diseases including sepsis. OBJECTIVE: The biological and clinical relevance of neutrophil-derived microparticles (NDMPs) within the MP population remains unclear. The objective of this study was to elucidate the relationship between plasma NDMPs and the prognosis of patients with sepsis and/or septic shock. METHODS: The study was designed as an observational, noninterventional clinical study. The cohort for this study included 40 sepsis and 40 septic shock patients together with 10 healthy controls admitted to the Intensive Care Unit (ICU) and the Health Surveillance Center in the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China, from January to November 2018, respectively. The degree of critical disease for sepsis and septic shock was evaluated, with data analyses conducted from 2018 to 2019. RESULTS: On days 1, 3 and 5 post-admission a series of data including plasma NDMP levels, patient demographics, TNF-α levels, IL-6 levels, sTREM-1 levels, and the sepsis severity score measurements were collected. A survival curve was plotted against levels of plasma NDMPs. Levels of NDMPs were observed to be higher in the septic shock patients than in the sepsis patients on days 1, 3, and 5 post-ICU admission (p < 0.05). NDMP levels were significantly increased in sepsis and septic shock patients with a parallel increase in pro-inflammatory mediators and sepsis severity score (p < 0.05) as well as mortality. CONCLUSION: Our data suggest that NDMPs may be a biomarker of sepsis severity and mortality although its implications on sepsis prognosis warrant further study.

Involvement of gap junctions in propylthiouracil-induced cytotoxicity in BRL-3A cells.

Gap junctions (GJs), which are important plasma membrane channels for the transfer of signaling molecules between adjacent cells, have been implicated in drug-induced liver injury. However, the influence and the underlying mechanisms of GJs in propylthiouracil (PTU)-induced hepatotoxicity are unclear. In the present study, distinct manipulations were performed to regulate GJ function in the BRL-3A rat liver cell line. The results indicated that the toxic effect of PTU in BRL-3A cells was mediated by GJ intercellular communication, as cell death was significantly attenuated in the absence of functional GJ channels. Furthermore, the specific knockdown of connexin-32 (Cx32; a major GJ component protein in hepatocytes) using small interfering RNA was observed to decrease necrosis, intracellular PTU content and the level of reactive oxygen species (ROS) following PTU exposure. These observations demonstrated that suppressing GJ Cx32 could confer protection against PTU-induced cytotoxicity through decreasing the accumulation of PTU and ROS. To the best of our knowledge, the present study is the first to demonstrate the role and possible underlying mechanisms of GJs in the regulation of PTU-induced toxicity in BRL-3A rat liver cells.

Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes.

The effect of gap junction intercellular communication (GJIC) on docetaxel-induced hepatotoxicity and its underlying mechanisms are largely unknown. The present study involved investigating the effect of downregulating GJs derived from connexin (Cx) 32 in BRL-3A cells by three different mechanisms: Using a low-density culture; suppression of Cx32 using small interfering RNA; and use of the chemical inhibitor 2­aminoethoxydiphenyl borate (2­APB), all of which led to attenuated docetaxel hepatotoxicity. In order to investigate the relevant mechanisms involved, apoptosis and caspase activities of BRL­3A cells were determined. The increase of apoptosis and the activation of caspase­3 and caspase­9, but not caspase-8, were detected following cell exposure with docetaxel, demonstrating that the mitochondrial­mediated apoptosis pathway is largely responsible for docetaxel hepatotoxicity. However, reduced apoptosis and caspase­3, and ­9 activities were observed following docetaxel application when BRL­3A GJIC was deficient from the knockdown of Cx32 expression or pretreatment with 2­APB. These observations illustrate that GJs are important in docetaxel-induced hepatotoxicity. Furthermore, inhibition of GJIC could prevent amplification of toxicity to docetaxel. Due to GJIC blockage, this hepatoprotection was associated, in part, with decreasing apoptosis of BRL­3A cells through the mitochondrial pathway. The present study provides evidence for potential therapeutic targets for the treatment of docetaxel-induced liver injury.

Endothelialization of TiO2 Nanorods Coated with Ultrathin Amorphous Carbon Films.

Carbon plasma nanocoatings with controlled fraction of sp(3)-C bonding were deposited on TiO2 nanorod arrays (TNAs) by DC magnetic-filtered cathodic vacuum arc deposition (FCVAD). The cytocompatibility of TNA/carbon nanocomposites was systematically investigated. Human umbilical vein endothelial cells (HUVECs) were cultured on the nanocomposites for 4, 24, and 72 h in vitro. It was found that plasma-treated TNAs exhibited excellent cell viability as compared to the untreated. Importantly, our results show that cellular responses positively correlate with the sp(3)-C content. The cells cultured on high sp(3)-C-contented substrates exhibit better attachment, shape configuration, and proliferation. These findings indicate that the nanocomposites with high sp(3)-C content possessed superior cytocompatibility. Notably, the nanocomposites drastically reduced platelet adhesion and activation in our previous studies. Taken together, these findings suggest the TNA/carbon scaffold may serve as a guide for the design of multi-functionality devices that promotes endothelialization and improves hemocompatibility.

Preliminary assessment of two non-destructive instrumental techniques for quality evaluation of Lobelia chinensis Lour.

Two non-destructive instrumental methods, infrared spectroscopy (IR) and X-ray diffraction (XRD), were studied for quality evaluation of Lobelia chinensis Lour. (L. chinensis). We obtained the IR spectra and XRD patterns of L. chinensis collected from different sources. The similarity of samples was analyzed by calculating the cosine coefficient. The cosine values were in the range of 0.83-0.90, indicating that the main components of L. chinensis samples are similar. Sample L1 and L6 showed a slightly lower similarity than that of L2, L3, L4, L5 detected by the two methods, which revealed that IR and XRD methods exhibited analogous detection ability for quality evaluation of L. chinensis. The two methods could be highly recommended as simple and rapid detection means for quality evaluation of L. chinensis.

PtrKOR1 is required for secondary cell wall cellulose biosynthesis in Populus.

KORRIGAN (KOR), encoding an endo-1,4-ß-glucanase, plays a critical role in the cellulose synthesis of plant cell wall formation. KOR sequence orthologs are duplicated in the Populus genome relative to Arabidopsis. This study reports an expression analysis of the KOR genes in Populus. The five PtrKOR genes displayed different expression patterns, suggesting that they play roles in different developmental processes. Through RNAi suppression, results demonstrated that PtrKOR1 is required for secondary cell wall cellulose formation in Populus. Together, the results suggest that the PtrKOR genes may play distinct roles in association with cell wall formation in different tissues.