Efficient remediation of di-(2-ethylhexyl) phthalate and plant-growth promotion with the application of a phosphate-solubilizing compound microbial agent.

The ecotoxic endocrine-disrupting chemical di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in agricultural soil, posing a serious threat to human health. Here, we report efficient soil-borne DEHP degradation and plant growth promotion by a microbial organic fertilizer GK-PPB prepared by combining a recycled garden waste-kitchen waste compost product with ternary compound microbial agent PPB-MA, composed of Penicillium oxalic MB08F, Pseudomonas simiae MB751, and Bacillus tequilensis MB05B. The combination of MB08F and MB751 provided synergistic phosphorus solubilization, and MB05B enhanced the DEHP degradation capacity of MB08F via bioemulsification. Under optimal conditions (25.70 °C and pH 7.62), PPB-MA achieved a 96.81 % degradation percentage for 1000 mg L-1 DEHP within 5 days. The degradation curve followed first-order kinetics with a half-life of 18.24 to 24.76 h. A complete mineralization pathway was constructed after identifying the degradation intermediates of 2H-labeled DEHP. Evaluation in Caenorhabditis elegans N2 showed that PPB-MA eliminated the ecological toxicity of DEHP. A pakchoi (Brassica chinensis L.) pot experiment demonstrated that GK-PPB promoted phosphorus solubilization and plant growth, reduced soil DEHP residue, and decreased DEHP accumulation in pakchoi, suggesting its potential practical utility in environmentally responsible and safe cultivation of vegetables.

A novel polymer enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are effective method for tumor treatment. However, the limited variety and quantity of photothermal agents (PTAs) and photosensitizer (PSs) are still major challenges. Moreover, the cell apoptosis mechanism induced by PDT and PTT is still elusive. A fused-ring small molecule acceptor-donor acceptor' donor-acceptor (A-DA'D-A) type of Y5 (Scheme 1) has a narrow band-gap and strong light absorption. Herein, we used Y5 to polymerize with thiophene unit to obtain polymer PYT based on polymerized small molecule strategy, and PYT nanoparticles (PYT NPs) was prepared via one-step nanoprecipitation strategy with DSPE-PEG2000. PYT NPs had excellent biocompatibility, good photostability, high photothermal conversion efficiency (67%) and reactive oxygen species (ROS) production capacity under 808 nm laser irradiation (PYT NPs + NIR). In vitro and in vivo experiments revealed that PYT NPs + NIR had the ability to completely ablate tumor cells. It was demonstrated that cell apoptosis induced by PYT NPs + NIR was closely related to mitochondrial damage. This study provides valuable guidance for constructing high-performance organic PTAs and PSs for tumor treatment. Scheme 1 PYT enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Catalysis-Mediated Male Contraception through Black Phosphorus Nanosheets.

Nanocontraception has been proposed and received extensive attention in recent years for population control. However, currently developed methods for nanocontraception still face problems in efficacy and safety. Here, we propose catalysis-mediated oxidation as a new strategy for nanocontraception. With the catalytic production of highly oxidative species, male contraception was successfully achieved after the administration of black phosphorus nanosheets into the testes of male mice. Further mechanistic studies revealed that contraception was induced by oxidative stress and apoptosis of spermatogenesis cells. Meanwhile, the apoptosis of germ cells released testis antigen and induced immune cell infiltration, which enhanced reproductive damage. Notably, the introduced black phosphorus nanosheets naturally degraded during the catalytic oxidation process and ultimately converted to harmless phosphates, indicating the safety of the strategy. Furthermore, the catalysis-mediated strategy avoids utilizing additional inducers, such as near-infrared irradiation, magnetic fields, or ultrasound, which may cause severe pain. In summary, the proposed catalysis-mediated contraception can be a self-cleared, convenient, and safe strategy for controlling male fertility.

Proteomic and metabolomic approaches elucidate the molecular mechanism of emodin against neuropathic pain through modulating the gamma-aminobutyric acid (GABA)-ergic pathway and PI3K/AKT/NF-κB pathway.

Neuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.

Systems biology strategy and experimental validation to uncover the pharmacological mechanism of Xihuang Pill in treating non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for almost 85% of lung cancer-related deaths worldwide. Xihuang Pill (XHP) is a representative anticancer Chinese patented medicine used to treat NSCLC in China. However, to date, a systematic analysis of XHP's antitumour effects and its impact on the immune microenvironment has not been performed. PURPOSE: Based on the systems biology strategy and experimental validation, the present study aimed to investigate the pharmacological mechanisms involved in treating NSCLC with XHP. METHODS: A subcutaneous tumour model was established to evaluate XHP's tumour-inhibitory effect in BALB/c nude mice. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to XHP treatment. Network analysis based on network pharmacology and protein-to-protein networks was applied to identify the compounds and genes targeted by XHP. External data from the TCGA-NSCLC cohort were used to verify the clinical significance of XHP-targeted genes in NSCLC. The expression of survival-related candidate genes after XHP treatment was verified via qPCR. The protein expression of calcium voltage-gated channel subunit alpha 1C (CACNA1C) in different NSCLC cell lines was analysed in the Human Protein Atlas database (HPA) and DepMap Portal. Using the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm and the single-sample gene set enrichment analysis (ssGSEA) algorithm uncovered the role of CACNA1C in the NSCLC tumour microenvironment (TME). RESULTS: XHP (2 g/kg/d) significantly inhibited the growth of transplanted A549 tumours. RNA-seq identified a total of 529 DEGs (189 upregulated and 340 downregulated). In addition, 542 GO terms, 41 significant KEGG pathways, 9 upregulated hallmarks pathways, and 18 downregulated hallmark pathways were enriched. These GO terms and signalling pathways were closely related to cell proliferation, immunity, energy metabolism, and the inflammatory response of NSCLC. In addition, XHP's network pharmacology analysis identified 301 compounds and 1,432 target genes. A comprehensive strategic analysis identified CACNA1C as a promising gene by which XHP targets and regulates the TME of NSCLC, benefiting patient survival. CACNA1C expression was positively correlated with both the immune score and stromal score but negatively correlated with the tumour purity score. Additionally, CACNA1C expression was significantly correlated with the infiltration levels of 15 types of immune cells and the expression levels of 6 well-known checkpoint genes. CONCLUSIONS: Our results show that by regulating the pathways associated with cell proliferation and immunity, XHP can suppress cancer cell growth in NSCLC. Additionally, XHP may increase the expression of CACNA1C to suppress immune cell infiltration and regulate the expression of checkpoint-related genes, thereby improving the overall survival of NSCLC patients.

Oral Administration of Branched-Chain Amino Acids Attenuates Atherosclerosis by Inhibiting the Inflammatory Response and Regulating the Gut Microbiota in ApoE-Deficient Mice.

Atherosclerosis (AS) is a chronic inflammatory disease that serves as a common pathogenic underpinning for various cardiovascular diseases. Although high circulating branched-chain amino acid (BCAA) levels may represent a risk factor for AS, it is unclear whether dietary BCAA supplementation causes elevated levels of circulating BCAAs and hence influences AS, and the related mechanisms are not well understood. Here, ApoE-deficient mice (ApoE-/-) were fed a diet supplemented with or without BCAAs to investigate the effects of BCAAs on AS and determine potential related mechanisms. In this study, compared with the high-fat diet (HFD), high-fat diet supplemented with BCAAs (HFB) reduced the atherosclerotic lesion area and caused a significant decrease in serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. BCAA supplementation suppressed the systemic inflammatory response by reducing macrophage infiltration; lowering serum levels of inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6); and suppressing inflammatory related signaling pathways. Furthermore, BCAA supplementation altered the gut bacterial beta diversity and composition, especially reducing harmful bacteria and increasing probiotic bacteria, along with increasing bile acid (BA) excretion. In addition, the levels of total BAs, primary BAs, 12α-hydroxylated bile acids (12α-OH BAs) and non-12α-hydroxylated bile acids (non-12α-OH BAs) in cecal and colonic contents were increased in the HFB group of mice compared with the HFD group. Overall, these data indicate that dietary BCAA supplementation can attenuate atherosclerosis induced by HFD in ApoE-/- mice through improved dyslipidemia and inflammation, mechanisms involving the intestinal microbiota, and promotion of BA excretion.

Black phosphorus quantum dots cause glucose metabolism disorder and insulin resistance in mice.

Black phosphorus quantum dots (BPQDs) are considered to have wide application prospects due to their excellent properties. However, there is no study on the effect of BPQDs on glucose metabolism. In this study, blood glucose was significantly increased when mice were continuously intragastrically administered 0.1 and 1 mg/kg bw BPQDs. The blood glucose level of the mice was elevated from Day 7 to Day 28. BPQD exposure also decreased the area under the curve (AUC) of the oral glucose tolerance test (OGTT). After exposure, the pancreas somatic index was increased. Moreover, the serum insulin and glucagon levels were elevated and the relative area of islet ß cells was increased in BPQD-exposed mice, while insulin signaling cascades were reduced in muscle tissues. In summary, our study demonstrated for the first time that BPQD exposure induces glucose disorder and insulin resistance in muscle, which is helpful to understand the biosafety of black phosphorus nanomaterials and promote the sustainable development of nanotechnology.

The establishment of LC-MS/MS assays-specific reference intervals for serum folates and its application in evaluating FA-supplemented folate deficiency patients: Appeals for a suitable and individualized supplementation.

BACKGROUND: Little known about folates status in folate deficiency patients. This study aims to establish liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay-specific reference intervals (RIs) for serum 5-Methyltetrahydrofolate (5MeTHF), folic acid (FA), 5-Formyltetrahydrofolate (5FoTHF), and total folate (TFOL), and investigate the folates status in FA-supplemented folate deficient patients. METHODS: Sera from 120 reference subjects were selected and measured. An LC-MS/MS method for serum 5MeTHF, FA, and 5FoTHF was employed. RIs were derived based on the CLSI C28-A3. Serum folate levels of 38 FA-supplemented folate deficiency patients were analyzed. RESULTS: RIs (median) for 5MeTHF, FA, 5FoTHF, and TFOL were 3.83-62.33 nmol/L (12.27 nmol/L), 0.30-0.92 nmol/L (0.49 nmol/L), <0.73 nmol/L (0.00 nmol/L), and 4.17-63.47 nmol/L (12.66 nmol/L), respectively. Approximately 53 % (20/38), 74 % (28/38), and 63 % (24/38) of patients presented high levels of 5MeTHF, FA, and TFOL, respectively, which far exceeded the upper reference limit (URL) of the corresponding RIs. A half (18/38) of patients showed simultaneously higher 5MeTHF and FA levels which were beyond the URLs of RIs. Near one-third (11/38) of patients exhibited extremely high FA levels which exceeded the 100-fold URL of RIs. The highest levels can be 539 nmol/L for FA, 364 nmol/L for 5MeTHF, and 686 nmol/L for TFOL. CONCLUSIONS: LC-MS/MS assay-specific RIs were established for folates vitamers without age or gender partitioning. Abnormally high levels of unmetabolized FA and 5MeTHF were observed in quite a few FA-supplemented patients. Considering the adverse risks caused by folates excess, we appeal for a justifiable and individualized FA supplementation. We also recommend establishing LC-MS/MS assay-specific RIs for routine monitoring of folates status.

Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms.

Branched-chain amino acids (BCAAs), essential amino acids for the human body, are mainly obtained from food. High levels of BCAAs in circulation are considered as potential markers of metabolic-associated fatty liver disease (MAFLD) in humans. However, there are conflicting reports about the effects of supplement of BCAAs on MAFLD, and research on BCAAs and gut microbiota is not comprehensive. Here, C57BL/6J mice were fed with a high-fat diet with or without BCAAs to elucidate the effects of BCAAs on the gut microbiota and metabolic functions in a mouse model of MAFLD. Compared to high-fat diet (HFD) feeding, BCAA supplementation significantly reduced the mouse body weight, ratio of liver/body weight, hepatic lipid accumulation, serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT), and the expressions of the lipogenesis-related enzymes Fas, Acc, and Scd-1 and increased expressions of the lipolysis-related enzymes Cpt1A and Atgl in the liver. BCAAs supplementation also counteracted HFD-induced elevations in serum BCAAs levels by stimulating the enzymatic activity of BCKDH. Furthermore, BCAAs supplementation markedly improved the gut bacterial diversity and altered the gut microbiota composition and abundances, especially those of genera, in association with MAFLD and BCAAs metabolism. These data suggest that BCAA treatment improves HFD-induced MAFLD through mechanisms involving intestinal microbes.

Beneficial effects of aloperine on inflammation and oxidative stress by suppressing necroptosis in lipopolysaccharide-induced acute lung injury mouse model.

RATIONALE: Alveolar epithelial cell death, inflammation, and oxidative stress are typical features of acute lung injury (ALI). Aloperine (Alo), an alkaloid isolated from Sophora alopecuroides, has been reported to display various biological effects, such as anti-inflammatory, immunoregulatory, and anti-oxidant properties. In this study, we investigated the effects and mechanisms of Alo in treating a lipopolysaccharide (LPS)-induced ALI in a murine model. METHODS: The effects of Alo in LPS-induced ALI were investigated in C57BL/6 mice. The RIPK1 inhibitor (Nec-1) and the RIPK3 inhibitor (GSK'872) were used to evaluate the relationship of necroptosis, NF-κB activation, and PDC subunits in LPS-treated mouse alveolar epithelial cells (MLE-12). Then the effects of Alo on necroptosis, inflammation, and oxidative stress of LPS-stimulated MLE-12 cells were evaluated. RESULTS: Alo significantly attenuated histopathological lung injuries and reduced lung wet/dry ratio in LPS-induced ALI mice. Alo also remarkedly reduced total protein and neutrophils recruitment in bronchoalveolar lavage fluid of ALI mice. Meanwhile, Alo ameliorated the LPS-induced necroptosis in the lungs of ALI mice. The RIPK3 inhibitor GSK'872, but not the RIPK1 inhibitor Nec-1, reversed LPS-induced p65 phosphorylation and translocation to the nucleus in MLE-12 cells. GSK'872 also reversed the LPS-induced increase in ROS and binding of RIPK3 and PDC subunits in MLE-12 cells. Moreover, Alo down-regulated the levels of p-RIPK1, p-RIPK3, p-MLKL, p-p65, the translocation of p65 to the nucleus, and reduced the expression of IL-6 and IL-8 in LPS-stimulated MLE-12 cells. Alo also inhibited the binding of RIPK3 and PDC-E1α, PDC-E1ß, PDC-E2, and PDC-E3 and the ROS production in LPS-treated MLE-12 cells. CONCLUSION: The present study validated the beneficial effects of Alo on LPS-induced ALI , suggesting Alo may be a new drug candidate against ALI.

Interfacially Super-Assembled Tyramine-Modified Mesoporous Silica-Alumina Oxide Heterochannels for Label-Free Tyrosinase Detection.

Tyrosinase (TYR) is a multifunctional copper-containing enzyme that plays a critical role in the biosynthetic pathway of melanin. Thus, the detection of TYR activity possesses vast importance from clinical diagnosis to the food industry. However, most TYR detection methods are expensive, complicated, and time-consuming. Herein, a functional nanofluidic heterochannel composed of an ultrathin tyramine-modified mesoporous silica layer (Tyr-MS) and alumina oxide (AAO) arrays is constructed by an interfacial super-assembly method. The heterochannel with plenty of enzyme catalytic sites for TYR provides the response of the ion current signal against TYR concentrations. Introducing enzymatic reaction paves the way for the heterochannel to achieve label-free, selective, specific detection of TYR. Notably, a highly sensitive detection of TYR with a limit of 2 U mL-1 was obtained by optimizing the modified conditions. Detailed investigations and theoretical calculations further reveal the mechanism for the detection performance. This work provides a simple, low-cost, quick response, and label-free platform based on functional nanofluidic devices for enzyme-sensing technologies.

Effects of acupoint injection for stroke patients with hemiplegia: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Acupoint injection has currently received increasing attention as a treatment for hemiplegia. A number of studies have reported that acupoint injection have some advantages in treatment of hemiplegia. However, currently no article has summarized the existing evidence. Our study will evaluate the efficacy and safety of acupoint injection as a clinical treatment for hemiplegia, so that it can provide an important reference for clinical decision-making. METHODS: Randomized controlled trials and case control studies of acupoint injection for hemiplegia according to the included and excluded standard were identified in searches of 6 databases from their inception to February 2021. All data were assessed and extracted by 2 authors independently. The risk of bias assessment recommended by the Cochrane Collaboration was used to assess the quality of the selected studies. Review Manager 5.4 (Cochrane Collaboration) was used to conduct meta-analysis for the efficacy and safety of acupoint injection. RESULT: The results of this systemic review and meta-analysis will be submitted to a recognized journal for publication. CONCLUSION: This systemic review and meta-analysis will evaluate the efficacy and safety of acupoint injection as a clinical treatment for hemiplegia. We hope this study can make a definitive conclusion for acupoint injection in the treatment of hemiplegia. REGISTRATION: PROSPERO (registration number CRD42021234453).

RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment.

Nanosafety is a major concern for nanotechnology development. Evaluation of the transcriptome and the DNA methylome is proposed for nanosafety assessments. RNA m6A modification plays a crucial role in development, disease, and cell fate determination through regulating RNA stability and decay. Here, since black phosphorus quantum dots (BPQDs), among many other types of QDs, increase the global m6A level and decrease the demethylase ALKBH5 level in lung cells, the epitranscriptome is taken into consideration for the first time to evaluate nanosafety. Both the transcriptome and m6A epitranscriptome analyses show that BPQDs alter many biological processes, such as the response to selenium ions and the lipoxygenase pathway, indicating possible ferroptosis activation. The results further show that BPQDs cause lipid peroxidation, mitochondrial dysfunction, and iron overload. Recognition of these modified mRNAs by YTHDF2 leads to mRNAs' decay and eventually ferroptosis. This study shows that RNA m6A modification not only is a more sophisticated indicator for nanosafety assessment but also provides novel insight into the role of RNA m6A in regulating BPQD-induced ferroptosis, which may be broadly applicable to understanding the functions of RNA m6A under stress.

Potassium permanganate as a promising pre-oxidant to treat low-viability cyanobacteria and associated removal of cyanotoxins and extracellular organic matters.

Cell-viability of cyanobacteria declines from development to decay stage during a successive bloom. Potassium permanganate (KMnO4) has demonstrated to be a superior pre-oxidant to treat high-viability cyanobacteria compared to other common oxidants (e.g., chlorine), but whether it is feasible to treat low-viability cyanobacteria is unknown. Here, effects of KMnO4 on membrane integrity, cyanotoxin fate and extracellular organic matters (EOMs) removal of high- and low-viability cyanobacteria were compared. Results showed that cell-viability of cyanobacteria could affect oxidant decay (kdecay), membrane damage (kloss), and cyanotoxins release (ki) and degradation (ke) during KMnO4 oxidation, similar to chlorination. However, unlike chlorination, initial low dosages of KMnO4 (0.5 and 1 mg L-1) minimized membrane damage for low-viability cyanobacteria (< 27%), and continuously decrease extracellular cyanotoxins, extracellular organic matters (EOMs), and aromatic compounds to some degrees (P<0.05). High dosages of KMnO4 (> 2 mg L-1) caused severe membrane destruction (> 89%) for low-viability cyanobacteria, leading to a fast increase of extracellular cyanotoxins within 1 h. However, total/extracellular cyanotoxins were oxidized to below the safety guideline of 1 µg L-1 after being dosed with sufficient oxidant exposure. EOMs and aromatic compounds were also reduced by 5-18% (P<0.05). Additionally, KMnO4-assisted coagulation significantly improved the removal of low-viability cyanobacteria (2-5 fold). Consequently, KMnO4 could be a promising pre-oxidant to treat low-viability cyanobacteria at decay stage of a successive bloom.

The Use of Magnesium Sulfate and Peripheral Nerve Blocks: An Updated Meta-analysis and Systematic Review.

OBJECTIVES: With the popularization of ultrasound, nerve blocks have been widely implemented in current clinical practice. Although, they have seen limited success due to their shorter duration and suboptimal analgesia. Magnesium sulfate as a local anesthetic adjuvant for peripheral nerve blocks could enhance the effects of local anesthetics. However, previous investigations have not thoroughly investigated the analgesic efficacy of magnesium sulfate as an adjunct to local anesthetics for peripheral nerve blocks. Thus, we attempted to fill the gap in the existing literature by conducting a meta-analysis. MATERIALS AND METHODS: We performed of a quantitative systematic review of randomized controlled trials published between May 30, 2011 and November 1, 2018. Inclusion criteria were: (1) magnesium sulfate used as adjuvant mixed with local anesthetic for nerve blockade, (2) complete articles and published abstracts of randomized controlled trials, (3) English language. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were time of onset, total duration of the sensory blockade, and Visual Analog Scale pain scores. The secondary outcomes were postoperative oral and intravenous analgesics consumption and the incidence of nausea and vomiting. RESULTS: The 21 trials analyzed in this study included 1323 patients. Magnesium sulfate effectively prolonged the total duration of sensory blockade (mean difference [MD]=114.59 min, 95% confidence interval [CI]: 89.31-139.88), reducing Visual Analog Scale pain scores at 6 hours (MD=1.36 points, 95% CI: -2.09 to -0.63) and 12 hours (MD=1.54 points, 95% CI: -2.56 to -0.53) postsurgery. Magnesium sulfate also effectively reduced postoperative analgesic use within 24 hours postsurgery (standard MD=-2.06, 95% CI: -2.67 to -1.35). Furthermore, adjuvant magnesium sulfate significantly reduced the incidence of nausea and vomiting after transversus abdominis plane blockade (odds ratio: 0.39, 95% CI: 0.18-0.81). CONCLUSION: Adjuvant magnesium sulfate enhanced the anesthetic effects of local anesthetics and improved postoperative analgesia following the perineural blockade.

Theaflavin alleviates oxidative injury and atherosclerosis progress via activating microRNA-24-mediated Nrf2/HO-1 signal.

Theaflavin (TF) in black tea has been shown to have significant antioxidant and anti-inflammatory capacity; however, the effects and the underlying mechanism of TF on atherosclerosis (AS) remain unclear. Herein, we investigated the effects and the potential mechanism of TF on AS progression in vivo and in vitro. ApoE-/- mice were administrated with high fat diet (HFD) or HFD + TF (5 or 10 mg, i.g.) for 12 weeks. The results indicated that TF administration effectively decreases the serum lipid levels and the production of MDA in HFD-fed mice. Meanwhile, TF promotes the activities of antioxidant enzymes (SOD, CAT, and GSH-Px) and inhibits the formation of atherosclerotic plaque and the process of histological alterations in the aorta. In vitro, TF pretreatment could protect against cholesterol-induced oxidative injuries in HUVEC cells, decreasing the level of ROS and MDA, maintaining the activities of antioxidant enzymes. Further study revealed that TF upregulates Nrf2/HO-1 signaling pathway in vascular endothelial cells. Moreover, TF increases the level of microRNA-24 (miR-24), and miR-24 inhibition markedly compromises TF-induced Nrf2 activation and protective effects. In conclusion, the present study indicated that theaflavins may achieve the anti-atherosclerotic effect via activating miR-24-mediated Nrf2/HO-1 signaling pathway.

Interfacial Super-Assembly of Nanofluidic Heterochannels from Layered Graphene and Alumina Oxide Arrays for Label-Free Histamine-Specific Detection.

Nanofluidic devices with well-defined channels have shown great potential for biosensing, separation and, energy conversion. Recently, two-dimensional (2D) materials have been widely used for constructing novel nanofluidic devices owing to their high specific surface, abundant surface charge, and low cost. However, 2D-based nanofluidic devices for highly sensitive biosensing have drawn little attention. Herein, we developed a 2D material-based nanofluidic heterochannel with an asymmetric T-mode nanochannel structure and surface charge polarization distribution. This heterochannel was composed of layered graphene oxide modified with Nα, Nα-bis(carboxymethyl)-l-lysine (containing metal-nitrilotriacetic chelates, NTA) and an oxide array (NTA-GO/AAO), which can achieve remarkable selectivity, specificity, and label-free detection of the neurotransmitter histamine based on a metal ion displacement mechanism. A detection limit of 1 nM can be obtained using the NTA-GO/AAO heterochannel. This study provides a simple and label-free platform for developing a 2D-based nanofluidic heterochannel for specific molecular detection.

Cytotoxicity of black phosphorus quantum dots on lung-derived cells and the underlying mechanisms.

Black phosphorus quantum dots (BP-QDs) are a new type of zero-dimensional (0D) nanomaterial that has been widely used due of their superior properties in many biomedical fields, but limited studies have focused on the biocompatibility of BP-QDs, particularly in the respiratory system. In this study, we investigated the potential lung cell toxicity of BP-QDs in vitro. Two human lung-derived cells, A549 and Beas-2B, were treated with 5∼20 µg/mL BP-QDs for 24 h. The results showed that BP-QDs triggered significant lung cell toxicity, including a dose-dependent decrease in cell viability, lactate dehydrogenase (LDH) leakage, cell shape changes, cellular oxidative stress and cell cycle arrest. In addition, pretreatment with the classical phagocytosis inhibitor cytochalasin D (Cyto D) alleviated the decrease in cell viability and LDH leakage induced by BP-QDs. In contrast, BP-QDs induced the production of cellular reactive oxygen species (ROS) and decreases in the glutathione level, whereas the ROS scavenger N-acetyl-L-cysteine (NAC) could protect A549 and Beas-2B cells from BP-QD-induced cellular oxidative stress. Taken together, the results from this study indicate that the potential toxic effects and mechanisms of BP-QDs in two different human lung cells should be considered to evaluate the lung cell safety of BP-QDs.

[Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules].

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Dendrobium officinale Attenuates Myocardial Fibrosis via Inhibiting EMT Signaling Pathway in HFD/STZ-Induced Diabetic Mice.

Cardiac fibrosis is a major contributor for diabetic cardiomyopathy and Dendrobium officinale possessed therapeutic effects on hyperglycemia and diabetic cardiomyopathy. To further investigate the possible mechanisms of the Dendrobium officinale on diabetic myocardial fibrosis in mice. Water-soluble extracts of Dendrobium officinale (DOE) from dry stem was analyzed by HPLC and phenol-sulfuric acid method. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ) (30 mg/kg) for 4 consecutive days after intragastric administration of a high-fat diet (HFD) for 2 weeks. The groups were as follows: control group, model group, DOE low, medium, high dose group (75, 150, 300 mg/kg) and Metformin positive group (125 mg/kg). The results showed that DOE dose-dependently lower serum insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and grew the high-density lipoprotein cholesterol (HDL-C) after 12 weeks of daily administration with DOE. Hematoxylin-eosin staining and Sirius red staining showed obvious amelioration of cardiac injury and fibrosis. In addition, the result of immunoblot indicated that DOE increased the expression of peroxisome proliferator activated receptor-α (PPAR-α), phosphorylation of insulin receptor substrate 1 (p-IRS1) and E-cadherin and repressed the expression of transforming growth factor ß1 (TGF-ß1), phosphorylation of c-Jun N-terminal kinase (p-JNK), Twist, Snail1 and Vimentin. The present findings suggested that DOE ameliorated HFD/STZ-induced diabetic cardiomyopathy (DCM). The possible mechanism mainly associated with DOE accelerating lipid transport, inhibiting insulin resistant and suppressing fibrosis induced by epithelial mesenchymal transition (EMT).