(-)-Epicatechin gallate ameliorates cyprodinil-induced cardiac developmental defects through inhibiting aryl hydrocarbon receptor in zebrafish.

BACKGROUND: Cyprodinil is a widely used fungicide with broad-spectrum activity, but it has been associated with cardiac abnormalities. (-)-Epicatechin gallate (ECG), a natural polyphenolic compound, has been shown to possess protective properties in cardiac development. METHODS: In this study, we investigated whether ECG could mitigate cyprodinil-induced heart defects using zebrafish embryos as a model. Zebrafish embryos were exposed to cyprodinil with or without ECG. RESULTS: Our results demonstrated that ECG significantly improved the survival rate, embryo movement, and hatching delay induced by cyprodinil. Furthermore, ECG effectively ameliorated cyprodinil-induced cardiac developmental toxicity, including pericardial anomaly and impairment of cardiac function. Mechanistically, ECG attenuated the cyprodinil-induced alterations in mRNA expression related to cardiac development, such as amhc, vmhc, tbx5, and gata4, as well as calcium ion channels, such as ncx1h, atp2a2a, and cdh2. Additionally, ECG was found to inhibit the activity of the aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. CONCLUSIONS: In conclusion, our findings provide evidence for the protective effects of ECG against cyprodinil-induced cardiac developmental toxicity, mediated through the inhibition of AhR activity. These findings contribute to a better understanding of the regulatory mechanisms and safe utilization of pesticide, such as cyprodinil.

Comparative analysis of multi-angle structural alterations and cold-water solubility of kudzu starch modifications using different methods.

Kudzu, a plant known for its medicinal value and health benefits, is typically consumed in the form of starch. However, the use of native kudzu starch is limited by its high pasting temperature and low solubility, leading to a poor consumer experience. In this study, kudzu starch was treated using six modification techniques: ball milling, extrusion puffing, alcoholic-alkaline, urea-alkaline, pullulanase, and extrusion puffing-pullulanase. The results of the Fourier transform infrared spectrum showed that the intensity ratio of 1047/1022 cm-1 for the modified starches (1.02-1.21) was lower than that of the native kudzu starch (1.22). The relative crystallinity of modified kudzu starch significantly decreased, especially after ball milling, extrusion puffing, and alcoholic-alkaline treatment. Furthermore, scanning electron microscopy and confocal laser scanning microscopy revealed significant changes in the granular structures of the modified starches. After modification, the pasting temperature of kudzu starch decreased (except for the urea-alkaline treatment), and the apparent viscosity of kudzu starch decreased from 517.95 Pa·s to 0.47 Pa·s. The cold-water solubility of extrusion-puffing and extrusion puffing-pullulanase modified kudzu starch was >70 %, which was significantly higher than that of the native starch (0.11 %). These findings establish a theoretical basis for the potential development of instant kudzu powder.

Brain-derived neurotrophic factor levels across psychiatric disorders: A systemic review and network meta-analysis.

As an important neurotrophic factor in the central nervous system, Brain-derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of psychiatric disorders in many studies. However, its value as a biomarker for the diagnosis and differential diagnosis of mental disorders is still controversial, and its change patterns among different mental disorders have not been compared. We conducted a network meta-analysis of BDNF levels in different psychiatric disorders including schizophrenia(SCZ), major depressive disorder(MDD), bipolar disorder(BD), panic disorder(PD), post-traumatic stress disorder(PTSD), obsessive-compulsive disorder(OCD), generalized anxiety disorder(GAD) and insomnia. Studies were identified by searching electronic databases through 31/05/2023. BDNF levels decreased in patients with BD, MDD, OCD, PD, SCZ compared with controls, while significantly increased in patients with PTSD. According to the network meta-analysis, BDNF levels were significantly decreased in MDD and SCZ compared with BD (-2.6, 95% CIs [-5.32 to -0.15] and - 2.68 95% CIs [-5.18 to -0.23] respectively). However, in the traditional meta-analysis, there was a trend towards lower BDNF levels in SCZ compared to BD, with no significant difference (SMD = -0.20, 95% CIs [-0.49 to 0.08]). In conclusion, abnormal BDNF levels have been found in psychiatric disorders, and the changes in peripheral BDNF levels in patients with psychiatric disorders were reconfirmed in this study, which suggests BDNF exhibits promising clinical utility and may hold diagnostic value in distinguishing between MDD and BD.

Sternal wound infections following internal mammary artery grafts for a coronary bypass: A meta-analysis.

The meta-analysis aims to evaluate and compare the sternal wound infections following internal mammary artery grafts for a coronary bypass. Examinations comparing bilateral internal mammary artery to single internal mammary artery for coronary artery bypass grafting were among the meta-analyses from various languages that met the inclusion criteria. Using dichotomous random- or fixed-effect models, the results of these investigations were examined, and the Odd Ratio (OR) with 95% confidence intervals (CIs) was computed. A total of 31 examinations from 2001 to 2023 were recruited for the current analysis including 181 503 personals with coronary artery bypass grafting. Bilateral internal mammary artery had significantly higher sternal wound infection (OR, 1.51; 95% CI, 1.37-1.68, p < 0.001), superficial sternal wound infection (OR, 1.72; 95% CI, 1.16-2.56, p = 0.007), deep sternal wound infection (OR, 1.62; 95% CI, 1.41-1.86, p < 0.001), sternal wound infection in diabetics (OR, 1.48; 95% CI, 1.16-1.90, p = 0.002), sternal wound infection in elderly (OR, 1.38; 95% CI, 1.22-1.57, p < 0.001), sternal wound infection in pedicled preparation (OR, 1.70; 95% CI, 1.30-2.23, p < 0.001) and sternal wound infection in skeletonized preparation (OR, 1.40; 95% CI, 1.09-1.81, p = 0.009) compared to single internal mammary artery in personals with coronary artery bypass grafting. Bilateral internal mammary artery grafting is linked to a higher risk of impaired wound healing, particularly in diabetic individuals, elderly, pedicled preparation, and skeletonized preparation. Nevertheless, caution should be exercised while interacting with its values since examinations were performed by different surgeons with different skills on different types of personals.

Association between monocyte to high-density lipoprotein-cholesterol ratio and osteoporosis: An analysis of the National Health and Nutrition Examination Survey 2013-2014.

The monocyte to high-density lipoprotein-cholesterol (HDL-C) ratio (monocyte-to-HDL-C ratio) was proposed as a marker of atherosclerosis. Osteoporosis and atherosclerosis share common risk factors and pathophysiological mechanisms. This study aimed to assess the relationship between monocyte-to-HDL-C ratio and osteoporosis. Participants aged ≥50 years with complete bone mineral density (BMD), monocyte, and HDL-C examination data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were included. Descriptive analysis was performed separately according to males and females. Weight linear regression and weight logistic regression analyses were used to analyze the association between the monocyte-to-HDL-C ratio and BMD and osteopenia and osteoporosis and vertebral fracture. A total of 1804 participants were included. Among the participants with osteopenia, 398 (48.31%) were males and 466 (51.91%) were females. Among those with osteoporosis, 38 (2.77%) were males and 95 (9.50%) were females. In females, monocyte-to-HDL-C ratio was negatively associated with femoral neck BMD (regression coefficient (ß) = -0.18; 95% confidence interval (CI): (-0.29, -0.07)) and high monocyte-to-HDL-C ratio was associated with higher odds of osteopenia (odds ratio (OR) = 1.22; 95% CI: (1.01, 1.47)) and osteoporosis (OR = 1.68; 95% CI: (1.13, 2.49)) after adjusting for confounders. In males, only monocyte-to-HDL-C ratio >0.35 was observed to be associated with higher odds of osteoporosis (OR = 1.96; 95% CI: (1.02, 3.79)). Stratified analyses showed that similar results were also found in different populations. This study showed that the monocyte-to-HDL-C ratio was negatively associated with BMD and the risk of osteopenia and osteoporosis in females. The monocyte-to-HDL-C ratio may be a new marker of osteoporosis or osteopenia.

Hypoxia promotes the growth and metastasis of ovarian cancer cells by suppressing ferroptosis via upregulating SLC2A12.

BACKGROUND: Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. METHOD: MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA. Finally, animal experiments including the xenograft model and tumor metastasis model were constructed to validate the role of SLC2A12 in vivo. RESULTS: Hypoxia treatment promoted the cell proliferation, mobility, and colony growth abilities of the two ovarian cancer cell lines HO-8910 and A2780. RNA-seq and enrichment analysis showed that SLC2A12 was hyper-expressed under hypoxia condition and it may be related to glutathione and lipid metabolism. Besides, the expression of SLC2A12 was negatively correlated with overall survival. Hypoxia suppressed ferroptosis by SLC2A12 because silencing SLC2A12 declined the cell viability of HO-8910 and A2780 cells under hypoxia conditions, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) breached that result and upregulated the expression of glutathione peroxidase 4 (GPX4). Moreover, hypoxia increased the expression of hypoxia inducible factor 1 A (HIF-1A), and the accumulated HIF-1A binds to hypoxia inducible factor 1 B (HIF1B) to form HIF-1 complex, then promoted the binding of hypoxic response elements (HRE) to SLC2A12 promoter by HIF-1/HRE signal. Subsequently, SLC2A12 regulated glutathione metabolism and in turn inhibited ferroptosis. The animal experiments indicated that silencing SLC2A12 could significantly inhibit tumor growth and metastasis in vivo. CONCLUSION: Hypoxia promoted ovarian cancer progression by upregulating SLC2A12 and then regulating glutathione metabolism to inhibit ferroptosis.

Efficient Removal of Antibiotic Resistance Genes through 4f-2p-3d Gradient Orbital Coupling Mediated Fenton-Like Redox Processes.

Peroxymonosulfate (PMS) mediated radical and nonradical active substances can synergistically achieve the efficient elimination of antibiotic resistance genes (ARGs). However, enhancing interface electron cycling and optimizing the coupling of the oxygen-containing intermediates to improve PMS activation kinetics remains a major challenge. Here, Co doped CeVO4 catalyst (Co-CVO) with asymmetric sites was constructed based on Ce 4f-O 2p-Co 3d gradient orbital coupling. The catalyst achieved approximately 2.51×105 copies/mL of extracellular ARGs (eARGs) removal within 15 minutes, exhibited ultrahigh degradation rate (k=1.24 min-1 ). The effective gradient 4f-2p-3d orbital coupling precisely regulates the electron distribution of Ce-O-Co active center microenvironment, while optimizing the electronic structure of Co 3d states (especially the occupancy of eg ), promoting the adsorption of oxygen-containing intermediates. The generated radical and nonradical generated by interfacial electron cycling enhanced by the reduction reaction of PMS at the Ce site and the oxidation reaction at the Co site achieved a significant mineralization rate of ARGs (83.4 %). The efficient removal of ARGs by a continuous flow reactor for 10 hours significantly reduces the ecological risk of ARGs in actual wastewater treatment.

Single cobalt atoms anchored on Ti3C2Tx with dual reaction sites for efficient adsorption-degradation of antibiotic resistance genes.

The assimilation of antibiotic resistance genes (ARGs) by pathogenic bacteria poses a severe threat to public health. Here, we reported a dual-reaction-site-modified CoSA/Ti3C2Tx (single cobalt atoms immobilized on Ti3C2Tx MXene) for effectively deactivating extracellular ARGs via peroxymonosulfate (PMS) activation. The enhanced removal of ARGs was attributed to the synergistic effect of adsorption (Ti sites) and degradation (Co-O3 sites). The Ti sites on CoSA/Ti3C2Tx nanosheets bound with PO43- on the phosphate skeletons of ARGs via Ti-O-P coordination interactions, achieving excellent adsorption capacity (10.21 × 1010 copies mg-1) for tetA, and the Co-O3 sites activated PMS into surface-bond hydroxyl radicals (•OHsurface), which can quickly attack the backbones and bases of the adsorbed ARGs, resulting in the efficient in situ degradation of ARGs into inactive small molecular organics and NO3. This dual-reaction-site Fenton-like system exhibited ultrahigh extracellular ARG degradation rate (k > 0.9 min-1) and showed the potential for practical wastewater treatment in a membrane filtration process, which provided insights for extracellular ARG removal via catalysts design.

Efficient photo-Fenton reaction for tetracycline and antibiotic resistant bacteria removal using hollow Fe-doped In2O3 nanotubes: From theoretical research to practical application.

The low exposure of active sites and the slow electron transfer rate still restrict the wide application of the photo-Fenton system of Fe-based photocatalyst in practical water treatment. Herein, we prepared a hollow Fe-doped In2O3 nanotube (h-Fe-In2O3) catalyst for activating hydrogen peroxide (H2O2) to remove tetracycline (TC) and antibiotic resistant bacteria (ARB). Incorporation of Fe could shorten the band gap and increase the absorption capacity of visible light. Meanwhile, the increase of electron density at the Fermi level promotes the interfacial electron transport. The large specific surface area of the tubular structure exposes more Fe active site and the Fe-O-In site reduces the energy barrier of H2O2 activation, resulting in more and faster formation of hydroxyl radicals (•OH). After continuous operation for 600 min, the h-Fe-In2O3 reactor still can remove 85% TC and about 3.5 log ARB in secondary effluent, showing good stability and durability for practical wastewater treatment.

Heart rate variability in generalized anxiety disorder, major depressive disorder and panic disorder: A network meta-analysis and systematic review.

BACKGROUND: Heart rate variability (HRV) in patients with emotional disorders and healthy controls (HCs) has been investigated in many studies but the difference between these emotional disorders was unclear. METHODS: The PubMed, Embase, Medline and Web of Science databases were systematically searched for studies published in English that compared HCs with generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD) patients in HRV. We conducted a network meta-analysis to compare HRV in patients with GAD, MDD, PD and HCs. HRV outcomes, including time domain indices (the standard deviation of NN intervals (SDNN) and the root mean square of the successive differences between normal heartbeats (RMSSD)), and frequency domain indices (High-frequency (HF), Low-frequency (LF) and the ratio of LF to HF (LF/HF)) were obtained. A total of 4008 participants from 42 studies were included. RESULTS: The results of pairwise meta-analysis showed that compared with controls, GAD, PD and MDD patients exhibited significantly reduced HRV. Similar findings were also confirmed in network meta-analysis. The most important finding from network meta-analysis was that GAD patients had significantly lower SDNN than PD patients (SMD = -0.60, 95 % CI [-1.09, -0.11]). CONCLUSION: Our findings provided a potential objective biological marker to distinguish between GAD and PD. In the future, a large sample of research is needed to directly compare HRV of various mental disorders, which is crucial for finding biomarkers to distinguish them.

Energy efficient portable air cathode electrochlorinator for point-of-use disinfection of toilet wastewater.

Active chlorine is the most widely used disinfectant for water disinfection as well as surface sterilization. Here, we report an air cathode electrochlorinator for point-of-use disinfection of toilet wastewater. The air cathode dominated by a four-electron pathway to reduce O2 to OH- was more suitable for chlorine synthesis than through a two-electron pathway to H2O2, which could reduce chlorine back to chloride ions. The minimum driving potential of the air cathode electrochlorinator was as low as 0.94 V, which made it possible to be directly powered by a piece of commercial mini photovoltaic solar panel without electronic converter. Under the cell voltage of 2 V, the Faraday current efficiency was 82.0 % and the electrical energy required to produce 1 kg active chlorine was estimated to be only 1.75 kWh. The normalized energy consumption to disinfect simulated toilet wastewater with a pathogen concentration of 107 CFU/mL was estimated to be 7.2 W h/m3. Moreover, the material cost for fabrication of the electrochlorinator was estimated to be less than $ 0.62. These features guarantee the air cathode electrochlorinator of high potential for point-of-use disinfection of toilet wastewater.

Persistent hiccups due to aripiprazole: a case report and review of the literature.

Introduction: Aripiprazole, a commonly prescribed antipsychotic, has been rarely associated with the onset of hiccups. This study aims to elucidate the prevalence, risk factors, and management of aripiprazole-induced hiccups. Methods: We report a case of aripiprazole-induced hiccups in a 32-year-old male diagnosed with Somatic Symptom Disorder per DSM-5 criteria.A comprehensive literature review was conducted, identifying 29 case reports of aripiprazole-induced hiccups. Patient demographics, dosage, onset and duration of hiccups, and management strategies were analyzed. Results: Aripiprazole-induced hiccups predominantly affected adolescents and middle-aged male patients (86.7%). The majority of hiccups developed within 1-2 days post-prescription (90.9%) and resolved within 1-4 days after discontinuation of aripiprazole. Discontinuation of aripiprazole was the most effective management strategy (51.7%). Co-administration with benzodiazepines was identified as a significant risk factor. Discussion: The findings suggest that clinicians should be vigilant for the onset of hiccups during the early stages of aripiprazole treatment, especially in male patients and those co-administered with benzodiazepines. Conclusion: Clinicians should be vigilant for hiccups during early aripiprazole treatment. Considering personality and psychological factors is crucial in managing hiccups in psychiatric patients.

Phyllosphere fungal communities of rubber trees exhibited biogeographical patterns, but not bacteria.

Phyllosphere microbiomes play an essential role in maintaining host health and productivity. Still, the diversity patterns and the drivers for the phyllosphere microbial community of the tropical cash crop Rubber tree (Hevea brasiliensis) - are poorly understood. We sampled the phyllosphere of field-grown rubber trees in South China. We examined the phyllosphere bacterial and fungal composition, diversity and main drivers of these microbes using the Illumina® sequencing and assembly. Fungal communities were distinctly different in different climatic regions (i.e. Xishuangbanna and Hainan Island) and climatic factors, especially mean annual temperature, and they were the main driving factors of foliar fungal communities, indicating fungal communities showed a geographical pattern. Significant differences of phyllosphere bacterial communities were detected in different habitats (i.e. endophytic and epiphytic). Most of the differences in taxa composition came from Firmicutes spp., which have been assigned as nitrogen-fixing bacteria. Since these bacteria cannot penetrate the cuticle like fungi, the abundant epiphytic Firmicutes spp. may supplement the deficiency of nitrogen acquisition. And the main factor influencing endophytic bacteria were internal factors, such as total nitrogen, total phosphorus and water content of leaves. External factors (i.e. climate) were the main driving force for epiphytic bacteria community assembly. Our work provides empirical evidence that the assembly of phyllosphere bacterial and fungal differed, which creates a precedent for preventing and controlling rubber tree diseases and pests and rubber tree yield improvement.

HPV16 E6 promotes cell proliferation, migration, and invasion of human cervical cancer cells by elevating both EMT and stemness characteristics.

In most cases of cervical cancer, the high risk of the disease is caused by the human papilloma virus (HPV). Surgery or radiation usually benefits patients with early cervical cancer, while the metastatic one is uncurable and new therapeutic strategies and approaches are required. In this study, HPV16 E6 silence or overexpression were carried out to evaluate the possible mechanisms of HPV16 E6 function in cervical cancer cells with different HPV16 E6 expression background. HPV16 E6-positive cervical cancer cell Siha exerts significantly stronger cell invasion and migration potentials than the HPV16 E6-negative C33A cells. HPV16 E6 silence significantly weakened the potentials of cell invasion and migration, cell proliferation and stemness characteristic in Siha cells. Meanwhile, the overexpression of HPV16 E6 effectively promoted the cell proliferation and stemness characteristic in C33A cells. Our data also indicated a positive association between HPV16 E6 and the levels of epithelial to mesenchymal transition (EMT), and cell stemness. The ectopic expression of OCT4 could effectively reverse the inhibitory roles of HPV16 E6 silence on cell migration, invasion, and stemness in Siha cells. More interestingly, we found that HPV16 E6 might promote the OCT4 expression by impairing the direct binding of p53 on the promoter and activate its transcription. Taken together, our results indicated that HPV16 E6 could promoted the potential cell proliferation, migration, and invasion of human cervical cancer cells by modulating EMT and cell stemness. Our data provide a novel mechanism for how HPV16 E6 acts as a key risk factor for cervical cancer development and progression.

Boosting the activation of molecular oxygen and the degradation of tetracycline over high loading Ag single atomic catalyst.

Photocatalytic activation of molecular oxygen (O2) is a promising way in oxidative degradation of organic pollutants. However, it suffers from low efficiency mainly due to the limited active sites for O2 activation over traditional photocatalysts. Therefore, we established a single atomic Ag-g-C3N4 (SAACN) catalyst with 10 wt% loading of Ag single sites for boosting the O2 activation during the degradation of tetracycline (TC), and 10 wt% loading of nanoparticle Ag-g-C3N4 (NPACN) was studied as a comparison. When using SAACN, the accumulative concentration of superoxide (•O2-), hydroxyl radical (•OH), singlet oxygen (1O2) reached up to 0.66, 0.19, 0.33 mmol L-1h-1, respectively, within 120 min, 11.7, 5.7 and 4.9 times compared with those using NPACN, representing 17.24% of dissolved O2 was converted to reactive oxygen species (ROS). When additionally feeding air or O2, the accumulative concentrations of •O2-, •OH, 1O2 were even higher (air: 4.21, 0.97, 2.02 mmol L-1 h-1; O2: 17.13, 1.32, 9.00 mmol L-1 h-1). The rate constants (k) for degrading the TC were 0.0409 min-1 over SAACN and 0.00880 min-1 over NPACN, respectively (mineralization rate: 95.7% vs. 59.9% after 3 h of degradation). Moreover, the degradation ability of SAACN did not decrease in a wide range of pH value (4-10) or under low temperature (10 °C). Besides the high exposure of Ag single sites, other advances of SAACN were: 1(O2 was more energetic favorable to adsorb on single atomic Ag sites; 2) Positive Ag single sites were easier to obtain the electrons from the surrounding N atoms, and facilitated electron transfer towards adsorbed O2.

Dietary fiber regulates intestinal flora and suppresses liver and systemic inflammation to alleviate liver fibrosis in mice.

OBJECTIVES: Liver fibrosis is a common pathologic process related to chronic liver disease. However, there are currently no effective methods to reverse liver fibrosis. Chronic liver disease is typically associated with a major imbalance in the intestinal flora, and targeting the regulation of the intestinal flora structure may facilitate the prevention and treatment of chronic liver disease. Therefore, in this study, we explored the effects of dietary fiber on the prevention of liver fibrosis in mice. METHODS: C57BL/6J mice were randomly divided into 4 groups: olive oil group (control), fibrosis (CCl4) group, resistant maltodextrin (RM) + CCl4 group, and wheat fiber (WF) + CCl4 group. In the latter 3 groups, liver fibrosis was established by treatment with CCl4. In the RM + CCl4 and WF + CCl4 groups, the mice were treated with soluble dietary fiber (RM) or insoluble dietary fiber (WF) for 3 wk before receiving CCl4. The effects of dietary fiber on various indexes of liver fibrosis in mice induced by CCl4 were observed. RESULTS: The results showed that increasing dietary fiber intake prevented liver fibrosis in mice, reduced serum levels of proinflammatory factors (e.g., tumor necrosis factor-alpha, interleukin [IL] 1-beta and IL-6) and increased IL-10 and interferon-gamma levels. Moreover, increased dietary fiber intake also reduced the infiltration of cluster of differentiation (CD) 3+, 4+, and 8+ T lymphocytes in the liver, regulated the structure of the intestinal flora, and increased the Bacteroidetes/Firmicutes ratio. CONCLUSIONS: Our findings revealed the complex relationships between dietary fiber, intestinal flora, and immunity, and suggested that dietary therapy could alleviate liver fibrosis.

Bio fabrication of gold nanoparticles and their combination with chemotherapy and ultrasound for effective treatment of tumors.

BACKGROUND AND OBJECTIVE: Chemotherapy is one of the important medical option for the cancer therapy, but still new combination of therapeutic treatment methods are needed to achieve efficient anti tumor activity. In this work, Pueraria lobata leaf extract was utilized as a bio reductant for the fabrication of the Gold nanoparticles (Au-NPs) by an ecological approach without using any harmful chemical. This work also evaluates whether the combined effect of chemotherapy along with Au-NPs and Ultrasound (US) is effective over the tumors or not. MATERIALS AND METHODS: About 10 mL of plant extract was added to 1mM of HAuCl4 solution (20.0 mL) and pH was maintained at 12 and allowed for stirring for half an hour. The change in solution color from yellow to purple signified the Au-NPs formation. RESULTS: XRD results and TEM images confirmed the formation of crystalline Au-NPs with sizes ranging from 23-30 nm. Further, biological studies revealed that the combination of Au-NPs and US along with chemotherapy improved the impact of anti-cancer drug. CONCLUSION: In conclusion, Pueraria lobata leaf extract mediated synthesis of Au-NPs by an eco-friendly approach was reported in this work. The plant biomolecules of the extract were involved in the reduction and capping of the Au-NPs formed. The major conclusion is that addition of Au-NPs with chemotherapy and ultrasound has shown more effective anti-tumor activity.

Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis.

Vα24-invariant natural killer T (NKT) cells have shown potent anti-tumor properties in murine tumor models and have been linked to favorable outcomes in patients with cancer. However, low numbers of these cells in humans have hindered their clinical applications. Here we report interim results from all three patients enrolled on dose level 1 in a phase 1 dose-escalation trial of autologous NKT cells engineered to co-express a GD2-specific chimeric antigen receptor (CAR) with interleukin-15 in children with relapsed or resistant neuroblastoma (NCT03294954). Primary and secondary objectives were to assess safety and anti-tumor responses, respectively, with immune response evaluation as an additional objective. We ex vivo expanded highly pure NKT cells (mean ± s.d., 94.7 ± 3.8%) and treated patients with 3 × 106 CAR-NKT cells per square meter of body surface area after lymphodepleting conditioning with cyclophosphamide/fludarabine (Cy/Flu). Cy/Flu conditioning was the probable cause for grade 3-4 hematologic adverse events, as they occurred before CAR-NKT cell infusion, and no dose-limiting toxicities were observed. CAR-NKT cells expanded in vivo, localized to tumors and, in one patient, induced an objective response with regression of bone metastatic lesions. These initial results suggest that CAR-NKT cells can be expanded to clinical scale and safely applied to treat patients with cancer.

Mechanistic insights for efficient inactivation of antibiotic resistance genes: a synergistic interfacial adsorption and photocatalytic-oxidation process.

Advanced oxidation processes (AOPs) have been applied to address multiple environmental concerns including antibiotic resistance genes (ARGs). ARGs have shown an increasing threat to human health, and they are either harbored by antibiotic-resistant bacteria (ARB) or free in the environment. However, the control of ARGs has been substantially limited by their low concentration and the limited knowledge about their interfacial behavior. Herein, a novel AOP catalyst, Ag/TiO2/graphene oxide (GO), combined with a polyvinylidene fluoride (PVDF) ultrafiltration membrane was designed with a synergistic interfacial adsorption and oxidation function to inactivate ARGs with high efficiency in both model solutions and in secondary wastewater effluent, especially when the residue concentration was low. Further analysis showed that the mineralization of bases and phosphodiesters mainly caused the inactivation of ARGs. Moreover, the interfacial adsorption and oxidation processes of ARGs were studied at the molecular level. The results showed that GO was rich in sp2 backbones and functional oxygen groups, which efficiently captured and enriched the ARGs via π-π interactions and hydrogen bonds. Therefore, the photogenerated active oxygen species attack the ARGs by partially overcoming the kinetic problems in this process. The Ag/TiO2/GO catalyst was further combined with a PVDF membrane to test its potential in wastewater treatment applications. This work offers an efficient method and a corresponding material for the inactivation and mineralization of intra/extracellular ARGs. Moreover, the molecular-level understanding of ARG behaviors on a solid-liquid interface will inspire further control strategies of ARGs in the future.

Construction of chimeric antigen receptor­modified T cells targeting EpCAM and assessment of their anti­tumor effect on cancer cells.

Colon cancer is a common malignancy worldwide and there is an urgent requirement to develop effective treatment strategies. In recent years, tumor immunotherapy has become a new method of effectively treating tumors. Chimeric antigen receptor (CAR) T cell technology combines the precise targeting specificity of monoclonal antibodies with the strong toxicity and persistence of cytotoxic T cells to specifically recognize tumor­associated antigens and promote tumor cell death efficiently and permanently, without depending on major histocompatibility complex restriction. In the present study, epithelial cell adhesion molecule (EpCAM)­targeting CAR T cells (EpCAM­CAR­T) were developed, and their ability to kill cancer cells in vitro was assessed. Firstly, an EpCAM­CAR plasmid was constructed using molecular biology techniques, and transfected into T cells to obtain EpCAM­CAR­T cells. Transfection efficiency was assessed using reverse transcription­quantitative PCR and flow cytometry. Next, the expression levels of EpCAM in five colon cancer cell lines were examined by western blotting and flow cytometry. Finally, the effect of EpCAM­CAR­T cells on cancer cell death was examined in vitro via co­culture experiments. T cells stably expressing EpCAM­CAR were successfully obtained, and the transduction efficiency according to flow cytometry was 50.4%. In vitro experiments showed that EpCAM­CAR­T cells exhibited a significantly higher apoptotic effect on cancer cells compared with untransfected T cells. Analyses also demonstrated that this effect was dependent on the ratio of EpCAM­CAR­T cells to tumor cells, and the expression of surface EpCAM. Similarly, the ELISA results showed that interleukin (IL)­2 IL­6 and interferon­Î³ levels were significantly elevated following exposure to EpCAM­CAR­T cells compared to exposure to untransfected T cells, and were dependent on the number of EpCAM­CAR­T cells and the amount of EpCAM expressed on the surface of tumor cells. The present study provided a basis for the clinical application of CAR­T cell therapy against solid tumors, and a provided a new strategy for the treatment of colon cancer.