Catalytic Oxidation Mechanism of Toluene over CexMn1-xO2: The Role of Oxygen Vacancies in Adsorption and Activation of Toluene.

Catalytic oxidation has been extensively studied as a promising technology for the removal of toluene from industrial waste gases and indoor air. However, the debate regarding the oxidation mechanism is far from resolved. CexMn1-xO2 catalysts with different mixing ratios are prepared by the sol-gel method and found to exhibit better catalytic activities for toluene oxidation than a single oxide. Characterizations and theoretical calculations reveal that the doped Mn increases the number of oxygen vacancies and the ability of oxygen vacancies to activate aromatic rings, which promotes the rate-determining step of toluene oxidation, i.e., ring-opening reactions. The oxidation products detected by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and Vocus proton transfer reaction mass spectrometry (Vocus-PTR-MS) show that the doped Mn significantly improves the ring-opening efficiency and subsequently yields more short-chain products, such as pyruvic acid and acetic acid. A comprehensive oxidation pathway of toluene is refined in this work.

Recent Advancements in Sensor Technologies for Healthcare and Biomedical Applications.

Biomedical sensors are the key units of medical and healthcare systems [...].

Electrocatalytic oxidation of gaseous toluene in an all-solid cell using a foam Ti/Sb-SnO2/ß-PbO2 anode.

Mineralization of benzene, toluene, and xylene (BTX) with high efficiency at room temperature is still a challenge for the purification of indoor air. In this work, a foam Ti/Sb-SnO2/ß-PbO2 anode catalyst was prepared for electrocatalytically oxidizing gaseous toluene in an all-solid cell at ambient temperature. The complex Ti/Sb-SnO2/ß-PbO2 anode, which was prepared by sequentially deposing Sb-SnO2 and ß-PbO2 on a foam Ti substrate, shows high electrocatalytic oxidation efficiency of toluene (80%) at 7 hr of reaction and high CO2 selectivity (94.9%) under an optimized condition, i.e., a cell voltage of 2.0 V, relative humidity of 60% and a flow rate of 100 mL/min. The better catalytic performance can be ascribed to the high production rate of ⋅OH radicals from discharging adsorbed water and the inhibition of oxygen evolution on the surface of foam Ti/Sb-SnO2/ß-PbO2 anode when compared with the foam Ti/Sb-SnO2 anode. Our results demonstrate that prepared complex electrodes can be potentially used for electrocatalytic removal of gaseous toluene at room temperature with a good performance.

A New Type of Quartz Smog Chamber: Design and Characterization.

Since the 1960s, many indoor and outdoor smog chambers have been developed worldwide. However, most of them are made of Teflon films, which have relatively high background contaminations due to the wall effect. We developed the world's first medium-size quartz chamber (10 m3), which is jointed with 32 pieces of 5 mm thick polished quartz glasses and a stainless-steel frame. Characterizations show that this chamber exhibits excellent performance in terms of relative humidity (RH) (2-80%) and temperature (15-30 ± 1 °C) control, mixing efficiency of the reactants (6-8 min), light transmittance (>90% above 290 nm), and wall loss of pollutants. The wall loss rates of the gas-phase pollutants are on the order of 10-4 min-1 at 298 K under dry conditions. It is 0.08 h-1 for 100-500 nm particles, significantly lower than those of Teflon chambers. The photolysis rate of NO2 (JNO2) is automatically adjustable to simulate the diurnal variation of solar irradiation from 0 to 0.40 min-1. The inner surface of the chamber can be repeatedly washed with deionized water, resulting in low background contaminations. Both experiments (toluene-NOx and α-pinene-ozone systems) and box model demonstrate that this new quartz chamber can provide high-quality data for investigating SOA and O3 formation in the atmosphere.

Deposition potential of 0.003-10 µm ambient particles in the humidified human respiratory tract: Contribution of new particle formation events in Beijing.

Ultrafine particles (UFPs) usually explosive growth during new particle formation (NPF) events. However, the risk of exposure to UFPs on NPF days has been ignored due to the prevalence of mass-based air quality standards. In this study, the daily deposited doses, i.e., the daily deposited particle number dose (DPNd), mass dose (DPMd), and surface area dose (DPSd), of ambient particles in the human respiratory tract in Beijing were evaluated based on the particle number size distribution (3 nm-10 µm) from June 2018 to May 2019 utilizing a Multiple-Path Particle Dosimetry Model (MPPD) after the hygroscopic growth of particles in the respiratory tract had been accounted for. Our observations showed a high frequency (72.6%) of NPF on excellent air quality days, with daily mean PM2.5 concentrations less than 35 µg m-3. The daily DPNd on excellent air quality days was comparable with that on polluted days, although the DPMd on excellent air quality days was as low as 15.6% of that on polluted days. The DPNd on NPF days was ~1.3 times that on non-NPF days. The DPNd in respiratory tract regions decreased in the order: tracheobronchial (TB) > pulmonary (PUL) > extrathoracic (ET) on NPF days, while it was PUL > TB > ET on non-NPF days. The number of deposited nucleation mode particles, which were deposited mainly in the TB region (45%), was 2 times higher on NPF days than that on non-NPF days. Our results demonstrated that the deposition potential due to UFPs in terms of particle number concentrations is high in Beijing regardless of the aerosol mass concentration. More toxicological studies related to UFPs on NPF days, especially those targeting tracheobronchial and pulmonary impairment, are required in the future.

Live attenuated rubella vectors expressing Plasmodium falciparum circumsporozoite protein (Pf-CSP) provide a novel malaria vaccine platform in the rhesus macaque.

There is an urgent need for a malaria vaccine that can prevent severe disease in young children and adults. Despite earlier work showing an immunological mechanism for preventing infection and reducing disease severity, there is currently no reliable vaccine that can provide durable protection. In part, this may reflect a limited number of ways that the host can respond to the NANP repeat sequences of circumsporozoite protein (CSP) in the parasite. In addition, it may reflect antigenic escape by the parasite from protective antibodies. To be successful, a vaccine must protect against repeated exposure to infected mosquitoes in endemic areas. We have created a series of live viral vectors based on the rubella vaccine strain that express multiple tandem repeats of NANP, and we demonstrate immunogenicity in a rhesus macaque model. We tested the vectors in a sequential immunization strategy. In the first step, the animals were primed with CSP-DNA vaccine and boosted with rubella/CSP vectors. In the second step, we gave rubella/CSP vectors again, followed by recombinant CSP protein. Following the second step, antibody titers were comparable to adult exposure to malaria in an endemic area. The antibodies were specific for native CSP protein on sporozoites, and they persisted for at least 1½ years in two out of three macaques. Given the safety profile of rubella vaccine in children, these vectors could be most useful in protecting young children, who are at greatest risk of severe malarial disease.

Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb.

Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and Aedes aegypti, the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naïve mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2-RNA and proteins are contained inside EVs. Viral plaque formation and dilution assays also showed securely contained infectious viral RNA and proteins in EVs are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no role in viral replication and transmission through EVs. In addition, qRT-PCR and immunoblotting results revealed that DENV2 up-regulates expression of a mosquito tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in A. aegypti mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs. Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein. Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission of viral RNA and proteins to naïve human cells. In summary, we report a very important finding on EV-mediated transmission of DENV2 from arthropod to mammalian cells through interactions with an arthropod EVs-enriched marker Tsp29Fb.

Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells.

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes with the size range of 30 to 200 nm in diameter. Both positive and negative strands of LGTV RNA and viral envelope-protein were detected inside exosomes derived from arthropod, murine and human cells. Detection of Nonstructural 1 (NS1) protein in arthropod and neuronal exosomes further suggested that exosomes contain viral proteins. Viral RNA and proteins in exosomes derived from tick and mammalian cells were secured, highly infectious and replicative in all tested evaluations. Treatment with GW4869, a selective inhibitor that blocks exosome release affected LGTV loads in both arthropod and mammalian cell-derived exosomes. Transwell-migration assays showed that exosomes derived from infected-brain-microvascular endothelial cells (that constitute the blood-brain barrier) facilitated LGTV RNA and protein transmission, crossing of the barriers and infection of neuronal cells. Neuronal infection showed abundant loads of both tick-borne LGTV and mosquito-borne West Nile virus RNA in exosomes. Our data also suggest that exosome-mediated LGTV viral transmission is clathrin-dependent. Collectively, our results suggest that flaviviruses uses arthropod-derived exosomes as a novel means for viral RNA and protein transmission from the vector, and the vertebrate exosomes for dissemination within the host that may subsequently allow neuroinvasion and neuropathogenesis.

Risk Factors of Chemotherapy-Induced Thrombocytopenia After Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancies.

PURPOSE: Thrombocytopenia is among the most common chemotherapy-related hematologic toxicities. We aim to determine the predictors of oxaliplatin chemotherapy-induced thrombocytopenia in patients with gastrointestinal tumors to guide the clinic. METHODS: Clinical data of 750 patients with a malignant gastrointestinal tumor were included as the primary cohort. Basic clinical data, serological indices, and anthropometric indices of these patients were collected. According to the presence or absence of CIT, univariate analysis was performed to identify significant factors for multivariate analysis. In R language software, nomogram was constructed based on the results of multi-factor analysis, and the calibration curve and ROC curve were drawn. RESULTS: Univariate analysis identified 17 factors as closely related to CIT occurrence, namely age, lymph node metastasis (N) stage, metastasis (M) stage, lung metastasis, other site metastasis, chemotherapy regimen, course of treatment, total dose of oxaliplatin, AST, albumin, neutrophils, monocytes, baseline platelets, transferrin, natural killer (NK) cell, phase angle, and SMI (P < 0.10). The binary logistic multivariate regression analysis revealed five independent risk factors for developing CIT (P < 0.05), including the M stage, total dose of oxaliplatin, albumin, baseline thrombocyte count, and NK cell. Based on the results of multivariate logistic regression analysis, R software was used to establish a nomogram model. The calibration curve shows that the combined predictor has good consistency. The area under the ROC curve was 0.877 and the best cut-off value was 0.3579613 (sensitivity, 78.9%; specificity, 81.8%), which showed the better prediction efficiency. CONCLUSION: The total dose of oxaliplatin, M stage, albumin, baseline platelet count, and NK cell was independent risk factors for CIT. The sequentially constructed histogram model had a good predictive effect on the risk of thrombocytopenia caused by oxaliplatin chemotherapy in patients with gastrointestinal malignancies.

Predictive value of ELWI combined with sRAGE/esRAGE levels in the prognosis of critically ill patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition. Accurate judgement of the disease progression is essential for controlling the condition in ARDS patients. We investigated whether changes in the level of serum sRAGE/esRAGE could predict the 28-day mortality of ICU patients with ARDS. A total of 83 ARDS patients in the ICU of the Second Affiliated Hospital of Nantong University from January 2021 to June 2022 were consecutively enrolled in this study. Demographic data, primary diagnosis and comorbidities were obtained. Multiple scoring systems, real-time monitoring systems, and biological indicators were determined within 6 h of admission. The clinical parameters for survival status of the ARDS patients were identified by multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis was employed to verify the accuracy of the prognosis of the related parameters. The admission level of sRAGE was significantly higher in the nonsurvival group than in the survival group (p < 0.05), whereas the serum esRAGE level showed the opposite trend. Multivariate logistic regression analysis showed that sRAGE (AUC 0.673, p < 0.05), esRAGE (AUC 0.704, p < 0.05), and ELWI (extravascular lung water index) (AUC 0.717, p < 0.05) were independent risk factors for the prognosis of ARDS. Model B (ELWI + esRAGE) could not be built as a valid linear regression model (ELWI, p = 0.079 > 0.05). Model C (esRAGE + sRAGE) was proven to have no significance because it had a predictive value similar to that of the serum levels of esRAGE (Z = 0.993, p = 0.351) or sRAGE (Z = 1.116, p = 0.265) alone. Subsequently, Model D (sRAGE + esRAGE + ELWI) showed the best 28-day mortality predictive value with a cut-off value of 0.426 (AUC 0.841; p < 0.001), and Model A (sRAGE + ELWI) had a cut-off value of 0.401 (AUC 0.820; p < 0.001), followed by sRAGE (AUC 0.704, p = 0.004), esRAGE (AUC 0.717, p = 0.002), and ELWI (AUC 0.637, p = 0.028). In addition, there was no statistically significant difference between Model A and Model D (Z = 0.966, p = 0.334). The admission level of sRAGE was higher in the nonsurvival group, while the serum esRAGE level showed the opposite trend. Model A and Model D could be used as reliable combined prediction models for predicting the 28-day mortality of ARDS patients.

FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.

Drug therapy, including chemotherapy, targeted therapy, immunotherapy, and endocrine therapy, stands as the foremost therapeutic approach for contemporary human malignancies. However, increasing drug resistance during antineoplastic therapy has become a substantial barrier to favorable outcomes in cancer patients. To enhance the effectiveness of different cancer therapies, an in-depth understanding of the unique mechanisms underlying tumor drug resistance and the subsequent surmounting of antitumor drug resistance is required. Recently, F-box and WD Repeat Domain-containing-7 (FBXW7), a recognized tumor suppressor, has been found to be highly associated with tumor therapy resistance. This review provides a comprehensive summary of the underlying mechanisms through which FBXW7 facilitates the development of drug resistance in cancer. Additionally, this review elucidates the role of FBXW7 in therapeutic resistance of various types of human tumors. The strategies and challenges implicated in overcoming tumor therapy resistance by targeting FBXW7 are also discussed.

Vaccines' New Era-RNA Vaccine.

RNA vaccines, including conventional messenger RNA (mRNA) vaccines, circular RNA (circRNA) vaccines, and self-amplifying RNA (saRNA) vaccines, have ushered in a promising future and revolutionized vaccine development. The success of mRNA vaccines in combating the COVID-19 pandemic caused by the SARS-CoV-2 virus that emerged in 2019 has highlighted the potential of RNA vaccines. These vaccines possess several advantages, such as high efficacy, adaptability, simplicity in antigen design, and the ability to induce both humoral and cellular immunity. They also offer rapid and cost-effective manufacturing, flexibility to target emerging or mutant pathogens and a potential approach for clearing immunotolerant microbes by targeting bacterial or parasitic survival mechanisms. The self-adjuvant effect of mRNA-lipid nanoparticle (LNP) formulations or circular RNA further enhances the potential of RNA vaccines. However, some challenges need to be addressed. These include the technology's immaturity, high research expenses, limited duration of antibody response, mRNA instability, low efficiency of circRNA cyclization, and the production of double-stranded RNA as a side product. These factors hinder the widespread adoption and utilization of RNA vaccines, particularly in developing countries. This review provides a comprehensive overview of mRNA, circRNA, and saRNA vaccines for infectious diseases while also discussing their development, current applications, and challenges.

Molecular mechanisms of flavonoid accumulation in germinating common bean (Phaseolus vulgaris) under salt stress.

Flavonoids are important secondary metabolites, active biomolecules in germinating beans, and have prominent applications in food and medicine due to their antioxidant effects. Rutin is a plant flavonoid with a wide biological activity range. In this study, flavonoid (rutin) accumulation and its related molecular mechanisms in germinating common bean (Phaseolus vulgaris) were observed at different time points (0-120 h) under salt stress (NaCl). The rutin content increased from germination onset until 96 h, after which a reducing trend was observed. Metabolome analysis showed that salt stress alters flavonoid content by regulating phenylpropanoid (ko00940) and flavonoid (ko00941) biosynthesis pathways, as well as their enzyme activities, including cinnamyl-alcohol dehydrogenase (CAD), peroxidase (POD), chalcone isomerase (CHI), and flavonol synthase (FLS). The RNA-seq and quantitative real-time PCR (qRT-PCR) analyses also showed that these two pathways were linked to changes in flavonoid content following salt treatment. These results reveal that salt stress effectively enhanced rutin content accumulation in germinating beans, hence it could be employed to enhance the functional quality of germinating common beans.

Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick-Human Skin Interface.

Ticks secrete various anti-coagulatory, anti-vasoconstrictory, anti-inflammatory, and anti-platelet aggregation factors in their saliva at the bite site during feeding to evade host immunological surveillance and responses. For the first time, we report successful isolation of exosomes (small membrane-bound extracellular signaling vesicles) from saliva and salivary glands of partially fed or unfed ixodid ticks. Our data showed a novel role of these in vivo exosomes in the inhibition of wound healing via downregulation of C-X-C motif chemokine ligand 12 (CXCL12) and upregulation of interleukin-8 (IL-8). Cryo-electron microscopy (cryo-EM) analysis revealed that tick saliva and salivary glands are composed of heterogeneous populations of in vivo exosomes with sizes ranging from 30 to 200 nm. Enriched amounts of tick CD63 ortholog protein and heat shock protein 70 (HSP70) were evident in these exosomes. Treatment of human skin keratinocytes (HaCaT cells) with exosomes derived from tick saliva/salivary glands or ISE6 cells dramatically delayed cell migration, wound healing, and repair process. Wound healing is a highly dynamic process with several individualized processes including secretion of cytokines. Cytokine array profiling followed by immunoblotting and quantitative-PCR analysis revealed that HaCaT cells treated with exosomes derived from tick saliva/salivary glands or ISE6 cells showed enhanced IL-8 levels and reduced CXCL12 loads. Inhibition of IL-8 or CXCL12 further delayed exosome-mediated cell migration, wound healing, and repair process, suggesting a skin barrier protection role for these chemokines at the tick bite site. In contrast, exogenous treatment of CXCL12 protein completely restored this delay and enhanced the repair process. Taken together, our study provides novel insights on how tick salivary exosomes secreted in saliva can delay wound healing at the bite site to facilitate successful blood feeding.

Exosomes mediate Zika virus transmission through SMPD3 neutral Sphingomyelinase in cortical neurons.

The harmful effects of ZIKA virus (ZIKV) infection are reflected by severe neurological manifestations such as microcephaly in neonates and other complications associated with Guillain-Barré syndrome in adults. The transmission dynamics of ZIKV in or between neurons, or within the developing brains of the foetuses are not fully understood. Using primary cultures of murine cortical neurons, we show that ZIKV uses exosomes as mediators of viral transmission between neurons. Cryo-electron microscopy showed heterogeneous population of neuronal exosomes with a size range of 30-200 nm. Increased production of exosomes from neuronal cells was noted upon ZIKV infection. Neuronal exosomes contained both ZIKV viral RNA and protein(s) that were highly infectious to naïve cells. RNaseA and neutralizing antibodies treatment studies suggest the presence of viral RNA/proteins inside exosomes. Exosomes derived from time- and dose-dependent incubations showed increasing viral loads suggesting higher packaging and delivery of ZIKV RNA and proteins. Furthermore, we noted that ZIKV induced both activity and gene expression of neutral Sphingomyelinase (nSMase)-2/SMPD3, an important molecule that regulates production and release of exosomes. Silencing of SMPD3 in neurons resulted in reduced viral burden and transmission through exosomes. Treatment with SMPD3 specific inhibitor GW4869, significantly reduced ZIKV loads in both cortical neurons and in exosomes derived from these neuronal cells. Taken together, our results suggest that ZIKV modulates SMPD3 activity in cortical neurons for its infection and transmission through exosomes perhaps leading to severe neuronal death that may result in neurological manifestations such as microcephaly in the developing embryonic brains.

Characterization of tick organic anion transporting polypeptides (OATPs) upon bacterial and viral infections.

BACKGROUND: Ixodes scapularis organic anion transporting polypeptides (OATPs) play important roles in tick-rickettsial pathogen interactions. In this report, we characterized the role of these conserved molecules in ticks infected with either Lyme disease agent Borrelia burgdorferi or tick-borne Langat virus (LGTV), a pathogen closely related to tick-borne encephalitis virus (TBEV). RESULTS: Quantitative real-time polymerase chain reaction analysis revealed no significant changes in oatps gene expression upon infection with B. burgdorferi in unfed ticks. Synchronous infection of unfed nymphal ticks with LGTV in vitro revealed no significant changes in oatps gene expression. However, expression of specific oatps was significantly downregulated upon LGTV infection of tick cells in vitro. Treatment of tick cells with OATP inhibitor significantly reduced LGTV loads, kynurenine amino transferase (kat), a gene involved in the production of tryptophan metabolite xanthurenic acid (XA), levels and expression of several oatps in tick cells. Furthermore, bioinformatics characterization of OATPs from some of the medically important vectors including ticks, mosquitoes and lice revealed the presence of several glycosylation, phosphorylation and myristoylation sites. CONCLUSIONS: This study provides additional evidence on the role of arthropod OATPs in vector-intracellular pathogen interactions.