Investigation of the Effect of Peptide p5 Targeting CDK5-p25 Hyperactivity on Munc18-1 (P67) Regulating Neuronal Exocytosis Using Molecular Simulations.

Munc18-1 is an SM (sec1/munc-like) family protein involved in vesicle fusion and neuronal exocytosis. Munc18-1 is known to regulate the exocytosis process by binding with closed- and open-state conformations of Syntaxin1, a protein belonging to the SNARE family established to be central to the exocytosis process. Our previous work studied peptide p5 as a promising drug candidate for CDK5-p25 complex, an Alzheimer's disease (AD) pathological target. Experimental in vivo and in vitro studies suggest that Munc18-1 promotes p5 to selectively inhibit the CDK5-p25 complex without affecting the endogenous CDK5 activity, a characteristic of remarkable therapeutic implications. In this paper, we identify several binding modes of p5 with Munc18-1 that could potentially affect the Munc18-1 binding with SNARE proteins and lead to off-target effects on neuronal communication using molecular dynamics simulations. Recent studies indicate that disruption of Munc18-1 function not only disrupts neurotransmitter release but also results in neurodegeneration, exhibiting clinical resemblance to other neurodegenerative conditions such as AD, causing diagnostic and treatment challenges. We characterize such interactions between p5 and Munc18-1, define the corresponding pharmacophores, and provide guidance for the in vitro validation of our findings to improve therapeutic efficacy and safety of p5.

COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Spatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. Here, we transplant a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and study the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells are uncommon in the porcine kidney cortex early after xenotransplantation and consist of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages express genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft is detectable. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression may be able to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

Nanotechnology in wood science: Innovations and applications.

Application of nanomaterials is gaining tremendous interest in the field of wood science and technology for value addition and enhancing performance of wood and wood-based composites. This review focuses on the use of nanomaterials in improving the properties of wood and wood-based materials and protecting them from weathering, biodegradation, and other deteriorating agents. UV-resistant, self-cleaning (superhydrophobic) surfaces with anti-microbial properties have been developed using the extraordinary features of nanomaterials. Scratch-resistant nano-coatings also improve durability and aesthetic appeal of wood. Moreover, nanomaterials have been used as wood preservatives for increasing the resistance against wood deteriorating agents such as fungi, termites and borers. Wood can be made more resistant to ignition and slower to burn by introducing nano-clays or nanoparticles of metal-oxides. The use of nanocellulose and lignin nanoparticles in wood-based products has attracted huge interest in developing novel materials with improved properties. Nanocellulose and lignin nanoparticles derived/synthesized from woody biomass can enhance the mechanical properties such as strength and stiffness and impart additional functionalities to wood-based products. Cellulose nano-fibres/crystals find application in wide areas of materials science like reinforcement for composites. Incorporation of nanomaterials in resin has been used to enhance specific properties of wood-based composites. This review paper highlights some of the advancements in the use of nanotechnology in wood science, and its potential impact on the industry.

Characterization and apportionment of carbonaceous aerosol emission factors from light-duty and heavy-duty vehicle fleets in Maharashtra, India.

This study aims to investigate the characteristics of carbonaceous aerosols and estimate emission factor (EF) based on roadway tunnel measurements, from two distinct vehicular fleets: an all light-duty vehicle (LDV) fleet, and a mixed fleet of 80% LDV and 20% heavy-duty vehicle (HDV). Carbonaceous content (organic carbon: OC and elemental carbon: EC) in total fine particles (PM2.5) accounted for 41% ± 6.8% in LDV fleet and 48% ± 7.2% in mixed fleet. While higher volatile OC dominated in the LDV fleet emissions, in mixed fleet, lower volatile OC and EC emissions dominated due to the presence of higher HDV and super-emitter (SE) fractions which led to significantly higher optically active absorbing aerosols. Reconstructed HDV fleet EF was higher than LDV fleet by 36 times (PM2.5), 19 times (OC) and 51 times (EC). Our findings emphasize the significance of implementing vehicle inspection and maintenance programs, coupled with decarbonization of HDVs to mitigate on-road vehicular emissions in India.

Our experience with liver and spleen elastography in the prediction of oesophageal varices.

Background: Variceal bleeding is an important cause of mortality in patients with chronic liver disease (CLD). The gold standard for detection and grading of oesophageal varices (EV) is upper gastrointestinal endoscopy. However, it is expensive, time-consuming and invasive. Objectives: This study aimed to find any association between splenic shear wave velocity (SWV) measured by acoustic radiation force imaging (ARFI) and the presence of EV. Method: The quasi-experimental study included 50 patients with CLD and 50 subjects without CLD as the control group. Both underwent upper abdominal ultrasonography followed by elastographic assessment on a Siemens Acuson S2000TM ultrasound system. A comparison of the findings was made between the control and patient groups. Results: Both groups had similar hepatic size while patients with CLD had larger splenic size and area (p < 0.05). The CLD patients had higher mean hepatic and splenic SWV compared with the control group (p < 0.05). The mean splenic size and splenic SWV were higher in patients with varices than in those without varices (p < 0.05). Conclusion: Chronic liver disease causes significant increase in liver and splenic stiffness with splenic SWV values being higher for patients with varices emphasising the role of elastography as a non-invasive predictor for the presence of EVs. Splenic SWV had the highest sensitivity and specificity, which was augmented by a combination of hepatic and splenic SWV. Thus, splenic SWV alone or in combination with hepatic SWV is a useful technique for prediction of the presence of EVs. Contribution: This study aims to find an alternative non-invasive and cost-effective technique for screening of EV.

Zika virus antibody-positivity among symptomatic/asymptomatic pregnant women in the Aseer region displays pre-exposure to dengue viruses.

Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.

Chemical and oxidative properties of fine particulate matter from near-road traffic sources.

The toxicity associated with the fine particulate matter (PM2.5) has not been well studied, particularly in relation to the emissions from on-road vehicles and other sources in low- and middle-income countries such as India. Thus, a study was conducted to examine the oxidative potential (OP) of PM2.5 at a roadside (RS) site with heavy vehicular traffic and an urban background (BG) site in Mumbai using the dithiothreitol (DTT) assay. Simultaneous gravimetric PM2.5 was measured at both sites and characterized for carbonaceous constituents and water-soluble trace elements and metals. Results depicted higher PM2.5, elemental carbon (EC), and organic carbon (OC) concentrations on the RS than BG (by a factor of 1.7, 4.6, and 1.2, respectively), while BG had higher water-soluble organic carbon (WSOC) levels (by a factor of 1.4) and a higher WSOC to OC ratio (86%), likely due to the dominance of secondary aerosol formation. In contrast, the measured OPDTTv at RS (8.9 ± 5.5 nmol/min/m3) and BG (8.1 ± 6.4 nmol/min/m3) sites were similar. However, OPDTTv at BG was higher during the afternoon, suggesting the influence of photochemical transformation on measured OPDTTv at BG. At RS, OC and redox-active metals (Cu, Zn, Mn, and Fe) were significantly associated with measured OP (p < 0.05), while at BG, WSOC was most strongly associated (p < 0.05). The coefficient of divergence (COD) for PM2.5, its chemical species, and OPDTTv was >0.2, indicating spatial heterogeneity between the sites, and differences in emission sources and toxicity. The estimated hazard index (HI) was not associated with OPDTTv, indicating that current PM2.5 mass regulations may not adequately capture the health effects of PM2.5. The study highlights the need for further studies examining PM2.5 toxicity and developing toxicity-based air quality regulations.

Infection of bats with Histoplasma species.

Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and in yeast form in infected tissues. In this narrative literature review, we summarize the occurrence of Histoplasma spp. in different species of bat tissues (n = 49) and in soil admixed with bat guano where the species of bat dwelling nearby has been identified (an additional 18 species likely infected) to provide an up-to-date summary of data. Most positive isolations are from the Americas and Caribbean, with some studies from Thailand, Malaysia, Nigeria, Slovenia, France, and Australia. We also summarize some of the early experimental work to elucidate pathogenicity, latency, immune response, and faecal excretion in bats. Given the recent recognition of the global extent of histoplasmosis, thermal dimorphism in Histoplasma spp., and global heating, additional work on understanding the complex relationship between Histoplasma and bats is desirable.

The fungal genus Histoplasma causes lung, disseminated, gut and adrenal disease in humans, many with AIDS, but also people with normally functioning immune systems. Exposure and outbreaks are often linked to visiting caves where bats reside. In some locations, considerable quantities of Histoplasma fungus are found in bat guano and, when airborne, can cause infection. There are over 1400 species of bat worldwide. We reviewed the literature from 1962, the first recorded description of bat infection by Histoplasma, and found 49 different species of bat recorded as being infected. Most of the data are from the Americas, very little from Africa, and some from hyperendemic areas in SE Asia. Histoplasma are temperature sensitive fungi and bats, especially those which hibernate and use torpor to survive winter-time shortages of insect prey, occupy environments with a wide range of temperatures. Our understanding of bat infection or latency, in a world with extremes of weather and general heating, is likely to change the Histoplasma/bat relationship in uncertain ways.

Reassessing the availability of crop residue as a bioenergy resource in India: A field-survey based study.

Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions. Here, we use comprehensive surveys and multivariate regression models to estimate the bioenergy potential of surplus crop residues in India. These are with high sub-national and crop disaggregation that can facilitate the development of efficient supply chain mechanisms for its widespread usage. The estimated potential for 2019 of 1313 PJ can increase the present bioenergy installed capacity by 82% but is likely insufficient alone to meet India's bioenergy targets. The shortage of crop residue for bioenergy, combined with the sustainability concerns raised by previous studies, imply a need to reassess the strategy for the use of this resource.

Spatiotemporal immune atlas of the first clinical-grade, gene-edited pig-to-human kidney xenotransplant.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

Synergistic antibacterial and mosquitocidal effect of Passiflora foetida synthesized silver nanoparticles.

Silver nanoparticles are opted to have various applications in different fields ranging from traditional medicines to culinary items. It is toxic and most effective against bacteria, fungi viruses, parasites, parasite carrying vectors such as mosquitoes and their larvae and other eukaryotic microorganisms at low concentration without any side effects and toxicity to humans. In view of these data, the present research has been investigated by synthesizing silver nanoparticles using 1mM silver nitrate and aqueous extract of Passiflora foetida. The variation of nanoparticles in size and shape concerning the concentration of extract prepared were analysed. The formation of silver nanoparticles was confirmed by colour changing from yellowish green to reddish-brown implicating the surface plasmon resonance. Further, it was concluded by obtaining an absorbance peak at 420 nm using UV-Visible spectrophotometer analysis. FTIR analysis was used to identify the capping ligands, which included alkanes, aromatic groups and nitro compounds. The average grain size of ~12 nm to 14 nm with crystalline phase was revealed by X-ray Diffraction studies. The SEM images depicted the surface morphology with agglomeration; TEM studies showed the shape of nanoparticles as spherical and hexagonal with sizes ranging from 40 nm to 100 nm and EDAX analysis confirmed the presence of elemental silver as the principal constituent. The characterized silver nanoparticles were then tested for synergistic antibacterial effects with tetracycline, and the results show that they are more active against E. coli and S. aureus, but moderately effective against B. cereus and K. pneumoniae . It also had a strong larval and pupal toxic effects on the dengue vector, Aedes aegypti with the highest mortality. As a result, silver nanoparticles could be a viable alternative for a variety of applications.

Zika virus antibody-positivity among symptomatic/asymptomatic pregnant women in the Aseer region displays pre-exposure to dengue viruses

@#Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.

Appraising the therapeutical potentials of Alchornea laxiflora (Benth.) Pax & K. Hoffm., an underexplored medicinal herb: A systematic review.

Ethnopharmacological relevance: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (Euphorbiaceae) is an important traditional medicinal plant grown in tropical Africa. The stem, leaves, and root have been widely used in the folk medicine systems in Nigeria, Cameroon, South Africa, and Ghana to treat various ailments, including inflammatory, infectious, and central nervous system disorders, such as anxiety and epilepsy. Material and methods: The scientific name of the plant was validated using the "The Plant List," "Kew Royal Botanic Gardens," and Tropicos Nomenclatural databases. The literature search on A. laxiflora was performed using electronic search engines and databases such as Google scholar, ScienceDirect, PubMed, AJOL, Scopus, and Mendeley. Results: To the best of our knowledge, no specific and detailed review has been reported on A. laxiflora. Consequently, this review provides an up-to-date systematic presentation on ethnobotany, phytoconstituents, pharmacological activities, and toxicity profiles of A. laxiflora. Phytochemical investigations disclosed the presence of important compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and fatty acids. Furthermore, various pharmacological activities and traditional uses reported for this botanical drug were discussed comprehensively. Conclusion: This systemic review presents the current status and perspectives of A. laxiflora as a potential therapeutic modality that would assist future researchers in exploring this African botanical drug as a source of novel drug candidates for varied diseases.

Cyclin-Dependent Kinase 5 Regulates cPLA2 Activity and Neuroinflammation in Parkinson's Disease.

Hyperactivation of cyclin-dependent kinase 5 (Cdk5) by p25, contributes to neuroinflammation causing neurodegeneration in Parkinson's disease (PD) and Alzheimer's disease. However, the mechanism by which Cdk5 induces neuroinflammation in the PD brain is largely unexplored. Here, we show that Cdk5 phosphorylates cytosolic phospholipase A2 (cPLA2) at Thr-268 and Ser-505 sites lead to its activation and generation of eicosanoid products. Mutational studies using site-directed mutagenesis and molecular simulations show that the architecture of the protein changes on each single-point mutation. Interestingly, double mutations also led to a severe decline in the activity of cPLA2 and to the disruption of its translocation to the plasma membrane. Further, the brain lysates of transgenic PD mouse models show hyperactivation of Cdk5, resulting in enhanced phosphorylation of Thr-268 and Ser-505 of cPLA2 and its heightened activity, confirming the findings observed in the cell culture model of PD. These phosphorylation sites of cPLA2 and Cdk5 could be explored as the future therapeutic targets against neuroinflammation in PD. Further, conjoint transcriptomic analysis of the publicly available human PD datasets strengthens the hypothesis that genes of the arachidonic acid, prostaglandin synthesis, and inflammatory pathways are significantly upregulated in the case of PD patients compared with that of healthy control subjects.

Lycopene Scavenges Cellular ROS, Modulates Autophagy and Improves Survival through 7SK snRNA Interaction in Smooth Muscle Cells.

The chance of survival rate and autophagy of smooth muscle cells under calcium stress were drastically improved with a prolonged inclusion of Lycopene in the media. The results showed an improved viability from 41% to 69% and a reduction in overall autophagic bodies from 7% to 3%, which was well in agreement with the LC3II and III mRNA levels. However, the proliferation was slow compared to the controls. The fall in the major inflammatory marker TNF-α and improved antioxidant enzyme GPx were regarded as significant restoration markers of cell survival. The reactive oxygen species (ROS) were reduced from 8 fold to 3 fold post addition of lycopene for 24 h. Further, the docking studies revealed binding of lycopene molecules with 7SK snRNA at 7.6 kcal/mol docking energy with 300 ns stability under physiological conditions. Together, these results suggest that Lycopene administration during ischemic heart disease might improve the functions of the smooth muscle cells and 7SK snRNA might be involved in the binding of lycopene and its antioxidant protective effects.

Epidermal Inspired Flexible Sensor with Buckypaper/PDMS Interfaces for Multimodal and Human Motion Monitoring Applications.

The advancements in the areas of wearable devices and flexible electronic skin have led to the synthesis of scalable, ultrasensitive sensors to detect and differentiate multimodal stimuli and dynamic human movements. Herein, we reveal a novel architecture of an epidermal sensor fabricated by sandwiching the buckypaper between the layers of poly(dimethylsiloxane) (PDMS). This mechanically robust sensor can be conformally adhered on skin and has the perception capability to detect real-time transient human motions and the multimodal mechanical stimuli of stretching, bending, tapping, and twisting. The sensor has feasibility for real-time health monitoring as it can distinguish a wide range of human physiological activities like breathing, gulping, phonation, pulse monitoring, and finger and wrist bending. This multimodal wearable epidermal sensor possesses an ultrahigh gauge factor (GF) of 9178 with a large stretchability of 56%, significant durability for 5000 stretching-releasing cycles, and a fast response/recovery time of 59/88 ms. We anticipate that this novel, simple, and scalable design of a sensor with outstanding features will pave a new way to consummate the requirements of wearable electronics, flexible touch sensors, and electronic skin.

Haematological Traits in Symptomatic and Asymptomatic COVID-19 Positive Patients for Predicting Severity and Hospitalization.

Objective: The present investigation aims on the clinical attributes and haematological parameters between symptomatic (COVID-19 ICU) and asymptomatic (COVID-19 homes isolation) patients as predisposing sign for COVID-19 related mortality. Materials and Methods: A retrospective cohort research was conducted of admitted patients to ICU, who were suffering from severe COVID-19 in Aseer Central Hospital, Abha, Kingdom of Saudi Arabia (KSA) from July 2020 until September 2020. The study included individuals with COVID -19 and ICU admission as symptomatic group and others who are COVID-19 positives with quarantine as asymptomatic group. Epidemiological, clinical and haematological laboratory data were retrospectively collected, analysed with control subjects. Results: Of the 38 ICU patients studied, the most common symptoms were fever and respiratory distress (100%), cough (86.8%). Majority were of Saudi origin (78.9%). Eighteen (47.4%) COVID-19 ICU patients showed leukocytosis, 6 (15.8%) had severe thrombocytopenia (with most having thrombocytopenia), 18 (47.4%) were anaemic. A significant correlation was observed between the WBC, RBC, Hb, platelets, neutrophil and lymphocyte count between ICU inmates compared with quarantine (p < 0.001) and RBC, Hb, neutrophil and lymphocyte count with control groups (p < 0.001). Conclusion: From the observations it is evident that, the blood tests have potential clinical value in predicting COVID-19 progression. Further, patient characteristics including age, leukocyte count, RBC, platelets and differential leukocyte counts may be significant predictors for monitoring the progression of the critical illness observed in SARS-COV-2 patients. Also, treatment procedures can be re-defined further to reduce COVID-19 mortalities in more critically ill COVID-19 individuals.

On-road vehicular emission characterization from the road-tunnel measurements in India: Morphology, emission factors, and sources.

In India, there is very limited data on vehicular emission characterization in real-world driving conditions and the contribution of non-exhaust vehicular emissions to ambient particulate matter (PM) is still unanswered. Furthermore, there are no real-world emission factors (EFs) for the PM constituents. Thus, this study aims to characterize the trace elements and metals, and black carbon (BC) in PM2.5 and PM10 from the light-duty vehicles (LDVs) and mixed vehicular fleet with significant contribution of heavy-duty vehicles (HDVs) through road-tunnel measurements. Real-world EFs were estimated for the measured PM chemical constituents. Further, source apportionment was carried out to find the plausible sources and their contribution to total PM2.5 and PM10 road traffic emissions. Air pollutant and traffic measurements were conducted at two roadway tunnels: Eastern Freeway tunnel (FT; only LDVs) and Kamshet-I tunnel (KT; 80% LDVs & 20% HDVs) in Mumbai, India covering both peak and off-peak traffic hours. Major elements (Al, Ca, Fe, K, Mg, and Na) constitute 90─93% of total measured elemental concentrations in both PM2.5 and PM10 road traffic emissions. Overall, the elemental concentrations were higher for the HDV-dominant fleet than the LDV-fleet for both PM2.5 and PM10. Similarly, BC was higher for the HDV-dominant fleet which is corroborated by the morphological analysis. The measured BC, trace elements and metals EFs in this study were higher than those reported than previous road tunnel studies with similar vehicle composition indicating the presence of high-emitting vehicles in this study. The dominant proportion of PM2.5 road traffic emissions was from the tailpipe (52%) followed by brake wear (30%) and vehicular driven resuspended road dust (18%). Whilst, resuspended road dust (63%) was identified as the major source of PM10 traffic emissions followed by vehicular exhaust (28%) and brake wear (9%). With the potential increase in the share of electric and hybrid vehicles in the vehicular fleet, the relative contribution of non-exhaust emissions to the airborne PM will be more significant. Hence, there is an imminent need to regulate non-exhaust vehicular emissions.

Inhibition realization of multidrug resistant bacterial and fungal isolates using Coccinia indica extracts.

The crude aqueous and ethanolic leaf extracts of Coccinia indica were screened for methicillin resistant Staphylococcus aureus (MRSA), multidrug resistant (MDR) Streptococcus pyogenes, Escherichia coli, Candida auris and Trichophyton rubrum. Antibacterial and antifungal activities were assessed by standard disc diffusion and tube dilution methods. The results showed that ethanolic extract inhibited MRSA, C. auris at 250 µg/mL and S. pyogenes at 200 µg/mL comparable to the susceptible antibiotics used as positive controls. There was no observable activity against T. rubrum, while a mild activity was observed with ethanolic extracts over E. coli at higher concentrations which did not turn out to be complete or significant inhibition. Aqueous extract did not exhibit any observable activity over the five organisms tested. Furthermore, the results showed clear cut concentration dependent antibacterial and antifungal activities with additional variation of specific activity over Gram positive and negative bacteria, yeast and filamentous fungi. So, it is evident that ethanolic extract of Coccinia indica could be further escalating for mechanistic studies in the era of multidrug resistance, indigenous preparations from herbs could be a safe choice over clinically challenging organisms.