Characterization of microplastics in outdoor and indoor air in Ranchi, Jharkhand, India: First insights from the region.

The study focused on detecting and characterizing microplastics in outdoor and indoor air in Ranchi, Jharkhand, India during post-monsoon (2022) and winter (2023). Stereo microscopic analysis showed that plastic fibres had a dominant presence, fragments were less abundant, whereas fewer films could be detected in indoor and outdoor air. The atmospheric deposition of microplastics outdoors observed 465 ± 27 particles/m2/day in PM10 and 12104 ± 665 and 13833 ± 1152 particles/m2/day in PM2.5 in quartz and PTFE, respectively during the post-monsoon months. During winter, microplastic deposition rates in PM10 samples were found to be 689 ± 52 particles/m2/day and 19789 ± 2957 and 30087 ± 13402 in quartz and PTFE particles/m2/day respectively in PM2.5. The mean deposition rate in indoor environment during post-monsoon was 8.3 × 104 and 1.03 × 105 particles/m2/day in winter. During the post-monsoon period in PM10, there were fibres from 7.7 to 40 µm and fragments from 2.3 µm to 8.6 µm. Indoor atmospheric microplastics, fibres ranged from 1.2 to 47 µm and fragments from 0.9 to 16 µm present respectively during the post-monsoon season. Fibres and fragment sizes witnessed during winter were 3.6-6.9 µm and 2.3-34 µm, respectively. Indoor air films measured in the range of 4.1-9.6 µm. Fourier transform infrared analysis showed that outdoor air contained polyethylene, polypropylene, Polystyrene, whereas indoor air had polyvinyl chloride. Polyethylene mainly was present in outdoor air, with lesser polypropylene and polystyrene than indoors, where polyvinyl chloride and polyethylene were in dominant proportions. Elemental mapping of outdoor and indoor air samples showed the presence of elements on the microplastics. The HYSPLIT models suggest that the particles predominantly were coming from North-West during the post-monsoon season. Principal component analysis indicated wind speed and direction influencing the abundance of microplastics. Microplastics concentration showed strong seasonal influence and potential to act as reservoir of contaminants.

MD simulations indicate Omicron P132H of SARS-CoV-2 Mpro is a potential allosteric mutant involved in modulating the dynamics of catalytic site entry loop.

The SARS-CoV-2 main protease Mpro, essential for viral replication is an important drug target. It plays a critical role in processing viral polyproteins necessary for viral replication assembly. One of the predominant SARS-CoV-2 Mpro mutations of Omicron variant is Pro132His. Structurally, this mutation site is located ∼22 Å away from the catalytic site. The solved crystal structure of this mutant in complex with inhibitors as well as its reported catalytic efficiency did not show any difference with respect to the wild type. Thus, the mutation was concluded to be non-allosteric. Based on microsecond long MD simulation of the Pro132His mutant and wild type, we show that Pro132His mutation affects the conformational equilibrium with more population of conformational substates having open catalytic site, modulated by the dynamics of the catalytic site entry loop, implying the allosteric nature of this mutation. The structural analysis indicates that rearrangement of hydrogen bonds between His132 and adjacent residues enhances the dynamics of the linker, which in turn is augmented by the inherent dynamic flexibility of the catalytic pocket entry site due to the presence of charged residues. The altered dynamics leading to loss of secondary structures corroborate well with the reported compromised thermal stability.

Application of machine learning (individual vs stacking) models on MERRA-2 data to predict surface PM2.5 concentrations over India.

The spatial coverage of PM2.5 monitoring is non-uniform across India due to the limited number of ground monitoring stations. Alternatively, Modern-Era Retrospective Analysis for Research and Applications, Version 2 (MERRA-2), is an atmospheric reanalysis data used for estimating PM2.5. MERRA-2 does not explicitly measure PM2.5 but rather follows an empirical model. MERRA-2 data were spatiotemporally collocated with ground observation for validation across India. Significant underestimation in MERRA-2 prediction of PM2.5 was observed over many monitoring stations ranging from -20 to 60 µg m-3. The utility of Machine Learning (ML) models to overcome this challenge was assessed. MERRA-2 aerosol and meteorological parameters were the input features used to train and test the individual ML models and compare them with the stacking technique. Initially, with 10% of randomly selected data, individual model performance was assessed to identify the best model. XGBoost (XGB) was the best model (r2 = 0.73) compared to Random Forest (RF) and LightGBM (LGBM). Stacking was then applied by keeping XGB as a meta-regressor. Stacked model results (r2 = 0.77) outperformed the best standalone estimate of XGB. Stacking technique was used to predict hourly and daily PM2.5 in different regions across India and each monitoring station. The eastern region exhibited the best hourly prediction (r2 = 0.80) and substantial reduction in Mean Bias (MB = -0.03 µg m-3), followed by the northern region (r2 = 0.63 and MB = -0.10 µg m-3), which showed better output due to the frequent observation of PM2.5 >100 µg m-3. Due to sparse data availability to train the ML models, the lowest performance was for the central region (r2 = 0.46 and MB = -0.60 µg m-3). Overall, India's PM2.5 prediction was good on an hourly basis compared to a daily basis using the ML stacking technique.

Assessment of NO2 concentrations over industrial state Jharkhand, at the time frame of pre, concurrent, and post-COVID-19 lockdown along with the meteorological behaviour: an overview from satellite and ground approaches.

Burning of fossil fuels in the form of coal or gasoline in thermal power plants, industries, and automobiles is a prime source of nitrogen dioxide (NO2), a major air pollutant causing health problems. In this paper, spatio-temporal unevenness of NO2 concentrations via both spaceborne Sentinel-5P and ground-based in situ data have been studied for the period of 2017-2021. Annual and seasonal distribution of TROPOMI-NO2 depict consistency over the Jharkhand region, highlighting six hotspot regions. As compared to 2019, a notable dip of 11% in the spatial annual average TROPOMI-NO2 was achieved in 2020, which were elevated again by 22% in 2021 as the lockdown gradually goes out of the picture. Among eight ground-monitoring stations, Tata and Golmuri stations always displayed a higher level of TROPOMI-NO2 ranges up to 15.2 ×1015molecules.cm-2 and 16.9 ×1015molecules.cm-2 respectively, as being located in the highly industrialised district of Jamshedpur. A big percentage reduction of up to 30% in TROPOMI-NO2 has been reported in Jharia and Bastacola stations in Dhanbad in the lockdown phase of 2020 compared to 2019. Good agreement between TROPOMI-NO2 and surface-NO2 has been achieved with R = 0.8 and R = 0.71 during winter and post-monsoon respectively. Among four meteorological parameters, TROPOMI-NO2 was majorly found to be influenced by precipitation, having R = 0.6-0.8 for almost all stations. More advanced satellite algorithms and ground-based data may be used to estimate NO2 in places where monitoring facilities are limited and thus can help in air pollution control policy.

Characterization of fine particulate matter water-soluble inorganic ions and estimation of aerosol acidity at three COALESCE network sites - Mysuru, Bhopal, and Mesra - in India.

The study was carried out to understand the chemical, spatiotemporal characteristics of water-soluble inorganic ions (WSIIs), their association with PM2.5 mass, and aerosol acidity in three COALESCE (carbonaceous aerosol emissions, source apportionment, and climate impacts) network sites of India (Mesra - Eastern India, Bhopal - Central India and Mysuru - Southern India). Alternate-day 24-h integrated bulk PM2.5 samples were collected during 2019 along with on-site meteorological parameters. Annual average PM2.5 concentrations were 67 ± 46 µg m-3, 54 ± 47 µg m-3, and 30 ± 24 µg m-3 at Mesra, Bhopal, and Mysuru, respectively. PM2.5 concentrations exceeded the annual mean (40 µg m-3) recommended by the National Ambient Air Quality Standards (NAAQS) at Mesra and Bhopal. WSIIs existed in PM2.5 mass at Mesra (50.5%), Bhopal (39.6%), and Mysuru (29.2%). SO42-, NO3-, and NH4+ (SNA) were major secondary inorganic ions in total WSIIs, with an annual average of 88.4% in Mesra and 82.0% in Bhopal 78.4% in Mysuru. Low NO3-/SO42- ratios annually at Mesra (0.41), Bhopal (0.44), and Mysuru (0.24) indicated that stationary sources dominated vehicular emissions (1.0). Aerosol acidity varied from region to region and season to season depending on the presence of NH4+, the dominant counter-ion to neutralize anions. Aerosols were near-neutral or alkaline at all three sites, except during the pre-monsoon season in Mysuru. An assessment of neutralization pathways for major anions [SO42- + NO3-] suggests that they mainly existed as sulfate and nitrate salts such as ammonium sulfate ((NH4)2SO4) and ammonium bisulfate (NH4HSO4) in conjunction with ammonium nitrate (NH4NO3).

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.

Global Lipidome Profiling Revealed Multifaceted Role of Lipid Species in Hepatitis C Virus Replication, Assembly, and Host Antiviral Response.

Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies.

Pollution characteristics and ecological risks of trace elements in PM2.5 over three COALESCE network sites - Bhopal, Mesra, and Mysuru, India.

Time-synchronized, 24 h integrated PM2.5 trace element (TE) measurements made as a part of the COALESCE project (Venkataraman et al., 2020) at Bhopal, Mesra, and Mysore during all of 2019 were analyzed in this study. The concentrations of 15 key elements ranged between 0.05 ng m-3 and 50 µg m-3 across the study sites. Pronounced seasonal variation of elements from multiple source classes showed that the crustal origin elements (Al, Si, Fe, Ti, and Ca) peaked during the pre-monsoon season, while the anthropogenic activities driven element (P, S, K, V, Mn, Cu, Zn, and Pb) concentrations increased during the winter and post-monsoon seasons. Spearman correlation coupled with hierarchical clustering separated the matrix of elements into three common clusters at all sites, corresponding to crustal sources, combustion and biomass burning emissions, and industrial/non-exhaust vehicular emissions, respectively. Furthermore, episodes of metal pollution throughout the year were examined using characteristic radar charts of TEs to identify the association between TE sources and poor air quality. For example, maximum metal pollution in Bhopal occurred during the post-monsoon season, attributable to biomass burning, dust storms, industrial and non-exhaust vehicular emissions. Finally, an ecological risk assessment revealed that the risk index was higher than the threshold value of 600 for all heavy metals at all sites. Pb, Cu, and Zn were the top contributors to 'extremely high risk' amongst all heavy metals. Overall, the results show that although TE concentrations at all three locations were much lower than in other urban locations in India, the risk from heavy metals to the ecosystem (and likely to human health) cannot be ignored. The findings warrant a full source apportionment of fine PM to better identify TE-rich source contributions and future studies to examine the atmospheric processing and eco-system uptake of TEs.

Role of emergency chest ultrasound in traumatic pneumothorax. An updated meta-analysis.

AIM: To assess chest ultrasound (US) diagnostic accuracy in pneumothorax diagnosing. MATERIAL AND METHODS: Prospec-tive studies related to the US pneumothorax diagnostic accuracy in trauma patients were extensively searched from 2000 up to November 2020. The studies features and findings were gathered using a standardised form and the methodological quality of the investigations was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULTS: Twelve articles were finally chosen for quantitative analysis. The overall sensitivity of US scan in pneumothorax diagnosis was 89% (95%CI 86-91%). Specificity was 96% (95%CI 95-97%). The diagnostic odds ratio was 193.94 (59.009-637.40) at 95%CI, thus demonstrating high chest US accuracy in pneumothorax diagnosis. CONCLUSION: Despite the limitations of the included studies, this systematic review and meta-analysis concluded that chest US is a reliable method for diagnosing pneu-mothorax in traumatized patients.

Bilateral Massive Complex Composite Odontoma of the Mandible: A Rare Case Report.

Rationale: Odontomas result from abnormal growth of differentiated epithelial and mesenchymal cells, which form ameloblasts and odontoblasts along with pulp tissue at times. Patient Concerns: A patient reported with a chief complaint of hard swelling of the lower jaw causing difficulty in mouth opening and facial deformity. Diagnosis: A provisional diagnosis of complex odontome based on clinicoradiological findings was made, which was later confirmed as complex composite odontome histologically. Treatment: Bilateral hard tissue mass was surgically removed from the mandible with utmost precaution to prevent jaw deformity. On fine separation, the specimen yielded nearly 82 small teeth-like structures. Outcomes: Histopathologically, multiple small teeth-like structures with haphazardly arranged central fibrofatty pulpal stroma surrounded by well-formed dentinal tubules and empty areas representing decalcified enamel matrix surrounded by fibrovascular stroma at the periphery were seen. Take-away Lessons: Early diagnosis and treatment ensures minimal surrounding deformities, better prognosis, and less chances of recurrence.

NSP4 and ORF9b of SARS-CoV-2 Induce Pro-Inflammatory Mitochondrial DNA Release in Inner Membrane-Derived Vesicles.

Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor of mortality. However, the underlying mechanism of mtDNA release is unexplored. Here, we show a novel mechanism of SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic mtDNA release and a rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened the effects of 29 SARS-CoV-2 proteins on mitochondrial damage and cell death and found that NSP4 and ORF9b caused extensive mitochondrial structural changes, outer membrane macropore formation, and the release of inner membrane vesicles loaded with mtDNA. The macropore-forming ability of NSP4 was mediated through its interaction with BCL2 antagonist/killer (BAK), whereas ORF9b was found to inhibit the anti-apoptotic member of the BCL2 family protein myeloid cell leukemia-1 (MCL1) and induce inner membrane vesicle formation containing mtDNA. Knockdown of BAK and/or overexpression of MCL1 significantly reversed SARS-CoV-2-mediated mitochondrial damage. Therapeutically, we engineered human mesenchymal stem cells (MSCs) with a simultaneous knockdown of BAK and overexpression of MCL1 (MSCshBAK+MCL1) and named these cells IMAT-MSCs (intercellular mitochondrial transfer-assisted therapeutic MSCs). Upon co-culture with SARS-CoV-2-infected or NSP4/ORF9b-transduced airway epithelial cells, IMAT-MSCs displayed functional intercellular mitochondrial transfer (IMT) via tunneling nanotubes (TNTs). The mitochondrial donation by IMAT-MSCs attenuated the pro-inflammatory and pro-apoptotic mtDNA release from co-cultured epithelial cells. Our findings thus provide a new mechanistic basis for SARS-CoV-2-induced cell death and a novel therapeutic approach to engineering MSCs for the treatment of COVID-19.

Advancements of sequencing batch biofilm reactor for slaughterhouse wastewater assisted with response surface methodology.

Slaughterhouse wastewater (SWW) contains a significant volume of highly polluted organic wastes. These include blood, fat, soluble proteins, colloidal particles, suspended materials, meat particles, and intestinal undigested food that consists of higher concentrations of organics such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), nitrogen and phosphorus hence an efficient treatment is required before discharging into the water bodies. The effluent concentrations and performance of simultaneous sequential batch biofilm reactor (SBBR) with recycled plastic carrier media support are better than the local single-stage sequential batch reactor (SBR), which is lacking in the literature in terms of COD, NH3, NO3, and PO4 treatment efficiency. The present study reports a novel strategy to remove the above mentioned contaminants using an intermittently aerated SBBR with recycled plastic carrier media support along with simultaneous nitrification and denitrification. The central composite design was evaluated to optimize the treatment performance of seven different process variables including; different alternating conditions (Oxic/anoxic) for aeration cycles (3/2 h in a 6 h cycle, 6/5 h in a 12 h cycle and 9/8 h in an 18 h cycle) and hydraulic retention time (6, 12 and 18 h). The average removal efficiencies are 94.5% for NH3, 93% for NO3 and 90.1% for PO4, and 99% for COD. The study reveals that the denitrification in the post-anoxic phase was more efficient than the pre-anoxic phase for pollutant removal and maintaining higher quality effluent. The effluent concentrations and performance of simultaneous SBBR with recycled polyethylene carrier support media were better than local SBR system in terms of COD, NH3, NO3 and PO4 treatment efficiency. Results stipulated the suitability of SBBR for wastewater treatment and reusability as a sustainable approach for wastewater management under optimum conditions.

Targeting allosteric pockets of SARS-CoV-2 main protease Mpro.

Repurposing of antivirals is an attractive therapeutic option for the treatment of COVID-19. Main protease (Mpro), also called 3 C-like protease (3CLpro) is a key protease of SARS-CoV-2 involved in viral replication, and is a promising drug target for antivirals. A major challenge to test the efficacy of antivirals is the conformational plasticity of Mpro and its future mutation prone flexibility. Suitable choice of drugs in catalytic and allosteric pockets appear to be essential for combination therapy. Current study, based on docking and extensive set of MD simulations, finds the combination of Elbasvir, Glecaprevir and Ritonavir to be a viable candidate for further experimental drug testing/pharmacophore design for Mpro.Communicated by Ramaswamy H. Sarma.

cGAS-STING-mediated sensing pathways in DNA and RNA virus infections: crosstalk with other sensing pathways.

Viruses cause a variety of diseases in humans and other organisms. The most important defense mechanism against viral infections is initiated when the viral genome is sensed by host proteins, and this results in interferon production and pro-inflammatory cytokine responses. The sensing of the viral genome or its replication intermediates within host cells is mediated by cytosolic proteins. For example, cGAS and IFI16 recognize non-self DNA, and RIG-I and MDA5 recognize non-self RNA. Once these sensors are activated, they trigger a cascade of reactions activating downstream molecules, which eventually results in the transcriptional activation of type I and III interferons, which play a critical role in suppressing viral propagation, either by directly limiting their replication or by inducing host cells to inhibit viral protein synthesis. The immune response against viruses relies solely upon sensing of viral genomes and their downstream signaling molecules. Although DNA and RNA viruses are sensed by distinct classes of receptor proteins, there is a possibility of overlap between the viral DNA and viral RNA sensing mechanisms. In this review, we focus on various host sensing molecules and discuss the associated signaling pathways that are activated in response to different viral infections. We further highlight the possibility of crosstalk between the cGAS-STING and the RIG-I-MAVS pathways to limit viral infections. This comprehensive review delineates the mechanisms by which different viruses evade host cellular responses to sustain within the host cells.

A Saliva-Based RNA Extraction-Free Workflow Integrated With Cas13a for SARS-CoV-2 Detection.

A major bottleneck in scaling-up COVID-19 testing is the need for sophisticated instruments and well-trained healthcare professionals, which are already overwhelmed due to the pandemic. Moreover, the high-sensitive SARS-CoV-2 diagnostics are contingent on an RNA extraction step, which, in turn, is restricted by constraints in the supply chain. Here, we present CASSPIT (Cas13 Assisted Saliva-based & Smartphone Integrated Testing), which will allow direct use of saliva samples without the need for an extra RNA extraction step for SARS-CoV-2 detection. CASSPIT utilizes CRISPR-Cas13a based SARS-CoV-2 RNA detection, and lateral-flow assay (LFA) readout of the test results. The sample preparation workflow includes an optimized chemical treatment and heat inactivation method, which, when applied to COVID-19 clinical samples, showed a 97% positive agreement with the RNA extraction method. With CASSPIT, LFA based visual limit of detection (LoD) for a given SARS-CoV-2 RNA spiked into the saliva samples was ~200 copies; image analysis-based quantification further improved the analytical sensitivity to ~100 copies. Upon validation of clinical sensitivity on RNA extraction-free saliva samples (n = 76), a 98% agreement between the lateral-flow readout and RT-qPCR data was found (Ct<35). To enable user-friendly test results with provision for data storage and online consultation, we subsequently integrated lateral-flow strips with a smartphone application. We believe CASSPIT will eliminate our reliance on RT-qPCR by providing comparable sensitivity and will be a step toward establishing nucleic acid-based point-of-care (POC) testing for COVID-19.

Molecular and Clinical Aspects of COVID-19 Vaccines and Other Therapeutic Interventions Apropos Emerging Variants of Concern.

Coronavirus disease 2019 (COVID-19) has overwhelmed the healthcare and economy of the world, with emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posing an everlasting threat to humanity. While most COVID-19 vaccines provide adequate protective immunological response against the original SARS-CoV-2 variant, there is a pressing need to understand their biological and clinical responses. Recent evidence suggests that some of the new variants of SARS-CoV-2 evade the protection conferred by the existing vaccines, which may impede the ongoing efforts to expedite the vaccination programs worldwide. These concerns have also highlighted the importance of a pan-COVID-19 vaccine, which is currently in the making. Thus, it is imperative to have a better molecular and clinical understanding of the various COVID-19 vaccines and their immunological trajectory against any emerging variant of concerns (VOCs) in particular to break this vicious cycle. Furthermore, other treatment regimens based on cellular therapies and monoclonal antibodies should be explored systematically as an alternative and readily available option considering the possibility of the emergence of more virulent SARS-CoV-2 mutants. In this review, we shed light on the various molecular mechanisms and clinical responses of COVID-19 vaccines. Importantly, we review the recent findings of their long-term immune protection and efficacy against emerging VOCs. Considering that other targeted and effective treatments will complement vaccine therapy, we provide a comprehensive understanding of the role of cell-based therapies, monoclonal antibodies, and immunomodulatory agents as alternative and readily available treatment modalities against any emerging SARS-CoV-2 variant.

Nanomedicinal strategies as efficient therapeutic interventions for delivery of cancer vaccines.

The applications of gene therapy-based treatment of cancers were started almost two decades back as a boon over the chemotherapeutic treatment strategies. Gene therapy helps in correcting the genetic sequences for treatment of cancers, thus also acts like a vaccine to induce the cellular and humoral immunity. However, the cancer vaccines typically suffer from a series of biopharmaceutical challenges due to poor solubility, low systemic availability and lack of targeting ability. Owing to these challenges, the physicians and pharmaceutical scientists have explored the applications of nanocarriers as quite promising systems for effective treatment against the tumors. A series of nanotherapeutic systems are available to date for diverse drug therapy applications. Systematic understanding on the preparation, evaluation and application of nanomedicines as a carrier system for delivering the cancer vaccines is highly important. The present review article provides an in-depth understanding on the challenges associated with cancer vaccine delivery and current opportunities with diverse nanomedicinal carriers being available for treatment of cancers.

Nanocarriers-loaded with natural actives as newer therapeutic interventions for treatment of hepatocellular carcinoma.

Introduction: Cancer has always been a menace for the society. Hepatocellular carcinoma (HCC) is one of the most lethal and 3rdlargest causes of deaths around the world.Area covered: The emergence of natural actives is considered as the greatest boon for fighting cancer. The natural actives take precedence over the traditional chemotherapeutic drugs in terms of their multi-target, multi-level and coordinated effects in the treatment of HCC. Literature reports have indicated the tremendous potential of bioactive natural products in inhibiting the HCC via molecular drug targeting, augmented bioavailability, and the ability for both passive or active targeting and stimulus-responsive drug release characteristics. This review provides a newer treatment approaches involved in the mechanism of action of different natural actives used for the HCC treatment via different molecular pathways. Besides, the promising advantage of natural bioactive-loaded nanocarriers in HCC treatment has also been also presented in this review. Expert opinion: The remarkable outcomes have been observed with therapeutic efficacy of the nanocarriers of natural actives in the treatment of HCC.Furthermore, it requires a thorough assessment of the safety and efficacy evaluation of the nanocarriers for the delivery of targeted natural active ingredients in HCC.].

An Update on Molecular Diagnostics for COVID-19.

A novel strain of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been recently identified as an infectious disease affecting the respiratory system of humans. This disease is caused by SARS-CoV-2 that was identified in Chinese patients having severe pneumonia and flu-like symptoms. COVID-19 is a contagious disease that spreads rapidly via droplet particles arising through sneezing and coughing action of an infected person. The reports of asymptomatic carriers changed the scenario of symptom based-diagnosis in COVID-19 and intensified the need for proper diagnosis of the majority of the population to combat the rapid transmission of virus. The diagnosis of positive cases is necessary to ensure prompt care to affected people and also to curb further spread of infection in the population. Collecting samples at the right time and from the exact anatomical site is crucial for proper molecular diagnosis. After the complete genome sequence was available, China formulated RT-PCR as a primary diagnostic procedure for detecting SARS-CoV-2. Many in-house and commercial diagnostic kits have been developed or are under development that have a potential to lower the burden of diagnosis on the primary diagnostic techniques like RT-PCR. Serological based diagnosis is another broad category of testing that can detect different serum antibodies like IgG, IgM, and IgA in an infected patient. PCR-based diagnostic procedures that are commonly used for pathogen detection need sophisticated machines and assistance of a technical expert. Despite their reliable accuracy, they are not cost-effective tests, which a common man can afford, so it becomes imperative to look for other diagnostic approaches, which could be cost effective, rapid, and sensitive with consistent accuracy. To make such diagnostics available to the common man, many techniques can be exploited among, which are Point of Care (POC), also known as bed side testing, which is developing as a portable and promising tool in pathogen diagnosis. Other lateral flow assay (LFA)-based techniques like SHERLOCK, CRISPR-Cas12a (AIOD-CRISPR), and FNCAS9 editor-limited uniform detection assay (FELUDA), etc. have shown promising results in rapid detection of pathogens. Diagnosis holds a critical importance in the pandemic situation when there is no potential drug for the pathogen available in the market. This review sums up the different diagnostic approaches designed or proposed to combat the crisis of widespread diagnosis due to the sudden outbreak of a novel pathogen, SARS-CoV-2 in 2019.

Use of Transgingival Lag Screw Osteosynthesis in the Management of Alveolar Process Fracture.

The purpose of this study is to check the efficacy of transgingival lag screw osteosynthesis in alveolar process fractures of maxilla and mandible. A single-arm nonrandomized observational study was performed for the treatment of alveolar process fractures of maxilla and mandible. In this study, 20 mixed age group patients with alveolar process fracture were included. All the patients were treated by a 2.0-mm transgingival screw fixation under local or general anesthesia. All the patients were evaluated for fracture stability, anatomical reduction, bone loss and bone resorption of alveolar process, tooth loss, and wound infection at 3 months of follow-up. A simple descriptive statistical analysis was done to evaluate the parameters and it was shown that the treatment of alveolar process fracture with two or three lag screws provides adequate fracture stability and anatomical reduction with no signs of bone loss and tooth loss, and wound infections were noted post lag screw fixation. The study concludes that transgingival lag screw fixation is a suitable alternative for alveolar process fractures in all the age groups and two to three lag screws are generally sufficient to fix fractured alveolar process either under local anesthesia or general anesthesia.