Single cell transcriptomic analyses reveal diverse and dynamic changes of distinct populations of lung interstitial macrophages in hypoxia-induced pulmonary hypertension.

Introduction: Hypoxia is a common pathological driver contributing to various forms of pulmonary vascular diseases leading to pulmonary hypertension (PH). Pulmonary interstitial macrophages (IMs) play pivotal roles in immune and vascular dysfunction, leading to inflammation, abnormal remodeling, and fibrosis in PH. However, IMs' response to hypoxia and their role in PH progression remain largely unknown. We utilized a murine model of hypoxia-induced PH to investigate the repertoire and functional profiles of IMs in response to acute and prolonged hypoxia, aiming to elucidate their contributions to PH development. Methods: We conducted single-cell transcriptomic analyses to characterize the repertoire and functional profiles of murine pulmonary IMs following exposure to hypobaric hypoxia for varying durations (0, 1, 3, 7, and 21 days). Hallmark pathways from the mouse Molecular Signatures Database were utilized to characterize the molecular function of the IM subpopulation in response to hypoxia. Results: Our analysis revealed an early acute inflammatory phase during acute hypoxia exposure (Days 1-3), which was resolved by Day 7, followed by a pro-remodeling phase during prolonged hypoxia (Days 7-21). These phases were marked by distinct subpopulations of IMs: MHCIIhiCCR2+EAR2+ cells characterized the acute inflammatory phase, while TLF+VCAM1hi cells dominated the pro-remodeling phase. The acute inflammatory phase exhibited enrichment in interferon-gamma, IL-2, and IL-6 pathways, while the pro-remodeling phase showed dysregulated chemokine production, hemoglobin clearance, and tissue repair profiles, along with activation of distinct complement pathways. Discussion: Our findings demonstrate the existence of distinct populations of pulmonary interstitial macrophages corresponding to acute and prolonged hypoxia exposure, pivotal in regulating the inflammatory and remodeling phases of PH pathogenesis. This understanding offers potential avenues for targeted interventions, tailored to specific populations and distinct phases of the disease. Moreover, further identification of triggers for pro-remodeling IMs holds promise in unveiling novel therapeutic strategies for pulmonary hypertension.

Leaching Approach for ß-Glucosidase Extraction from Fermented Rice Husk in Solid State Cultivation by Aspergillus protuberus.

Environmental problems are caused by the disposal of agrowastes in developing countries. It is imperative to convert such wastes into useful products, which require enzymes such as ß-glucosidase. ß-Glucosidase has variety of applications in biotechnology including food, textile, detergents, pulp and paper, pharmaceutical and biofuel industries. ß-Glucosidase production was performed using the locally isolated Aspergillus protuberus using best growth circumstances on rice husk in solid-state fermentation (SSF). Leaching of ß-glucosidase from fermented rice husk with number of solvents to evaluate their extraction efficacy. Among the different solvents examined, acetate buffer (0.02 M, pH 5.0) proved to be the best solvent. The subsequent parameters were optimized with acetate buffer. Two washes with acetate buffer each by shaking (30 min) in a ratio of 1 g of rice husk: 5 ml of acetate buffer together attained maximum recovery of ß-glucosidase with 41.95 U/g of rice husk.

Modulated Self-Assembly of Catalytically Active Metal-Organic Nanosheets Containing Zr6 Clusters and Dicarboxylate Ligands.

Two-dimensional metal-organic nanosheets (MONs) have emerged as attractive alternatives to their three-dimensional metal-organic framework (MOF) counterparts for heterogeneous catalysis due to their greater external surface areas and higher accessibility of catalytically active sites. Zr MONs are particularly prized because of their chemical stability and high Lewis and Brønsted acidities of the Zr clusters. Herein, we show that careful control over modulated self-assembly and exfoliation conditions allows the isolation of the first example of a two-dimensional nanosheet wherein Zr6 clusters are linked by dicarboxylate ligands. The hxl topology MOF, termed GUF-14 (GUF = Glasgow University Framework), can be exfoliated into monolayer thickness hns topology MONs, and acid-induced removal of capping modulator units yields MONs with enhanced catalytic activity toward the formation of imines and the hydrolysis of an organophosphate nerve agent mimic. The discovery of GUF-14 serves as a valuable example of the undiscovered MOF/MON structural diversity extant in established metal-ligand systems that can be accessed by harnessing the power of modulated self-assembly protocols.

Effect of nonsteroidal anti-inflammatory drugs (aspirin and naproxen) on inflammation-associated proteomic profiles in mouse plasma and prostate during TMPRSS2-ERG (fusion)-driven prostate carcinogenesis.

Recent preclinical studies have shown that the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin and naproxen could be an effective intervention strategy against TMPRSS2-ERG fusion-driven prostate tumorigenesis. Herein, as a follow-up mechanistic study, employing TMPRSS2-ERG (fusion) positive tumors and plasma from TMPRSS2-ERG. Ptenflox/flox mice, we profiled the stage specific proteomic changes (focused on inflammatory circulating and prostate tissue/tumor-specific cytokines, chemokines, and growth factors/growth signaling-associated molecules) that contribute to prostate cancer (PCa) growth and progression in the TMPRSS2-ERG fusion-driven mouse model of tumorigenesis. In addition, the association of the protective effects of NSAIDs (aspirin 1400 ppm and naproxen 400 ppm) with the modulation of these specific molecular pathways was determined. A sandwich Elisa based membrane array-proteome profiler identifying 111 distinct signaling molecules was employed. Overall, the plasma and prostate tissue sample analyses identified 54 significant and differentially expressed cytokines, chemokines, and growth factors/growth signaling-associated molecules between PCa afflicted mice (TMPRSS2-ERG. Ptenflox/flox, age-matched noncancerous controls, NSAIDs-supplemented and no-drug controls). Bioinformatic analysis of the array outcomes indicated that the protective effect of NSAIDs was associated with reduced expression of (a) tumor promoting inflammatory molecules (M-CSF, IL-33, CCL22, CCL12, CX3CL1, CHI3L1, and CD93), (b) growth factors- growth signaling-associated molecules (Chemerin, FGF acidic, Flt-3 ligand, IGFBP-5, and PEDF), and (c) tumor microenvironment/stromal remodeling proteins MMP2 and MMP9. Overall, our findings corroborate the pathological findings that protective effects of NSAIDs in TMPSS2-ERG fusion-driven prostate tumorigenesis are associated with antiproliferative and anti-inflammatory effects and possible modulation of the immune cell enriched microenvironment.

Degradation of SDS by psychrotolerant Staphylococcus saprophyticus and Bacillus pumilus isolated from Southern Ocean water samples.

Bioremediation of surfactants in water bodies holds significant ecological importance as they are contaminants of emerging concern posing substantial threats to the aquatic environment. Microbes exhibiting special ability in terms of bioremediation of contaminants have always been reported to thrive in extraordinary environmental conditions that can be extreme in terms of temperature, lack of nutrients, and salinity. Therefore, in the present investigation, a total of 46 bacterial isolates were isolated from the Indian sector of the Southern Ocean and screened for degradation of sodium dodecyl sulphate (SDS). Further, two Gram-positive psychrotolerant bacterial strains, ASOI-01 and ASOI-02 were identified with significant SDS degradation potential. These isolates were further studied for growth optimization under different environmental conditions. The strains were characterized as Staphylococcus saprophyticus and Bacillus pumilus based on morphological, biochemical, and molecular (16S RNA gene) characteristics. The study reports 88.9% and 93.4% degradation of SDS at a concentration of 100 mgL-1, at 20 °C, and pH 7 by S. saprophyticus ASOI-01 and B. pumilus ASOI-02, respectively. The experiments were also conducted in wastewater samples where a slight reduction in degradation efficiency was observed with strains ASOI-01 and ASOI-02 exhibiting 76.83 and 64.93% degradation of SDS respectively. This study infers that these bacteria can be used for the bioremediation of anionic surfactants from water bodies and establishes the potential of extremophilic microbes for the utilization of sustainable wastewater management.

Putative Role of Anti-microbial Peptide Recovered from Lactiplantibacillus spp. in Biocontrol Activity.

Antimicrobial peptides (AMPs) stand as a promising alternative to conventional pesticides, leveraging a multifaceted approach to combat plant pathogens. This study focuses on identifying and characterizing the AMP produced by Lactiplantibacillus argentoratensis strain IT, demonstrating potent antibacterial activity against various harmful microorganisms. Evaluation of AMPs' antibacterial activity was conducted through an agar well diffusion assay, a reliable method for assessing secondary metabolite antimicrobial efficacy. The study unveils the antimicrobial potential of the purified extract obtained from Lactiplantibacillus argentoratensis IT, isolated from goat milk. Notably, the AMP exhibited robust antibacterial activity against phytopathogens affecting solanaceous crops, including the Gram-negative Ralstonia solanacearum. Expression conditions and purification methods were optimized to identify the peptide's mass and sequence, utilizing LC-MS and SDS-PAGE. This paper underscores the application potential of Lactiplantibacillus spp. IT as a biocontrol agent for managing bacterial infectious diseases in plants. Results indicate optimal AMP production at 37 °C, with a culture broth pH of 5 during fermentation. The obtained peptide sequence corresponded to peaks at 842.5 and 2866.4 m/z ratio, with a molecular weight of approximately 5 kDa according to tricine SDS-PAGE analysis. In conclusion, this study lays the foundation for utilizing Lactiplantibacillus spp. IT derived AMPs in plant biocontrol strategies, showcasing their efficacy against bacterial phytopathogens. These findings contribute valuable insights for advancing sustainable agricultural practices.

Comparative Analysis of TAVR (Transcatheter Aortic Valve Replacement) and Surgical Valve Replacement for Low-Risk Patients.

"Aortic stenosis" (AS) refers to a cardiac condition in which the aortic valve narrows, creating an obstruction that hinders the flow of blood from the left ventricle to the aorta. This contraction of the arteries influences normal blood circulation, leading to elevated pressure within the left ventricle and potentially culminating in heart failure. The management of AS typically involves two primary treatments, i.e. "surgical aortic valve replacement" (SAVR) and "transcatheter aortic valve replacement" (TAVR). In both cases, the goal is to replace a dysfunctional aortic valve with a functional substitute. Presently, TAVR has gained much preference over SAVR in clinical practice. However, there is a dearth of comprehensive research directly comparing the real-world outcomes of TAVR and SAVR. In recent years, TAVR has emerged as an attractive alternative to SAVR, yet studies that provide a detailed comparison of their real-world solutions are limited. This review article assesses the mortality of patients who underwent TAVR vis-a-vis patients who underwent SAVR.

Differential Effect of Non-Steroidal Anti-Inflammatory Drugs Aspirin and Naproxen against TMPRSS2-ERG (Fusion)-Driven and Non-Fusion-Driven Prostate Cancer.

The consumption of the non-steroidal anti-inflammatory drug (NSAID) aspirin is associated with a significant reduction in the risk of developing TMPRSS2-ERG (fusion)-positive prostate cancer (PCa) compared to fusion-negative PCa in population-based case-control studies; however, no extensive preclinical studies have been conducted to investigate and confirm these protective benefits. Thus, the focus of this study was to determine the potential usefulness of aspirin and another NSAID, naproxen, in PCa prevention, employing preclinical models of both TMPRSS2-ERG (fusion)-driven (with conditional deletion of Pten) and non-TMPRSS2-ERG-driven (Hi-Myc+/- mice) PCa. Male mice (n = 25 mice/group) were fed aspirin- (700 and 1400 ppm) and naproxen- (200 and 400 ppm) supplemented diets from (a) 6 weeks until 32 weeks of Hi-Myc+/- mice age; and (b) 1 week until 20 weeks post-Cre induction in the fusion model. In all NSAID-fed groups, compared to no-drug controls, there was a significant decrease in higher-grade adenocarcinoma incidence in the TMPRSS2-ERG (fusion)-driven PCa model. Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79-91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc+/- mice, suggesting that NSAIDs exert a specific protective effect against TMPRSS2-ERG (fusion)-driven PCa.

Evaluation of bamboo derived biochar as anode catalyst in microbial fuel cell for xylan degradation utilizing microbial co-culture.

This study aimed to examine the microbial degradation of xylan through Bacillus sp. isolated from wastewater. Co-culture of Bacillus licheniformis strain and MTCC-8104 strain of Shewanella putrefaciens were employed in a microbial fuel cell (MFC) to facilitate energy production simultaneous xylan degradation under optimum conditions. Electrochemical properties of MFC and degradation analysis were used to validate xylan degradation throughout various experimental parameters. Degradation of the optimal xylan concentration using co-culture, resulting in a power density of 7.8 W/m3, the anode surface was modified with bamboo-derived biochar in order to increase power density under the same operational condition. Under optimum circumstances, increasing the anode's surface area boosted electron transport and electro-active biofilm growth, resulting in a higher power density of 12.9 W/m3. Co-culture of hydrolyzing and electro-active bacteria was found beneficial for xylan degradation and anode modifications enhance power output while microbial degradation.

Assessment and Biodegradation of Polycyclic Aromatic Hydrocarbons in Soil and Water Around Petroleum Products Depot Suleja, Nigeria.

Petroleum contamination constitutes a frequent incidence in various petroleum depots in Nigeria. In this study, the polycyclic aromatic hydrocarbons (PAHs) present in soil and water in communities around Petroleum Products Marketing Company (PPMC) Suleja, Nigeria, were evaluated and degraded using indigenous microorganisms. The samples sites were divided into 7 plots from where samples of water and soil were obtained: one within the PPMC depot, five from communities surrounding the depot, and the control 93,000 km from the depot. The microbial counts were determined using spread plate inoculation technique on minimal salt media. The microbial isolates were characterized and identified based on their cultural, biochemical, and molecular characteristics. The potential of the microbial isolates to utilize 0.05 mL of diesel, kerosene, engine oil, and crude oil was determined in a Bushnell Haas Broth, and the biodegradation was determined by total viable cell counts and spectrophotometry. The ability of the isolates to mineralize PAHs was also evaluated in a minimum salt media. The bacterial isolates were species of Streptococcus, Pseudomonas, Staphylococcus, Proteus, Escherichia, and Bacillus, while species of Penicillium, Aspergillus, Mucor, and Rhizopus were isolated among the fungi. Aspergillus niger strain ATCC 1015 and Bacillus thuringiensis strain M43 showed high capacity to utilize the 16 priority PAHs. The pahE1 gene was used by Bacillus thuringiensis, Pseudomonas aeruginosa and A. niger, while Penicillium notatum used pahE2 gene for the degradation of the PAH. The current study identified microbial isolates that can utilize priority PAHs, making them beneficial for oil spill bioremediation in tropical environments.

Filamentous cyanobacteria and hydrophobic protein in extracellular polymeric substances facilitate algae-bacteria aggregation during partial nitrification.

In algae-bacteria symbiotic wastewater treatment, the excellent settling performance of algae-bacteria aggregates is critical for biomass separation and recovery. Here, the composition of extracellular polymeric substances (EPS), microbial profiles, and functional genes of algae-bacteria aggregates were investigated at different solid retention times (SRTs) (10, 20, and 40 d) during partial nitrification in photo sequencing bioreactors (PSBRs). Results showed that SRTs greatly influenced the nitrogen transformation and the formation and morphological structure of algae-bacteria aggregates. The highest nitrite accumulation, the largest particle size (~1.54 mm) and the best settling performance were observed for the algae-bacteria aggregates in the PSBR with an SRT of 10 d, where the abundant occurrence of filamentous cyanobacteria with the highest ratio of chlorophyll a/b and the lowest EPS amount with the highest protein-to-polysaccharide ratio were observed. In particular, the EPS at 10 d of SRT contained a higher amount of protein-related hydrophobic groups and a lower ratio of α-helix/(ß-sheet + random coil), indicating a looser protein structure, which might facilitate the formation and stabilization of algae-bacteria aggregates. Moreover, algal-bacterial aggregation greatly depended on the composition and evolution of filamentous cyanobacteria (unclassified _o__Oscillatoriales and Phormidium accounted for 56.29 % of the identified algae at SRT 10 d). The metagenomic analysis further revealed that functional genes related to amino acid metabolism (e.g., genes of phenylalanine, tyrosine, and tryptophan biosynthesis) were expressed at high levels within 10 d of SRT. Overall, this study demonstrates the influence of EPS structures and filamentous cyanobacteria on algae-bacteria aggregation and reveals the biological mechanisms driving photogranule structure and function.

Microalgae and biogas: a boon to energy sector.

The global energy generation market immensely depends on fossil fuels which balances our survival on this planet. Energy can be called as the "master element" for our daily needs, starting from household power supply, agricultural purpose, automobile and transportation, industrial workload to economic and research domains. Fuel switching initiatives are being adapted by environmentalist and scientists to bring a novel sustainable source of energy. An environment and renewable alternative to fossil fuels are a must. Over the years, the world has shifted toward generating green fuels immensely. One such potential alternative to fossil fuels are biogases. Being versatile and renewable in nature, it has drawn immense attention globally. Despite having such potentials there exist some major drawbacks which mainly deal with the starting material. One such source for biogases can be microalgae. Microalgae based biogas production can produce huge amount of energy and that has been implemented by many foreign countries and their companies. Despite being in use in many countries, there are issues which needs to be addressed which will overall improve the biogas potential from microalgae even more. This review mainly focuses on generation of biogas from microalgae as a feedstock which are very economical and sustainable in its nature, presenting improvement strategies which can be impended to boost the over biogas sector globally.

Improving the Growth and Productivity of Macrotyloma uniflorum Medicinal Plant by the Co-inoculation of P, Zn and K-Solubilizing Fungi Under Field Conditions.

The presence of small amount of soluble forms of Phosphorus (P), Potassium (K) and Zinc (Zn) in most soils is one of the limiting factors for agronomic crop production. The current study focuses on Macrotyloma uniflorum (horse gram or gahat), the most commonly cultivated crop in Uttarakhand. The current initiative and study were started, because there is a little information available on the impact of co-inoculation of beneficial fungi on crops in agricultural fields. Aspergillus niger K7 and Penicillium chrysogenum K4 were isolated and selected for the study on the basis of in vitro P, K and Zn-solubilizing activity. The solubilizing efficiency of K4 strain was 140% and K7 was 173.9% for P. However, the solubilizing efficiencies of K4 and K7 were 160% and 138.46% for Zn and 160% and 466% for K, respectively. The field trials were performed for two consecutive years, and growth and yield related parameters were measured for evaluation of the effect of P, K and Zn-solubilizing fungal strains on the crop. All the treatments showed a significant (P < 0.05) increase in growth and yield of M. uniflorum plants over uninoculated control; however, the best treatment was found to be soil inoculated with P. chrysogenum K4 + A. niger K7 in which the yield was enhanced by 71% over control. Thus, the co-inoculation of K4 and K7 strains showed a great potential to improve the growth and yield of plants. Both the fungal strains simultaneously solubilized three important nutritional elements in soil, which is a rare trait. Moreover, the capacity of these fungal strains to enhance the plant root nodulation and microbial count in soil makes the co-inoculation practice quite beneficial for sustainable agriculture.

A Novel Study on Anionic Surfactant Degradation Potential of Psychrophillic and Psychrotolerant Pseudomonas spp. Identified from Surfactant-contaminated River Water.

The Yamuna River, a tributary of the holy Ganga, is heavily polluted in the Delhi-NCR region, India and has been gaining attention due to the excessive foaming of the river over the past few years. This can be directly or indirectly related to the overuse of surfactants and the discharge of untreated domestic and textile wastewater into the river. To determine the surfactant load and investigate potential surfactant-degrading bacteria in the region, 96 water samples from four sites in the Okhla Barrage stretch of the river were collected and analysed. The results showed that the selected sites have surfactant concentrations more than the permissible limit (1.00 mgL-1). Also, at most of the sites, the concentration crossed the desirable limit of BIS (0.2 mgL-1) during the period of analysis. The concentration of anionic surfactant reported in the region was found in the range of 0.29 mgL-1 and 2.83 mgL-1. A total of 38 different bacteria were isolated using selective media from the same water samples, out of which 7 bacterial isolates were screened for sodium dodecyl sulphate (SDS) tolerance activity. Based on 16S rRNA gene sequencing, 2 species, namely Pseudomonas koreensis YRW-02 and Pseudomonas songnenensis YRW-05 have been identified and their degradation potential was assessed at different SDS concentrations. The results showed that our strains YRW-02 and YRW-05 degraded 78.29 and 69.24% of SDS respectively. Growth optimization was also performed at different substrate concentrations, pH, and temperature to investigate optimum degradation conditions. This study plays a significant role in assessing the surfactant load and also gives a promising background for future use in in-situ bioremediation experiments.

Isolation and Characterization of a Novel Laccase-Producing Bacteria Bhargavaea beijingensis from Paper and Pulp Effluent-Treated Soil Using In Silico Approaches.

Laccases (EC 1.10.3.2) are considered one of the most prominent multicopper enzymes that exhibit the inherent properties of oxidizing a range of phenolic substrates. Mostly, reported laccases have been isolated from the plants and fungi species, whereas bacterial laccases are yet to be explored. Bacterial laccases have numerous distinctive properties over fungal laccases, including stability at high temperatures and high pH. This study includes the isolation of bacteria through the soil sample collected from the paper and pulp industry; the highest laccase-producing bacteria was identified as Bhargavaea bejingensis, using 16S rRNA gene sequencing. The extracellular and intracellular activities after 24 h incubation were 1.41 U/mL and 4.95 U/mL, respectively. The laccase-encoding gene of the bacteria was sequenced; moreover, the in vitro translated protein was bioinformatically characterized and asserted that the laccase produced by the bacteria Bhargavaea bejingensis was structurally and sequentially homologous to the CotA protein of Bacillus subtilis. The enzyme laccase produced from B. bejingensis was classified as three-domain laccase with several copper-binding residues, where a few crucial copper-binding residues of the laccase enzyme were also predicted.

SIRT3 Is a Critical Regulator of Mitochondrial Function of Fibroblasts in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a heterogeneous and life-threatening cardiopulmonary disorder in which mitochondrial dysfunction is believed to drive pathogenesis, although the underlying mechanisms remain unclear. To determine if abnormal SIRT3 (sirtuin 3) activity is related to mitochondrial dysfunction in adventitial fibroblasts from patients with idiopathic pulmonary arterial hypertension (IPAH) and hypoxic PH calves (PH-Fibs) and whether SIRT3 could be a potential therapeutic target to improve mitochondrial function, SIRT3 concentrations in control fibroblasts, PH-Fibs, and lung tissues were determined using quantitative real-time PCR and western blot. SIRT3 deacetylase activity in cells and lung tissues was determined using western blot, immunohistochemistry staining, and immunoprecipitation. Glycolysis and mitochondrial function in fibroblasts were measured using respiratory analysis and fluorescence-lifetime imaging microscopy. The effects of restoring SIRT3 activity (by overexpression of SIRT3 with plasmid, activation SIRT3 with honokiol, and supplementation with the SIRT3 cofactor nicotinamide adenine dinucleotide [NAD+]) on mitochondrial protein acetylation, mitochondrial function, cell proliferation, and gene expression in PH-Fibs were also investigated. We found that SIRT3 concentrations were decreased in PH-Fibs and PH lung tissues, and its cofactor, NAD+, was also decreased in PH-Fibs. Increased acetylation in overall mitochondrial proteins and SIRT3-specific targets (MPC1 [mitochondrial pyruvate carrier 1] and MnSOD2 [mitochondrial superoxide dismutase]), as well as decreased MnSOD2 activity, was identified in PH-Fibs and PH lung tissues. Normalization of SIRT3 activity, by increasing its expression with plasmid or with honokiol and supplementation with its cofactor NAD+, reduced mitochondrial protein acetylation, improved mitochondrial function, inhibited proliferation, and induced apoptosis in PH-Fibs. Thus, our study demonstrated that restoration of SIRT3 activity in PH-Fibs can reduce mitochondrial protein acetylation and restore mitochondrial function and PH-Fib phenotype in PH.

Deciphering the fertilizing and disease suppression potential of phytofabricated zinc oxide nanoparticles on Brassicajuncea.

Every year 30-50% of crops suffer from fungal and bacterial diseases. Use of various chemically synthesized fungicides and bactericides make the soil environment more toxic and harmful to the plant health. Therefore, there is need to find non-toxic and cost effective alternative against plant pathogen. In recent years, nanotechnology has got attention because of its wide application in different areas of agriculture. Various nanoparticles have been used in agriculture for their fertilizing and antimicrobial potential. Among them zinc oxide nanoparticles (ZnO NPs) have gained the attention of agriculturists as zinc is an essential micronutrient for plants. Antifungal activity of Tb-ZnO NPs (Terminalia bellerica synthesized zinc oxide nanoparticles) against Alternaria brassicae causative agent of blight disease in Brassica juncea has been reported in our previous study. To use Tb-ZnO NPs as nanofungicides and simultaneously as nanofertilizers, the doses of Tb-ZnO NPs beneficial to the Brassica juncea crop is need to be known. Therefore, experiment has been designed to see the protective and curative potential of Tb-ZnO NPs in alluvial and calcareous soil. Biochemical constituents and stress enzymes analysis has shown significant potential of Tb-ZnO NPs at 200 ppm concentration in alleviating the stress caused by A. brassicae by modulating the photosynthetic, biochemical and enzymatic characteristics. Growth parameter analysis confirmed the role of Tb-ZnO NPs in increasing root and shoot length of B. juncea. Yield component such as seed number, seed weight and oil content of B. juncea crop also has been increased. There was one-fold increase in oil content of B. juncea as compared to control. Maximum percent disease control was found to be 70% in alluvial soil (protective method) grown plants. Therefore, present study supports the hypothesis of a relationship between nutrients and disease suppression.

Inhibition of miR-214 expression by small molecules alleviates head and neck cancer metastasis by targeting ALCAM/TFAP2 signaling.

Predominantly, head and neck cancer (HNC) is considered a regional disease and develops in the nasal cavity, oral cavity, tongue, pharynx, and larynx. In the advanced stage, the HNC spread into distant organs. By the time head and neck cancer diagnosed, the estimated metastasis is occurred in 10-40% cases. The most important vital organs affected by distant metastasis are the lungs, bones, and liver. Despite several advancements in chemotherapies, no significant changes are observed as 5-year survival rate remains the same. Therefore, it is crucial to decipher molecular mechanisms contributing to the metastatic dissemination of head and neck cancer. Here, we tested a novel ALCAM/TFAP2 signaling by targeting multidisciplinary miR-214 expression in head and cancer cells. Our results revealed that HNC cell lines (CAL27, SCC-9, SCC-4, and SCC-25) exhibit higher expression of miR-214 compared with normal human bronchial epithelial (NHBE) cells. Higher expression of miR-214 drives the invasive potential of these cell lines. Down-regulation of miR-214 in CAL27 and SCC-9 cells either using an anti-miR-214 inhibitor (50nM) or a small molecule of green tea (EGCG) inhibited cell invasion. Treating CAL27 and SCC-9 cells with EGCG also reduces ALCAM expression, a key activated leukocyte cell adhesion molecule, potentially blocking mesenchymal phenotype. Dietary administration of EGCG significantly inhibits distant metastasis of SCC-9 cells into the lungs, liver, and kidneys. Our results also demonstrate that the reduction of miR-214 expression influences in vitro cell movement and extravasation, as evident by reduced CD31 expression, a neovascularization marker. Together, these studies suggest that identifying bioactive molecules that can inhibit distant metastasis regulated by the miRNAs may provide potent interventional approaches and a better understanding of the complex functions of miRNAs and their therapeutic targets for clinical application.

Local Complement Contributes to Pathogenic Activation of Lung Endothelial Cells in SARS-CoV-2 Infection.

Endothelial dysfunction and inflammation contribute to the vascular pathology of coronavirus disease (COVID-19). However, emerging evidence does not support direct infection of endothelial or other vascular wall cells, and thus inflammation may be better explained as a secondary response to epithelial cell infection. In this study, we sought to determine whether lung endothelial or other resident vascular cells are susceptible to productive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and how local complement activation contributes to endothelial dysfunction and inflammation in response to hypoxia and SARS-CoV-2-infected lung alveolar epithelial cells. We found that ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) mRNA expression in lung vascular cells, including primary human lung microvascular endothelial cells (HLMVECs), pericytes, smooth muscle cells, and fibroblasts, was 20- to 90-fold lower compared with primary human alveolar epithelial type II cells. Consistently, we found that HLMVECs and other resident vascular cells were not susceptible to productive SARS-CoV-2 infection under either normoxic or hypoxic conditions. However, viral uptake without replication (abortive infection) was observed in HLMVECs when exposed to conditioned medium from SARS-CoV-2-infected human ACE2 stably transfected A549 epithelial cells. Furthermore, we demonstrated that exposure of HLMVECs to conditioned medium from SARS-CoV-2-infected human ACE2 stably transfected A549 epithelial cells and hypoxia resulted in upregulation of inflammatory factors such as ICAM-1 (intercellular adhesion molecule 1), VCAM-1 (vascular cell adhesion molecule 1), and IL-6 (interleukin 6) as well as complement components such as C3 (complement C3), C3AR1 (complement C3a receptor 1), C1QA (complement C1q A chain), and CFB (complement factor B). Taken together, our data support a model in which lung endothelial and vascular dysfunction during COVID-19 involves the activation of complement and inflammatory signaling and does not involve productive viral infection of endothelial cells.