Structural Models for a Series of Allosteric Inhibitors of IGF1R Kinase.

The allosteric inhibition of Insulin-like Growth Factor Receptor 1 Kinase (IGF1RK) is a potential strategy to overcome selectivity barriers in targeting receptor tyrosine kinases. We constructed structural models of a series of 12 indole-butyl-amine derivatives which have been reported as allosteric inhibitors of IGF1RK. We further studied dynamics and interactions of each inhibitor in the allosteric pocket via all-atom explicit-solvent molecular dynamics (MD) simulations. We discovered that a bulky carbonyl substitution at the R1 indole ring is structurally unfavorable for inhibitor binding in the IGF1RK allosteric pocket. Moreover, we found that the most potent derivative (termed C11) acquires a distinct conformation, forming an allosteric pocket channel with better shape complementarity and interactions with the receptor. In addition to a hydrogen bonding interaction with V1063, the cyano derivative C11 forms a stable hydrogen bond with M1156, which is responsible for its unique binding conformation in the allosteric pocket. Our findings show that the position of chemical substituents at the R1 indole ring with different pharmacophore features influences molecular interactions and binding conformations of the indole-butyl-amine derivatives, hence dramatically affecting their potencies. Our results provide a structural framework for the design of allosteric inhibitors with improved affinities and specificities against IGF1RK.

Molecular basis for differential recognition of an allosteric inhibitor by receptor tyrosine kinases.

Understanding kinase-inhibitor selectivity continues to be a major objective in kinase drug discovery. We probe the molecular basis of selectivity of an allosteric inhibitor (MSC1609119A-1) of the insulin-like growth factor-I receptor kinase (IGF1RK), which has been shown to be ineffective for the homologous insulin receptor kinase (IRK). Specifically, we investigated the structural and energetic basis of the allosteric binding of this inhibitor to each kinase by combining molecular modeling, molecular dynamics (MD) simulations, and thermodynamic calculations. We predict the inhibitor conformation in the binding pocket of IRK and highlight that the charged residues in the histidine-arginine-aspartic acid (HRD) and aspartic acid-phenylalanine-glycine (DFG) motifs and the nonpolar residues in the binding pocket govern inhibitor interactions in the allosteric pocket of each kinase. We suggest that the conformational changes in the IGF1RK residues M1054 and M1079, movement of the ⍺C-helix, and the conformational stabilization of the DFG motif favor the selectivity of the inhibitor toward IGF1RK. Our thermodynamic calculations reveal that the observed selectivity can be rationalized through differences observed in the electrostatic interaction energy of the inhibitor in each inhibitor/kinase complex and the hydrogen bonding interactions of the inhibitor with the residue V1063 in IGF1RK that are not attained with the corresponding residue V1060 in IRK. Overall, our study provides a rationale for the molecular basis of recognition of this allosteric inhibitor by IGF1RK and IRK, which is potentially useful in developing novel inhibitors with improved affinity and selectivity.

Collinsella aerofaciens linked with increased ethanol production and liver inflammation contribute to the pathophysiology of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.

Multilocular cystic nephroma in an adult: a diagnostic quandary.

Multilocular cystic nephroma (MLCN) is an unusual, benign slow-growing renal cystic neoplasm which mimics other cystic renal lesions and has such clinical, radiological, and morphological features that causes diagnostic dilemma. MLCN lies in the spectrum of mixed epithelial and stromal tumor (MEST) family of kidney. According to World Health Organization (WHO 2016 classification), MEST encompasses spectrum of tumors ranging from predominantly cystic tumors, adult cystic nephroma (ACN) to tumors that are variably solid (MEST), thus creating diagnostic dilemma. Moreover, it has several benign and malignant differentials due to its several overlapping histomorphological features which when not cautiously dealt with may result in misdiagnosing it as malignant lesion. We hereby present a case of a woman in late twenties who presented with left flank swelling and pain since 6 months which was misdiagnosed as renal cell carcinoma on radiology which turned out to be ACN on histology and further verified on immunohistochemistry.

Genomic and functional insights into antibiotic resistance genes floR and strA linked with the SXT element of Vibrio cholerae non-O1/non-O139.

The emergence and spread of antibiotic-resistant bacterial pathogens are a critical public health concern across the globe. Mobile genetic elements (MGEs) play an important role in the horizontal acquisition of antimicrobial resistance genes (ARGs) in bacteria. In this study, we have decoded the whole genome sequences of multidrug-resistant Vibrio cholerae clinical isolates carrying the ARG-linked SXT, an integrative and conjugative element, in their large chromosomes. As in others, the SXT element has been found integrated into the 5'-end of the prfC gene (which encodes peptide chain release factor 3 involved in translational regulation) on the large chromosome of V. cholerae non-O1/non-O139 strains. Further, we demonstrate the functionality of SXT-linked floR and strAB genes, which confer resistance to chloramphenicol and streptomycin, respectively. The floR gene-encoded protein FloR belongs to the major facilitator superfamily efflux transporter containing 12 transmembrane domains (TMDs). Deletion analysis confirmed that even a single TMD of FloR is critical for the export function of chloramphenicol. The floR gene has two putative promoters, P1 and P2. Sequential deletions reveal that P2 is responsible for the expression of the floR. Deletion analysis of the N- and/or C-terminal coding regions of strA established their importance for conferring resistance against streptomycin. Interestingly, qPCR analysis of the floR and strA genes indicated that both of the genes are constitutively expressed in V. cholerae cells. Further, whole genome-based global phylogeography confirmed the presence of the integrative and conjugative element SXT in non-O1/non-O139 strains despite being non-multidrug resistant by lacking antimicrobial resistance (AMR) gene cassettes, which needs monitoring.

Identification of potential novel inhibitors against the SARS-CoV-2 spike protein: targeting RBD and ACE2 interaction.

The SARS-CoV-2, responsible for the COVID-19 pandemic has wrecked devastation throughout the globe. The SARS-CoV-2 spike (S) glycoprotein plays crucial role in virus attachment, fusion, and entry. This study aims to identify inhibitors targeting the receptor binding domain (RBD) of the S protein using computational and experimental techniques. We carried out virtual screening of four datasets against the S-RBD. Six potential candidate inhibitors were selected for experimental evaluation. Here, we provide experimental evidence that the molecules 9‴-MethyllithosperMate, Epimedin A, Pentagalloylglucose, and Theaflavin-3-gallate have a high binding affinity towards SARS-CoV-2 S-RBD. 9‴-MethyllithosperMate with a KD value of 1.3 nM serves as the best inhibitor, followed by others with KD values in micromolar range. We performed molecular dynamics simulation to assess the binding stability of these inhibitors. Hence, our study reports novel inhibitors against the SARS-CoV-2 S-RBD and their predicted binding mode also suggest the possibility to interfere with the ACE2 binding.Communicated by Ramaswamy H. Sarma.

From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology.

Prognostic survival prediction in colorectal cancer (CRC) plays a crucial role in guiding treatment decisions and improving patient outcomes. In this research, we explore the application of deep learning techniques to predict survival outcomes based on histopathological images of human colorectal cancer. We present a retrospective multicenter study utilizing a dataset of 100,000 nonoverlapping image patches from hematoxylin & eosin-stained histological images of CRC and normal tissue. The dataset includes diverse tissue classes such as adipose, background, debris, lymphocytes, mucus, smooth muscle, normal colon mucosa, cancer-associated stroma, and colorectal adenocarcinoma epithelium. To perform survival prediction, we employ various deep learning architectures, including convolutional neural network, DenseNet201, InceptionResNetV2, VGG16, VGG19, and Xception. These architectures are trained on the dataset using a multicenter retrospective analysis approach. Extensive preprocessing steps are undertaken, including image normalization using Macenko's method and data augmentation techniques, to optimize model performance. The experimental findings reveal promising results, demonstrating the effectiveness of deep learning models in prognostic survival prediction. Our models achieve high accuracy, precision, recall, and validation metrics, showcasing their ability to capture relevant histological patterns associated with prognosis. Visualization techniques are employed to interpret the models' decision-making process, highlighting important features and regions contributing to survival predictions. The implications of this research are manifold. The accurate prediction of survival outcomes in CRC can aid in personalized medicine and clinical decision-making, facilitating tailored treatment plans for individual patients. The identification of important histological features and biomarkers provides valuable insights into disease mechanisms and may lead to the discovery of novel prognostic indicators. The transparency and explainability of the models enhance trust and acceptance, fostering their integration into clinical practice. Research demonstrates the potential of deep learning models for prognostic survival prediction in human colorectal cancer histology. The findings contribute to the understanding of disease progression and offer practical applications in personalized medicine. By harnessing the power of deep learning and histopathological analysis, we pave the way for improved patient care, clinical decision support, and advancements in prognostic prediction in CRC.

Comparative Study of Complications Associated with Coblation Versus Conventional Tonsillectomy.

Tonsillectomy is one of the most common ear, nose and throat surgical procedure, carried out worldwide1. Amongst the various method of tonsillectomy (diathermy, laser, harmonic scalpel, radiofrequency cautery cryosurgery and coblation), dissection and snare method is commonest procedure done by otorhinolaryngologist. To compare the post operative complications associated with coblation versus conventional cold-dissection steel tonsillectomy. We carried out the prospective study of complications associated with coblation versus conventional cold steel tonsillectomy in postoperative pain, anesthesia, hemorrhage, fever, pharyngitis, injury of adjacent structure & cautery burn. Average blood loss on Coblation side was 18.74 ml while on conventional side it was 44.2 ml. Post operative pain score, injury to adjacent structure and cautery burn were found to be significantly decreased in coblation. No such difference was observed in pharyngitis and fever in both methods. The use of coblator reduces the post-operative pain, peri or post-operative blood loss, injury to adjacent structure & cautery burn too.

Attenuation of celecoxib cardiac toxicity using Poly(δ-decalactone) based nanoemulsion via oral route.

Celecoxib (CLX), a poorly soluble anti-inflammatory drug, requires administration in higher concentrations to produce therapeutic effects, oftentimes resulting in cardiac toxicity. Therefore, in this study, we employed a nanoemulsion technology to improve the solubility of CLX using poly(δ-decalactone) (PDL) polymer as an oil and mPEG-b-PDL as a surfactant. The nanoemulsion (NE) was successfully prepared via the nanoprecipitation method. In vitro characterization was performed for size, drug release, and stability. In vivo studies were performed to establish anti-inflammatory activity, CLX induced cardiac toxicity, and pharmacokinetic profile of NE, post-oral administration. The globular size of less than 100 nm was obtained in NE with high CLX loading. The in vitro drug release studies suggested ∼90% of CLX release from NE within 96 h. A significant anti-inflammatory activity with lowered cardiac marker values was observed for CLX NE compared to a marketed drug formulation. The pharmacokinetic study revealed that the mean retention time of CLX was significantly increased with NE in contrast to the marketed formulation, suggesting the advantage of administering CLX in the form of NE owing to the higher solubility and sustained release pattern. The long-term storage stability study reveals that NE does not show significant changes in terms of size with only a slight decrement in CLX content was observed after 24 months. The obtained results indicate that CLX bioavailability has been considerably improved without being toxic to the heart with the aid of NE and advocate the use of PDL NE for developing oral formulations for poorly soluble drugs.

Lipid-Polymer Hybrid Nanosystems: A Rational Fusion for Advanced Therapeutic Delivery.

Lipid nanoparticles (LNPs) are spherical vesicles composed of ionizable lipids that are neutral at physiological pH. Despite their benefits, unmodified LNP drug delivery systems have substantial drawbacks, including a lack of targeted selectivity, a short blood circulation period, and in vivo instability. lipid-polymer hybrid nanoparticles (LPHNPs) are the next generation of nanoparticles, having the combined benefits of polymeric nanoparticles and liposomes. LPHNPs are being prepared from both natural and synthetic polymers with various techniques, including one- or two-step methods, emulsification solvent evaporation (ESE) method, and the nanoprecipitation method. Varieties of LPHNPs, including monolithic hybrid nanoparticles, core-shell nanoparticles, hollow core-shell nanoparticles, biomimetic lipid-polymer hybrid nanoparticles, and polymer-caged liposomes, have been investigated for various drug delivery applications. However, core-shell nanoparticles having a polymeric core surrounded by a highly biocompatible lipid shell are the most commonly explored LPHNPs for the treatment of various diseases. In this review, we will shed light on the composition, methods of preparation, classification, surface functionalization, release mechanism, advantages and disadvantages, patents, and clinical trials of LPHNPs, with an emphasis on core-shell-structured LPHNPs.

Relationship between Cardiovascular Risk Factors and Composite Cardiovascular Outcomes in Patients Hospitalized with Takotsubo Syndrome: A Nationwide Analysis.

The association of traditional cardiovascular disease (CVD) risk factors with outcomes of Takotsubo syndrome (TTS) is not well-defined. This study examined how modifiable CVD risk factors affect composite cardiovascular outcomes in TTS hospitalizations. TTS admissions were identified using ICD-10 codes and compared for demographics and comorbidities using the 2019 National Inpatient Sample. A multivariable regression examined the association of traditional CVD risk variables with adverse composite cardiovascular outcomes in TTS, controlling for confounders including sociodemographic or hospital-level characteristics and other relevant comorbidities. A total of 16,055 (38.1%) of the 41,855 adult TTS admissions had composite cardiovascular outcomes (TACCO). The TACCO cohort was 81.5% white, 77.3% female, and 72 years old. This group had higher rates of diabetes and peripheral vascular disease (PVD). The results showed that a higher prevalence of diabetes with chronic complications (OR = 1.18) and complicated hypertension (HTN) (OR = 1.1) predicted TACCO, whereas tobacco use disorder (OR = 0.84), hyperlipidemia (OR = 0.76), and uncomplicated HTN (OR = 0.65) (p < 0.001) showed a paradoxical effect with TACCO. TACCO had fewer routine discharges (35.3% vs. 63.4%), longer stays (6 vs. 3 days), and higher median hospital costs (78,309 USD vs. 44,966 USD). This population-based study found that complicated HTN and DM with chronic complications are strongly associated with adverse cardiovascular outcomes in TTS hospitalizations. But still, some risk factors, such as hyperlipidemia and uncomplicated HTN, have counterintuitive effects that require further evaluation. To prevent cardiac events in TTS patients, traditional CVD risk factors must be addressed.

Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

A Narrative Review of Signaling Pathway and Treatment Options for Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy is a progressive kidney disease that frequently results in end-stage renal disorders and is characterized by proteinuria, albuminuria, decreased filtration, and renal fibrosis. Despite the fact that there are a number of therapeutic alternatives available, DN continues to be the main contributor to end-stage renal disease. Therefore, significant innovation is required to enhance outcomes in DN patients. MATERIAL AND METHODS: Information was collected from online search engines like, Google Scholar, Web of Science, PubMed, Scopus, and Sci-Hub databases using keywords like diabetes, nephropathy, kidney disease, autophagy, etc. Result: Natural compounds have anti-inflammatory and antioxidant properties and impact various signaling pathways. They ameliorate kidney damage by decreasing oxidative stress, inflammatory process, and fibrosis and enhance the antioxidant system, most likely by activating and deactivating several signaling pathways. This review focuses on the role of metabolic memory and various signaling pathways involved in the pathogenesis of DN and therapeutic approaches available for the management of DN. Special attention is given to the various pathways modulated by the phytoconstituents.

Involvement of the non-active site Residues in the Catalytic Activity of NDM-4 Metallo beta-lactamase.

The rise of New Delhi metallo beta-lactamase (NDM) producing bacteria imposes a significant threat to the treatment of bacterial infections due to their broad spectrum against beta-lactams. The activity of metallo beta-lactamases is affected by active site residues as well as residues near the active site. Therefore, we aimed to identify the amino acid residues around the active site of NDM-4 which influence its function. To achieve that, seven substitution mutations (S191A, D192A, S213A, K216A, S217A, D223A and D225A) of NDM-4 were generated through site-directed mutagenesis. Out of these, expression of NDM-4_D192A and NDM-4_S217A in Escherichia coli cells increased the beta-lactam susceptibility as compared to NDM-4. Further, proteins were purified to assess the effect of substitution mutations on zinc content, in vitro catalytic efficiency, and stability of NDM-4. The catalytic efficiency was reduced for these mutants (D192A and S217A) towards beta-lactam substrates, while the thermal stability remained insubstantial as compared to NDM-4. However, the purified NDM-4_D192A exhibited altered zinc content. In silico studies reveal that these changes might be the outcomes of alterations in hydrogen bonding networks and substrate interactions. Taken together, we infer that the D192 and the S217 residues play a substantial role in the activity of NDM-4.

Two non-active site residues W165 and L166 prominently influence the beta-lactam hydrolytic ability of OXA-23 beta-lactamase.

Dissemination of class D OXA-type carbapenemases is one of the significant causes of beta-lactam resistance in Gram-negative bacteria. The amino acid residues present near the active site are involved in hydrolytic mechanism of class D carbapenemases, though it is not identified in OXA-23. Here, with the help of site-directed mutagenesis, we aimed to explicate the importance of the residues W165, L166 and V167 of the possible omega loop and residue D222 in the short ß5-ß6 loop on the activity of OXA-23. All the residues were substituted with alanine. The resultant proteins were assayed for the changes in activity in E. coli cells and purified for in vitro activity, and stability assessment. E. coli cells harboring OXA-23_W165A and OXA-23_L166A, individually, exhibited a significant decrease in resistance towards beta-lactam antibiotics as compared to OXA-23. Further, purified OXA-23_W165A and OXA-23_L166A imparted about >4-fold decrease in catalytic efficiency and displayed reduced thermal stability as compared to OXA-23. Bocillin-FL binding assay revealed that W165A substitution results in improper N-carboxylation of K82, leading to deacylation deficient OXA-23. Therefore, we infer that the residue W165 maintains the integrity of N-carboxylated lysine (K82) of OXA-23 and the residue L166 might be responsible for properly orientating the antibiotic molecules.

Spatio-temporal investigation of physico-chemical water quality parameters based on comparative assessment of QUAL 2Kw and WASP model for the upper reaches of Yamuna River stretching from Paonta Sahib, Sirmaur district to Cullackpur, North Delhi districts of North India.

An accurate investigation of bio-physical and chemical parameters as proxy of in situ water quality conditions in the Himalayan region is highly challenging owing to cumbersome, strenuous, and physically exhausting sampling exercises at high altitude locations. The upper stretches of Yamuna River in the Himachal Pradesh are typical examples of such sampling locations that have rarely been examined in the past studies. A widely accepted and recognized QUAL 2Kw model is applied for estimating the water quality parameters on the upper segment of the Yamuna River from Paonta Sahib to Cullackpur. These water quality indicators mainly included electric conductivity, pH, dissolved oxygen, temperature, carbonaceous biological oxygen demand (CBOD), inorganic suspended solids, total nitrogen, total phosphorus, and alkalinity, which were systematically investigated for predicting the spatio-temporal trends during the year 2018. A total of 12 distantly located river sites were identified for sample collection and data validation using QUAL 2Kw model. The present investigation attempts to reveal long-term degraded impact of untreated wastewater and biased agricultural practices on the water quality conditions over the upper stretches of Yamuna River. The QUAL 2Kw-derived values for selected variables were inter-compared with in situ values, and any deviation from measured values was ascertained based on meaningful statistical measures. The lower error of RMSE, MRE, and BIAS, corresponding to < 15%, ± 10%., ± 20%, and ~ 1 slope evidently indicated better matchup of values, wherein, higher slope correlation coefficient (R2) of ~ 90% indicated the robust performance of the QUAL 2Kw algorithm in accurately predicting the chosen variables. A comparative assessment of QUAL 2Kw and WASP has been performed to justify aptness of water quality model in scenarios of lean flow.

In silico identification of small molecule protein-protein interaction inhibitors: targeting hotspot regions at the interface of MXRA8 and CHIKV envelope protein.

Chikungunya virus (CHIKV) is an arthritogenic arbovirus responsible for re-emerging epidemics of Chikungunya fever around the world for centuries. Chikungunya has become endemic in Africa, Southeast Asia, the Indian subcontinent, and subtropical regions of the Americas. The unavailability of antiviral therapy or vaccine against the CHIKV and its continuous re-emergence demands an urgent need to develop potential candidate therapeutics. CHIKV entry into the host cell is mediated by its envelope proteins engaging the cellular receptor MXRA8 to invade the susceptible cells. We report here two essential target binding sites at the CHIKV E1-E2 proteins by identifying hotspot regions at the E1-E2-MXRA8 binding interface. Further, we employed high throughput computational screening to identify potential small molecule protein-protein interaction (PPI) modulators which could effectively bind at the identified target sites. Molecular dynamics simulations and binding free energy calculations confirmed the stability of three compounds, viz., ZINC299817498, ZINC584908978, and LAS52155651, at both the predicted interface binding sites. The polar and charged residues at the interface were responsible for energetically holding the ligands at the binding sites. Altogether, our findings suggest that the predicted target binding sites at the E1-E2 dimer could be essential to block the receptor interaction as well as the fusion process of the CHIKV particles. Thus, we identified a few small molecule PPI inhibitors with great potential to block the E1-E2-MXRA8 interaction and act as promising templates to design anti-CHIKV drugs.Communicated by Ramaswamy H. Sarma.

Evaluation of air pollution tolerance index and anticipated performance index of selected roadside tree species in Ludhiana, India.

Air quality has deteriorated in most big cities and becoming the fifth major cause of mortality in India. Among others, vehicle gaseous emission is a major contributor. Plants have different tolerance levels, which can be identified based on Air Pollution Tolerance Index (APTI). The objectives were to study the morphological and biochemical parameters for Air Pollution Tolerance Index (APTI) of selected roadside tree species (Acacia auriculiformis, Alstonia scholaris, Chukrasia tabularis, Cassia fistula, Cassia siamea, Dalbergia sissoo, Heterophragma adenophyllum, and Putranjiva roxburghii) at control (PAU campus) and polluted sites (roadside) during summer and winter seasons. The total chlorophyll content, ascorbic acid, leaf extract pH, leaf relative water content, total soluble sugar, phenols, and carotenoids ranged from 0.59 to 4.16 mg g-1, 1.03 to 3.75 mg g-1, 3.16 to 7.04, 46.01 to 71.65%, 10.78 to 23.83 mg g-1, 0.51 to 1.35 mg -1, and 0.19 to 1.96 mg g-1, respectively. The Air Pollution Tolerance Index of the selected trees ranged between7.65 and 11.19 and followed an order of Cassia fistula > Acacia auriculiformis > Dalbergia sissoo > Alstonia scholaris > Putranjiva roxburghii > Heterophragma adenophyllum > Cassia siamea > Chukrasia tabularis. The evaluation of Anticipated Performance Index (API) categorized the trees into poor (Dalbergia sissoo and Cassia siamea), moderate (Cassia fistula), and good (Acacia auriculiformis, Alstonia scholaris, Chukrasia tabularis, Heterophragma adenophyllum, and Putranjiva roxburghii) categories.

Gut microbiome dysbiosis in neonatal sepsis.

Sepsis is a highly heterogeneous, life-threatening organ dysfunction primarily caused by a dysregulated immune response to counter bacterial, viral, or fungal infections, resulting in haemodynamic changes and significant morbidity and mortality across all ages. In recent times, it has become one of the foremost causes of morbidity and mortality among newborns globally. The neonates, particularly the preterm neonates, due to their immature immune systems and non-canonical microbial community acquisition in the gastrointestinal tract and other body habitats, are adversely affected compared to the elderly with immunocompromised conditions. The neonates could acquire microbiota in utero or during delivery from the mother's genital tract or postnatally from contact with hospital personnel and the immediate hospital environment after the birth. Other factors that may enhance the risk include early colonization of microbiota by pathogens that trigger dysbiosis of the gut microbiome accompanied by a dysregulated immune response, organ dysfunction, and potential death. The sepsis-linked mortality could be prevented by timely diagnosis, selective antibiotic therapy, and supportive postnatal care. Infections due to antibiotic-resistant bacteria severely restrict possible therapeutic options, thus extending hospital stays. A comprehensive analysis of the infecting pathogens, cognate host responses, and the microbiota present would certainly help formulate appropriate interventions.