Structural insight into the binding mode of cefotaxime and meropenem to TEM-1, SHV-1, KPC-2, and Amp-C type beta-lactamases.

Antimicrobial resistance is an emerging threat to public health around the world. The study employs computational and biophysical methods to investigate the properties of cefotaxime and meropenem's binding to various beta-lactamases like TEM-1, SHV-1, KPC-2, and Amp-C. The enzyme kinetics of purified proteins revealed an increase in Michaelis constant (Km) value in the presence of meropenem and cefotaxime, indicating a decrease in enzyme affinity for nitrocefin. Proteins interact with meropenem/cefotaxime, causing quenching through complex formation. All proteins have one binding site, and binding constant (Kb) values are 104, indicating strong interaction. The study found that meropenem and cefotaxime had high fitness scores for Amp-C, KPC-2,TEM-1 and SHV-1, with binding energy ranging from -7.4 to -7.8, and hydrogen bonds between them. Molecular Dynamic simulation of protein-ligand complexes revealed cefotaxime-binding proteins have slightly lower Root Mean Square Deviation(RMSD) than meropenem-binding proteins, indicating stable association antibiotics with these proteins.

Genome analyses of colistin-resistant high-risk blaNDM-5 producing Klebsiella pneumoniae ST147 and Pseudomonas aeruginosa ST235 and ST357 in clinical settings.

BACKGROUND: Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT). RESULTS: This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 µg/mL), while broth microdilution identified 48 (MIC = 32-128 µg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated blaNDM-5 (K. pneumoniae ST147) and chromosomally mediated blaNDM-1 (P. aeruginosa ST357). CONCLUSION: The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Locating-dominating number of certain infinite families of convex polytopes with applications.

A convex hull of finitely many points in the Euclidean space Rd is known as a convex polytope. Graphically, they are planar graphs i.e. embeddable on R2. Minimum dominating sets possess diverse applications in computer science and engineering. Locating-dominating sets are a natural extension of dominating sets. Studying minimizing locating-dominating sets of convex polytopes reveal interesting distance-dominating related topological properties of these geometrical planar graphs. In this paper, exact value of the locating-dominating number is shown for one infinite family of convex polytopes. Moreover, tight upper bounds on γl-d are shown for two more infinite families. Tightness in the upper bounds is shown by employing an updated integer linear programming (ILP) model for the locating-dominating number γl-d of a fixed graph. Results are explained with help of some examples. The second part of the paper solves an open problem in Khan (2023) [28] which asks to find a domination-related parameter which delivers a correlation coefficient of ρ>0.9967 with the total π-electronic energy of lower benzenoid hydrocarbons. We show that the locating-dominating number γl-d delivers such a strong prediction potential. The paper is concluded with putting forward some open problems in this area.

Advanced polymers and recent advancements on gastroretentive drug delivery system; a comprehensive review.

Oral route of drug administration is typically the initial option for drug administration because it is both practical and affordable. However, major drawback of this route includes the release of drug at a specified place thus reduces the bioavailability. This could be overcome by utilising the gastroretentive drug delivery system (GRRDS). Prolonged stomach retention improves bioavailability and increases solubility for medicines that are unable to dissolve in high pH environments. Many recent advancements in the floating, bio adhesive, magnetic, expandable, raft forming and ion exchange systems have been made that had led towards advanced form of drug delivery. From the past few years, floating drug delivery system has been most commonly utilised for the delivery of drug in a delayed manner. Various polymers have been utilised for manufacturing of these systems, including alginates, chitosan, pectin, carrageenan's, xanthan gum, hydroxypropyl cellulose, carbomer, polyethylene oxide and sodium carboxy methyl cellulose. Chitosan, pectin and xanthan gum have been found to be most commonly used polymers in the manufacturing of drug inclusion complex for gastroretentive drug delivery. This study aimed to define various types and advanced polymers as well as also highlights recent advances and future perspectives of gastroretentive drug delivery system.

Does early stable fixation reduce complications in paediatric femoral neck fractures?

The primary objective of this study was to juxtapose the union rate and incidence of complications in paediatric patients presenting early (≤ 7 days) following injury with children presenting later (> 7 days) with femoral neck fractures. This critical appraisal evaluated 15 patients according to their timing of presentation and surgery from the initial day of injury (Group A: operated ≤ 7 days or Group B: > 7 days of injury). Patients with traumatic femoral neck fractures with Delbet 1 to 4 subtypes who were skeletally immature (age ≤ 16 years) were included in the study. Pathological fractures and post-infective fractures were not included. Each patient's secondary loss of reduction was calculated by measuring the Neck shaft angle (NSA) on the immediate post-operative radiograph and at the union. A change in NSA of ≥ 5 degrees was considered a significant loss of reduction. Ratliff's Criteria was used to analyze the final result, and a thorough record of complications was kept. There were no significant variations in the two groups' with respect to distributions of age, sex, injury mechanism, or fracture pattern. The most frequent injury culprit in both groups was falling from a height. Type II fracture pattern (54.54%) was more common in group A, while Type III and Type II fracture pattern was equally distributed in group B. In group A, the mean operation time was 55 ± 8.25 minutes, whereas in group B, it was 65 ± 15 minutes (p-value > 0.05). In group A, 90.9% of patients underwent CCS fixation, and in group B, 75% underwent fixation by CCS. The quality of reduction in post-operative radiographs was anatomical in 10 (90.9%) patients and unacceptable in 1 (9.1%) patient. In group B, 2 (50%) patients had an anatomical reduction, while 2 (50%) patients had an unacceptable reduction. Timing of reduction and its association with complications showed that early stable reduction and fixation decrease the occurrence of complications in femoral neck fractures (p-value = 0.033). Fracture union was seen in all our patients in both groups and none of our patients underwent non-union. The mean union time was 11.11 ± 7.06 weeks in group A and 16.5 ± 2.59 weeks in group B (p-value = 0.0189). In group A, only 1 (9.1%) patient developed coxa vara. In group B, out of 4 patients, the femoral head of one patient underwent avascular necrosis, one patient exhibited coxa vara, and 1 patient developed premature physeal closure with limb length inequality. Management of femoral neck fractures in children is challenging because of the paediatric bone's peculiar anatomic and physiological considerations. In our study, patients operated within 7 days developed fewer complications as compared to patients who were operated after 7 days, which was statistically significant. Although AVN is a frequent adverse consequence of pediatric femoral neck fractures, early reduction and stable fixation lowers AVN rates, as observed in our study. Our short-term functional and radiological results using the Ratliff scoring system were comparable to previous studies owing to stable anatomic reduction. Based on our findings and the existing literature, we emphasize long-term follow-up and recommend an early stable anatomic reduction in the treatment of paediatric femoral neck fractures.

Novel yellowish-green single-phased spinel Mg1-xBaxAl2O4:Mn2+ phosphor(s) for color rendering white-light-emitting diodes.

For white light-rendering research activities, interpretation by using colored emitting materials is an alternative approach. But there are issues in designing the white color emitting materials. Particularly, differences in thermal and decay properties of discrete red, green, and blue emitting materials led to the quest for the search of a single-phased material, able to emit primary colors for white light generation. The current study is an effort to design a simple, single-phase, and cost-effective material with the tunable emission of primary colors by a series of Mg1-xBaxAl2O4:Mn2+ nanopowders. Doping of manganese ion (Mn2+) in the presence of the larger barium cation (Ba2+) at tetrahedral-sites of the spinel magnesium aluminate (MgAl2O4) structure led to the creation of antisite defects. Doped samples were found to have lower bandgaps compared with MgAl2O4, and hybridization of 3d-orbitals of Mn2+ with O(2p), Mg(2s)/Al(2s3p) was found to be responsible for narrowing the bandgap. The distribution of cations at various sites at random results in a variety of electronic transitions between the valance band and oxygen vacancies as well as electron traps produced the antisite defects. The suggested compositions might be used in white light applications since they have three emission bands with centers at 516 nm (green), 464 nm (blue) and 622 nm (red) at an excitation wavelength of 380 nm. A detailed discussion to analyze the effects of the larger cationic radius of Ba2+ on the lattice strain, unit cell parameters, and cell volumes using X-ray diffraction analysis is presented.

Development of novel polymer haemoglobin based particles as an antioxidant, antibacterial and an oxygen carrier agents.

This innovative work aims to develop highly biocompatible and degradable nanoparticles by encapsulating haemoglobin (Hb) within poly-ε-caprolactone for novel biomedical applications. We used a modified double emulsion solvent evaporation method to fabricate the particles. A Scanning electron microscope (SEM) characterized them for surface morphology. Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible spectroscopies (UV-visible) elucidated preserved chemical and biological structure of encapsulated haemoglobin. The airproof equilibrium apparatus obtained the oxygen-carrying capacity and P50 values. The DPPH assay assessed free radical scavenging potential. The antibacterial properties were observed using four different bacterial strains by disk diffusion method. The MTT assay investigates the cytotoxic effects on mouse fibroblast cultured cell lines (L-929). The MTT assay showed that nanoparticles have no toxicity over large concentrations. The well-preserved structure of Hb within particles, no toxicity, high oxygen affinity, P50 value, and IC50 values open the area of new research, which may be used as artificial oxygen carriers, antioxidant, and antibacterial agents, potential therapeutic agents as well as drug carrier particles to treat the cancerous cells. The novelty of this work is the antioxidant and antibacterial properties of developed nanoparticles are not been reported yet. Results showed that the prepared particles have strong antioxidant and antibacterial potential.

Antibiotic resistance: a global crisis, problems and solutions.

Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.

Exploring moisture adsorption on cobalt-doped ZnFe2O4 for applications in atmospheric water harvesting.

Sorption-based atmospheric water harvesting (SBAWH) is a highly promising approach for extracting water from the atmosphere thanks to its sustainability, exceptional energy efficiency, and affordability. In this work, ZnFe2O4 and Zn0.4Co0.6Fe2O4 were evaluated for moisture adsorption. The desired materials were synthesized by a surfactant-assisted sol-gel method. Synthesized samples were characterized using X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), and point of zero charge (PZC). Crystallinity and phase composition were evaluated by XRD analysis. Several parameters were determined using XRD analysis: lattice parameter, unit cell volume, crystallite size, and bulk density. The morphology of synthesized materials was assessed via SEM, and unveiled the acquisition of consistent, homogeneous, and uniform crystals. Elemental composition was determined through EDX spectroscopy. Water adsorption on the surface was evaluated by FTIR spectroscopy. The magnetic properties of synthesized ZnFe2O4 and cobalt-doped ZnFe2O4 ferrites were investigated using VSM. The negative charge on the Zn0.4Co0.6Fe2O4 surface was explored using PZC. Adsorption studies on synthesized materials were conducted with the help of an atmospheric water harvesting (AWH) plant created by our team. Moisture adsorption isotherms of synthesized materials were determined using a gravimetric method under varying temperature and relative humidity (45-95%) conditions. The moisture content (Mc) of Zn0.4Co0.6Fe2O4 and ZnFe2O4 was 597 mg g-1 and 104 mg g-1, respectively. Key thermodynamic properties, including isosteric heat of adsorption (Qst), change in Gibbs free energy (ΔG), and change in sorption entropy (ΔS), were evaluated. Qst was negative, which confirmed the sorption of water vapors on the material surface. ΔG and ΔS indicated that water-vapor adsorption was spontaneous and exothermic. A second-order kinetics study was carried out on synthesized materials, demonstrating their chemisorption behavior. The latter was due to the oxygen defects created by replacement of Co2+ and Fe3+ at tetrahedral and octahedral sites. Water vapors in the atmosphere became attached to the surface and deprotonation occurred, and the hydroxyl ions were formed. Water vapor attached to these hydroxyl ions. A second-order kinetics study was carried out to confirm the chemisorption behavior of synthesized materials.

Assessment of health-related quality of life among Afghan refugees in Quetta, Pakistan.

The study aims to assess the health-related Quality of Life (HRQOL) and its association with socio-demographic factors among the Afghan refugees residing in Quetta, Pakistan. For this purpose, a cross-sectional, descriptive study design by adopting Euro QOL five dimensions questionnaire (EQ-5D) for the assessment of HRQOL was conducted by approaching Afghan refugees from the camp and other areas of Quetta, Pakistan. Furthermore, this study also involved descriptive analysis to expound participant's demographic characteristics while inferential statistics (Kruskal-Wallis and Mann-Whitney test, P < 0.05) were used to compare EQ-5D scale scores. All analyses were performed using SPSS v 20. Herein, a total of 729 participants were enrolled and were subsequently (n = 246, 33.7%) categorized based on their age of 22-31 years (31.30 ± 15.40). The results of mean EQ-5D descriptive score (0.85 ± 0.20) and EQ-VAS score (78.60 ± 11.10) indicated better HRQOL in the current study respondents as compared to studies conducted in other refugee camps around the globe. In addition, demographic characteristics including age, marital status, locality, years of living as refugees, life as a refugee residing out of Pakistan, place of residence in Afghanistan, educational qualification, occupation, and arrested for crime were the statistically significant predictors (P < 0.05) of EQ-5D index scores. However, gender, living status, monthly income, preferred place of treatment were non-significant predictors (P > 0.05). The results of current study provided evidence for a model that correlated with participant's socio-demographic information and HRQOL. Moreover, this study also revealed a baseline assessment for the health status of Afghan refugees, interestingly, these results could be applied for improving HRQOL of the given participants. In conclusion, the HRQOL of Afghan refugees residing in Quetta, Pakistan can largely be improved by providing adequate healthcare facilities, education and employment opportunities, mental and social support, and providing adequate housing and basic necessities of life.

Graphs with given connectivity and their minimum Sombor index having applications to QSPR studies of monocarboxylic acids.

The Sombor index, introduced by Gutman in 2021, represents a novel graphical topological descriptor reliant upon graph degree information. It holds promise for elucidating the thermodynamic behavior of compounds. Denoting by Vnk (respectively, Enk) the set encompassing all connected graphs comprising n vertices with a specific vertex-connectivity (correspondingly, edge-connectivity) value of k. In Problem 1 (resp. Problem 2) of Hayat et al. (2022) [33], the question of finding minimum Sombor index of graphs in Vnk (resp. Enk) is proposed. In this note, we solve both of the open problems by characterizing minimizing graphs in Enk and Vnk corresponding to the Sombor index. We employed commonly occurring valency-based graphical indices in a QSPR studies of the physicochemical characteristics for monocarboxylic acids. The proposed statistical models infer that the Sombor index predicts various physicochemical characteristics for monocarboxylic acids having strong predictive coefficients such as ρ=0.99998.

Intelligent prediction modeling for flexural capacity of FRP-strengthened reinforced concrete beams using machine learning algorithms.

Fiber-reinforced polymers (FRP) are widely utilized to improve the efficiency and durability of concrete structures, either through external bonding or internal reinforcement. However, the response of FRP-strengthened reinforced concrete (RC) members, both in field applications and experimental settings, often deviates from the estimation based on existing code provisions. This discrepancy can be attributed to the limitations of code provisions in fully capturing the nature of FRP-strengthened RC members. Accordingly, machine learning methods, including gene expression programming (GEP) and multi-expression programming (MEP), were utilized in this study to predict the flexural capacity of the FRP-strengthened RC beam. To develop data-driven estimation models, an extensive collection of experimental data on FRP-strengthened RC beams was compiled from the experimental studies. For the assessment of the accuracy of developed models, various statistical indicators were utilized. The machine learning (ML) based models were compared with empirical and conventional linear regression models to substantiate their superiority, providing evidence of enhanced performance. The GEP model demonstrated outstanding predictive performance with a correlation coefficient (R) of 0.98 for both the training and validation phases, accompanied by minimal mean absolute errors (MAE) of 4.08 and 5.39, respectively. In contrast, the MEP model achieved a slightly lower accuracy, with an R of 0.96 in both the training and validation phases. Moreover, the ML-based models exhibited notably superior performances compared to the empirical models. Hence, the ML-based models presented in this study demonstrated promising prospects for practical implementation in engineering applications. Moreover, the SHapley Additive exPlanation (SHAP) method was used to interpret the feature's importance and influence on the flexural capacity. It was observed that beam width, section effective depth, and the tensile longitudinal bars reinforcement ratio significantly contribute to the prediction of the flexural capacity of the FRP-strengthened reinforced concrete beam.

Severity of Atelectasis during Bronchoscopy: Descriptions of a New Grading System (AtelectasisSeverity Scoring System-"ASSESS") and At-Risk-Lung Zones.

Atelectasis during bronchoscopy under general anesthesia is very common and can have a detrimental effect on navigational and diagnostic outcomes. While the intraprocedural incidence and anatomic location have been previously described, the severity of atelectasis has not. We reviewed chest CT images of patients who developed atelectasis in the VESPA trial (Ventilatory Strategy to Prevent Atelectasis). By drawing boundaries at the posterior chest wall (A), the anterior aspect of the vertebral body (C), and mid-way between these two lines (B), we delineated at-risk lung zones 1, 2, and 3 (from posterior to anterior). An Atelectasis Severity Score System ("ASSESS") was created, classifying atelectasis as "mild" (zone 1), "moderate" (zones 1-2), and "severe" (zones 1-2-3). A total of 43 patients who developed atelectasis were included in this study. A total of 32 patients were in the control arm, and 11 were in the VESPA arm; 20 patients (47%) had mild atelectasis, 20 (47%) had moderate atelectasis, and 3 (6%) had severe atelectasis. A higher BMI was associated with increased odds (1.5 per 1 unit change; 95% CI, 1.10-2.04) (p = 0.0098), and VESPA was associated with decreased odds (0.05; 95% CI, 0.01-0.47) (p = 0.0080) of developing moderate to severe atelectasis. ASSESS is a simple method used to categorize intra-bronchoscopy atelectasis, which allows for a qualitative description of this phenomenon to be developed. In the VESPA trial, a higher BMI was not only associated with increased incidence but also increased severity of atelectasis, while VESPA had the opposite effect. Preventive strategies should be strongly considered in patients with risk factors for atelectasis who have lesions located in zones 1 and 2, but not in zone 3.

Inhibitors against New Delhi metallo-betalactamase-1 (NDM-1) and its variants endemic in Indian settings along with the laboratory functional gain mutant of NDM-1.

PURPOSE: The emergence of NDM-1 producing bacteria has become common in both hospital and community settings, but no inhibitor has yet been available for clinical treatment. Hence, demanding the urgent need of NDM-1 inhibitors, we initiated to screen broad spectrum inhibitors against NDM natural variants and laboratory mutant. METHODS: We used docking and molecular dynamics simulations, in silico pharmacokinetic investigations, and density functional theory calculation to characterize molecules. Furthermore, an in vitro study, including MIC, kinetics, and fluorescence study were carried out to confirm the efficacies of the selected compounds. RESULTS: According to the findings of the computational studies, three compounds were effective against NDM variants. Fourfold reduction in MIC of imipenem and meropenem was observed when combined with inhibitors (D2573, D2148, and D63) against blaNDM-1, blaNDM-4, blaNDM-6, and blaNDM-1Q123A, while twofold reduction in MIC of imipenem and meropenem was observed against blaNDM-5 and blaNDM-7. Similarly in the presence of inhibitors (D2573, D2148, and D63) the efficiency of nitrocefin hydrolysis by NDM-4, NDM-6, and Q123A decreases to much more extent as compared to NDM-5 and NDM-7. These results showed that the efficacy of these broad spectrum inhibitors decreases with increasing resistance of NDM variants. CONCLUSION: This is the first time inhibitors were tested against different NDM natural variants which are endemic in Indian settings. Moreover, a functional gain laboratory mutant was also checked for their efficacies. We may propose these molecules for the pre-clinical trial to further translate.

Provenance, diagenesis, and depositional environment of Miocene Kamlial Formation, Azad Jammu and Kashmir, Sub Himalayas, Pakistan: Evidences from field observations and petrography.

Petrographical characterization and field observations were caried out to evaluate Kamlial Formation in Bagh district, Azad Jammu and Kashmir. Based on detailed petrography, the lithic arenite consisted of quartz (20-25%), feldspar (7-11%), rock fragments (20-37%), cementing materials (11-21%), and accessory minerals. Grains are mostly angular to subrounded and poorly to moderately sorted. The analysis revealed that the lithic arenite is mineralogically immature; also, the current activity during the time of deposition was low. Polycrystalline quartz indicates that the sandstone was derived from metamorphic source, while monocrystalline quartz indicates a granitic origin. Quartz having an angular shape suggests the source rock was near the depositional site, while quartz having a rounded shape represents long transportation. The presence of feldspar in the lithic arenite suggests the rocks were deposited at high relief or cold temperatures. Primary porosity in sandstone was reduced by calcite cements around the grain, while secondary porosity was developed by fracturing of quartz and feldspar. Tectonic uplift in the study area was demonstrated by fractured quartz and mica in thin sections. Field observations of various sedimentary structures were observed such as load casts, ripple marks, and mud cracks, etc. The presence of conglomerates and load casts in the study area indicates that the Kamlial sandstone was deposited by fluvial and shallow marine environment. Furthermore, the ripple marks indicate that the tidal flat environment controlled the deposition of the sediments.

Predicting the bandgap and efficiency of perovskite solar cells using machine learning methods.

Rapid and accurate prediction of bandgaps and efficiency of perovskite solar cells is a crucial challenge for various solar cell applications. Existing theoretical and experimental methods often accurately measure these parameters; however, these methods are costly and time-consuming. Machine learning-based approaches offer a promising and computationally efficient method to address this problem. In this study, we trained different machine learning(ML) models using previously reported experimental data. Among the different ML models, the CatBoostRegressor performed better for both bandgap and efficiency approximations. We evaluated the proposed model using k-fold cross-validation and investigated the relative importance of input features using Shapley Additive Explanations (SHAP). SHAP interprets valuable insights into feature contributions of the prediction of the proposed model. Furthermore, we validated the performance of the proposed model using an independent dataset, demonstrating its robustness and generalizability beyond the training data. Our findings show that machine learning-based approaches, with the aid of SHAP, can provide a promising and computationally efficient method for the accurate and rapid prediction of perovskite solar cell properties. The proposed model is expected to facilitate the discovery of new perovskite materials and is freely available at GitHub (https://github.com/AsadKhanJBNU/perovskite_bandgap_and_efficiency.git) for the perovskite community.

Bacterial abundance and antimicrobial resistance patterns of uropathogens among pregnant women with asymptomatic bacteriuria: Association with glycemic status.

Objectives: Antimicrobial resistance (AMR), a growing global menace, poses a significant threat to maternal and fetal health. Gestational diabetes mellitus (GDM) causes double trouble in pregnancy, increasing the risk of a variety of infectious morbidities while also raising the possible association with AMR. Asymptomatic bacteriuria (ASB) is a common problem in pregnancy, but little research has been done to date explicitly examining the relationship between GDM and ASB and yielded conflicting results. Even fewer studies have specifically examined the relationship between GDM and AMR in women with ASB. Retrieving the most recent information on the disease burden, the range of causative pathogens, their patterns of AMR, and associated risk factors in pregnant women is crucial to stop the exponential rise in AMR in pregnancy and improve maternal and neonatal outcomes of infectious morbidities. Hence, this study was planned to investigate the association between glycemic status and the contemporary bacterial profile, antimicrobial resistance(AMR), and associated variables among pregnant women with ASB. Study design: This prospective, hospital-based, cross-sectional study was conducted among 320 pregnant women; divided into two groups, GDM and non-GDM. Data regarding sociodemographic and clinical characteristics were collected using a structured questionnaire. Clean-catch midstream urine samples were investigated for the presence of significant bacterial uropathogens and their AMR pattern was determined using recommended culture methods. Results: We found ASB in 46.25% of study participants with significantly higher occurrence in the GDM group. Dominant isolates were Escherichia coli followed by Klebsiella pneumoniae. AMR was noted in 51.35% and multidrug resistance(MDR) in 23.65% of isolates. Overall AMR, MDR and higher degrees of AMR were higher among uropathogens isolated from the GDM group as compared to the non GDM group, although the difference was not statistically significant. Conclusion: The high occurrence of ASB in pregnancy along with substantially high AMR in this study suggests the need for effective infection control and stewardship programmes. By defining the association of ASB and AMR with hyperglycemia, our study calls for the exploitation of this potential association in halting the pandemic of AMR and in improving the management of infectious morbidities, thus in-turn alleviating their undesired maternal and infant outcomes.

Cellular signaling in the hypoxic cancer microenvironment: Implications for drug resistance and therapeutic targeting.

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.