Many-body quantum chaos in mixtures of multiple species.

We study spectral correlations in many-body quantum mixtures of fermions, bosons, and qubits with periodically kicked spreading and mixing of species. We take two types of mixing, namely, Jaynes-Cummings and Rabi, respectively, satisfying and breaking the conservation of a total number of species. We analytically derive the generating Hamiltonians whose spectral properties determine the spectral form factor in the leading order. We further analyze the system-size (L) scaling of Thouless time t^{*}, beyond which the spectral form factor follows the prediction of random matrix theory. The L dependence of t^{*} crosses over from lnL to L^{2} with an increasing Jaynes-Cummings mixing between qubits and fermions or bosons in a finite-size chain, and it finally settles to t^{*}∝O(L^{2}) in the thermodynamic limit for any mixing strength. The Rabi mixing between qubits and fermions leads to t^{*}∝O(lnL), previously predicted for single species of qubits or fermions without total-number conservation.

Furanocoumarins promote proteasomal degradation of viral HBx protein and down-regulate cccDNA transcription and replication of hepatitis B virus.

Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.

Comparative evaluation of full and partial pulpotomy in permanent teeth with irreversible pulpitis: A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to conduct a comparative evaluation of partial and full pulpotomy techniques in cariously exposed teeth with symptoms indicative of symptomatic irreversible pulpitis. Databases such as PubMed, EMBASE, Cochrane, and Web of Science were searched. Studies evaluating and/or comparing clinical and/or radiographic success of partial and full pulpotomy in teeth diagnosed with irreversible pulpitis with a minimum of 12 months follow-up were included. The risk of bias (ROB) tool was used for the assessment of ROB. A meta-analysis was conducted to compare the healing outcome of partial and full pulpotomy. Three studies fulfilled the inclusion criteria, there was a low risk of bias in each of the five domains. Full pulpotomy had a higher success rate than partial pulpotomy, according to meta-analysis, but the difference was not statistically significant.

Xbra modulates the activity of linker region phosphorylated Smad1 during Xenopus development.

The Bmp/Smad1 pathway plays a crucial role in developmental processes and tissue homeostasis. Mitogen-activated protein kinase (Mapk)/Erk mediated phosphorylation of Smad1 in the linker region leads to Smad1 degradation, cytoplasmic retention and inhibition of Bmp/Smad1 signaling. While Fgf/Erk pathway has been documented to inhibit Bmp/Smad1 signaling, several studies also suggests the cooperative interaction between these two pathways in different context. However, the precise role and molecular pathway of this collaborative interaction remain obscure. Here, we identified Xbra induced by Fgf/Erk signaling as a factor in a protective mechanism for Smad1. Xbra physically interacted with the linker region phosphorylated Smad1 to make Xbra/Smad1/Smad4 trimeric complex, leading to Smad1 nuclear localization and protecting it from ubiquitin-mediated proteasomal degradation. This interaction of Xbra/Smad1/Smad4 led to sustained nuclear localization of Smad1 and the upregulation of lateral mesoderm genes, while concurrently suppression of neural and blood forming genes. Taken together, the results suggests Xbra-dependent cooperative interplays between Fgf/Erk and Bmp/Smad1 signaling during lateral mesoderm specification in Xenopus embryos.

Immune Homeostasis: A Novel Example of Teamwork.

All living organisms must maintain homeostasis to survive, reproduce, and pass their traits on to the next generation. If homeostasis is not maintained, it can result in various diseases and ultimately lead to death. Physiologists have coined the term "homeostasis" to describe this process. With the emergence of immunology as a separate branch of medicine, the concept of immune homeostasis has been introduced. Maintaining immune homeostasis is crucial to support overall homeostasis through different immunological and non-immunological routes. Any changes in the immune system can lead to chronic inflammatory or autoimmune diseases, immunodeficiency diseases, frequent infections, and cancers. Ongoing scientific advances are exploring new avenues in immunology and immune homeostasis maintenance. This chapter introduces the concept of immune homeostasis and its maintenance through different mechanisms.

Deep Drug Synergy Prediction Network Using Modified Triangular Mutation-Based Differential Evolution.

Drug combination therapy is crucial in cancer treatment, but accurately predicting drug synergy remains a challenge due to the complexity of drug combinations. Machine learning and deep learning models have shown promise in drug combination prediction, but they suffer from issues such as gradient vanishing, overfitting, and parameter tuning. To address these problems, the deep drug synergy prediction network, named as EDNet is proposed that leverages a modified triangular mutation-based differential evolution algorithm. This algorithm evolves the initial connection weights and architecture-related attributes of the deep bidirectional mixture density network, improving its performance and addressing the aforementioned issues. EDNet automatically extracts relevant features and provides conditional probability distributions of output attributes. The performance of EDNet is evaluated over two well-known drug synergy datasets, NCI-ALMANAC and deep-synergy. The results demonstrate that EDNet outperforms the competing models. EDNet facilitates efficient drug interactions, enhancing the overall effectiveness of drug combinations for improved cancer treatment outcomes.

Exploring the Potential of Exosomes as Biomarkers in Tuberculosis and Other Diseases.

Tuberculosis (TB) is a major cause of morbidity and mortality and remains an important public health issue in developing countries worldwide. The existing methods and techniques available for the diagnosis of TB are based on combinations of laboratory (chemical and biological), radiological, and clinical tests. These methods are sophisticated and laborious and have limitations in terms of sensitivity, specificity, and accuracy. Clinical settings need improved diagnostic biomarkers to accurately detect biological changes due to pathogen invasion and pharmacological responses. Exosomes are membrane-bound vesicles and mediators of intercellular signaling processes that play a significant role in the pathogenesis of various diseases, such as tuberculosis, and can act as promising biomarkers for the monitoring of TB infection. Compared to conventional biomarkers, exosome-derived biomarkers are advantageous because they are easier to detect in different biofluids, are more sensitive and specific, and may be useful in tracking patients' reactions to therapy. This review provides insights into the types of biomarkers, methods of exosome isolation, and roles of the cargo (proteins) present in exosomes isolated from patients through omics studies, such as proteomics. These findings will aid in developing new prognostic and diagnostic biomarkers and could lead to the identification of new therapeutic targets in the clinical setting.

Computational insights into dynamics and conformational stability of N-acetylmannosamine kinase mutations.

The activity of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) is essential for the biosynthesis of sialic acid, which is involved in cellular processes in health and diseases. GNE contains an N-terminal epimerase domain and a C-terminal kinase domain (N-acetylmannosamine kinase, MNK). Mutations of the GNE protein led to hypoactivity of the enzyme and cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. Here, we used all-atom molecular dynamics (MD) simulations to comprehend the folding, dynamics and conformational stability of MNK variants, including the wild type (WT) and three mutants (H677R, V696M and H677R/V696M). The deleterious and destabilizing nature of MNK mutants were predicted using different prediction tools. Results predicted that mutations modulate the stability, flexibility and function of MNK. The effect of mutations on the conformational stability and dynamics of MNK was next studied through the free-energy landscape (FEL), hydrogen-bonds and secondary structure changes. The FEL results show that the mutations interfere with various conformational transitions in both WT and mutants, exposing the structural underpinnings of protein destabilization and unfolding brought on by mutation. We discover that, when compared to the other two mutations, V696M and H677R/V696M, H677R has the most harmful effects. These findings have a strong correlation with published experimental studies that demonstrate how these mutations disrupt MNK activity. Hence, this computational study describes the structural details to unravel the mutant effects at the atomistic resolution and has implications for understanding the GNE's physiological and pathological role.Communicated by Ramaswamy H. Sarma.

Ho3+ -doped BaGd2 ZnO5 green-emitting phosphor for solid-state lighting: synthesis, characterization, and photoluminescence properties.

In this work, we present the synthesis of a green-emitting series of BaGd2 ZnO5 :xHo3+ (0.5-3 mol%) phosphors using a high-temperature solid-state reaction method. Phase purity and crystal structure information were evaluated through X-ray powder diffraction patterns. Optical properties were examined through diffuse reflectance spectra, revealing that the prepared phosphor exhibited a band gap of 4.65 eV. The effect of Ho3+ doping on the morphology and ion distribution on the surface was assessed using scanning electron microscopy and time-of-flight secondary ion mass spectrometry techniques, respectively. The excitation spectra of the synthesized phosphor exhibited a charge transfer band and strong absorption transitions. The emission spectra displayed typical holmium emission characteristics, featuring a strong green emission band associated with f-f transitions from 5 F4 + 2 S2 → 5 I8 . Decay dynamics of the synthesized phosphor exhibited a single-exponential decay pattern, with lifetimes ranging from 0.103 to 0.053 ms. The intrinsic radiative lifetime, calculated through Auzel's fitting was determined to be 0.14 ms. Using the emission spectra, colorimetric behaviour was analyzed, revealing that the Commission Internationale de l'éclairage (CIE) coordinates exclusively lay within the green region at (0.285, 0.705), with an impressive colour purity of 99.6%. Given these marked properties, the synthesized phosphor exhibits great potential for a wide range of green-emitting applications, including displays, white light-emitting diodes, and security signage.

Development of a community severance index for urban areas in the United States: A case study in New York City.

BACKGROUND AND AIMS: Traffic-related exposures, such as air pollution and noise, have a detrimental impact on human health, especially in urban areas. However, there remains a critical research and knowledge gap in understanding the impact of community severance, a measure of the physical separation imposed by road infrastructure and motorized road traffic, limiting access to goods, services, or social connections, breaking down the social fabric and potentially also adversely impacting health. We aimed to robustly quantify a community severance metric in urban settings exemplified by its characterization in New York City (NYC). METHODS: We used geospatial location data and dimensionality reduction techniques to capture NYC community severance variation. We employed principal component pursuit, a pattern recognition algorithm, combined with factor analysis as a novel method to estimate the Community Severance Index. We used public data for the year 2019 at census block group (CBG) level on road infrastructure, road traffic activity, and pedestrian infrastructure. As a demonstrative application of the Community Severance Index, we investigated the association between community severance and traffic collisions, as a proxy for road safety, in 2019 in NYC at CBG level. RESULTS: Our data revealed one multidimensional factor related to community severance explaining 74% of the data variation. In adjusted analyses, traffic collisions in general, and specifically those involving pedestrians or cyclists, were nonlinearly associated with an increasing level of Community Severance Index in NYC. CONCLUSION: We developed a high spatial-resolution Community Severance Index for NYC using data available nationwide, making it feasible for replication in other cities across the United States. Our findings suggest that increases in the Community Severance Index across CBG may be linked to increases in traffic collisions in NYC. The Community Severance Index, which provides a novel traffic-related exposure, may be used to inform equitable urban policies that mitigate health risks and enhance well-being.

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model.

Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY's antioxidant properties, with a standard reduction potential ( E o ) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3ß, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.

A Review on the Traditional Applications, Phytochemistry, and Pharmacology of the Genus Physochlaina G. Don.

Physochlaina is a genus of flowering plants belonging to the family Solanaceae and consists of 10 species distributed in various Asian countries. The species of the genus have been traditionally used to cure a variety of illnesses due to their highly valuable medicinal properties, including cancer, asthma, cough, weakness, stomachache, diarrhea, swelling, spasms, toothache, boils, ulcers, rheumatic pain, chronic bronchitis, gastric problems, abdominal pain, palpitation, and insomnia. The species have gained significant attention due to their remarkable ethnopharmacological and ethnomedicinal significance. The researchers have isolated so far 71 biologically active secondary metabolites from different Physochlaina species, which include flavonoids, alkaloids, coumarins, phenolic acids, iridoids, and sterols. These compounds exhibit diverse biological activities, such as antibacterial, anti-oxidant, anti-inflammatory, cytotoxic, and anticancer properties. The present review has been compiled with the intention of providing a comprehensive overview of the botany, distribution, traditional uses, phytochemical profile, and biological activities of the genus Physochlaina for future exploration of plant-based drugs and therapeutic approaches. The present review contributes to understanding the significant pharmacological potential of Physochlaina species and unraveling their chemical composition, highlighting their relevance in developing therapeutic agents. Till date, numerous pharmacological properties and isolated phytochemicals of Physochlaina species that support the species traditional and ethnobotanical history have been documented in a number of scientific publications. However, greater emphasis should be paid to in vivo investigations on various extracts and their phytoconstituents as well as mechanistic analysis to help drug developers better understand how to use Physochlaina species as significant therapeutic resources for herbal formulations using various techniques.

Influence of the severity of periodontal disease on the outcome of non-surgical endodontic therapy: A prospective cohort study.

OBJECTIVE: To investigate the influence of severity of periodontal disease on periapical healing after non-surgical endodontic therapy (NSET). MATERIAL AND METHODS: In this prospective study, subjects (n = 45) requiring NSET in a mandibular molar tooth with the diagnosis of pulp necrosis and asymptomatic apical periodontitis exhibiting radiographic periapical index (PAI) score ≥ 3 and concomitant endodontic periodontal lesion (CEPL) without communication were enrolled. After dividing as per the classification of Periodontal and Peri-Implant Diseases and Conditions, subjects were equally allocated into three groups. Group I- only endodontic lesion {control: healthy periodontium (n = 15)}, Group II- CEPL having stage I and II periodontitis (n = 15) and Group III- CEPL having stage III periodontitis (n = 15). Standardized two-visit NSET was performed with 2% chlorhexidine gel as an intracanal medicament. Periodontal therapy was instituted wherever required. Subjects were recalled at 6-and 12-months for clinical and radiographic assessment. Chi-square test was performed to evaluate the difference between the groups. RESULTS: At 12-month follow-up, all teeth in the three study groups were asymptomatic. On radiographic evaluation of the periapical region, healing was observed in 80%, 47% and 50% of teeth in Groups I, Group II and Group III, respectively. However, the difference was not statistically significant between the groups (p = 0.150). CONCLUSION: The severity of periodontal disease had no influence on periapical healing after NSET in teeth with concomitant endodontic periodontal lesions without communication. CLINICAL RELEVANCE: Periodontal disease has significant impact on apical periodontitis however severity of the periodontitis does not negatively impact the apical periodontitis.

Cdx1 and Gsc distinctly regulate the transcription of BMP4 target gene ventx3.2 by directly binding to the proximal promoter region in Xenopus gastrulae.

A comprehensive regulatory network of transcription factors controls the dorsoventral patterning of the body axis in developing vertebrate embryos. Bone morphogenetic protein signaling is essential for activating the Ventx family of homeodomain transcription factors, which regulates embryonic patterning and germ layer identity during Xenopus gastrulation. Although Ventx1.1 and Ventx2.1 of the Xenopus Ventx family have been extensively investigated, Ventx3.2 remains largely understudied. Therefore, this study aimed to investigate the transcriptional regulation of ventx3.2 during the embryonic development of Xenopus. We used goosecoid (Gsc) genome-wide chromatin immunoprecipitation-sequencing data to isolate and replicate the promoter region of ventx3.2. Serial deletion and site-directed mutagenesis were used to identify the cis-acting elements for Gsc and caudal type homeobox 1 (Cdx1) within the ventx3.2 promoter. Cdx1 and Gsc differentially regulated ventx3.2 transcription in this study. Additionally, positive cis-acting and negative response elements were observed for Cdx1 and Gsc, respectively, within the 5' flanking region of the ventx3.2 promoter. This result was corroborated by mapping the active Cdx1 response element (CRE) and Gsc response element (GRE). Moreover, a point mutation within the CRE and GRE completely abolished the activator and repressive activities of Cdx1 and Gsc, respectively. Furthermore, the chromatin immunoprecipitation-polymerase chain reaction confirmed the direct binding of Cdx1 and Gsc to the CRE and GRE, respectively. Inhibition of Cdx1 and Gsc activities at their respective functional regions, namely, the ventral marginal zone and dorsal marginal zone, reversed their effects on ventx3.2 transcription. These results indicate that Cdx1 and Gsc modulate ventx3.2 transcription in the ventral marginal zone and dorsal marginal zone by directly binding to the promoter region during Xenopus gastrulation.

Co-Assembly of Cancer Drugs with Cyclo-HH Peptides: Insights from Simulations and Experiments.

Peptide-based nanomaterials can serve as promising drug delivery agents, facilitating the release of active pharmaceutical ingredients while reducing the risk of adverse reactions. We previously demonstrated that Cyclo-Histidine-Histidine (Cyclo-HH), co-assembled with cancer drug Epirubicin, zinc, and nitrate ions, can constitute an attractive drug delivery system, combining drug self-encapsulation, enhanced fluorescence, and the ability to transport the drug into cells. Here, we investigated both computationally and experimentally whether Cyclo-HH could co-assemble, in the presence of zinc and nitrate ions, with other cancer drugs with different physicochemical properties. Our studies indicated that Methotrexate, in addition to Epirubicin and its epimer Doxorubicin, and to a lesser extent Mitomycin-C and 5-Fluorouracil, have the capacity to co-assemble with Cyclo-HH, zinc, and nitrate ions, while a significantly lower propensity was observed for Cisplatin. Epirubicin, Doxorubicin, and Methorexate showed improved drug encapsulation and drug release properties, compared to Mitomycin-C and 5-Fluorouracil. We demonstrated the biocompatibility of the co-assembled systems, as well as their ability to intracellularly release the drugs, particularly for Epirubicin, Doxorubicin, and Methorexate. Zinc and nitrate were shown to be important in the co-assembly, coordinating with drugs and/or Cyclo-HH, thereby enabling drug-peptide as well as drug-drug interactions in successfully formed nanocarriers. The insights could be used in the future design of advanced cancer therapeutic systems with improved properties.

Still in Search for an EAAT Activator: GT949 Does Not Activate EAAT2, nor EAAT3 in Impedance and Radioligand Uptake Assays.

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain scarce. Recently, GT949 was proposed as a selective activator of EAAT2, as tested in a radioligand uptake assay. In the presented research, we aimed to validate the use of GT949 to activate EAAT2-driven glutamate transport by applying an innovative, impedance-based, whole-cell assay (xCELLigence). A broad range of GT949 concentrations in a variety of cellular environments were tested in this assay. As expected, no activation of EAAT3 could be detected. Yet, surprisingly, no biological activation of GT949 on EAAT2 could be observed in this assay either. To validate whether the impedance-based assay was not suited to pick up increased glutamate uptake or if the compound might not induce activation in this setup, we performed radioligand uptake assays. Two setups were utilized; a novel method compared to previously published research, and in a reproducible fashion copying the methods used in the existing literature. Nonetheless, activation of neither EAAT2 nor EAAT3 could be observed in these assays. Furthermore, no evidence of GT949 binding or stabilization of purified EAAT2 could be observed in a thermal shift assay. To conclude, based on experimental evidence in the present study GT949 requires specific assay conditions, which are difficult to reproduce, and the compound cannot simply be classified as an activator of EAAT2 based on the presented evidence. Hence, further research is required to develop the tools needed to identify new EAAT modulators and use their potential as a therapeutic target.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Statistical analysis of air quality dataset of Kathmandu, Nepal, with a New Extended Kumaraswamy Exponential Distribution.

This paper aims to create a new probability distribution and conducts statistical analysis on air quality dataset from Kathmandu. Using this innovative distribution, we have studied the ground reality of air quality conditions of Kathmandu, Nepal. In our research, we have developed a new probability distribution known as the New Extended Kumaraswamy Exponential Distribution by introducing an additional shape parameter to the Extended Kumaraswamy Exponential (EKwE) Distribution. Statistical characteristics such as cumulative distribution function, probability density function, hazard function, reversed hazard function, skewness, kurtosis, survival function, and hazard rate function are studied. The suggested model is non-normal and positively skewed with increasing and inverted bathtub-shaped hazard rate curves. To assess the model's suitability, we utilized a real dataset comprising air quality data from Kathmandu, Nepal, during the year 2021. Study shows that the air quality data exhibit an increasing failure rate, but the P2.5, P10, and total suspended particle concentrations exhibited its lowest levels during the monsoon season and its highest levels during the winter season. Parameters of the model are estimated by using the least square estimation (LSE), maximum likelihood estimation (MLE), and Cramér-von Mises (CVM) approach for P10 at Ratnapark Station, Kathmandu. To assess the model's validity, P-P plots and Q-Q plots are employed. Model comparisons are carried out using Akaike Information Criterion (AIC), Corrected Akaike Information Criterion (CAIC), Bayesian Information Criterion (BIC), and Hannan-Quinn Information Criterion (HQIC). Furthermore, the goodness of fit of the proposed model is evaluated using test statistics such as Anderson-Darling (A2) test, Cramér-von Mises (CVM) test, and the Kolmogorov-Smirnov (KS) test along with their respective p-values. From the findings, we have found that the air quality status of Kathmandu, Nepal, was found to be poor. Proposed distribution provides a better fit with greater flexibility for forecasting air quality data and conducting reliability data analyses. Dataset is analyzed and visualized using R programming.

Association between urban upbringing and functional brain connectivity in schizophrenia.

Background: Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. Methods: This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. Results: The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). Conclusions: These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

Preventing biofilm formation and eradicating pathogenic bacteria by Zn doped histidine derived carbon quantum dots.

Bacterial infections are of major medical concern due to antibiotic resistance. Carbon quantum dots (CDs) have emerged as potentially excellent biomaterials for multifunctional applications due to their low toxicity, outstanding water solubility, high fluorescence, and high biocompatibility. All of these properties allow CDs to be exceptional biomaterials for inhibiting the growth of bacteria and stopping biofilm formation due to their strong binding affinity, cell wall penetration, and solubilizing biofilm in water. Here, we describe a strategy for one-pot synthesis of histidine-derived zinc-doped N-doped CDs (Zn-NCDs) by a hydrothermal method for inhibiting the growth of both Gram-positive and Gram-negative bacteria without harming mammalian cells. The NCDs and Zn-NCDs showed uniform sizes (∼6 nm), crystallinity, good photostability, high quantum yield (76%), and long decay time (∼5 ns). We also studied their utilization for live cell bio-imaging and the antimicrobial properties towards the Gram-positive Staphylococcus aureus and the Gram-negative Pseudomonas aeruginosa. Importantly, the Zn-NCDs could penetrate the biofilm and bacterial cell wall to effectively inhibit the growth of bacteria and subsequently inhibit biofilm formation. Thus, the structure, chemical composition, and low toxicity properties of the newly-developed Zn-NCDs exemplify a promising novel method for the preparation of nano-level antibacterial drugs.