Methyl CpG binding protein MBD2 has a regulatory role on the BRCA1 gene expression and its modulation by resveratrol in ER+, PR+ & triple-negative breast cancer cells.

BACKGROUND: Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells. METHODS: Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay. RESULTS: The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer. CONCLUSIONS: In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells.

Dual functionality of the BiN monolayer: unraveling its photocatalytic and piezocatalytic water splitting properties.

To achieve scalable and economically viable green hydrogen (H2) production, the photocatalytic and piezocatalytic processes are promising methods. The key to successful overall water splitting (OWS) for H2 production in these processes is using suitable semiconductor catalysts with appropriate band edge potentials, efficient optical absorption, higher mechanical flexibility, and piezoelectric coefficients. Thus, we explore the bismuth nitride (BiN) monolayer using density functional theory simulations, revealing intriguing catalytic properties. The BiN monolayer is a semiconductor with an indirect electronic bandgap (Eg) of 2.08 eV and displays excellent visible light absorption (approximately 105 cm-1). Detailed analyses show that the band edges satisfy the redox potential for photocatalytic OWS via biaxial strain engineering and pH variation. Notably, the solar to hydrogen conversion efficiency (ηSTH) for the BiN monolayer can reach 17.18%, which exceeds the 10% efficiency limit of photocatalysts for economical green H2 production. The obtained in-plane piezoelectric coefficient of e11 = 16.18 ŠC m-1 is superior to widely studied 2D materials. Moreover, the generated piezopotential under oscillatory strain stands at 28.34 V, which can initiate the water redox reaction via the piezocatalytic mechanism. This originates from the mechanical flexibility coupled with higher piezoelectric coefficients. The result highlights the BiN monolayer's potential application in photocatalytic, piezocatalytic, and photo-piezo-catalytic OWS.

Analysis of the b, p values, and the fractal dimension of aftershocks sequences following two major earthquakes in central Himalaya.

On April 25 of 2015, earthquake of 7.6 ML struck the central Himalayan region having epicenter at Barpak village in the Gorkha district of Nepal. The event was followed by 7.0 ML earthquake known as Dolakha earthquake, epicenter on the border of Dolakha and Sindhupalchowk. In this study, the b-value, aftershock decay rate p-value, and correlation fractal dimension were estimated for the aftershock sequences. The data used were obtained from the National Earthquake Monitoring and Research Centre (NEMRC), Nepal. The b-values 0.89 ± 0.05 and 0.90 ± 0.07 were computed for aftershocks after Gorkha and Dolakha event, respectively. A significant increase in b-values were reported following the Gorkha earthquake and Dolakha earthquake. The slip procured in the primary fault is respectively 60 % and 56 % after the events. The aftershocks sequences after both events were modelled by the Omori-Utsu law with p = 1.2 ± 0.11 and p = 0.76 ± 0.04. The observed b and p values after the earthquake sequences may correlate well with the large slip experienced by the seismogenic fault. This study sheds light on the mechanism behind the preparation of the significant earthquakes in the tectonic regions of the Himalaya.

Ionic Conductivity of K-ion Glassy Solid Electrolytes of K2S-P2S5-KOTf System.

Ternary glassy electrolytes containing K2S as a glass modifier and P2S5 as a network former are synthesized by introducing a new type of complex and asymmetric salt, potassium triflate (KOTf), to obtain unprecedented K+ ion conductivity at ambient temperature. The glasses are synthesized using a conventional quenching technique at a low temperature. In general, alkali ionic glassy electrolytes of ternary systems, specifically for Li+ and Na+ ion conductivity, have been studied with the addition of halide salts or oxysalts such as M2SO4, M2SiO4, M3PO4 (M = Li or Na), etc. We introduce a distinct and complex salt, potassium triflate (KOTf) with asymmetric anion, to the conventional glass modifier and former to synthesize K+-ion-conducting glassy electrolytes. Two series of glassy electrolytes with a ternary system of (0.9-x)K2S-xP2S5-0.1KOTf (x = 0.15, 0.30, 0.45, 0.60, and 0.75) and z(K2S-2P2S5)-yKOTf (y = 0.05, 0.10, 0.15, 0.20, and 0.25) on a straight line of z(K2S-2P2S5) are studied for their K+ ionic conductivities by using electrochemical impedance spectroscopy (EIS). The composition 0.3K2S-0.6P2S5-0.1KOTf is found to have the highest conductivity among the studied glassy electrolytes at ambient temperature with the value of 1.06 × 10-7 S cm-1, which is the highest of all pure K+-ion-conducting glasses reported to date. Since the glass transition temperatures of the glasses are near 100 °C, as demonstrated by DSC, temperature-dependent conductivities are studied within the range of 25 to 100 °C to determine the activation energies. A Raman spectroscopic study shows the variation in the structural units PS43-, P2S74-, and P2S64- of the network former for different glassy electrolytes. It seems that there is a role of P2S74- and P2S64- in K+-ion conductivity in the glassy electrolytes because the spectroscopic results are compatible with the composition-dependent, room-temperature conductivity trend.

Genome size estimation of false daisy, cheek weed, pot marigold and marigold.

We report the genome size estimated using flow cytometry for four closely related species, including false daisy (Eclipta prostrate), cheek weed (Ageratum conyzoides), pot marigold (Calendula officinalis), and marigold (Tagetes erecta) belonging to Asteraceae family. The detected genome size for false daisy, cheek weed, pot marigold, and marigold was, 2.435, 3.266, 3.413, and 1.897, Gbp, respectively, while their respective 2C DNA content was 2.5, 3.3, 3.5, and 1.9, pg. The information on genome size presented here will be useful for understanding genomic evolution and will also clear the way for additional genomic research in these species.

Solanum americanum genome-assisted discovery of immune receptors that detect potato late blight pathogen effectors.

Potato (Solanum tuberosum) and tomato (Solanum lycopersicon) crops suffer severe losses to late blight caused by the oomycete pathogen Phytophthora infestans. Solanum americanum, a relative of potato and tomato, is globally distributed and most accessions are highly blight resistant. We generated high-quality reference genomes of four S. americanum accessions, resequenced 52 accessions, and defined a pan-NLRome of S. americanum immune receptor genes. We further screened for variation in recognition of 315P. infestans RXLR effectors in 52 S. americanum accessions. Using these genomic and phenotypic data, we cloned three NLR-encoding genes, Rpi-amr4, R02860 and R04373, that recognize cognate P. infestans RXLR effectors PITG_22825 (AVRamr4), PITG_02860 and PITG_04373. These genomic resources and methodologies will support efforts to engineer potatoes with durable late blight resistance and can be applied to diseases of other crops.

Efficient and stereoselective synthesis of sugar fused pyrano[3,2-c]pyranones as anticancer agents.

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2-c]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, ß-C-glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1-C-formyl glycals were synthesized from these ß-C-glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1-C-formyl galactal and 4-hydroxycoumarin. Next, 1-C-formyl galactal and 1-C-formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2-c]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds.

Burden of human metapneumovirus infections among children with acute respiratory tract infections attending a Tertiary Care Hospital, Kathmandu.

BACKGROUND: Acute respiratory infections (ARIs) are one of the most common causes of mortality and morbidity worldwide. Every year millions of children suffer from viral respiratory tract infections (RTIs) ranging from mild to severe illnesses. Human Metapneumovirus (HMPV) is among the most frequent viruses responsible for RTIs. However, HMPV infections and their severity among children have not been explored yet in Nepal. PURPOSE: Therefore, the study was focused on HMPV infections and other potential viral etiologies or co-infections using multiplex PCR among children attending Kanti Children's Hospital and assessed the clinical characteristics of the infections as well as found the co-infections. A hospital-based cross-sectional study was designed and a convenience sampling method was used to enroll children of less than 15 years with flu-like symptoms from both outpatients and inpatients departments over three months of the study period. RESULTS: HMPV infection (13.3%) was the most predominant infection among the different viral infections in children with ARIs in Kanti Children's Hospital. The HMPV was more prevalent in the age group less than three years (21.8%). Cough and fever were the most common clinical features present in all children infected with HMPV followed by rhinorrhea, sore throat, and wheezing. HMPV-positive children were diagnosed with pneumonia (42.9%), bronchiolitis (28.5%), upper respiratory tract infections (14.3%), and asthma (14.3%). The prevalence of HMPV was high in late winter (14.3%) followed by early spring (13.5%). CONCLUSIONS: This study provides the baseline information on HMPV and associated co-infection with other respiratory viruses for the differential diagnosis based on molecular methods and also the comparison of clinical presentations among the different respiratory syndromes.

Spatial mapping of b-value and fractal dimension prior to November 8, 2022 Doti Earthquake, Nepal.

An earthquake of magnitude 5.6 mb (6.6 ML) hit western Nepal (Doti region) in the wee hours of wednesday morning local time (2:12 AM, 2022.11.08) killing at least six people. Gutenberg-Richter b-value of earthquake distribution and correlation fractal dimension (D2) are estimated for 493 earthquakes with magnitude of completeness 3.6 prior to this earthquake. We consider earthquakes in western Nepal Himalaya and adjoining region (80.0-83.5°E and 27.3-30.5°N) for the period of 1964 to 2022 for the analysis. The b-value 0.68±0.03 implies a high stress zone and the spatial correlation dimension 1.81±0.02 implies a highly heterogeneous region where the epicenters are spatially distributed. Low b-values and high D2 values identify the study region as a high hazard zone. Focal mechanism styles and low b-values correlate with thrust nature of earthquakes and show that the earthquake's occurrence is associated with the dynamics of the faults responsible for generating the past earthquakes.

Hip-Spine Discordance in Bone Mineral Densities in Patients Undergoing Dual Energy X-Ray Absorptiometry Scan in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: The discordance in the diagnosis of osteoporosis is characterized by the variation in bone mineral density measurements at different skeletal sites. The presence of discordance significantly alters the treatment plan as different treatment is required for different skeletal sites. The aim of this study was to find out the prevalence of hip-spine discordance in bone mineral densities in patients undergoing dual-energy x-ray absorptiometry scans for suspected osteoporosis. Methods: A descriptive cross-sectional study was conducted among patients undergoing dual-energy x-ray absorptiometry scans from 1 December 2020 to 30 October 2022. Ethical approval was taken from the Institutional Review Committee (Reference number: IRC-2020-11-18-08). Patients undergoing dual-energy x-ray absorptiometry scans for suspected osteoporosis were included. Patients aged less than 50 years, already diagnosed and under treatment for osteoporosis, and incomplete information about T-scores of hips and spine were excluded. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 1028 patients, 602 (58.56%) (55.55-61.57, 95% Confidence Interval) had discordance in hip and spine bone mineral densities. The majority of them, 570 (94.68%) were female and 32 (5.71%) were male. Major discordance was observed in 101 (16.77%) patients and minor discordance was observed in 501 (83.22%) patients. Conclusions: The prevalence of discordance in hip and spine bone mineral densities in patients undergoing dual-energy x-ray absorptiometry scans was higher than that reported in other similar studies done in similar settings. Keywords: bone density; osteoporosis; prevalence.

Lumbosacral Transitional Vertebra among Patients Visiting the Department of Orthopaedics in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Lumbosacral transitional vertebra is a normal anatomical variant at the L5-S1 junction with an incidence as high as 4-36%. This alteration results in incorrect identification of vertebral segments leading to wrong surgery. The aim of the study was to find out the prevalence of lumbosacral transitional vertebra among patients visiting the department of orthopaedics in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted from 11 September 2021 to 31 May 2022, after receiving ethical clearance from the Institutional Review Committee (Reference number: IRC-2021-9-10-09). The patients with plain radiographs of the lumbosacral spine (anteroposterior view) were assessed and evaluated by a fellow and consultant of the orthopaedic spine and classified as per Castellvi's radiographic classification. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 1002 patients, lumbosacral transitional vertebra was detected in 95 (9.48%) patients (9.40-9.56, 95% Confidence Interval). Out of 95 (9.48%), patients with the lumbosacral transitional vertebra, 67 (70.53%) had sacralisation and 28 (29.47%) had lumbarization. The mean age of the patients at the time of the study included in the study was 41.6±15.12 years (range 18-85 years). The lumbosacral transitional vertebra was more common in females than males. According to the Castellvi classification, type IIa was the most common type 47 (49.47%). Conclusions: The prevalence of lumbosacral transitional vertebra was similar to other studies done in similar settings. Keywords: lumbar vertebrae; orthopedics; prevalence.

Genomic surveillance uncovers a pandemic clonal lineage of the wheat blast fungus.

Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance.

A folded π-system with supramolecularly oriented dipoles: single-component piezoelectric relaxor with NLO activity.

Organic molecules with an active dipole moment have a natural propensity to align in an antiparallel fashion in the solid state, resulting in zero macroscopic polarization. This primary limitation makes the material unresponsive to switching with electric fields, mechanical forces, and to intense laser light. A single-component organic material that bestows macroscopic dipole-driven electro-mechanical and optical functions, e.g., piezoelectric, ferroelectric and nonlinear optical (NLO) activity, is unprecedented due to the design challenges imparted by crystal symmetry and dipole orientations. Herein we report a crystalline organic material that self-assembles with a polar order (P 1), and is endowed with a high piezoelectric coefficient (d 33-47 pm V-1), as well as ferroelectric and Debye-type relaxor properties. In addition, it shows second harmonic generation (SHG) activity, which is more than five times that of the benchmark potassium dihydrogen phosphate. Piezoelectric force microscopy (PFM) images validated electro-mechanical deformations. Piezoresponse force spectroscopy (PFS) studies confirmed a signature butterfly-like amplitude and a phase loop. To the best of our knowledge, this is the first report of a folded supramolecular π-system that manifests unidirectionally oriented dipoles and exhibits piezoelectricity, ferroelectricity, and has excellent ability to generate second harmonic light. These findings can herald new design possibilities based on folded architectures to explore opto-, electro- and mechano-responsive multifaceted functions.

Role of identified proteins in the proteome profiles of CDK4/6 inhibitor-resistant breast cancer cell lines.

Abemaciclib (Ab) and palbociclib (Pb) are CDK4/6 inhibitors used to cure advanced breast cancer (BC). However, acquired resistance is a major challenge. The molecular mechanisms and signature proteins of therapy resistance for Ab and Pb drugs need to be explored. Here we developed resistant cells for Ab and Pb drugs in MCF-7 cell lines and explored the mechanisms and signature proteins of therapy resistance in BC. Proteome profiling was performed using the label-free proteome-orbitrap-fusion-MS-MS technique. Gene ontology (GO)-terms, KEGG pathways and network analysis were performed for the proteome data. Drug-resistant cells showed increased drug tolerance, enhanced colony formation potential and an increased gap-healing tendency for the respective drug. Up-regulation of survival genes (BCL-2 and MCL-1) and down-regulation of apoptosis inducers were observed. Drug-resistance markers (MDR-1 and ABCG2 (BCRP)) along with ESR-1, CDK4, CDK6, and cyclin-D1 genes were up-regulated in resistant cells. A total of 237 and 239 proteins were found to be differentially expressed in the Ab and Pb-resistant cells, respectively. Down-regulated proteins induce apoptosis signalling and nucleotide metabolisms and restrict EGFR signalling; however, up-regulated proteins induce Erk, wnt-ß-catenin, VEGFR-PI3K-AKT, glucose transportation, and hypoxia signalling pathways and regulate hydrogen peroxide signalling pathways. The panel of identified proteins associated with these pathways might have characteristics of molecular signature and new drug targets for overcoming drug resistance in breast cancer.

Principle of Information Causality Rationalizes Quantum Composition.

The principle of information causality, proposed as a generalization of no signaling principle, has efficiently been applied to outcast beyond quantum correlations as unphysical. In this Letter, we show that this principle, when utilized properly, can provide physical rationale toward structural derivation of multipartite quantum systems. In accordance with the no signaling condition, the state and effect spaces of a composite system can allow different possible mathematical descriptions, even when descriptions for the individual systems are assumed to be quantum. While in one extreme, namely, the maximal tensor product composition, the state space becomes quite exotic and permits composite states that are not allowed in quantum theory, the other extreme-minimal tensor product composition-contains only separable states, and the resulting theory allows only Bell local correlation. As we show, none of these compositions is commensurate with information causality, and hence cannot be the bona-fide description of nature. Information causality therefore promises an information-theoretical derivation of self duality of the state and effect cones for composite quantum systems.

Nutritional status and psychosocial stimulation associated with cognitive development in preschool children: A cross-sectional study at Western Terai, Nepal.

Quality education at the age of foundation to produce dynamic manpower is a public concern in developing countries including Nepal. Preschool children do not get proper care and support from their parents due to insufficient knowledge of proper feeding habits, nutrition status and methods of psychosocial stimulation, which may affect their proper cognitive development. This study aimed to identify the factors that influence cognitive development in preschool children aged 3-5 years in Rupandehi district of western Terai, Nepal. In this school based cross-sectional survey, a total of 401 preschool children were selected using a multistage random sampling technique. The study was conducted from 4th February to 12th April, 2021 in Rupandehi district of Nepal. Data on the children's socio-economic and demographic status, level of psychosocial stimulation, nutritional status, and stage of cognitive development were collected through scheduled interviews and direct observation. Stepwise regression analysis was performed to determine the predictors of cognitive development in preschool children. A p-value less than 0.05 considered as statistical significance. Of 401 participants, 44.1% had a normal nutritional status based on height for age Z-score (HAZ). Only 1.2% of primary caregivers provided their children with high levels of psychosocial stimulation, and 49.1% of children had a medium level of cognitive development. Furthermore, cognitive development in preschoolers is positively associated with nutritional status based on the height for age z score (ß = 0.280; p<0.0001), psychological stimulation from caregivers (ß = 0.184; p<0.0001), and advantageous castes/ethnicity (ß = 0.190; p<0.0001), but negatively associated with the child's age (ß = - 0.145; p = 0.002) and family type (ß = -0.157; p = 0.001). Nutritional status and psychosocial stimulation appear to be major factors affecting cognitive development of preschoolers. Nutritional promotion strategies, as well as techniques for optimal psychosocial stimulation behavior, may play an important role in enhancing preschoolers' cognitive development.

DNA Code from Cyclic and Skew Cyclic Codes over F4[v]/〈v3〉.

The main motivation of this work is to study and obtain some reversible and DNA codes of length n with better parameters. Here, we first investigate the structure of cyclic and skew cyclic codes over the chain ring R:=F4[v]/⟨v3⟩. We show an association between the codons and the elements of R using a Gray map. Under this Gray map, we study reversible and DNA codes of length n. Finally, several new DNA codes are obtained that have improved parameters than previously known codes. We also determine the Hamming and the Edit distances of these codes.

The effect of infant vitamin B12 supplementation on neurodevelopment: a follow-up of a randomised placebo-controlled trial in Nepal.

The most critical period for brain development is before a child's second birthday. Standardised tests measuring neurodevelopment are more reliable when administered after this period. Severe vitamin B12 deficiency affects brain development and function. In a randomised, double-blind, placebo-controlled trial in 600 Nepalese infants (6-11 months at enrolment), we found no effect of 2 µg vitamin B12 daily for a year on neurodevelopment. The primary objective of the current study was to measure the effect of the intervention on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) full scale intelligence quotient (FSIQ). We measured the effect on the Bayley Scales of Infant and Toddler Development 3rd edition at age 30-35 months (n 555). At age 42-47 months (n 533), we used the WPPSI-IV and subtests from the Neuropsychological Assessment, 2nd edition (NEPSY-II). We also used the FSIQ to estimate subgroup specific effects. The mean (sd) WPPSI-IV FSIQ in the vitamin B12 group was 84·4 (8·4) and 85·0 (8·6) in the placebo group (mean difference -0·5 (95 % CI -1·97, 0·94), P = 0·48). There were no effect of the vitamin B12 on any of the other neurodevelopmental outcomes and no beneficial effect in any of the subgroups. In conclusion, providing 2 µg of vitamin B12 for a year in infants at risk of vitamin B12 deficiency does not improve preschool cognitive function.