lncRNA-gene network analysis reveals the effects of early maternal nutrition on mineral homeostasis and energy metabolism in the fetal liver transcriptome of beef heifers.

Maternal nutrition during pregnancy influences fetal development; however, the regulatory markers of fetal programming across different gestational phases remain underexplored in livestock models. Herein, we investigated the regulatory role of long non-coding RNAs (lncRNAs) on fetal liver gene expression, the impacts of maternal vitamin and mineral supplementation, and the rate of maternal body weight gain during the periconceptual period. To this end, crossbred Angus heifers (n = 31) were randomly assigned to a 2 × 2 factorial design to evaluate the main effects of the rate of weight gain (low gain [LG, avg. daily gain of 0.28 kg/day] vs. moderate gain [MG, avg. daily gain of 0.79 kg/day]) and vitamins and minerals supplementation (VTM vs. NoVTM). On day 83 ± 0.27 of gestation, fetuses were collected for morphometric measurements, and fetal liver was collected for transcriptomic and mineral analyses. The maternal diet significantly affected fetal liver development and mineral reserves. Using an RNA-Seq approach, we identified 320 unique differentially expressed genes (DEGs) across all six comparisons (FDR < 0.05). Furthermore, lncRNAs were predicted through the FEELnc pipeline, revealing 99 unique differentially expressed lncRNAs (DELs). The over-represented pathways and biological processes (BPs) were associated with energy metabolism, Wnt signaling, CoA carboxylase activity, and fatty acid metabolism. The DEL-regulated BPs were associated with metal ion transport, pyrimidine metabolism, and classical energy metabolism-related glycolytic, gluconeogenic, and TCA cycle pathways. Our findings suggest that lncRNAs regulate mineral homeostasis- and energy metabolism-related gene networks in the fetal liver in response to early maternal nutrition.

Molecular characterization of rotavirus indicates predominance of G9P[4] genotype among children with acute gastroenteritis: First report after vaccine introduction in Pakistan.

Globally, Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in children under 5 years old, with Pakistan having the highest rates of RVA-related morbidity and mortality. The current study aims to determine the genetic diversity of rotavirus and evaluate the impact of Rotarix-vaccine introduction on disease epidemiology in Pakistan. A total of 4749 children, hospitalized with acute gastroenteritis between 2018 and 2020, were tested at four hospitals in Lahore and Karachi. Of the total, 19.3% (918/4749) cases were tested positive for RVA antigen, with the positivity rate varying annually (2018 = 22.7%, 2019 = 14.4%, 2020 = 20.9%). Among RVA-positive children, 66.3% were under 1 year of age. Genotyping of 662 enzyme-linked immuno sorbent assay-positive samples revealed the predominant genotype as G9P[4] (21.4%), followed by G1P[8] (18.9%), G3P[8] (11.4%), G12P[6] (8.7%), G2P[4] (5.7%), G2P[6] (4.8%), and 10.8% had mixed genotypes. Among vaccinated children, genotypes G9P[4] and G12P[6] were more frequently detected, whereas a decline in G2P[4] was observed. Phylogenetic analysis confirmed the continued circulation of indigenous genotypes detected earlier in the country except G9 and P[6] strains. Our findings highlight the predominance of G9P[4] genotype after the vaccine introduction thus emphasizing continual surveillance to monitor the disease burden, viral diversity, and their impact on control of rotavirus gastroenteritis in children.

Influence of Maternal Nutrition and One-Carbon Metabolites Supplementation during Early Pregnancy on Bovine Fetal Small Intestine Vascularity and Cell Proliferation.

To investigate the effects of nutrient restriction and one-carbon metabolite (OCM) supplementation (folate, vitamin B12, methionine, and choline) on fetal small intestine weight, vascularity, and cell proliferation, 29 (n = 7 ± 1 per treatment) crossbred Angus beef heifers (436 ± 42 kg) were estrous synchronized and conceived by artificial insemination with female sexed semen from a single sire. Then, they were allotted randomly to one of four treatments in a 2 × 2 factorial arrangement with the main factors of nutritional plane [control (CON) vs. restricted feed intake (RES)] and OCM supplementation [without OCM (-OCM) or with OCM (+OCM)]. Heifers receiving the CON level of intake were fed to target an average daily gain of 0.45 kg/day, which would allow them to reach 80% of mature BW by calving. Heifers receiving the RES level of intake were fed to lose 0.23 kg/heifer daily, which mimics observed production responses in heifers that experience a diet and environment change during early gestation. Targeted heifer gain and OCM treatments were administered from d 0 to 63 of gestation, and then all heifers were fed a common diet targeting 0.45 kg/d gain until d 161 of gestation, when heifers were slaughtered, and fetal jejunum was collected. Gain had no effect (p = 0.17) on the fetal small intestinal weight. However, OCM treatments (p = 0.02) displayed less weight compared to the -OCM groups. Capillary area density was increased in fetal jejunal villi of RES - OCM (p = 0.02). Vascular endothelial growth factor receptor 2 (VEGFR2) positivity ratio tended to be greater (p = 0.08) in villi and was less in the crypts (p = 0.02) of the RES + OCM group. Cell proliferation decreased (p = 0.02) in villi and crypts of fetal jejunal tissue from heifers fed the RES + OCM treatment compared with all groups and CON - OCM, respectively. Spatial cell density increased in RES - OCM compared with CON + OCM (p = 0.05). Combined, these data show OCM supplementation can increase expression of VEGFR2 in jejunal villi, which will promote maintenance of the microvascular beds, while at the same time decreasing small intestine weight and crypt cell proliferation.

Energy transition and environmental stability prospects for OECD economies: The prominence role of environmental governance, and economic complexity: Does the geopolitical risk matter?

The global increase in temperature and climate change signals the need for humanity to reduce greenhouse gas emissions and to adopt eco-friendly lifestyles. The 2023 United Nations Climate Change Conference (COP28) in the UAE emphasized this, urging nations to commit to the Paris Agreement and pursue a greener, carbon-free future. In recent decades, climate change has become a critical issue, primarily because of the extensive use of fossil fuels and conventional energy resources. Economic growth has led to an increase in energy consumption and widespread environmental damage. The present study empirically explores whether any changes in environmental governance, economic complexity, geopolitical risk, and the interaction term influence energy transition and environmental stability in OECD economies over the period 1990-2021. Novel econometric methods, including Westerlund co-integration and the Method of Moments Quantile Regression (MMQR), are employed to address complexities such as cross-sectional dependency and panel causality. The key findings from the MMQR technique showed a positive link between environmental governance and economic complexity in driving sustainable energy transitions, thus bolstering environmental resilience in OECD countries. However, economic complexity counterbalances environmental stability. Significantly, geopolitical risk acts as a moderating variable, enhancing the effects of governance and complexity on sustainable energy practices and environmental stability. Based on these insights, this study recommends strategic initiatives, including investment in eco-friendly technologies, to fast-track the shift to clean energy and strengthen environmental resilience in OECD countries. These strategies align with the broader objectives of global sustainable development, offering a path towards a greener and more sustainable future.

Characteristics, distribution, and origin of ferruginous deposits within the Late Ordovician glaciogenic setting of Arabia.

Ferruginous deposits are iron-rich sediments or sedimentary rocks found in various sizes, shapes, and compositions within sedimentary strata in different depositional settings. This study investigates the characteristics, distribution, and origin of ferruginous deposits found in the Late Ordovician glaciogenic Sarah Formation and surrounding deposits in central Saudi Arabia. Several types of ferruginous deposits have been identified through field observations and laboratory investigations, including thin-section petrography, geochemical, surface, and bulk mineralogical analyses, and computed tomography scans. The identified ferruginous deposits include solid and rinded concretions, pipes, layers, ferricretes, liesegang bands, and fracture infills. They were associated with the periglacial and proglacial facies of the Sarah Formation. For instance, ferruginous deformed layers were mainly observed in subglacial facies, while rinded concretions occurred in bleached glaciofluvial facies. Ferruginous deposits were also found in the uppermost parts of non-glacial facies, such as the shallow marine Quwarah Member of the Qasim Formation and the braided deltaic Sajir Member of the Saq Formation. Compositionally, goethite was the dominant iron oxide mineral in all ferruginous deposits, and it is mostly distributed as cement, filling pore spaces. In comparison to ferruginous deposits reported in different depositional settings on Earth and Mars, the studied ferruginous deposits in an ancient glaciogenic setting exhibit different mineralogical characteristics. Specifically, the studied solid concretions are less abundant and primarily amalgamated, while the rinded concretions appear to be more mature than those reported in other depositional environments. This study suggests that the weathered basement rocks of the Arabian Shield were the primary source of iron. The iron-bearing rocks were eroded and transported by Hirnantian glaciation and deglaciation processes.

Influence of Zirconium (Zr4+) Substitution on the Crystal Structure and Optical and Dielectric Properties of Sr0.8Mg0.2(Sn1-xZrx)O3 Ceramics.

In this work, new compositions of Sr0.8Mg0.2(Sn1-xZrx)O3 0.00 ≤ x ≤ 0.06 ceramics are designed and synthesized by the conventional solid-state route. The influence of Zr doping on the phase, microstructural, optical, and dielectric properties is thoroughly investigated. The peaks (0 0 4) and (1 1 0) are observed to shift toward lower 2θ values, due to the variation of the ionic radius between Zr4+ and Sn4+. X-ray diffraction patterns reveal the orthorhombic structure with the space group Pbnm. Scanning electron microscopy images reveal the presence of pores and particles with a high degree of agglomeration. The functional groups and modes of vibration are determined by Fourier transform infrared spectroscopy of the prepared metal oxide samples. The existence of green emission of all the synthesized samples around 554.91 nm is identified by photoluminescence spectroscopy. The dielectric properties of the fabricated samples are measured by using an impedance analyzer. The values of the tangent loss and relative permittivity are found to decrease with increasing frequency.

Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.

INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each. METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories. RESULTS: The average age was 44.28±9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively). CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.

A Novel Insight into the Identification of Potential SNP Markers for the Genomic Characterization of Buffalo Breeds in Pakistan.

Domestic buffaloes (Bubalus bubalis), known as water buffaloes, play a key role as versatile multipurpose agricultural animals in the Asiatic region. Pakistan, with the second-largest buffalo population in the world, holds a rich domestication history of buffaloes. The overall trends in buffalo production demand the genomic characterization of Pakistani buffalo breeds. To this end, the resequencing data of Pakistani breeds, along with buffalo breeds from 13 other countries, were retrieved from our previous study. This dataset, which contained 34,671,886 single-nucleotide polymorphisms (SNPs), was analyzed through a pipeline that was developed to compare possible allele differences among breeds at each SNP position. In contrast, other available tools only check for positional SNP differences for breed-specific markers. In total, 1918, 1549, 404, and 341 breed-specific markers were identified to characterize the Nili, Nili-Ravi, Azakheli, and Kundi breeds of Pakistani buffalo, respectively. Sufficient evidence in the form of phenotypic data, principal component analysis, admixture analysis, and linkage analysis showed that the Nili breed has maintained its distinct breed status despite sharing a close evolutionary relationship with the Nili-Ravi breed of buffalo. In this era of genome science, the conservation of these breeds and the further validation of the given selection markers in larger populations is a pressing need.

High platelet count as a predicting factor of histopathological grading among invasive breast cancer individuals: a single centre experience from Indonesia.

Background: The interplay between platelet and breast cancer (BC) pathology may have the potential to represent the malignancy status itself, evidently through predicting the histopathological results of each individual. This study aims to elaborate on the diagnostic value of a higher platelet count or thrombocytosis and the histopathological status of invasive BC in our center, explaining its correlation from the diagnostic perspective. Materials and methods: A retrospective cohort study was conducted using breast cancer patients' medical records from January to March 2022 at the Haji Adam Malik General Hospital, Medan, Indonesia. The patients' histopathological records and complete blood counts were collected from the hospital's medical records. We analyzed the risk analysis model in receiver operator characteristics analysis and diagnostic parameters, e.g., sensitivity and specificity, which we analyzed further using the correlation test to fulfill our objective. Result: The mean age of the 69 subjects we included, in the final analysis, was 49.0 ± 11.1 years old, of whom 35 (50.7%) individuals were histologically confirmed to be high-grade BC. By applying the cut-off value of 299 × 103 cells/µL, the diagnostic value of a platelet count was 60.0 % in sensitivity, 61.8% in specificity, and an area under the curve (AUC) value of 0.597 (0.462-0.732) in 95% confidence interval (CI) as presented by receiver operating characteristic (ROC). We also found that a higher platelet count may also predict the diagnosis of invasive BC by 2.423 times as shown in the odd ratio (OR) analysis. Conclusion: Platelet counts investigation is an applicable yet potential hematological biomarker to predict invasive BC histopathological grading.

Maternal Mineral Nutrition Regulates Fetal Genomic Programming in Cattle: A Review.

Maternal mineral nutrition during the critical phases of fetal development may leave lifetime impacts on the productivity of an individual. Most research within the developmental origins of the health and disease (DOHaD) field is focused on the role of macronutrients in the genome function and programming of the developing fetus. On the other hand, there is a paucity of knowledge about the role of micronutrients and, specifically, minerals in regulating the epigenome of livestock species, especially cattle. Therefore, this review will address the effects of the maternal dietary mineral supply on the fetal developmental programming from the embryonic to the postnatal phases in cattle. To this end, we will draw a parallel between findings from our cattle model research with data from model animals, cell lines, and other livestock species. The coordinated role and function of different mineral elements in feto-maternal genomic regulation underlies the establishment of pregnancy and organogenesis and, ultimately, affects the development and functioning of metabolically important tissues, such as the fetal liver, skeletal muscle, and, importantly, the placenta. Through this review, we will delineate the key regulatory pathways involved in fetal programming based on the dietary maternal mineral supply and its crosstalk with epigenomic regulation in cattle.

Optimizing Structural, Optical, Dielectric, and Magnetic Properties of (Bi1-x La x )FeO3 (0.00 ≤ x ≤ 0.06) Sintered Ceramics.

(Bi1-x La x )FeO3 (0.00 ≤ x ≤ 0.06) ceramics have been synthesized through a mixed oxide route to investigate their structural, morphological, optical, dielectric, and magnetic properties. All the samples are revealed to be in rhombohedral structures along with the R3c space group and 161 space group number. A high relative permittivity and the lowest tangent loss are observed in BLFO samples at the frequency range 1-100 MHz. The optical studies show that the excitation energy increases with the increasing La content. Moreover, the magnetization being strongly affected by crystallite size and microstrain has been investigated. The band gap energy increases with the increasing La content. The overall result of pure and doped La contents in BFO ceramics shows enhanced structural, dielectric, and optical properties.

Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families.

BACKGROUND: Autosomal recessive cutis laxa type 2A (ARCL2A; OMIM: 219200) is characterized by neurovegetative, developmental and progeroid elastic skin anomalies. It is caused by biallelic variation in ATPase, H+ transporting V0 subunit A2 (ATP6V0A2; OMIM: 611716) located on chromosome 12q24.31. Autosomal recessive cutis laxa type 3A (ARCL3A; OMIM: 219150) is another subclinical type characterized by short stature, ophthalmological abnormalities and a progeria-like appearance. The ARCL3A is caused by loss of function alterations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1; OMIM: 138250) gene located at chromosome 10q24.1. METHODS: Whole-exome sequencing (WES), and Sanger sequencing were performed for molecular diagnosis. 3D protein modeling was performed to investigate the deleterious effect of the variant on protein structure. RESULTS: In this study, clinical and molecular diagnosis were performed for two families, ED-01 and DWF-41, which displayed hallmark features of ARCL2A and ARCL3A, respectively. Three affected individuals in the ED-01 family (IV-4, IV-5 and V-3) displayed sagging loose skin, down-slanting palpebral fissures, excessive wrinkles on the abdomen, hands and feet, and prominent veins on the trunk. Meanwhile the affected individuals in the DWF-41 family (V-2 and V-3) had progeroid skin, short stature, dysmorphology, low muscle tone, epilepsy, lordosis, scoliosis, delayed puberty and internal genitalia. WES in the index patient (ED-01: IV-4) identified a novel homozygous deletion (NM_012463.3: c.1977_1980del; p.[Val660LeufsTer23]) in exon 16 of the ATP6V0A2 while in DWF-41 a novel homozygous missense variant (NM_001323413.1:c.1867G>A; p.[Asp623Asn]) in exon 15 of the ALDH18A1 was identified. Sanger validation in all available family members confirmed the autosomal recessive modes of inheritances in each family. Three dimensional in-silico protein modeling suggested deleterious impact of the identified variants. Furthermore, these variants were assigned class 1 or "pathogenic" as per guidelines of American College of Medical Genetics 2015. Screening of ethnically matched healthy controls (n = 200 chromosomes), excluded the presence of these variations in general population. CONCLUSIONS: To the best of our knowledge, this is the first report of ATP6V0A2 and ALDH18A1 variations in the Pakhtun ethnicity of Pakistani population. The study confirms that WES can be used as a first-line diagnostic test in patients with cutis laxa, and provides basis for population screening and premarital testing to reduce the diseases burden in future generations.

Volumetric thermo-convective casson fluid flow over a nonlinear inclined extended surface.

The thermophysical features of Casson fluid flow caused by a nonlinear permeable stretchable surface are assessed in the present study. The computational model of Casson fluid is used to define viscoelasticity, which is quantified rheologically in the momentum equation. Exothermic chemical reactions, heat absorption/generation, magnetic field and nonlinear volumetric thermal/mass expansion over the stretched surface are also considered. The proposed model equations are lessened by the similarity transformation to the dimensionless system of ODEs. The obtained set of differential equations are numerically computed through parametric continuation approach. The results are displayed and discussed via figures and tables. The outcomes of the proposed problem are compared to the existing literature and bvp4c package for the validity and accuracy purposes. It has been perceived that the energy and mass transition rate of Casson fluid increased with the flourishing trend of heat source parameter and chemical reaction respectively. Casson fluid velocity can be elevated by the rising effect of thermal, mass Grashof number and nonlinear thermal convection.

Report of Hermansky-Pudlak Syndrome in Two Families with Novel Variants in HPS3 and HPS4 Genes.

Background: Hermansky-Pudlak syndrome (HSP) was first reported in 1959 as oculocutaneous albinism with bleeding abnormalities, and now consists of 11 distinct heterogenic genetic disorders that are caused by mutations in four protein complexes: AP-3, BLOC1, BLOC2, and BLOC3. Most of the patients show albinism and a bleeding diathesis; additional features may present depending on the nature of a defective protein complex. The subtypes 3 and 4 have been known for mutations in HSP3 and HSP4 genes, respectively. Methods: In this study, two Pakhtun consanguineous families, ALB-09 and ALB-10, were enrolled for clinical and molecular diagnoses. Whole-exome sequencing (WES) of the index patient in each family followed by Sanger sequencing of all available samples was performed using 3Billion. Inc South Korea rare disease diagnostics services. Results: The affected individuals of families ALB-09 and ALB-10 showed typical phenotypes of HPS such as oculocutaneous albinism, poor vision, nystagmus, nystagmus-induced involuntary head nodding, bleeding diathesis, and enterocolitis; however, immune system weakness was not recorded. WES analyses of one index patient revealed a novel nonsense variant (NM_032383.4: HSP3; c.2766T > G) in family ALB-09 and a five bp deletion (NM_001349900.2: HSP4; c.1180_1184delGTTCC) variant in family ALB-10. Sanger sequencing confirmed homozygous segregation of the disease alleles in all affected individuals of the respective family. Conclusions: The substitution c.2766T > G creates a premature protein termination at codon 922 in HPS3, replacing tyrosine amino acid with a stop codon (p.Tyr922Ter), while the deletion mutation c.1180_1184delGTTCC leads to a reading frameshift and a premature termination codon adding 23 abnormal amino acids to HSP4 protein (p:Val394Pro395fsTer23). To the best of our knowledge, the two novel variants identified in HPS3 and HPS4 genes causing Hermansky-Pudlak syndrome are the first report from the Pakhtun Pakistani population. Our work expands the pathogenic spectrum of HPS3 and HPS4 genes, provides successful molecular diagnostics, and helps the families in genetic counselling and reducing the disease burden in their future generations.

Tamoxifen-associated Endometrial Cancer after Treatment in Young Premenopausal Women with Breast Cancer: A Case Report.

Background: Tamoxifen has been successfully administered as adjunctive therapy for breast cancer. However, the effect of tamoxifen as an estrogen agonist and antagonist can cause pathological changes in the uterus. The agonist effect may stimulate endometrial proliferation leading to endometrial polyps, hyperplasia, and, rarely, endometrial cancer. Objective: We present the case of tamoxifen-treated breast cancer case to better understand one of the most serious consequences, endometrial cancer. Case presentation: A 37-year-old woman came to our centre with complaints of abnormal vaginal bleeding. She has diagnosed with grade I infiltrative ductal carcinoma in 2018, with primary complaints of right breast mass and axillary lymphadenopathy. During this period, adjuvant chemotherapy was given tamoxifen 20 mg once daily. There were no complaints or relapses at a six-month follow-up over three years. In the fourth year, the patient complained of vaginal bleeding. A vaginal biopsy was performed, and the results showed low-grade endometrioid-type endometrial carcinoma. Total hysterectomy and bilateral salpingo-oophorectomy were performed with the resultant mass of up to half of the myometrial lining with metastatic negative parallax lymph nodes. Conclusion: Following tamoxifen therapy, endometrial cancer is more likely to occur in patients. Patients who experience irregular vaginal hemorrhage should have hysteroscopy or uterine ultrasound performed, and if the cause is unknown, a biopsy should be performed.

Comprehensive Risk Assessment of Carbon Nanotubes Used for Agricultural Applications.

Carbon-based nanomaterials (CBNs) are often used for potential agricultural applications. Since CBNs applied to plants can easily enter plant organs and reach the human diet, the consequences of the introduction of CBNs into the food chain need to be investigated. We created a platform for a comprehensive investigation of the possible health risks of multiwalled carbon nanotubes (CNTs) accumulated in the organs of exposed tomato plants. Quantification and visualization of CNTs absorbed by plant organs were determined by microwave-induced heating (MIH) and radio frequency (RF) heating methods. Feeding mice with CNT-contaminated tomatoes showed an absence of toxicity for all assessed animal organs. The amount of CNTs accumulated inside the organs of mice fed with CNT-containing fruits was assessed by an RF heating technique and was found to be negligible. Our work provides the experimental evidence that the amount of CNTs accumulated in plant organs as a result of nanofertilization is not sufficient to induce toxicity in mice.