Balanced spatiotemporal arrangements of histone H3 and H4 posttranslational modifications are necessary for meiotic prophase I chromosome organization.

Dynamic nuclear architecture and chromatin organizations are the key features of the mid-prophase I in mammalian meiosis. The chromatin undergoes major changes, including meiosis-specific spatiotemporal arrangements and remodeling, the establishment of chromatin loop-axis structure, pairing, and crossing over between homologous chromosomes, any deficiencies in these events may induce genome instability, subsequently leading to failure to produce gametes and infertility. Despite the significance of chromatin structure, little is known about the location of chromatin marks and the necessity of their balance during meiosis prophase I. Here, we show a thorough cytological study of the surface-spread meiotic chromosomes of mouse spermatocytes for H3K9,14,18,23,27,36, H4K12,16 acetylation, and H3K4,9,27,36 methylation. Active acetylation and methylation marks on H3 and H4, such as H3K9ac, H3K14ac, H3K18ac, H3K36ac, H3K56ac, H4K12ac, H4K16ac, and H3K36me3 exhibited pan-nuclear localization away from heterochromatin. In comparison, repressive marks like H3K9me3 and H3K27me3 are localized to heterochromatin. Further, taking advantage of the delivery of small-molecule chemical inhibitors methotrexate (heterochromatin enhancer), heterochromatin inhibitor, anacardic acid (histone acetyltransferase inhibitor), trichostatin A (histone deacetylase inhibitor), IOX1 (JmjC demethylases inhibitor), and AZ505 (methyltransferase inhibitor) in seminiferous tubules through the rete testis route, revealed that alteration in histone modifications enhanced the centromere mislocalization, chromosome breakage, altered meiotic recombination and reduced sperm count. Specifically, IOX1 and AZ505 treatment shows severe meiotic phenotypes, including altering chromosome axis length and chromatin loop size via transcriptional regulation of meiosis-specific genes. Our findings highlight the importance of balanced chromatin modifications in meiotic prophase I chromosome organization and instability.

Vaccination and associated factors among tribal children of 1 year age in nine Indian districts: A cross-sectional study.

OBJECTIVE: To report on vaccination status by 12 months of age among tribal children from nine districts of India. METHODS: Cross-sectional study of 2631 tribal women having a child aged 12 months or below from nine Indian districts with a considerable proportion of the tribal population. Socio-demographic details, reception of various vaccines by 12 months of age, mother's antenatal care utilisation and health system-related details were collected through a pre-tested, interviewer-administered questionnaire from mothers. Multiple logistic regression analysis was used to identify the factors associated with complete vaccination by 12 months of age. RESULTS: Only 52% of children were fully vaccinated by the age of 12 months among the tribal populations; 11% did not receive any vaccine, and 37% of the tribal children received some vaccines. The age-appropriate vaccination was unsatisfactory as only 75% of the infants received all birth dose vaccines, and only 60.5% received all doses by 14 weeks. Only 73% were vaccinated against measles. Illness of the child, home births and communication gaps concerning vaccination were the main reasons for an infant not being vaccinated appropriately. Frequency of health worker's visits to the village, hospital birth, reception of advice on vaccination and educational status of the head of the households were significantly associated with full vaccination status. CONCLUSION: A relatively low proportion of children were fully vaccinated among the tribal populations. Health systems factors, mainly the outreach services and advice by the health workers, were positively and significantly associated with a child being fully vaccinated by 12 months of age. Improving outreach services is crucial to improve vaccination coverage in tribal areas, and there is a need to address the social determinants in the long run.

Adolescent intermittent ethanol exposure induces sex-dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice.

With alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. They are also more prone to substance use disorder in adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long-lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence (Experiment 1) and during emerging adulthood (Experiment 2). The present set of experiments were divided into four stages: (1) adolescent intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using intermittent vapor inhalation from postnatal day (PND) 28-42. Following this, mice underwent short-term abstinence from PND 43-49 (Experiment 1) or protracted abstinence from PND 43-69 (Experiment 2). Beginning on PND 50-76 or PND 70-97, mice were assessed for intermittent voluntary ethanol consumption using a two-bottle choice drinking procedure over 28 days. Male adolescent ethanol-exposed mice showed increased ethanol consumption following short-term abstinence and following protracted abstinence. In contrast, female mice showed no changes in ethanol consumption following short-term abstinence and decreased ethanol consumption following protracted abstinence. There were modest changes in open field behavior following voluntary ethanol consumption in both experiments. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These results highlight sex-dependent vulnerability to developing substance use disorders in adulthood.

A rapid method for solubilization of chimeric human interferon regulatory factor-1 (IRF-1) protein in Escherichia coli.

Interferon regulatory factor-1 (IRF-1) is a vertebrate transcription factor that plays significant roles in cell cycle regulation, anti-viral response, tumor suppression and immune response. High-level expression of recombinant IRF-1 at 37 °C leads to the formation of insoluble aggregates (insoluble fraction) in Escherichia coli (E. coli), which usually devoid of biological activity. In this study, we use chemical additives such as mannitol, proline, L-arginine and CTAB (cetyl trimethly ammonium bromide) at the recommended concentration during cell lysis to aid in solubility at 37 °C. The use of additives resulted in the increased solubility of the recombinant glutathione S-transferase-linked human IRF-1, with L-arginine being most effective. Here, we developed an efficient process for the manufacturing of soluble IRF-1 with the aid of minimizing the formation of degradation products and optimizing protein purification conditions. This result was further confirmed by western blot with anti-GST and anti-IRF-1 polyclonal antibodies. The functionality of GST-huIRF-1 was attained by elerophoretic mobility shift assay study as a clear band shifting showed with virus response element-Interferon beta (VRE-IFNß) promoter region. Taken together, the biological activity of purified GST-huIRF-1 was also optimized and confirmed by supershift assay concluded that GST-huIRF-1 interacts with the VRE motif of IFNß promoter that reflected to require for IFNß gene regulation. We describe a straightforward approach for the production of absolutely soluble and biologically active IRF-1 in E. coli. This method can be further used for the study of other recombinant proteins and this study will pave way for the analysis of IRF-1 function in vitro.

First Report of Stem Rot Caused by Athelia rolfsii on Curry Leaf Tree (Murraya koenigii) in Tripura, India.

Murraya koenigii is an important medicinal plant of India and commonly known as curry leaf tree grown in tropical and subtropical regions. The leaves of curry tree are used as a herb due to the presence of following important active constituent bismahanine, murrayanine, murrayafoline-A, bi-koeniquinone-A, murrayazolidine etc. (Jain et al. 2017). During mid-July 2019, stem rot disease symptoms were observed on curry leaf trees at the College of Agriculture, Lembucherra, Tripura (India). The disease symptoms consisted of rotting, wilting and blighting with disease incidence ranging from 8 to 10%. Initially, infected plants gradually withered and white mycelia mats appeared on the surface of the lower stem at the soil line. Infected stem samples were collected and surface was sterilized with 0.25% sodium hypochlorite for 1 min, washed thrice with sterilized distilled water and placed in Petri plates containing 2% water agar. After three days of incubation at 26°C, hyphae produced from plant bits were transferred into Petri plates containing potato dextrose agar. Ten isolates were collected from the diseases samples. Pure cultures were obtained as abundant, aerial and white mycelia with round to irregular sclerotia of 0.8 to 1.5 mm in diam. The sclerotia were initially white in color but later turned into brown color. The pathogen was identified as Athelia rolfsii based on morphology (Aycock 1966). To confirm the identification, the genomic DNA was extracted from a mycelia mat of the isolates using ZR fungal/Bacterial DNA miniprep kit (Irvine, CA) and the internal transcribed spacer (ITS) region of rDNA was amplified using the universal primers, ITS1 and ITS4 (White et al. 1990). A 550 bp PCR product was sequenced and showed 99% similarity with Athelia rolfsii isolate (GenBank accession MH854711).The generated sequence was submitted to GenBank (Accession MT535585). After identification of the pathogen a pot experiment was conducted to confirm the pathogenicity. Earthen pots (29 cm. diam.) were filled with sterilized soil and kept in a green house. Ten curry leaf plants (50 days old) were grown from seed in the separate pot were inoculated with 15-day old mycelia mats prepared in potato dextrose broth. The stem of each curry plant were artificially injured with the help of sterile blade and wrapped with moistened sterilized cotton containing the mycelial mat. Five curry leaf plants artificially injured and inoculated with sterilized distilled water were used as control. The Earthen pots with plants were individually covered with plastic bags and kept in the green house at 26°C for approximately 15 days. The inoculated plants started showing symptoms of stem rot six days after inoculation and started drying onward. The symptoms of stem rot on the inoculated plants were similar to those observed in the field. The fungus was re-isolated from the inoculated plants and A. rolfsii identification was confirmed based on morphology. No symptoms were observed on the control plants. The obtained culture was deposited in the Indian Type Culture Collection, Division of Plant Pathology, ICAR - Indian Agricultural Research Institute, New Delhi, India (ITC-8666). To the best of our knowledge this is the first report of stem rot disease of curry leaf plant caused by A. rolfsii in India and worldwide. Due to medicinal, flavour and aroma properties, it is regularly used in India. Curry leaf plant is regularly used as a medical herb in India and therefore this disease poses a significant risk to production.

Magnesium-Dependent Ecto-ATP Diphosphohydrolase Activity in Leishmania donovani.

In this work, we have described the expression of ecto-ATPDase on the external surface of Leishmania donovani. This enzyme has the ability to hydrolyze extracellular ATP. There is a low level of ATP hydrolysis in the absence of divalent cation 2.5 ± 0.51 nM Pi 107 cells/h which shows the divalent cation-dependent activity of this enzyme in the intact parasite. However, MgCl2 stimulated the ATP hydrolysis to a greater extent compared with CaCl2 and ZnCl2. This activity was also observed when replaced by MnCl2. The Mg-dependent ecto-ATPase activity was 46.58 ± 6.248 nM Pi 107 cells/h. The apparent K m for ATP was 5.76 mM. Since Leishmania also possesses acid phosphatase activity and to discard the possibility that the observed ATP hydrolysis was due to acid phosphatase, the effect of pH was examined. In the pH range 6.0-9.0, in which the cells were viable, the phosphatase activity decreased while ATPase activity increased. To show that the observed ATP hydrolysis was not due to phosphatase or nucleotidase activity, certain inhibitors for these enzymes were tested. Vandate and NaF inhibited the phosphatase activity; Ammonium molybdate inhibited 5'-nucleotidase activity, but these inhibitors did not inhibit the observed ATP hydrolysis. However, when ADP was used as a substrate, there was no inhibition of ATP hydrolysis showing the possibility of ATP diphosphohydrolase activity. To confirm that this Mg-dependent ATPase activity is an ecto-ATPase activity, we used an impermeable inhibitor, 4,4'-diisothiocyanostilbene 2,-2'-disulfonic acid, as well as suramin, an antagonist of P2-purinoceptors and inhibitor of some ecto-ATPases. These two reagents inhibited the Mg2+-dependent ATPase activity in a dose-dependent manner. The presence of L. donovani E-NTPDase activity was demonstrated using antibodies against NTPDase by Western blotting and flow cytometry. The presence of Mg2+-dependent ATP diphosphohydrolase activity on the surface of L. donovani modulates the nucleotide concentration and protects the parasite from the lytic effects of the nucleotides mainly ATP. Ecto-ATPDase from L. donovani may be further characterized as a good antigen and as a target for immunodiagnosis and drug development, respectively.

Role of Magnetic Resonance Spectroscopy in Evaluating Choline Levels in Gallbladder Carcinoma: A Comprehensive Review.

Gallbladder carcinoma (GBC) presents a significant clinical challenge due to its aggressive nature and often asymptomatic progression, resulting in late-stage diagnoses and a poor prognosis. Early detection and accurate staging are pivotal for improving patient outcomes, highlighting the critical role of advanced imaging techniques in oncological practice. Magnetic resonance spectroscopy (MRS) has emerged as a valuable non-invasive tool capable of assessing biochemical changes within tissues, including alterations in choline metabolism-a biomarker indicative of cell membrane turnover and proliferation. This review explores the application of MRS in evaluating choline levels in gallbladder carcinoma, synthesizing current literature to elucidate its potential in clinical settings. By analyzing studies investigating the correlation between choline levels detected via MRS and tumor characteristics, this review underscores MRS's role in enhancing diagnostic precision and guiding therapeutic decision-making. Moreover, it discusses the challenges and limitations associated with MRS in clinical practice alongside future research and technological advancement directions. Ultimately, integrating MRS into the diagnostic armamentarium for gallbladder carcinoma promises to improve early detection and treatment outcomes. This review provides insights into the evolving landscape of MRS in oncology, emphasizing its contribution to personalized medicine approaches aimed at optimizing patient care and management strategies for GBC.

Radiation Dose Optimization in Radiology: A Comprehensive Review of Safeguarding Patients and Preserving Image Fidelity.

Radiation dose optimization in radiology is a critical aspect of modern healthcare, aimed at balancing the necessity of diagnostic imaging with the imperative of patient safety. This comprehensive review explores the fundamental principles, techniques, and considerations in optimizing radiation dose to safeguard patients while preserving image fidelity. Beginning with acknowledging the inherent risks associated with medical radiation exposure, the review highlights strategies such as the As Low as Reasonably Achievable (ALARA) principle, technological advancements, and quality assurance measures to minimize radiation dose without compromising diagnostic accuracy. Regulatory guidelines and the importance of patient education and informed consent are also discussed. Through a synthesis of current knowledge and emerging trends, the review underscores the pivotal role of radiation dose optimization in radiology practice. Furthermore, it emphasizes the need for ongoing research and collaboration to advance dose reduction strategies, establish standards for radiation safety, and explore personalized dose optimization approaches. By prioritizing radiation dose optimization, healthcare providers can ensure the highest standards of patient care while minimizing potential risks associated with medical radiation exposure.

Assessment of Health-Related Quality of Life and Its Determinants in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

Background Type 2 diabetes mellitus is a complex metabolic disorder associated with several complications that determine the quality of life of the patients. Health-related quality of life (HRQoL) is a measurable outcome of the self-perception of a patient's health which is affected due to age, lifestyle changes, medication, and treatment modalities. This study was undertaken to understand the impact of individual parameters of age, medication type and duration, diabetes-associated complications, and levels of glycated hemoglobin (HbA1c) on the quality of life (QoL) of the patient.  Methodology This single-center prospective, cross-sectional study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. Participants were recruited from the Outpatient Department of General Medicine, IGIMS. HRQoL was measured using a validated and reliable EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire developed by the EuroQol Research Foundation, along with the EuroQol-Visual Analogue Scale (EQ-VAS). The eligibility criteria included adult diabetic patients above 18 years of age with complete medical records, who had been treated at the outpatient department for a minimum of three months and could be interviewed. Results The results from this study show that 46% of the patients belonged to the age group of 45-65 years. The quality of health index scores and EQ-VAS scores significantly correlated with age (p-values: 1.11 e-4 and 3.09 e-5; <0.05). Of the subjects, 66.4%, 6.7%, and 26.8% were under oral hypoglycaemic agents (OHA), insulin, and both insulin with OHA medications respectively. HbA1C levels were statistically significantly correlated with mobility, self-care, usual activities, pain or discomfort, and anxiety or depression (p-value 0.032; <0.05), along with self-perception of the patient's health (p-value 0.00026; <0.05). Also, the perception of having slight problems in mobility, self-care, usual activities, pain or discomfort, and anxiety or depression was similar irrespective of gender (EQ-5D-5L score for males: 9.47 and females: 9.3). Despite suffering from diabetes-associated chronic complications, 60.5% of the subjects perceived their overall health to be good as indicated by the scores. Conclusion The self-perception of HRQoL concerning mobility, self-care, usual activities, pain or discomfort, and anxiety or depression was correlated with age, duration of anti-diabetic medication, and HbA1C level. Good mobility, self-care, and performing usual activities reduce anxiety or depression as opposed to age, pain, and discomfort. However, the subjects in this study cohort perceived overall good health in themselves in terms of EQ-VAS and 5D-5L scores, indicating effective diabetic care and management options available to them.

Leiomyosarcoma of the Duodenum: A Case Report on a Rarely Encountered Tumor.

Leiomyosarcoma (LMS) is an extremely rare malignant pathology affecting smooth muscle cells, with the uterus being the predominant location of LMS. Its occurrence in the duodenum is rare, making it a diagnostic challenge for radiologists. Patients with duodenal LMS can present with very vague symptoms such as abdominal discomfort, loss of weight, or manifestations associated with internal gastrointestinal bleeding. In this case report, we have an 82-year-old female presenting with duodenal LMS, which is a very atypical location. An esophagogastroduodenoscopy and further workup revealed a duodenal mass, which was biopsied. The lump was identified as an LMS using immunohistochemistry and histopathology. Despite its rarity, it presents diagnostic and therapeutic challenges due to its nonspecific clinical manifestations and radiological findings. By exploring the existing literature and clinical insights, we aim to provide a comprehensive understanding of this rare condition, highlighting the need for interdisciplinary collaboration and tailored therapeutic strategies to diagnose and manage this disease entity effectively.

Lost and Found: A Case Report of the Journey of Two Teeth Into the Bronchus After a Road Tragedy.

Traumatic foreign body aspiration (FBA) in adults is a rare yet potentially life-threatening event that requires prompt recognition and management to prevent adverse outcomes. While less common in adults compared to paediatric populations, traumatic FBA incidents often occur in occupational settings, post-trauma, or during high-risk activities, presenting with acute respiratory symptoms and varying degrees of airway obstruction. Diagnosis can be challenging due to the lack of classic symptoms and the potential for delayed presentation, necessitating a thorough history, a focused physical examination, and appropriate imaging techniques such as computed tomography (CT) and bronchoscopy. Prompt intervention is crucial to mitigating complications such as airway obstruction, pneumothorax, and respiratory compromise. Here, we describe an interesting case of a patient with a road traffic accident who aspirated two teeth and thought he lost them in this process. Surprisingly, two lost teeth were found after undergoing diagnostic procedures for mild shortness of breath, further causing aspiration pneumonitis.

Case Report: A Case Report on an 18-Year-Old Female with Cerebral Vasculitis in Systemic Lupus Erythematosus (SLE).

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient's neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.

Ovarian Torsion Leading to Necrosis: A Case Report of Acute Abdominal Pain in a 25-Year-Old Female.

Ovarian torsion is a critical gynecological emergency that presents with sudden-onset abdominal pain and requires immediate intervention to prevent irreversible ovarian damage. This case report describes a 25-year-old female who presented with acute right lower quadrant pain, which had escalated to excruciating levels over the past 45 minutes, accompanied by persistent nausea and vomiting. She had no fever, vaginal bleeding, or dysuria, and her urine pregnancy test was negative. A physical examination revealed significant tenderness and guarding in the right lower abdomen, with no evidence of organomegaly or abnormal pelvic findings. Imaging studies, including ultrasound, confirmed the diagnosis of a complete ovarian torsion with associated necrosis. The patient underwent successful laparoscopic surgery, which involved the removal of the necrotic ovary and affected fallopian tube. Postoperative recovery was uneventful, and the patient fully recovered within a week. This case underscores the importance of early diagnosis and surgical intervention in managing ovarian torsion to preserve ovarian function and prevent complications.

A Comprehensive Review on the Role of MRI in the Assessment of Supratentorial Neoplasms: Comparative Insights Into Adult and Pediatric Cases.

Magnetic resonance imaging (MRI) is a critical diagnostic tool in assessing supratentorial neoplasms, offering unparalleled detail and specificity in brain imaging. Supratentorial neoplasms in the cerebral hemispheres, basal ganglia, thalamus, and other structures above the tentorium cerebelli present significant diagnostic and therapeutic challenges. These challenges vary notably between adult and pediatric populations due to differences in tumor types, biological behavior, and patient management strategies. This comprehensive review explores the role of MRI in diagnosing, planning treatment, monitoring response, and detecting recurrence in supratentorial neoplasms, providing comparative insights into adult and pediatric cases. The review begins with an overview of the epidemiology and pathophysiology of these tumors in different age groups, followed by a detailed examination of standard and advanced MRI techniques, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and magnetic resonance spectroscopy (MRS). We discuss the specific imaging characteristics of various neoplasms and the importance of tailored approaches to optimize diagnostic accuracy and therapeutic efficacy. The review also addresses the technical and interpretative challenges unique to pediatric imaging and the implications for long-term patient outcomes. By highlighting the comparative utility of MRI in adult and pediatric cases, this review aims to enhance the understanding of its pivotal role in managing supratentorial neoplasms. It underscores the necessity of age-specific diagnostic and therapeutic strategies. Emerging MRI technologies and future research directions are also discussed, emphasizing the potential for advancements in personalized imaging approaches and improved patient care across all age groups.

Craniovertebral Junction Deformity Diagnosed by Computed Tomography: A Case Report.

Craniovertebral junction (CVJ) deformities, including basilar invagination and atlanto-occipital assimilation, present significant challenges in diagnosis and management due to their complex nature and impact on neurological function. We report a case of a 28-year-old female who experienced neck pain, weakness, tingling in the upper limbs, restricted neck movements, occipital headaches, and intermittent dizziness. These symptoms progressively worsened over six months, markedly affecting her quality of life. Neurological examination revealed reduced motor power in the upper limbs and a diminished bicipital tendon reflex, while other assessments remained normal. Cervical spine CT imaging was done which revealed basilar invagination and atlanto-occipital assimilation. This case underscores the importance of recognizing and managing CVJ deformities, highlighting the need for a multidisciplinary approach to address anatomical and associated neurological symptoms. Early and accurate diagnosis and a tailored treatment strategy are crucial for improving patient outcomes.

Ab initio investigations of the structure-stability, mechanical, electronic, thermodynamic and optical properties of Ti2FeAs Heusler alloy.

In this study, we employed density functional theory coupled with the full-potential linearized augmented plane-wave method (FP-LAPW) to investigate the structural, electronic, and magnetic properties of the Ti2FeAs alloy adopting the Hg2CuTi-type structure. Our findings demonstrate that all the examined structures exhibit ferromagnetic (FM) behaviour. By conducting electronic band structure calculations, we observed an energy gap of 0.739 eV for Ti2FeAs in the spin-down state and metallic intersections at the Fermi level in the spin-up state. These results suggest the half-metallic (HM) nature of Ti2FeAs, where the Ti-d and Fe-d electronic states play a significant role near the Fermi level. Additionally, the obtained total magnetic moments are consistent with the Slater-Pauling rule (Mtot = Ztot - 18), indicating 100% spin polarization for these compounds. To explore their optical properties, we employed the dielectric function to compute various optical parameters, including absorption spectra, energy-loss spectra, refractive index, reflectivity, and conductivity. Furthermore, various thermodynamic parameters were evaluated at different temperatures and pressures. The results obtained from the elastic parameters reveal the anisotropic and ductile nature of the Ti2FeAs compound. These findings suggest that Ti2FeAs has potential applications in temperature-tolerant devices and optoelectronic devices as a UV absorber.

Diminished NAD+ levels and activation of retrotransposons promote postovulatory aged oocyte (POAO) death.

Death is the fate of postovulatory aged or unfertilized oocytes (POAO) in many animals. However, precise molecular mechanisms are yet to be discovered. Here, we demonstrate that increased amounts of reactive oxygen species (ROS), calcium ion (Ca+2) channels, and retrotransposon activity induce apoptosis, which in turn causes POAO death. Notably, suppression of ROS, Ca+2 channels, and retrotransposons delayed POAO death. Further, we found that the histone H4K12 and K16 acetylation increased via downregulation of NAD+ and NAD+ -dependent histone deacetylase SIRT3. Furthermore, adding NMN, sodium pyruvate, or CD38 inhibition delayed the death of postovulatory aged oocytes. Finally, we demonstrate the conservation of retrotransposon-induced DNA damage-dependent POAO death in higher-order vertebrates. Our findings suggest that POAO mortality is caused by cyclic cascade metabolic interactions in which low NAD+ levels increase histone acetylation by inhibiting histone deacetylases, resulting in an increase in retrotransposons, ROS, and Ca+2 channel activity and thus contributing to DNA damage-induced apoptosis.

Maternal healthcare seeking and determinants of adequate antenatal care and institutional childbirth among Indian tribes: A cross-sectional study from nine districts.

OBJECTIVE: To report the utilisation of maternal healthcare services and factors associated with adequate antenatal care and institutional childbirths among mothers in the tribal communities from nine districts in India. METHODS: Cross-sectional data were collected from 2636 tribal women who had a childbirth experience in the past 12 months. Socio-demographic, maternal healthcare services and health system-related details were collected. Multiple logistic regression analyses were done to identify factors associated with adequate antenatal care (receiving at least four antenatal care visits, the first visit being in the first trimester and receiving a minimum of 100 iron-folic acid tablets) and institutional childbirth (mother giving birth in a health facility). RESULTS: Only 23% of the mothers received adequate antenatal care. 82% were institutional childbirths. The logistic regression revealed that particularly vulnerable tribal groups (PVTGs), those lacking all-weather roads, and women of advanced age were at risk of inadequate antenatal care. Mother's education, health worker's home visits during pregnancy and reception of advice on antenatal care were significantly associated with the reception of adequate antenatal care. Having all-weather roads, and education of the mother and head of the household were positively associated with institutional childbirths, whereas PVTGs, children of birth order three or above, and working mothers were more likely to give childbirth at home. CONCLUSION: PVTGs are at risk of foregoing adequate antenatal care and are more likely to give childbirth at home. Having all-weather roads is a strong correlate of adequate maternal care. Outreach activities by the health workers are to be strengthened as they are positively and significantly associated with the reception of adequate antenatal care. Investing in education and other social determinants and addressing certain socio-cultural practices is important to improve maternal health.

Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).

Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.

The emerging potential of siRNA nanotherapeutics in treatment of arthritis.

RNA interference (RNAi) using small interfering RNA (siRNA) has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes. However, siRNA delivery faces several challenges, including stability, targeting, off-target effects, endosomal escape, immune response activation, intravascular degradation, and renal clearance. A variety of nanotherapeutics like lipidic nanoparticles, liposomes, polymeric nanoparticles, and solid lipid nanoparticles have been developed to improve siRNA cellular uptake, protect it from degradation, and enhance its therapeutic efficacy. Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity. This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases, including rheumatoid arthritis, osteoarthritis, etc. siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology, nanotechnology, and formulation sciences.