Unlocking genetic insights: Evaluating wheat RILs for physiobiochemical traits under terminal heat stress conditions.

BACKGROUND: The increasing impacts of heat stress on wheat production due to climate change has entailed the development of heat-resilient crop varieties. To address this, two hundred recombinant inbred lines (RILs) derived from a cross between WH711/WH1021 were evaluated in a randomized block design (RBD) with two replications at CCSHAU, Hisar, during 2018-19 under heat stress and non-stress conditions. Heat stress was induced by altering the date of sowing so that the grain filling stage coincide with heat stress. RESULTS: Heat stress adversely affects RILs performance, as illustrated by alterations in phenotypic traits. Highest coefficients of variations were recorded for TAA, CTD 1, WUE, CTD 2, Cc and A under non-stress and heat stress conditions whereas gs, WUEi and GY under non-stress and SPAD 1, SPAD 2, GY and NDVI 2 under heat-stress conditions recorded moderate estimates of coefficient of variations. CTD 2, TAA, E, WUE and A displayed a significant occurrence of both high heritability and substantial genetic advance under non-stress. Similarly, CTD 2, NDVI 2, A, WUEi, SPAD 2, gs, E, Ci, MDA and WUE exhibited high heritability with high genetic advance under heat-stress conditions. CONCLUSIONS: Complementary and duplicate types of interactions with number of controlling genes were observed for different parameters depending on the traits and environments. RILs 41, 42, 59, 74, 75, 180 and 194 were categorized as heat tolerant RILs. Selection preferably for NDVI 1, RWC, TAA, A, E and WUEi to accumulate heat tolerance favorable alleles in the selected RILs is suggested for development of heat resilient genotypes for sustainable crop improvement. The results showed that traits such as such as NDVI, RWC, TAA, A, E, and WUEi, can be effective for developing heat-resilient wheat genotypes and ensuring sustainable crop improvement.

Contrast Enhanced CT Versus MRI for Accurate Diagnosis of Wall-thickening Type Gallbladder Cancer.

Introduction: Diagnosis of wall-thickening type gallbladder cancer (GBC) is challenging. Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly utilized to evaluate gallbladder wall thickening. However, there is a lack of data comparing the performance of CT and MRI for the detection of wall-thickening type GBC. Aim: We aim to compare the diagnostic accuracy of CT and MRI in diagnosis of wall-thickening type GBC. Materials and methods: This prospective study comprised consecutive patients suspected of wall-thickening type GBC who underwent preoperative contrast-enhanced CT and MRI. The final diagnosis was based on the histopathology of the resected gallbladder lesion. Two radiologists independently reviewed the characteristics of gallbladder wall thickening at CT and MRI. The association of CT and MRI findings with histological diagnosis and the interobserver agreement of CT and MRI findings were assessed. Results: Thirty-three patients (malignancy, 13 and benign, 20) were included. None of the CT findings were significantly associated with GBC. However, at MRI, heterogeneous enhancement, indistinct interface with the liver, and diffusion restriction were significantly associated with malignancy (P = 0.006, <0.001, and 0.005, respectively), and intramural cysts were significantly associated with benign lesions (P = 0.012). For all MRI findings, the interobserver agreement was substantial to perfect (kappa = 0.697-1.000). At CT, the interobserver agreement was substantial to perfect (k = 0.631-1.000). Conclusion: These findings suggest that MRI may be preferred over CT in patients with suspected wall thickening type GBC. However, larger multicenter studies must confirm our findings.

Paediatricians' perspectives in treating lower urinary tract symptoms: a qualitative exploratory needs assessment study.

BACKGROUND: Paediatric lower urinary tract symptoms (LUTS) are common experiences among school-aged children, with prevalence rates reaching as high as 20%. Paediatricians are often first-line stakeholders in providing treatment for these bothersome symptoms, yet there is no formal resource to support them with the treatment of LUTS. Evaluating paediatricians' experiences is an important step in informing health promotion efforts to improve health outcomes in children. This study aims to explore paediatricians' knowledge, beliefs, practice patterns, and perceived barriers and facilitators in providing LUTS care. METHODS: In this qualitative study, we conducted semistructured focus groups of paediatricians within California. Focus groups were conducted via Zoom, and participants were enrolled until thematic saturation was reached. Participants were asked about their current practices, knowledge and beliefs, barriers and facilitators to care, training and education, and responsibility for behaviour and action. Thematic analysis was performed using deductive and inductive approaches; themes were mapped through an iterative, team-based process. RESULTS: 15 paediatricians, aged 30-69 years, with 13 (86.7%) women, were interviewed. Most (11, 73.3%) practised in general outpatient settings. Interviewed paediatricians recognised paediatric LUTS as a common problem that can significantly impact children's well-being. In practice, paediatricians did not actively screen for LUTS beyond the potty-training milestone due to short visit duration and competing healthcare demands. Lack of guidelines, parental mistrust and inadequate clinical education were barriers identified by paediatricians. CONCLUSIONS: Paediatricians expressed a willingness to help patients but indicated several limitations to providing adequate LUTS care. Future professional development work can emphasise guideline development, early screening strategies to support timely intervention and better education for clinicians.

Identifying the mitochondrial metabolism network by integration of machine learning and explainable artificial intelligence in skeletal muscle in type 2 diabetes.

Imbalance in glucose metabolism and insulin resistance are two primary features of type 2 diabetes/diabetes mellitus. Its etiology is linked to mitochondrial dysfunction in skeletal muscle tissue. The mitochondria are vital organelles involved in ATP synthesis and metabolism. The underlying biological pathways leading to mitochondrial dysfunction in type 2 diabetes can help us understand the pathophysiology of the disease. In this study, the mitochondrial gene expression dataset were retrieved from the GSE22309, GSE25462, and GSE18732 using Mitocarta 3.0, focusing specifically on genes that are associated with mitochondrial function in type 2 disease. Feature selection on the expression dataset of skeletal muscle tissue from 107 control patients and 70 type 2 diabetes patients using the XGBoost algorithm having the highest accuracy. For interpretation and analysis of results linked to the disease by examining the feature importance deduced from the model was done using SHAP (SHapley Additive exPlanations). Next, to comprehend the biological connections, study of protein-protien and mRNA-miRNA networks was conducted using String and Mienturnet respectively. The analysis revealed BDH1, YARS2, AKAP10, RARS2, MRPS31, were potential mitochondrial target genes among the other twenty genes. These genes are mainly involved in the transport and organization of mitochondria, regulation of its membrane potential, and intrinsic apoptotic signaling etc. mRNA-miRNA interaction network revealed a significant role of miR-375; miR-30a-5p; miR-16-5p; miR-129-5p; miR-1229-3p; and miR-1224-3p; in the regulation of mitochondrial function exhibited strong associations with type 2 diabetes. These results might aid in the creation of novel targets for therapy and type 2 diabetes biomarkers.

Significance of Soy-Based Fermented Food and Their Bioactive Compounds Against Obesity, Diabetes, and Cardiovascular Diseases.

Soybean-based fermented foods are commonly consumed worldwide, especially in Asia. These fermented soy-products are prepared using various strains of Bacillus, Streptococcus, Lactobacillus, and Aspergillus. The microbial action during fermentation produces and increases the availability of various molecules of biological significance, such as isoflavones, bioactive peptides, and dietary fiber. These dietary bio active compounds are also found to be effective against the metabolic disorders such as obesity, diabetes, and cardiovascular diseases (CVD). In parallel, soy isoflavones such as genistein, genistin, and daidzin can also contribute to the anti-obesity and anti-diabetic mechanisms, by decreasing insulin resistance and oxidative stress. The said activities are known to lower the risk of CVD, by decreasing the fat accumulation and hyperlipidemia in the body. In addition, along with soy-isoflavones fermented soy foods such as Kinema, Tempeh, Douchi, Cheonggukjang/Chungkukjang, and Natto are also rich in dietary fiber (prebiotic) and known to be anti-dyslipidemia, improve lipolysis, and lowers lipid peroxidation, which further decreases the risk of CVD. Further, the fibrinolytic activity of nattokinase present in Natto soup also paves the foundation for the possible cardioprotective role of fermented soy products. Considering the immense beneficial effects of different fermented soy products, the present review contextualizes their significance with respect to their anti-obesity, anti-diabetic and cardioprotective roles.

Comprehensive transcriptome analyses of Fusarium-infected root xylem tissues to decipher genes involved in chickpea wilt resistance.

Fusarium wilt is the most destructive soil-borne disease that poses a major threat to chickpea production. To comprehensively understand the interaction between chickpea and Fusarium oxysporum, the xylem-specific transcriptome analysis of wilt-resistant (WR315) and wilt-susceptible (JG62) genotypes at an early timepoint (4DPI) was investigated. Differential expression analysis showed that 1368 and 348 DEGs responded to pathogen infection in resistant and susceptible genotypes, respectively. Both genotypes showed transcriptional reprogramming in response to Foc2, but the responses in WR315 were more severe than in JG62. Results of the KEGG pathway analysis revealed that most of the DEGS in both genotypes with enrichment in metabolic pathways, secondary metabolite biosynthesis, plant hormone signal transduction, and carbon metabolism. Genes associated with defense-related metabolites synthesis such as thaumatin-like protein 1b, cysteine-rich receptor-like protein kinases, MLP-like proteins, polygalacturonase inhibitor 2-like, ethylene-responsive transcription factors, glycine-rich cell wall structural protein-like, beta-galactosidase-like, subtilisin-like protease, thioredoxin-like protein, chitin elicitor receptor kinase-like, proline transporter-like, non-specific lipid transfer protein and sugar transporter were mostly up-regulated in resistant as compared to susceptible genotypes. The results of this study provide disease resistance genes, which would be helpful in understanding the Foc resistance mechanism in chickpea. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03803-9.

Chimeric antigen receptor-modified T cells therapy in prostate cancer: A comprehensive review on the current state and prospects.

Recent immunotherapy research has focused on chimeric antigen receptor-modified T cells (CAR-Ts). CAR-T therapies have been clinically applied to manage hematologic malignancies with satisfactory effectiveness. However, the application of CAR-T immunotherapy in solid tumors remains challenging. Even so, current CAR-T immunotherapies for prostate cancer (PCa) have shown some promise, giving hope to patients with advanced metastatic PCa. This review aimed to elucidate different types of prostate tumor-associated antigen targets, such as prostate-specific membrane antigen and prostate stem cell antigen, and their effects. The current status of the corresponding targets in clinical research through their applications was also discussed. To improve the efficacy of CAR-T immunotherapy, we addressed the possible applications of multimodal immunotherapy, chemotherapy, and CAR-T combined therapies. The obstacles of solid tumors were concisely elaborated. Further studies should aim to discover novel potential targets and establish new models by overcoming the inherent barriers of solid tumors, such as tumor heterogeneity and the immunosuppressive nature of the tumor microenvironment.

Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice.

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.

Acetyl transferase EP300 deficiency leads to chronic replication stress mediated by defective fork protection at stalled replication forks.

Mutations in the epigenetic regulator and global transcriptional activator, E1A binding protein (EP300), is being increasingly reported in aggressive hematological malignancies including adult T-cell leukemia/lymphoma (ATLL). However, the mechanistic contribution of EP300 dysregulation to cancer initiation and progression are currently unknown. Independent inhibition of EP300 in human cells results in the differential expression of genes involved in regulating the cell cycle, DNA replication and DNA damage response. Nevertheless, specific function played by EP300 in DNA replication initiation, progression and replication fork integrity has not been studied. Here, using ATLL cells as a model to study EP300 deficiency and an p300-selective PROTAC degrader, degrader as a pharmacologic tool, we reveal that EP300-mutated cells display prolonged cell cycle kinetics, due to pronounced dysregulations in DNA replication dynamics leading to persistent genomic instability. Aberrant DNA replication in EP300-mutated cells is characterized by elevated replication origin firing due to increased replisome pausing genome-wide. We demonstrate that EP300 deficiency results in nucleolytic degradation of nascently synthesized DNA at stalled forks due to a prominent defect in fork stabilization and protection. This in turn results in the accumulation of single stranded DNA gaps at collapsed replication forks, in EP300-deficient cells. Inhibition of Mre11 nuclease rescues the ssDNA accumulation indicating a dysregulation in downstream mechanisms that restrain nuclease activity at stalled forks. Importantly, we find that the absence of EP300 results in decreased expression of BRCA2 protein expression and a dependency on POLD3-mediated error-prone replication restart mechanisms. The overall S-phase abnormalities observed lead to under-replicated DNA in G2/M that instigates mitotic DNA synthesis. This in turn is associated with mitotic segregation defects characterized by elevated micronuclei formation, accumulation of cytosolic DNA and transmission of unrepaired inherited DNA lesions in the subsequent G1-phase in EP300-deficient cells. We demonstrate that the DNA replication dynamics of EP300-mutated cells ATLL cells recapitulate features of BRCA-deficient cancers. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress and defective replication fork restart results in persistent genomic instability that underlie aggressive chemo-resistant tumorigenesis in humans.

Compliance With the Royal College of Radiologists Guideline for Actionable Reporting and Its Impact on Patient Care: A Retrospective Analysis of Reporting Practices From a Major Trauma Center.

Introduction Prompt diagnosis forms the mainstay of management of any patient arriving at the hospital. In developed settings, apart from clinical assessment, imaging in the form of computed tomography (CT) scan plays a vital role in arriving at the patient diagnosis. The reporting should follow pre-defined Royal College of Radiologists (RCR) standards to improve the quality of the diagnostic process. Objectives To identify the compliance of reporting as per the RCR standards for the communication of radiological reports and fail-safe alert notification. Materials and methods A retrospective review of body CT scans was done in two cycles within a span of three months. A total of 100 randomized scans were assessed in each cycle, both from the A&E (accident and emergency) and inpatients. Normal scans and outpatient scans were excluded from the study. Data were collected using the online portal (CRIS) and statistical analysis was performed. Results After the first cycle of the audit, 95 reports out of 100 met the standard RCR criteria. After the second cycle, 97 reports met the criteria of the audit. One inpatient scan and two A&E reports did not meet the specified criteria in the second cycle. Conclusion After the two cycles of the audit carried out over three months, we were able to achieve almost 97% of reporting standards as compared to 95% obtained previously through a quality improvement project and create awareness.

Factors of transurethral incision effectiveness for ureteroceles in pediatric patients: A 28-year, single-institution retrospective review.

BACKGROUND: As a congenital anomaly, ureteroceles occur in 1 in 4000 children, and are usually diagnosed prenatally. However, there remains a lack of definite consensus on the optimal management of congenital ureteroceles. OBJECTIVE: We evaluated factors associated with success of primary transurethral incision (TUI) in ureterocele pediatric patients. METHODS: Demographic and clinical information for 120 pediatric patients who were diagnosed with congenital ureterocele between 1993 and 2021 at our institution were obtained through retrospective chart review. Data were analyzed using Fisher's exact tests, t-tests, and logistic regression with a significance threshold of p < 0.05. The primary outcome of ureterocele management was TUI effectiveness, defined by no need for further surgical intervention. RESULTS: Of the 120 patients (39 boys, 81 girls) with ureteroceles, 75 patients (22 boys, 53 girls) met our inclusion criteria of undergoing initial TUI ureterocele. Initial TUI was effective in 51/75 patients (68.0%). We analyzed possible correlative factors for TUI efficacy. Simplex system was a significant predictor of primary TUI efficacy (85% effective in simplex systems, 62% in duplex systems). Prior urinary tract infection, prenatal diagnosis, and electrocautery technique were all associated with an increased risk of needing additional surgeries after primary TUI. DISCUSSION: The most significant predictors of effective primary TUI were simplex system and the absence of preoperative vesicoureteral reflux. Prenatal diagnosis, preoperative febrile urinary tract infection, higher preoperative hydronephrosis grade, and the use of electrocautery were all associated with decreased primary TUI efficacy. Study limitations include that it was a retrospective chart review, and cohort size was limited by incomplete urology follow-up and operative records. CONCLUSIONS: Initial TUI was an effective procedure for the majority of our pediatric ureterocele patients, a higher success rate compared to other cohorts. Patients with a simplex system were more likely to have an effective first TUI than patients with duplex systems, as were patients without preoperative reflux. Although not statistically significant, our data suggest prior UTI, prenatal diagnosis, higher preoperative hydronephrosis grade, and the use of electrocautery may be associated with having additional surgeries.

Iron Profile in Term Small for Gestational Age Infants at 10 Weeks of Age and Correlation With Maternal Iron Profile : A Prospective Cohort Study.

BACKGROUND: Term small for gestational age (SGA) babies are at risk for developing iron deficiency anemia. The association between maternal and infant iron stores is not clear. OBJECTIVE: To assess proportion of term SGA neonates developing iron deficiency anemia by 10 weeks of age, and measure correlation between iron profile and hepcidin of babies at birth and at 10 weeks of age with maternal iron profile. DESIGN: Prospective cohort study conducted from November, 2018 to April, 2020. PARTICIPANTS: 120 term SGA babies and their mothers. INTERVENTION: Hemogram, iron profile and serum hepcidin (every fourth case) estimated in mother, cord blood and baby at 10 weeks. Babies developing anemia at 6 weeks detected by hemogram and ferritin were started on iron supplementation and excluded from the study. OUTCOME: Proportion of babies developing iron deficiency anemia at 10 weeks of age. RESULTS: 35 (29.2%) of 120 term SGA babies developed anemia (hemoglobin <9 g/dL) at 6 weeks. Proportion of infants who developed iron deficiency anemia (hemoglobin <9 g/dL and serum ferritin <40 µ/dL) at 6 and 10 weeks of age was 14.2% and 23.3%, respectively. No significant correlation was found bet-ween hemoglobin, iron and hepcidin of the baby in cord blood and at 10 weeks of age with that of mothers. Serum hepcidin in babies at birth (137.5 ng/mL) were higher than maternal values (128 ng/mL). CONCLUSION: A significant proportion of term SGA infants deve-loped anemia during early infancy, irrespective of maternal iron status.

hsa-miR-23a~27a~24-2 cluster members inhibit aggressiveness of breast cancer cells by commonly targeting NCOA1, NLK and RAP1B.

Targeted therapy is receiving considerable attention from the researchers around the globe owing to the increased drug-resistance and incidences of cancer recurrences. MicroRNAs (miRNAs) exhibits tremendous potential as a candidate for molecular targeted therapy in cancer. Unfortunately, majority of research related to microRNAs are focussed on either a particular miRNA or a set of unrelated miRNAs. There is lack of holistic knowledge on differential co-expression of miRNA clusters in regulating the gene expression under physiological conditions. Previously, we reported the cooperative effect of hsa-miR-23a~27a~24-2 cluster in inducing ER (Endoplasmic Reticulum) stress-mediated apoptotic cell death of HEK cells. In the present study, we have investigated the common anti-cancer effects of individual members of this cluster. Our in silico analysis identified twelve common target genes distributed across three independent clusters. Furthermore, we found NCOA1, NLK, and RAP1B to fall in a single cluster with NCOA1 as a central hub molecule. Prognostic analysis showed profound involvement of these three genes in the breast cancer progression and metastasis. We further demonstrated that alteration in the levels of individual members of miR-23a~27a~24-2 cluster commonly regulates the invasive migration of breast cancer cells by modulating EMT and cytoskeletal pathway proteins. Our results reveal a new insight into the therapeutic potential of individual members of the pro-apoptotic hsa-miR-23a~27a~24-2 cluster family against metastatic breast cancer.

COVID-19: Consequences on pregnant women and neonates.

Introduction: Human species is confronting with a gigantic global COVID-19 pandemic. Initially, it was observed in Wuhan, China, and the COVID-19 cases spread across the globe with lightning speed and resulted in the 21st century pandemic. If scientific reports are taken care of, it is noteworthy that this virus possesses more specific characteristics due to its structure. The distinctive structure has a higher binding affinity with angiotensin-converting enzyme 2 (ACE2) protein, and this is used as an access point to gain access to hosts. Methods: A complete literature search was conducted using PubMed, Google Scholar, SciFinder, and deep-diving Google Search using keywords such as "Pregnancy, COVID-19, Newborn, Fetus, Coronavirus 2019, Neonate, Pregnant women, and vertical transmission". Result and discussion: The SARS-CoV-2 virus is unlike its former analogs: SARS-CoV, and MERS-CoV in 2002 and 2012, respectively, or anything mankind has faced earlier concerning viciousness, global spread, and gravity of a causative agent. The current review has delved into articles published in various journals worldwide including the latest studies on the impact of COVID-19 on pregnant women and neonates and has discussed complications and challenges, psychological health, immunological response, vertical transmission, concurrent disorders, vaccine debate, management recommendations, recent news of the approval of COVID-19 vaccine for 6 months and older babies, and future perspectives.

Optogenetic Control of Human Stem Cell-Derived Neurons.

Spontaneous and optogenetically evoked activities of human induced pluripotent stem cell (hiPSC)-derived neurons can be assessed by patch clamp and multi-electrode array (MEA) electrophysiology. Optogenetic activation of these human neurons facilitates the characterization of their functional properties at the single neuron and circuit level. Here we showcase the preparation of hiPSC-derived neurons expressing optogenetic actuators, in vitro optogenetic stimulation and simultaneous functional recordings using patch clamp and MEA electrophysiology.