From Warm to Cold: Feeding Cold Milk in Preterm Infants with Uncoordinated Oral Feeding Patterns.

OBJECTIVE: Premature infants frequently face feeding challenges due to disrupted coordination of sucking, swallowing, and breathing, increasing their risk of dysphagia. There are few effective treatment options available. This study aims to assess the safety of cold milk feedings in preterm infants diagnosed with uncoordinated feeding patterns and its effect on feeding performance. STUDY DESIGN: Preterm infants with uncoordinated feeding patterns (n=26) were randomized to be fed milk at either room or cold temperature (refrigerator cold) using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. RESULT: The findings suggest that preterm infants can safely tolerate cold milk without any clinically significant changes in temperature or mesenteric blood flow, and it may enhance feeding performance. CONCLUSION: Cold milk feeding could be a safe therapeutic option for preterm infants, however additional comprehensive studies are still needed. Registered at clinicaltrials.org #NCT04421482.

Early blood glucose screening in asymptomatic high-risk neonates.

OBJECTIVES: Detecting and treating severe hypoglycemia promptly after birth is crucial due to its association with adverse long-term neurodevelopmental outcomes. However, limited data are available on the optimal timing of glucose screening in asymptomatic high-risk neonates prone to hypoglycemia. Risk factors associated with asymptomatic high-risk neonates include late prematurity ≥35 and <37 weeks gestation (LPT), small-for-gestational-age (SGA), large-for-gestational-age (LGA), and infant-of-a-diabetic mother (IDM). This study aims to determine the incidence and the impact of individual risk factors on early hypoglycemia (defined as blood glucose ≤25 mg/dL in the initial hour after birth) in asymptomatic high-risk neonates. METHODS: All asymptomatic high-risk neonates ≥35 weeks gestation underwent early blood glucose screening within the first hour after birth (n=1,690). A 2-year retrospective analysis was conducted to assess the incidence of early neonatal hypoglycemia in this cohort and its association with hypoglycemia risk factors. RESULTS: Out of the 9,919 births, 1,690 neonates (17 %) had risk factors for neonatal hypoglycemia, prompting screening within the first hour after birth. Incidence rates for blood glucose ≤25 mg/dL and ≤15 mg/dL were 3.1 and 0.89 %, respectively. Of concern, approximately 0.5 % of all asymptomatic at-risk neonates had a blood glucose value of ≤10 mg/dL. LPT and LGA were the risk factors significantly associated with early neonatal hypoglycemia. CONCLUSIONS: Asymptomatic high-risk neonates, particularly LPT and LGA neonates, may develop early severe neonatal hypoglycemia identified by blood glucose screening in the first hour of life. Additional investigation is necessary to establish protocols for screening and managing asymptomatic high-risk neonates.

Glycogen synthase kinase 3 activity enhances liver inflammation in MASH.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear. Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]). Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3ß as the major kinase hub in MASH. GSK3ß-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells. Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH. Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

Exploring Cannabinoids as Potential Inhibitors of SARS-CoV-2 Papain-like Protease: Insights from Computational Analysis and Molecular Dynamics Simulations.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus's papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns. The results showed cannabinoids with binding affinities ranging from -6.1 kcal/mol to -4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro's active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid-PLpro complexes, highlighting stable binding conformations and conformational changes over time. These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19.

Glycemic Management in Insulin-Naive Patients in the Inpatient Setting.

Objective: The ideal inpatient insulin regimen efficiently attains the target blood glucose range, effectively treats hyperglycemia, and minimizes the risk of hypoglycemia. The objective of this study was to compare glycemic targets achieved by using correctional monotherapy (CM) and basal-bolus therapy (BBT) in insulin-naive patients in the inpatient setting to determine optimal blood glucose management for these patients. Design: This was a retrospective observational cohort study of 792 patients with diabetes not on home insulin therapy who were admitted to an academic hospital over a 5.5-month period. The percentages of hyperglycemic and hypoglycemic values in each group were compared. Results: Among the 3,112 measured blood glucose values obtained from 792 patients within the first 24 hours of insulin administration, 28.5% were hyperglycemic in the BBT group compared with 23.5% in the CM group. When adjusted for covariates, there was a 23% decrease in hyperglycemia in the BBT group (incidence rate ratio = 0.77, 95% CI 0.64-0.95, P = 0.006). Increases in A1C and admission blood glucose, as well as decreases in admission creatinine and inpatient steroid use, were independently associated with higher rates of hyperglycemia, adjusted for all other covariates. There was no significant difference between the groups in the rate of hypoglycemia in the first 24 hours, which was 1.9% in the BBT group and 1.4% in the CM group (P = 0.301). Conclusion: Utilizing BBT in insulin-naive patients admitted to the hospital within the first 24 hours of insulin administration results in lower rates of hyperglycemia without higher rates of hypoglycemia when compared with CM.

The Effect of the COVID-19 Pandemic on the Factors Influencing Iranian Medical Residents' Specialty Selection: A Qualitative Study.

Background: Medical students' specialty selection influences the composition of the physician workforce and the effectiveness of health systems. Therefore, the identification of factors that influence the choice of specialty is critical for an evidence-based health policy. This study aimed to investigate the effect of the Coronavirus Disease 2019 (COVID-19) pandemic on the determinants of specialty choice among Iranian medical residents. Methods: In early 2022, this qualitative study was conducted among Iranian medical residents in seven provinces, including Tehran, Isfahan, Fars, Khorasan Razavi, Kerman, Kermanshah, and Khuzestan. The participants were selected using a purposeful sampling method. Data were collected using 74 semi-structured in-depth face-to-face interviews. Finally, a thematic content analysis (conventional content analysis) method was applied for data synthesis. Results: The participant's mean age was 28.7±2.5 years, and more than 52% (N=39) were men. Following data synthesis, 10 sub-themes and four main themes were identified, including educational aspects affected by the pandemic, career-related hazards, personal and professional lifestyles affected by the disease, and experiences and beliefs regarding the pandemic. Conclusion: The COVID-19 pandemic has had a significant impact on medical students' educational, professional, and personal aspects of specialty choices. This study demonstrated how the disease affected the choice of specialty. Therefore, the findings could be used for developing national health policy and planning.

Enhanced recovery after surgery: Preoperative carbohydrate loading and insulin management in type 2 diabetes.

We assessed our institutional practice of individualized insulin dosing for patients with type 2 diabetes receiving preoperative carbohydrate loading (CHO-L) within an enhanced recovery after surgery (ERAS®) protocol. Patients enrolled in an ERAS® protocol with concomitant type 2 diabetes received rapid acting insulin (Novolog®[insulin aspart]) prior to 50 g CHO-L on the day of surgery. Following CHO-L and the administration of insulin, no hypoglycemic episodes occurred with preoperative POC glucose values between 6.8 and 12.3 mmol/L (123 and 221 mg/dL). Our experience demonstrates that administering rapid acting insulin prior to CHO-L in patients with type 2 diabetes is feasible and targets the potentially negative influence CHO-L may impose on preoperative glycemia in this population. Important considerations of this approach are highlighted and an insulin dosing algorithm designed for non-specialty providers is suggested.

Bulky hydrophobic side chains in the ß1-sandwich of microsomal triglyceride transfer protein are critical for the transfer of both triglycerides and phospholipids.

Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apolipoprotein B-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglyceride (TG) and not phospholipid (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different ß-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in ß2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in ß1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, whereas negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention.

Allelic heterogeneity of TTNtv dilated cardiomyopathy can be modeled in adult zebrafish.

Allelic heterogeneity (AH) has been noted in truncational TTN-associated (TTNtv-associated) dilated cardiomyopathy (DCM); i.e., mutations affecting A-band-encoding exons are pathogenic, but those affecting Z-disc-encoding exons are likely benign. The lack of an in vivo animal model that recapitulates AH hinders the deciphering of the underlying mechanism. Here, we explored zebrafish as a candidate vertebrate model by phenotyping a collection of zebrafish ttntv alleles. We noted that cardiac function and sarcomere structure were more severely disrupted in ttntv-A than in ttntv-Z homozygous embryos. Consistently, cardiomyopathy-like phenotypes were present in ttntv-A but not ttntv-Z adult heterozygous mutants. The phenotypes observed in ttntv-A alleles were recapitulated in null mutants with the full titin-encoding sequences removed. Defective autophagic flux, largely due to impaired autophagosome-lysosome fusion, was also noted only in ttntv-A but not in ttntv-Z models. Moreover, we found that genetic manipulation of ulk1a restored autophagy flux and rescued cardiac dysfunction in ttntv-A animals. Together, our findings presented adult zebrafish as an in vivo animal model for studying AH in TTNtv DCM, demonstrated TTN loss of function is sufficient to trigger ttntv DCM in zebrafish, and uncovered ulk1a as a potential therapeutic target gene for TTNtv DCM.

Assessing Trace Metal-Based Human Health Risks for Commonly Used Body Soaps in Bangladesh.

In Bangladesh, body soaps are very popular among consumers due to their flavors and low alkali content. The current study assesses the contamination of several trace metals (TMs) such as iron (Fe), copper (Cu), zinc (Zn), chromium (Cr), manganese (Mn), nickel (Ni), cadmium (Cd), and lead (Pb) in some of the body soaps most commonly used in Bangladesh. The concentrations of Fe, Cu, Zn, Cr, and Mn were found within the acceptable limits stipulated by the World Health Organization (WHO); however, in contrast, the concentrations of Ni, Cd, and Pb remained below the detection limit. Notably, the concentration of Cr in two soap samples (S-2, S-3) out of twenty-one soap samples exceeded the permissible limit stipulated by the WHO. Health risks associated with the TM intake via dermal routes were evaluated in terms of chronic daily intake (CDI) and hazard quotient (HQ). The results indicated that no non-carcinogenic risks (NCR) are likely to occur owing to the use of those body soaps. The carcinogenic risk (CR) estimated for Cr revealed no possibility of probable carcinogenic diseases. Though the NCR and CR are unlikely to occur resulting from the long-term uses of these soaps, the present study provides baseline information on the possible contaminations of TMs in the beauty soaps that do not seem to have been reported so far in Bangladesh. In light of the above information, it can be concluded that the presence of TMs in the body soaps could be a warning for people in general thereby suggesting continuous monitoring.

Discovery of Nirmatrelvir Resistance Mutations in SARS-CoV-2 3CLpro: A Computational-Experimental Approach.

The COVID-19 pandemic has emphasized the urgency for effective antiviral therapies against SARS-CoV-2. Targeting the main protease (3CLpro) of the virus has emerged as a promising approach, and nirmatrelvir (PF-07321332), the active component of Pfizer's oral drug Paxlovid, has demonstrated remarkable clinical efficacy. However, the emergence of resistance mutations poses a challenge to its continued success. In this study, we employed alchemical free energy perturbation (FEP) alanine scanning to identify nirmatrelvir-resistance mutations within SARS-CoV-2 3CLpro. FEP identified several mutations, which were validated through in vitro IC50 experiments and found to result in 8- and 72-fold increases in nirmatrelvir IC50 values. Additionally, we constructed SARS-CoV-2 omicron replicons containing these mutations, and one of the mutants (S144A/E166A) displayed a 20-fold increase in EC50, confirming the role of FEP in identifying drug-resistance mutations. Our findings suggest that FEP can be a valuable tool in proactively monitoring the emergence of resistant strains and guiding the design of future inhibitors with reduced susceptibility to drug resistance. As nirmatrelvir is currently widely used for treating COVID-19, this research has important implications for surveillance efforts and antiviral development.

Racial Disparities in Hospitalization Rates During Long-Term Follow-Up After Deceased-Donor Kidney Transplantation.

OBJECTIVE: To compare hospitalization rates between African American (AA) and European American (EA) deceased-donor (DD) kidney transplant (KT) recipients during over a10-year period. METHOD: Data from the Scientific Registry of Transplant Recipients and social determinants of health (SDoH), measured by the Social Deprivation Index, were used. Hospitalization rates were estimated for kidney recipients from AA and EA DDs who had one kidney transplanted into an AA and one into an EA, leading to four donor/recipient pairs (DRPs): AA/AA, AA/EA, EA/AA, and EA/EA. Poisson-Gamma models were fitted to assess post-transplant hospitalizations. RESULT: Unadjusted hospitalization rates (95% confidence interval) were higher among all DRP involving AA, 131.1 (122.5, 140.3), 134.8 (126.3, 143.8), and 102.4 (98.9, 106.0) for AA/AA, AA/EA, and EA/AA, respectively, compared to 97.1 (93.7, 100.6) per 1000 post-transplant person-years for EA/EA pairs. Multivariable analysis showed u-shaped relationships across SDoH levels within each DRP, but findings varied depending on recipients' race, i.e., AA recipients in areas with the worst SDoH had higher hospitalization rates. However, EA recipients in areas with the best SDoH had higher hospitalization rates than their counterparts. CONCLUSIONS: Relationship between healthcare utilization and SDoH depends on DRP, with higher hospitalization rates among AA recipients living in areas with the worst SDoH and among EA recipients in areas with the best SDoH profiles. SDoH plays an important role in driving disparities in hospitalizations after kidney transplantation.

Nutrition transition, double burden of malnutrition, and urbanization patterns in secondary cities of Bangladesh, Kenya and Rwanda.

BACKGROUND: By 2050, approximately 68% of the global population will live in cities, but nutrition data on urban populations of low- and middle-income countries are scarce. Fast growing secondary cities, combining characteristics and hurdles of urban and rural settings, are hotspots for the double burden of malnutrition. The Nutrition in City Ecosystems (NICE) project focuses on 6 secondary cities in Bangladesh, Kenya and Rwanda, to improve health and nutrition, and reduce poverty. To assess the baseline situation and guide future interventions, food insecurity, dietary diversity, nutrition status, and food production and purchasing patterns were explored. METHODS: In a cross-sectional study design, data were collected from urban and peri-urban households of Dinajpur and Rangpur in Bangladesh, Bungoma and Busia in Kenya, and Rubavu and Rusizi in Rwanda. Approximately 1200 households, in neighborhoods prone to malnutrition, were involved from April to June 2021. We assessed Household Food Insecurity Access Score (HFIAS), both current and before COVID-19, Household Dietary Diversity Score (HDDS), Minimum Dietary Diversity for Women (MDD-W), anthropometric measurements, household and socioeconomic information, and questions related to food production and consumer behavior. Further we collected secondary data on low birthweight and anemia during pregnancy. RESULTS: All cities experienced a substantial increase in food insecurity during the COVID-19 pandemic. Stunting rates in children under 5 years varied among the cities and ranged from 7.8% in Busia to 46.6% in Rubavu, while half of adult women were overweight (between 42.1% in Rusizi and 55.8% in Bungoma). Furthermore, many women did not consume an adequately diverse diet (MDD-W < 5 for 29.3% in Bangladesh, 47.5% in Kenya, and 67.0% in Rwanda), however many of the urban and peri-urban households were engaged in farming (58-78%). CONCLUSIONS: The double burden of malnutrition is high in secondary cities and the COVID-19 pandemic has exacerbated levels of food insecurity. Demand for, and access to, an affordable healthy diverse diet that comprises local, nutritious, and agroecologically produced foods present a pathway for overcoming the complex challenges of malnutrition.

Smart Crop Cultivation System Using Automated Agriculture Monitoring Environment in the Context of Bangladesh Agriculture.

The Internet of Things (IoT) is a transformative technology that is reshaping industries and daily life, leading us towards a connected future that is full of possibilities and innovations. In this paper, we present a robust framework for the application of Internet of Things (IoT) technology in the agricultural sector in Bangladesh. The framework encompasses the integration of IoT, data mining techniques, and cloud monitoring systems to enhance productivity, improve water management, and provide real-time crop forecasting. We conducted rigorous experimentation on the framework. We achieve an accuracy of 87.38% for the proposed model in predicting data harvest. Our findings highlight the effectiveness and transparency of the framework, underscoring the significant potential of the IoT in transforming agriculture and empowering farmers with data-driven decision-making capabilities. The proposed framework might be very impactful in real-life agriculture, especially for monsoon agriculture-based countries like Bangladesh.

Wheat Water-Soluble Carbohydrate Remobilisation under Water Deficit by 1-FEH w3.

Fructan 1-exohydrolase (1-FEH) is one of the major enzymes in water-soluble carbohydrate (WSC) remobilisation for grains in wheat. We investigated the functional role of 1-FEH w1, w2, and w3 isoforms in WSC remobilisation under post-anthesis water deficit using mutation lines derived from the Australian wheat variety Chara. F1 seeds, developed by backcrossing the 1-FEH w1, w2, and w3 mutation lines with Chara, were genotyped using the Infinium 90K SNP iSelect platform to characterise the mutated region. Putative deletions were identified in FEH mutation lines encompassing the FEH genomic regions. Mapping analysis demonstrated that mutations affected significantly longer regions than the target FEH gene regions. Functional roles of the non-target genes were carried out utilising bioinformatics and confirmed that the non-target genes were unlikely to confound the effects considered to be due to the influence of 1-FEH gene functions. Glasshouse experiments revealed that the 1-FEH w3 mutation line had a slower degradation and remobilisation of fructans than the 1-FEH w2 and w1 mutation lines and Chara, which reduced grain filling and grain yield. Thus, 1-FEH w3 plays a vital role in reducing yield loss under drought. This insight into the distinct role of the 1-FEH isoforms provides new gene targets for water-deficit-tolerant wheat breeding.

Synthesis and Characterization of the Donor-Acceptor Conjugated Polymer PBDB-T Implementing Group IV Element Germanium.

Here, we synthesized and characterized a novel two-dimensional (2D) conjugated electron donor-acceptor (D-A) copolymer (PBDB-T-Ge), wherein the substituent of triethyl germanium was added to the electron donor unit of the polymer. The Turbo-Grignard reaction was used to implement the group IV element into the polymer, resulting in a yield of 86%. This corresponding polymer, PBDB-T-Ge, exhibited a down-shift in the highest occupied molecular orbital (HOMO) level to -5.45 eV while the lowest unoccupied molecular orbital (LUMO) level was -3.64 eV. The peaks in UV-Vis absorption and the PL emission of PBDB-T-Ge were observed at 484 nm and 615 nm, respectively.

RNA-NRD: a non-redundant RNA structural dataset for benchmarking and functional analysis.

The significance of RNA functions and their role in evolution and disease control have remarkably increased the research scope in the field of RNA science. Though the availability of RNA structure data in PBD has been growing tremendously, maintaining their quality and integrity has become the greater challenge. Since the data available in PDB are results of different independent research, they might contain redundancy. As a result, there remains a possibility of data bias for both protein and RNA chains. Quite a few studies have been conducted to remove the redundancy of protein structures by introducing high-quality representatives. However, the amount of research done to remove the redundancy of RNA structures is still very low. To remove RNA chain redundancy in PDB, we have introduced RNA-NRD, a non-redundant dataset of RNA chains based on sequence and 3D structural similarity. We compared RNA-NRD with the existing non-redundant RNA structure dataset RS-RNA and showed that it has better-formed clusters of redundant RNA chains with lower average RMSD and higher average PSI, thus improving the overall quality of the dataset.

The putative vacuolar processing enzyme gene TaVPE3cB is a candidate gene for wheat stem pith-thickness.

KEY MESSAGE: The vacuolar processing enzyme gene TaVPE3cB is identified as a candidate gene for a QTL of wheat pith-thickness on chromosome 3B by BSR-seq and differential expression analyses. The high pith-thickness (PT) of the wheat stem could greatly enhance stem mechanical strength, especially the basal internodes which support the heavier upper part, such as upper stems, leaves and spikes. A QTL for PT in wheat was previously discovered on 3BL in a double haploid population of 'Westonia' × 'Kauz'. Here, a bulked segregant RNA-seq analysis was applied to identify candidate genes and develop associated SNP markers for PT. In this study, we aimed at screening differentially expressed genes (DEGs) and SNPs in the 3BL QTL interval. Sixteen DEGs were obtained based on BSR-seq and differential expression analyses. Twenty-four high-probability SNPs in eight genes were identified by comparing the allelic polymorphism in mRNA sequences between the high PT and low PT samples. Among them, six genes were confirmed to be associated with PT by qRT-PCR and sequencing. A putative vacuolar processing enzyme gene TaVPE3cB was screened out as a potential PT candidate gene in Australian wheat 'Westonia'. A robust SNP marker associated with TaVPE3cB was developed, which can assist in the introgression of TaVPE3cB.b in wheat breeding programs. In addition, we also discussed the function of other DEGs which may be related to pith development and programmed cell death (PCD). A five-level hierarchical regulation mechanism of stem pith PCD in wheat was proposed.

Current Progress and Future Prospect of Wheat Genetics Research towards an Enhanced Nitrogen Use Efficiency.

To improve the yield and quality of wheat is of great importance for food security worldwide. One of the most effective and significant approaches to achieve this goal is to enhance the nitrogen use efficiency (NUE) in wheat. In this review, a comprehensive understanding of the factors involved in the process of the wheat nitrogen uptake, assimilation and remobilization of nitrogen in wheat were introduced. An appropriate definition of NUE is vital prior to its precise evaluation for the following gene identification and breeding process. Apart from grain yield (GY) and grain protein content (GPC), the commonly recognized major indicators of NUE, grain protein deviation (GPD) could also be considered as a potential trait for NUE evaluation. As a complex quantitative trait, NUE is affected by transporter proteins, kinases, transcription factors (TFs) and micro RNAs (miRNAs), which participate in the nitrogen uptake process, as well as key enzymes, circadian regulators, cross-talks between carbon metabolism, which are associated with nitrogen assimilation and remobilization. A series of quantitative genetic loci (QTLs) and linking markers were compiled in the hope to help discover more efficient and useful genetic resources for breeding program. For future NUE improvement, an exploration for other criteria during selection process that incorporates morphological, physiological and biochemical traits is needed. Applying new technologies from phenomics will allow high-throughput NUE phenotyping and accelerate the breeding process. A combination of multi-omics techniques and the previously verified QTLs and molecular markers will facilitate the NUE QTL-mapping and novel gene identification.