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This work aims to study the effect of milk powder incorporation on the nutritional and sensory quality of our traditional indigenous food, bhakka. Different samples were prepared replacing the rice flour by milk powder at different ratios (2.5:97.5, 5:95, 7.5:92.5, 10:90). Bhakka prepared from 100% rice flour was considered as control. Sensory-related results showed that 7.5% milk powder and 92.5% rice flour can be mixed to prepare an acceptable quality. The proximate analysis showed protein content of 5.18% in rice flour bhakka and 6.7% in milk-powder-incorporated bhakka. The milk-powder-incorporated bhakka had a fat content of 1.51%, crude fibre content of 0.18%, crude protein content of 6.70%, total ash content of 0.44%, and carbohydrate content of 62.3%, which was higher than that of rice flour bhakka. The product prepared can help in combating protein–energy malnutrition, adds a new taste as well as value to our traditional indigenous food.

Renal involvement and acute kidney injury (AKI) are common clinical manifestations seen in scrub typhus, a vector-borne tropical disease. There are no data on renal manifestation in scrub typhus in Nepal. We conducted a prospective study to analyze the incidence, urinary abnormalities, course, severity, outcome, and the predictors of AKI in patients with scrub typhus during a major outbreak in Central Nepal. Total 1398 patients admitted with acute febrile illness were subjected for Scrub Typhus Detect™ Immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) test, of which 502 (35.90%) patients tested positive and were included in the study. Mean age of the patients was 30.37 ± 18.81 years (range, 1-79 years) with 26.29% in the pediatric age group. Female-to-male ratio was 1.26:1. Mean duration of fever was 6.8 ± 3.1 days. Mean IgM ELISA value for scrub typhus was 2.17 ± 1.70 without difference in AKI and non-AKI groups (2.17 ± 1.76 vs. 2.16 ± 1.62; P = 0.94). Urinary abnormalities were seen in 42.3% of patients. Mean serum creatinine was 1.37 ± 0.69 mg/dl with significant difference in two groups (1.85 ± 0.87 vs. 1.03 ± 0.17; P = 0.003). AKI was seen in 35.8% of patients with majority having Stage 1 AKI (68.3%) followed by Stage 2 (34.1%) and Stage 3 (1.2%). Hemodialysis was required for 3.94% of patients. In 54% of patients, AKI occurred in fifth and sixth day of fever. ICU admission was required for 18.73% of patients and 8.57% required ventilator support. Mortality rate was 1.79%, which was higher among patients with AKI (2.96% vs. 1.0%; P = 0.106). Multivariate analysis revealed that the presence of pneumonia, shock, and acute respiratory distress syndrome predicted the development of AKI. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Heme oxygenase-1 (HO-1) is contributed to odontoblast differentiation in human dental pulp cells (HDPCs). In this study, pachymic acid from mushroom Formitopsis niagra is examined to determine whether it affects pulpal inflammation and promotes odontogenesis via HO-1 gene expression. MATERIALS AND METHODS: The HDPCs were given H2O2 for inflammation. The anti-inflammatory character and odontoblast differentiation by pachymic acid were analyzed by Western blotting, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of pachymic acid via HO-I induction, the cells were treated with zinc protoporphyrin IX (ZnPP: HO-1 inhibitor). RESULTS: H2O2 induced pulp inflammation and disturbed odontoblast differentiation. However, the HDPCs treated with pachymic acid affected anti-inflammatory effect and induction of odontoblast differentiation through increasing HO-1 expression. In addition, pachymic acid has potent cytoprotection and mineralization under H2O2 treatment. Furthermore, pachymic acid significantly suppressed nuclear factor-kappa B (NF-κB) translocation into nucleus and induced NE-E2-related factor-2 (Nrf2) translocation into nucleus. Overall, NF-κB and Nrf2 translocation were regulated by the HO-1 pathway. CONCLUSIONS: The pachymic acid showed anti-inflammatory function and odontoblast differentiation via HO-1 pathway. These results suggested that pachymic acid may be applicable for prevention of oral inflammation or to improve dentin mineralization against several stresses. [ABSTRACT FROM AUTHOR]

Local implantation or supplementation of magnesium gluconate (MgG) is being investigated as an effective approach to bone repair. Although studies have highlighted the possible mechanisms in Mg ion-stimulated new bone formation, the role of MgG in healing bone defects and the signaling mechanisms are not yet completely understood. In this study, we explored how supplemental MgG has bone-specific beneficial effects by delivering MgG locally and orally in animal models. We fabricated MgG-incorporated (CMC-M) and -free chitosan (CMC) scaffolds with good microstructures and biocompatible properties. Implantation with CMC-M enhanced bone healing in rat model of mandible defects, compared with CMC, by activating Wnt signals and Wnt-related osteogenic and angiogenic molecules. Oral supplementation with MgG also stimulated bone healing in mouse model of femoral defects along with the increases in Wnt3a and angiogenic and osteogenic factors. Supplemental MgG did not alter nature bone accrual and bone marrow (BM) microenvironment in adult mouse model, but enhanced the functioning of BM stromal cells (BMSCs). Furthermore, MgG directly stimulated the induction of Wnt signaling-, angiogenesis-, and osteogenesis-related molecules in cultures of BMSCs, as well as triggered the migration of endothelial cells. These results suggest that supplemental MgG improves bone repair in a way that is synergistically enhanced by Wnt signal-associated angiogenic and osteogenic molecules. Overall, this study indicates that supplemental MgG might ameliorate oxidative damage in the BM, improve the functionality of BM stem cells, and maintain BM-microenvironmental homeostasis., (© 2024 Wiley Periodicals LLC.)

Dysregulated Wnt signaling causes age-related characteristics such as oxidative stress, stem cell senescence, and abnormal bone homeostasis. Here we explored whether supplemental n-acetyl-l-cysteine (NAC) recovers the age-associated complications relative to osteoblastic Wntless (Wls) ablation and examined the possible mechanisms therein. For this work, we administered Col2.3-Cre;Wls fl/fl mutant and littermate control (Wls fl/fl ) mice (14 weeks of age) with NAC (40 mM)-supplemented or NAC-free water for four weeks. A proportion of these mice received non-critical-sized femoral defects at 16 weeks of age. Blood, bone, and bone marrow (BM) samples were collected and adjusted for in vivo, ex vivo, and in vitro analyses. Osteoblastic Wls deletion delayed bone mass accrual and the healing of bone defects, stimulated osteoclastic activation and inflammatory factor expression, and decreased antioxidant enzyme activity in the BM. Osteoblastic Wls deletion also promoted oxidative stress, apoptosis, and senescence in BM stromal cells (BMSCs) and decreased BMSC' multipotencies. Supplementation of Wls fl/fl mice with NAC enhanced bone mass accrual and regenerative bone healing via a Wnt signal-associated osteogenic activation. However, supplemental NAC induced new bone formation in the mutant mice by inhibiting the age-related complications of BM/BMSCs, as well as by restoring endogenous antioxidant system without any alterations in Wnt ligand secretion, hematopoiesis, and expression of osteogenic and growth factors. This study indicates that supplemental NAC protects mice against Wnt deficiency-mediated and age-associated degenerative complications. Overall, this study highlights the therapeutic potency of NAC for restoring the antioxidant system, stem cell function, and regenerative bone homeostasis in osteoblastic Wls-dispensable manner., Competing Interests: Declaration of Competing Interest All authors declare no potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pecan scab, caused by the fungal pathogen Venturia effusa, is the most devastating disease of pecan (Carya illinoinensis) in the southeastern United States. Resistance to this pathogen is determined by a complex interaction between host genetics and disease pathotype with even field-susceptible cultivars being resistant to most scab isolates. To understand the underlying molecular mechanisms of scab resistance in pecan, we performed a transcriptome analysis of the pecan cultivar, 'Desirable', in response to inoculation with a pathogenic and a non-pathogenic scab isolate at three different time points (24, 48, and 96 hrs. post-inoculation). Differential gene expression and gene ontology enrichment analyses showed contrasting gene expression patterns and pathway enrichment in response to the contrasting isolates with varying pathogenicity. The weighted gene co-expression network analysis of differentially expressed genes detected 11 gene modules. Among them, two modules had significant enrichment of genes involved with defense responses. These genes were particularly upregulated in the resistant reaction at the early stage of fungal infection (24 h) compared to the susceptible reaction. Hub genes in these modules were predominantly related to receptor-like protein kinase activity, signal reception, signal transduction, biosynthesis and transport of plant secondary metabolites, and oxidoreductase activity. Results of this study suggest that the early response of pathogen-related signal transduction and development of cellular barriers against the invading fungus are likely defense mechanisms employed by pecan cultivars against non-virulent scab isolates. The transcriptomic data generated here provide the foundation for identifying candidate resistance genes in pecan against V. effusa and for exploring the molecular mechanisms of disease resistance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

An aqueous bark extract of A. nepalensis D. Don was utilized to prepare zinc oxide (ZnO) nanoparticles through a green method, which is more economical, eco-friendly, and effective for exploring several biological applications and toxicity assessments against brine shrimp nauplii. The prepared ZnO nanoparticles were characterized using several characterizing techniques. The surface morphology and the elemental composition of the prepared ZnO NPs was analyzed by field emission scanning electron microscopy (FE-SEM), and energy dispersive X-ray (EDX) analysis. The colour of the solution was changed from reddish-brown to white indicating the formation of ZnO NPs which shows UV-vis absorption at 361 nm. The various functional groups of the organic compounds present in plant extract act as reducing and stabilizing agents in the formation of nanoparticles. The involvement of these functionalities in the formation of nanoparticles is indicated by the shifts and changes in the IR spectra of both the plant extract and the ZnO nanoparticles. The size of the nanoparticles was determined to be 15.31 nm with XRD analysis while the FE-SEM revealed the average grain size of 67.29 nm with irregular shape. The elemental composition of ZnO NPs shows a greater atomic percentage of zinc compared to other elements (C, N, Ni, O, and Ag), with an intense peak of zinc observed at approximately 1 keV. The trace amount of silver is due to the impurities present in the reagent used in the experiment. The antioxidant property of ZnO nanoparticles was evaluated with an IC₅₀ of 53.02 ± 3.43 μg/mL. The ZnO nanoparticles exhibited significant antibacterial activity against Klebsiella pneumoniae and Escherichia coli , with zones of inhibition (ZOI) of 18 mm and 23 mm, respectively as compared to the positive control neomycin of ZOI 28 mm against K. pneumoniae . The potential antibacterial activity of the ZnO NPS was revealed as the MIC and MBC against K. pneumoniae of 0.39 mg/mL and 0.78 mg/mL, respectively. In addition, the prepared ZnO nanoparticles showed toxicity against brine shrimp nauplii of LC₅₀ 16.59 μg/mL. The results of this study impart that plant-assisted synthesized ZnO nanoparticles possess significant antibacterial properties that reduce oxidative stress in human cells, ultimately contributing to cancer prevention., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Khaga Raj Sharma reports financial support was provided by 10.13039/501100009647University Grants Commission. Khaga raj Sharma reports a relationship with 10.13039/501100009647University Grants Commission that includes: funding grants. Khaga Raj Sharma has patent Not pending to Not. Not any financial support from other institutions support If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Health literacy is crucial in maintaining good health and well-being, yet community-based studies on health literacy in Nepal are scarce. This study aimed to assess the level of health literacy and identify associated factors among adults in Rasuwa, Nepal. A community-based cross-sectional study was conducted among 253 adults aged above 18 years residing in Kalika Rural Municipality, Rasuwa. Data were collected through face-to-face interviews using the Psychometric Assessment of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). Multivariable logistic regression was used to evaluate independent correlates of health literacy levels. The mean ± SD age of participants was 46.3 ± 16 years. Only about a quarter (23.3%) of participants had adequate health literacy. The participants aged ≤ 45 years (aOR:1.9,95% CI: 1.0-3.6), people who perceived their health status as satisfactory (aOR: 3.1,95% CI: 1.5-6.3), had satisfactory self-rated financial status (aOR: 2.9,95% CI: 1.5-5.5), had satisfactory level of self- related esteem (aOR = 2.7,95% CI: 1.2-6.2), had a stable income (aOR = 1.9, 95% CI:1.0-3.5) were more likely to demonstrate adequate health literacy level. Conversely, illiterate participants (aOR: 0.1, 95% CI: 0.04-0.4) and those engaged in agriculture (aOR: 0.49, 95% CI: 0.2-0.9) had lower odds of having adequate health literacy. This study highlights inadequate health literacy status among approximately three-quarters of the participants. Factors such as age, self-rated health status, financial stability, self-esteem, and income were associated with health literacy levels. These findings underscore the importance of addressing socio-economic and individual factors in promoting health literacy initiatives, particularly targeting vulnerable populations, to improve overall health outcomes and healthcare utilization., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Suicide is a major public health concern globally as well as in Nepal. It is important to have baseline data regarding suicide attempts to develop a prevention strategy. This study aims to describe the methodology used to develop a suicide registry and use it to collect data from patient visiting emergency or psychiatric outpatient department with suicide attempts in a tertiary care hospital., Methods: This is a descriptive cross-sectional study conducted retrospectively after obtaining ethical approval (Reference number: drs2005211371) from institutional review committee. Total sampling was done from the database covering the period from October 1, 2017, to September 30, 2023. The database was in the form of suicide registry that was developed after reviewing the existing data of primary health care centres, private hospitals, and tertiary care centers and a series of discussions among mental health experts. Data was entered in Microsoft Excel and analysis was done., Results: Among the 248 patients, there were 109 (43.95%) male and 139 (56.05%) female. There were 209 (84.27%) patients who attempted suicide inside home, poisoning was seen in 90 (36.29%) and 183 (73.79%) had impulsive intention. Out of total patients, 59 (23.79%) had prior communication and 84 (33.87%) had previous attempts, 109 (43.95%) patients had impulsive attempts as diagnosis and 75 (30.24%) had depression., Conclusions: As per the suicide registry, most of the patients attempted suicide inside home and the most common method used was ingestion of poison.

Subarachnoid hemorrhage is a neurological emergency in which arterial blood accumulates in the subarachnoid space with cerebral aneurysmal rupture being the most common cause. Subarachnoid hemorrhage is often misdiagnosed in the emergency department and mortality rates range from 8% to 67%. It may be the manifestation of the chronicity of the migraine. The difference in severity or quality compared to previous headaches, and other symptoms, particularly neck stiffness, but also seizure, syncope, focal neurological deficit, and vomiting are the key factors differentiating subarachnoid hemorrhage from the migraine. We report a case of a 37-year-old female with a previous history of migraines who presented with acute onset of excruciating headaches in the occiput associated with nausea, vomiting, and photophobia in whom a non-contrast computed tomography scan of the head showed hyper-densities involving the bilateral cerebral cortical sulcus and Sylvian fissure and the cerebral angiography showed a complex aneurysm in anterior communicating artery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Breast cancer ranks as the second most prevalent malignancy among women in Nepal. This cancer has a high likelihood of cure, if detected early. Therefore, it is imperative to emphasize awareness and screening for breast cancer in Nepal. It indeed underscores the importance of clinical breast examination. The study aims to find the disease burden, association of abnormal breast condition with sociodemographic variables, and the need for change in the breast cancer screening protocol., Methods: A cross-sectional study was conducted from July to September 2023 on 100 female participants who were older than 18 years. Data were collected through face-to-face interviews using a structured questionnaire. The chi-square test was used to compare nominal variables while the independent sample t -test and the paired sample t -test were used to compare nominal and continuous variables., Results: The findings of the study showed that 19% of all participants complained about abnormal breast, out of which 31.7% reported lumps, 26.31% reported discharge , another 26.31% reported pain, and the remaining 15.7% reported soreness. The upper outer quadrant and lower inner quadrant each individually accounted for 33.33% of the abnormal findings. The complaints of the participants in our study were significantly correlated with age at marriage, number of pregnancies, and use of contraception., Conclusion: Our study revealed considerable abnormal breast findings. This warrants the need for the change in breast cancer screening protocols which lead to early diagnosis and higher curability., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Sangam Shah et al.)

The European honey bee, Apis mellifera, serves as the principle managed pollinator species globally. In recent decades, honey bee populations have been facing serious health threats from combined biotic and abiotic stressors, including diseases, limited nutrition, and agrochemical exposure. Understanding the molecular mechanisms underlying xenobiotic adaptation of A. mellifera is critical, considering its extensive exposure to phytochemicals and agrochemicals present in the environment. In this study, we conducted a comprehensive structural and functional characterization of AmGSTD1, a delta class glutathione S-transferase (GST), to unravel its roles in agrochemical detoxification and antioxidative stress responses. We determined the 3-dimensional (3D) structure of a honey bee GST using protein crystallography for the first time, providing new insights into its molecular structure. Our investigations revealed that AmGSTD1 metabolizes model substrates, including 1-chloro-2,4-dinitrobenzene (CDNB), p-nitrophenyl acetate (PNA), phenylethyl isothiocyanate (PEITC), propyl isothiocyanate (PITC), and the oxidation byproduct 4-hydroxynonenal (HNE). Moreover, we discovered that AmGSTD1 exhibits binding affinity with the fluorophore 8-Anilinonaphthalene-1-sulfonic acid (ANS), which can be inhibited with various herbicides, fungicides, insecticides, and their metabolites. These findings highlight the potential contribution of AmGSTD1 in safeguarding honey bee health against various agrochemicals, while also mitigating oxidative stress resulting from exposure to these substances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The harmful effects of fine particulate matter ≤2.5 µm in size (PM 2.5 ) on human health have received considerable attention. However, while the impact of PM 2.5 on the respiratory and cardiovascular systems has been well studied, less is known about the effects on stem cells in the bone marrow (BM). With an emphasis on the invasive characteristics of PM 2.5 , this review examines the current knowledge of the health effects of PM 2.5 exposure on BM-residing stem cells. Recent studies have shown that PM 2.5 enters the circulation and then travels to distant organs, including the BM, to induce oxidative stress, systemic inflammation and epigenetic changes, resulting in the reduction of BM-residing stem cell survival and function. Understanding the broader health effects of air pollution thus requires an understanding of the invasive characteristics of PM 2.5 and its direct influence on stem cells in the BM. As noted in this review, further studies are needed to elucidate the underlying processes by which PM 2.5 disturbs the BM microenvironment and inhibits stem cell functionality. Strategies to prevent or ameliorate the negative effects of PM 2.5 exposure on BM-residing stem cells and to maintain the regenerative capacity of those cells must also be investigated. By focusing on the complex relationship between PM 2.5 and BM-resident stem cells, this review highlights the importance of specific measures directed at safeguarding human health in the face of rising air pollution., (© 2024. The Author(s).)

Introduction: Dihydropyridines calcium channel blockers at high dose can have conduction abnormalities, reduced inotropism, and non-cardiogenic pulmonary oedema (NCPE) which otherwise, at standard dosage have only vascular selectivity. They remain one of the commonly used anti-hypertensive exhibiting very lethal outcomes (50% mortality rates) in its overdose., Case Presentation: The authors present a case of a 21-year-old male with amlodipine intoxication with 43 tabs of 10 mg (total of 430 mg) ingestion manifested by loss of consciousness, hypotension, tachycardia, and respiratory distress., Discussion: An amlodipine overdose causes refractory hypotension due to vasodilation and impaired cardiac metabolism and contractility. Further amlodipine toxicity can result in NCPE that manifests clinically as respiratory distress and low oxygen levels due to lung injury caused by inflammation and increased vascular permeability., Conclusion: This case report emphasizes the significance of early recognition and prompt treatment of amlodipine intoxication, which can result in serious complications like fluid overload and respiratory distress., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The common bean ( Phaseolus vulgaris L.) is a globally cultivated leguminous crop. Fusarium wilt (FW), caused by Fusarium oxysporum f. sp. phaseoli ( Fop ), is a significant disease leading to substantial yield loss in common beans. Disease-resistant cultivars are recommended to counteract this. The objective of this investigation was to identify single nucleotide polymorphism (SNP) markers associated with FW resistance and to pinpoint potential resistant common bean accessions within a core collection, utilizing a panel of 157 accessions through the Genome-wide association study (GWAS) approach with TASSEL 5 and GAPIT 3. Phenotypes for Fop race 1 and race 4 were matched with genotypic data from 4740 SNPs of BARCBean6K_3 Infinium Bea Chips. After ranking the 157-accession panel and revealing 21 Fusarium wilt-resistant accessions, the GWAS pinpointed 16 SNPs on chromosomes Pv04, Pv05, Pv07, Pv8, and Pv09 linked to Fop race 1 resistance, 23 SNPs on chromosomes Pv03, Pv04, Pv05, Pv07, Pv09, Pv10, and Pv11 associated with Fop race 4 resistance, and 7 SNPs on chromosomes Pv04 and Pv09 correlated with both Fop race 1 and race 4 resistances. Furthermore, within a 30 kb flanking region of these associated SNPs, a total of 17 candidate genes were identified. Some of these genes were annotated as classical disease resistance protein/enzymes, including NB-ARC domain proteins, Leucine-rich repeat protein kinase family proteins, zinc finger family proteins, P-loopcontaining nucleoside triphosphate hydrolase superfamily, etc. Genomic prediction (GP) accuracy for Fop race resistances ranged from 0.26 to 0.55. This study advanced common bean genetic enhancement through marker-assisted selection (MAS) and genomic selection (GS) strategies, paving the way for improved Fop resistance.

Cowpea ( Vigna unguiculata L. Walp., 2 n = 2 x = 22) is a protein-rich crop that complements staple cereals for humans and serves as fodder for livestock. It is widely grown in Africa and other developing countries as the primary source of protein in the diet; therefore, it is necessary to identify the protein-related loci to improve cowpea breeding. In the current study, we conducted a genome-wide association study (GWAS) on 161 cowpea accessions (151 USDA germplasm plus 10 Arkansas breeding lines) with a wide range of seed protein contents (21.8~28.9%) with 110,155 high-quality whole-genome single-nucleotide polymorphisms (SNPs) to identify markers associated with protein content, then performed genomic prediction (GP) for future breeding. A total of seven significant SNP markers were identified using five GWAS models (single-marker regression (SMR), the general linear model (GLM), Mixed Linear Model (MLM), Fixed and Random Model Circulating Probability Unification (FarmCPU), and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK), which are located at the same locus on chromosome 8 for seed protein content. This locus was associated with the gene Vigun08g039200 , which was annotated as the protein of the thioredoxin superfamily, playing a critical function for protein content increase and nutritional quality improvement. In this study, a genomic prediction (GP) approach was employed to assess the accuracy of predicting seed protein content in cowpea. The GP was conducted using cross-prediction with five models, namely ridge regression best linear unbiased prediction (rrBLUP), Bayesian ridge regression (BRR), Bayesian A (BA), Bayesian B (BB), and Bayesian least absolute shrinkage and selection operator (BL), applied to seven random whole genome marker sets with different densities (10 k, 5 k, 2 k, 1 k, 500, 200, and 7), as well as significant markers identified through GWAS. The accuracies of the GP varied between 42.9% and 52.1% across the seven SNPs considered, depending on the model used. These findings not only have the potential to expedite the breeding cycle through early prediction of individual performance prior to phenotyping, but also offer practical implications for cowpea breeding programs striving to enhance seed protein content and nutritional quality.

Research on the negative impacts of PM 2.5 have been focused on lung, brain, immune, and metabolism-related diseases. However, little is known about the mechanism underlying the effects of PM 2.5 on the modulation of hematopoietic stem cell (HSC) fate. Maturation of the hematopoietic system and differentiation of hematopoietic stem progenitor cells (HSPCs) occurs soon after birth when infants are susceptible to external stresses. We investigated how exposure to atmospherically relevant artificial particulate matter of diameter < 2.5 µm (termed, PM 2.5 ) affects HSPCs in newborns. The lungs of newborn mice exposed to PM 2.5 exhibited higher levels of oxidative stress and inflammasome activation, which continued during aging. PM 2.5 also stimulated oxidative stress and inflammasome activation in bone marrow (BM). PM 2.5 -exposed infant mice at 12 months but not at 6 months displayed progressive senescence of HSCs accompanied by preferential impairment of the BM microenvironment with age-related phenotypes, as evidenced by colony-forming assay and serial transplantation and animal survival experiments. Further, PM 2.5 -exposed middle-aged mice did not exhibit radioprotective potential. Collectively, exposure of newborns to PM 2.5 causes progressive senescence of HSCs. These findings revealed a novel mechanism by which PM 2.5 affects the fate of HSCs, highlighting the crucial role of early life exposure to air pollution in determining human health outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Ionizing irradiation (IR) causes bone marrow (BM) injury, with senescence and impaired self-renewal of hematopoietic stem cells (HSCs), and inhibiting Wnt signaling could enhance hematopoietic regeneration and survival against IR stress. However, the underlying mechanisms by which a Wnt signaling blockade modulates IR-mediated damage of BM HSCs and mesenchymal stem cells (MSCs) are not yet completely understood. We investigated the effects of osteoblastic Wntless (Wls) depletion on total body irradiation (TBI, 5 Gy)-induced impairments in hematopoietic development, MSC function, and the BM microenvironment using conditional Wls knockout mutant mice (Col-Cre;Wls fl/fl ) and their littermate controls (Wls fl/fl ). Osteoblastic Wls ablation itself did not dysregulate BM frequency or hematopoietic development at a young age. Exposure to TBI at 4 weeks of age induced severe oxidative stress and senescence in the BM HSCs of Wls fl/fl mice but not in those of the Col-Cre;Wls fl/fl mice. TBI-exposed Wls fl/fl mice exhibited greater impairments in hematopoietic development, colony formation, and long-term repopulation than TBI-exposed Col-Cre;Wls fl/fl mice. Transplantation with BM HSCs or whole BM cells derived from the mutant, but not Wls fl/fl mice, protected against HSC senescence and hematopoietic skewing toward myeloid cells and enhanced survival in recipients of lethal TBI (10 Gy). Unlike the Wls fl/fl mice, the Col-Cre;Wls fl/fl mice also showed radioprotection against TBI-mediated MSC senescence, bone mass loss, and delayed body growth. Our results indicate that osteoblastic Wls ablation renders BM-conserved stem cells resistant to TBI-mediated oxidative injuries. Overall, our findings show that inhibiting osteoblastic Wnt signaling promotes hematopoietic radioprotection and regeneration.

The combination of scaffolds with recombinant human epidermal growth factor (rhEGF) protein can enhance defective bone healing via synergistic activation to stimulate cellular growth, differentiation, and survival. We examined the biopotentials of an rhEGF-loaded absorbable collagen scaffold (ACS) using a mouse model of calvarial defects, in which the rhEGF was produced from a plant cell suspension culture system because of several systemic advantages. Here, we showed a successful and large-scale production of plant-cell-derived rhEGF protein (p-rhEGF) by introducing an expression vector that cloned with its cDNA under the control of rice α-amylase 3D promoter into rice calli ( Oryza sativa L. cv. Dongjin). Implantation with p-rhEGF (5 μg)-loaded ACSs into critical-sized calvarial defects enhanced new bone formation and the expression of osteoblast-specific markers in the defected regions greater than implantation with ACSs alone did. The potency of p-rhEGF-induced bone healing was comparable with that of Escherichia coli -derived rhEGF protein. The exogenous addition of p-rhEGF increased the proliferation of human periodontal ligament cells and augmented the induction of interleukin 8, bone morphogenetic protein 2, and vascular endothelial growth factor in the cells. Collectively, this study demonstrates the successful and convenient production of p-rhEGF, as well as its potency to enhance ACS-mediated bone regeneration by activating cellular responses that are required for wound healing.

Commercial production of spinach ( Spinacia oleracea L.) is centered in California and Arizona in the US, where downy mildew caused by Peronospora effusa is the most destructive disease. Nineteen typical races of P. effusa have been reported to infect spinach, with 16 identified after 1990. The regular appearance of new pathogen races breaks the resistance gene introgressed in spinach. We attempted to map and delineate the RPF2 locus at a finer resolution, identify linked single nucleotide polymorphism (SNP) markers, and report candidate downy mildew resistance ( R ) genes. Progeny populations segregating for RPF2 locus derived from resistant differential cultivar Lazio were infected using race 5 of P. effusa and were used to study for genetic transmission and mapping analysis in this study. Association analysis performed with low coverage whole genome resequencing-generated SNP markers mapped the RPF2 locus between 0.47 to 1.46 Mb of chromosome 3 with peak SNP (Chr3&#95;1, 221, 009) showing a LOD value of 61.6 in the GLM model in TASSEL, which was within 1.08 Kb from Spo12821, a gene that encodes CC-NBS-LRR plant disease resistance protein. In addition, a combined analysis of progeny panels of Lazio and Whale segregating for RPF2 and RPF3 loci delineated the resistance section in chromosome 3 between 1.18-1.23 and 1.75-1.76 Mb. This study provides valuable information on the RPF2 resistance region in the spinach cultivar Lazio compared to RPF3 loci in the cultivar Whale. The RPF2 and RPF3 specific SNP markers, plus the resistant genes reported here, could add value to breeding efforts to develop downy mildew resistant cultivars in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press.)

Studies of PrP C -derived prion disease generally focus on neurodegeneration. However, little is known regarding the modulation of hematopoietic stem progenitor cells (HSPCs) that express PrP C in prion infection. Among bone marrow (BM) hematopoietic cells, hematopoietic stem cells (HSCs) strongly express PrP C . A bioassay revealed the presence of misfolded prion protein (PrP Sc ) in BM cells derived from prion-infected mice; these BM cells demonstrated reproducible prion infectivity. At 5 months after infection with ME7, mice exhibited a significant decrease in the number of HSPCs. This decrease was mainly driven by increased apoptotic cell death, rather than cell cycle progression and senescence, in PrP C -positive but not PrP C -negative HSPC populations through a cell-autonomous mechanism. Notably, both PrP C -positive and PrP C -negative HSCs underwent cellular senescence, as indicated by high levels of senescence-associated factors and deficits in repopulation and self-renewal capacities at 7 months after infection. Senescence of HSCs occurred in the ME7-impaired BM microenvironment with aging phenotypes through non-cell autonomous mechanisms. These data provide novel evidence that prion infection differentially modulates HSC fate through both cell-autonomous and non-autonomous mechanisms., (© 2023. The Author(s).)