Dietary manganese supplementation decreases hepatic lipid deposition by regulating gene expression and enzyme activity involved in lipid metabolism in the liver of broilers.

This study aimed to characterize the effects of different dietary forms of supplemental manganese (Mn) on hepatic lipid deposition, gene expression, and enzyme activity in liver fat metabolism in 42-day-old broiler chickens. In total 420 one day-old Arbor Acres (AA) broilers (rooster: hen = 1:1) were assigned randomly based on body weight and sex to one of six treatments (ten replicate cages per treatment and seven broilers per replicate cage) in a completely randomized design using a 2 (sex) × 3 (diet) factorial arrangement. The three diets were basal control diets without Mn supplementation and basal diets supplemented with either Mn sulfate or Mn proteinate. No sex × diet interactions were observed in any of the measured indexes; thus, the effect of diet alone was presented in this study. Dietary Mn supplementation increased Mn content in the plasma and liver, adipose triglyceride lipase (ATGL) activity, and ATGL mRNA and its protein expression in the liver by 5.3%-24.0% (P < 0.05), but reduced plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels, liver TG content, fatty acid synthase (FAS) and malic enzyme (ME) activities, mRNA expression of sterol regulatory element-binding protein 1 (SREBP1), FAS, stearoyl-coA desaturase (SCD), and ME, as well as the protein expression of SREBP1 and SCD in the liver by 5.5%-22.8% (P < 0.05). No differences were observed between the two Mn sources in all of the determined parameters. Therefore, it was concluded that dietary Mn supplementation, regardless of Mn source, decreased hepatic lipid accumulation in broilers by inhibiting SREBP1 and SCD expression, FAS and ME activities, and enhancing ATGL expression and activity.

Occurrence, distribution, and genetic diversity of faba bean viruses in China.

With worldwide cultivation, the faba bean (Vicia faba L.) stands as one of the most vital cool-season legume crops, serving as a major component of food security. China leads global faba bean production in terms of both total planting area and yield, with major production hubs in Yunnan, Sichuan, Jiangsu, and Gansu provinces. The faba bean viruses have caused serious yield losses in these production areas, but previous researches have not comprehensively investigated this issue. In this study, we collected 287 faba bean samples over three consecutive years from eight provinces/municipalities of China. We employed small RNA sequencing, RT-PCR, DNA sequencing, and phylogenetic analysis to detect the presence of viruses and examine their incidence, distribution, and genetic diversity. We identified a total of nine distinct viruses: bean yellow mosaic virus (BYMV, Potyvirus), milk vetch dwarf virus (MDV, Nanovirus), vicia cryptic virus (VCV, Alphapartitivirus), bean common mosaic virus (BCMV, Potyvirus), beet western yellows virus (BWYV, Polerovirus), broad bean wilt virus (BBWV, Fabavirus), soybean mosaic virus (SMV, Potyvirus), pea seed-borne mosaic virus (PSbMV, Potyvirus), and cucumber mosaic virus (CMV, Cucumovirus). BYMV was the predominant virus found during our sampling, followed by MDV and VCV. This study marks the first reported detection of BCMV in Chinese faba bean fields. Except for several isolates from Gansu and Yunnan provinces, our sequence analysis revealed that the majority of BYMV isolates contain highly conserved nucleotide sequences of coat protein (CP). Amino acid sequence alignment indicates that there is a conserved NAG motif at the N-terminal region of BYMV CP, which is considered important for aphid transmission. Our findings not only highlight the presence and diversity of pathogenic viruses in Chinese faba bean production, but also provide target pathogens for future antiviral resource screening and a basis for antiviral breeding.

Zinc proteinate with moderate chelation strength enhances zinc absorption by up-regulating the expression of zinc and amino acid transporters in primary cultured duodenal epithelial cells of broiler embryos.

Recent study showed that zinc (Zn) and amino acid transporters may be involved in enhancing Zn absorption from Zn proteinate with moderate chelation strength (Zn-Prot M) in the duodenum of broilers. However, the specific mechanisms by which Zn-Prot M promotes the above Zn absorption are unknown. Therefore, in this study, three experiments were conducted to investigate specific and direct effects of Zn-Prot M and Zn sulfate (ZnS) on Zn absorption and expression of related transporters in primary duodenal epithelial cells of broiler embryos so as to preliminarily address possible mechanisms. In experiment 1, cells were treated with 100 µmol Zn/L as ZnS or Zn-Prot M for 20, 40, 60, 80, 100 or 120 min. Experiment 2 consisted of 3 sub-experiments. In experiment 2A, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 100 or 200 µmol Zn/L as ZnS or Zn-Prot M for 60 min; in experiment 2B, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 200 µmol Zn/L of as the ZnS or Zn-Prot M for 120 min; in experiment 2C, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 or 800 µmol Zn/L as ZnS or Zn-Prot M for 120 min. In experiment 3, cells were treated with a Zn-unsupplemented basal medium (Control) or the basal medium supplemented with 400 µmol Zn/L as ZnS or Zn-Prot M for 120 min. The results of experiment 1 indicated that the minimum incubation time for saturable Zn absorption was determined to be 50.83 min using the best fit line. The results in experiment 2 demonstrated that a Zn concentration of 400 µmol/L and an incubation time of 120 min were suitable to increase the absorption of Zn from Zn-Prot M compared to ZnS. In experiment 3, Zn absorption across cell monolayers was significantly increased by Zn addition (P < 0.05), and was significantly greater with Zn-Prot M than with ZnS (P < 0.05). Compared to the control, Zn addition significantly decreased Zn transporter 10 and peptide-transporter 1 mRNA expression levels and increased y+L-type amino transporter 2 (y+LAT2) protein abundance (P < 0.05). Moreover, protein expression levels of zrt/irt-like protein 3 (ZIP3), ZIP5 and y+LAT2 were significantly greater for Zn-Prot M than for ZnS (P < 0.05). These findings suggest that Zn-Prot M promote Zn absorption by increasing ZIP3, ZIP5 and y+LAT2 protein expression levels in primary duodenal epithelial cells.

Navigating Both Roles: A Photovoice Exploration of the Young Adult Balancing Daughterhood and Caregiving for a Mother With Young-Onset Dementia.

Young adults thrust into the role of caregiving for parents with young-onset dementia (YOD) face unique challenges during their formative years. While existing research acknowledges the crucial role of young adult caregivers, a gap persists in understanding how this group experiences and redefines their identity amidst these circumstances, along with the psychological and societal challenges encountered. This knowledge deficit hinders the identification of suitable social support, adversely affecting the personal growth and well-being of these young adult caregivers. In this single-case study, we used a combination of a semi-structured interview and photovoice to explore the journey of a 19-year-old caregiver, Alice, whose mother had been diagnosed with dementia in the preceding 3 years. Through this unique perspective, we aimed to illuminate how caregiving for a mother with YOD may profoundly redefine familial roles and relationships. Over 3 months, Alice captured significant life moments through photography, selecting meaningful images for bi-weekly meetings. These images served as pivotal themes, triggering in-depth conversations during subsequent interviews to provide nuanced insights into her life experiences. Findings reveal four major themes faced by a young caregiver: (1) challenges adapting to an unexpected role, (2) navigating the complex emotional terrain of losing a loved one to YOD, (3) prioritizing the well-being of the healthy parent, and (4) expressing a profound desire for both informal and formal support. These results underscore the intricate identity and emotional challenges faced by young adult caregivers, emphasizing the urgency of addressing their unique needs through family-centered systemic support services.

The vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans.

The transition between yeast and hyphae is crucial for regulating the commensalism and pathogenicity in Candida albicans. The mechanisms that affect the invasion of hyphae in solid media, whose deficiency is more related to the pathogenicity of C. albicans, have not been elucidated. Here, we found that the disruption of VAM6 or VPS41 which are components of the homotypic vacuolar fusion and protein sorting (HOPS) complex, or the Rab GTPase YPT72, all responsible for vacuole fusion, led to defects in hyphal growth in both liquid and solid media, but more pronounced on solid agar. The phenotypes of vac8Δ/Δ and GTR1OE-vam6Δ/Δ mutants indicated that these deficiencies are mainly caused by the reduced mechanical forces that drive agar and organs penetration, and confirmed that large vacuoles are required for hyphal mechanical penetration. In summary, our study revealed that large vacuoles generated by vacuolar fusion support hyphal penetration and provided a perspective to refocus attention on the role of solid agar in evaluating C. albicans invasion.

The analysis of factors affecting medication adherence in patients with myasthenia gravis: a cross-sectional study.

Background: Clinically, patients with myasthenia gravis are generally treated with drugs to improve their physical condition, and poor medication adherence can hinder their recovery. Many studies have shown the importance of medication adherence for effective treatment. Various factors may affect a patient's medication adherence; however, studies concerning medication adherence in patients with myasthenia gravis are rare. Objectives: This study aimed to identify the factors related to medication adherence in patients with myasthenia gravis, and determine the possibility of predicting medication adherence. Methods: This cross-sectional observational study was conducted among inpatients and outpatients with myasthenia gravis of the First Affiliated Hospital of Guangzhou University of Chinese Medicine in China. Data on patient demographics, disease-related characteristics, and medical treatment were collected. We evaluated medication adherence of the patients using the Morisky Medication Adherence Scale-8, Beliefs about Medicines Questionnaire, and the Self-efficacy for Appropriate Medication Use Scale. Results: We distributed 200 questionnaires and finally retrieved 198 valid questionnaires. A total of 139 (70.2%) women participated in this study, and 81 (40.9%) among the 198 participants were aged 40-59 years. In total, 103 (52.0%) participants exhibited bad adherence to pharmacological treatment, and factors such as taking medication irregularly [odds ratio (OR) = 0.242, 95% CI = 0.093-0.627], the necessity of taking medicine (OR = 1.286, 95% CI = 1.142-1.449), the concerns of taking medicine (OR = 0.890, 95% CI = 0.801-0.988), and the self-efficacy for taking medications under difficult circumstances (OR = 1.194, 95% CI = 1.026-1.389) had statistically significant impacts on medication adherence. Conclusion: Our study shows that taking medication irregularly and concerns of taking medicine are the risk factors for medication adherence. Meanwhile, the necessity of talking medicine and self-efficacy for taking medications under difficult circumstances are the protective factors for medication adherence. Our findings can help medical staff to enhance patients' medication adherence by informing patients necessary medical knowledge, emphasizing the necessity for medication, relieving patients' concerns regarding medication, and improving the self-efficacy for taking medications under difficult circumstances.

Dietary Zn Deficiency Inhibits Cell Proliferation via the GPR39-Mediated Suppression of the PI3K/AKT/mTOR Signaling Pathway in the Jejunum of Broilers.

A prior investigation revealed that a lack of Zinc (Zn) could hinder intestinal cell proliferation in broiler chickens; however, the mechanisms responsible for this effect remain unclear. We aimed to investigate the possible mechanisms of dietary Zn deficiency in inhibiting the jejunal cell proliferation of broilers. For this study, a total of 112 chickens (21 days old) were randomly divided into two treatments (seven replicate cages per treatment, eight chickens per replicate cage): the control group (CON) and the Zn deficiency group. The duration of feeding was 21 d. Chickens in the control group were provided with a basal diet containing an extra addition of 40 mg Zn/kg in the form of Zn sulfate, whereas chickens in the Zn deficiency group were given the basal diet with no Zn supplementation. The results indicated that, in comparison to the CON, Zn deficiency increased (p < 0.05) the duodenal and jejunal crypt depth (CD) of broilers on d 28 and jejunal and ileal CD on d 35, and decreased (p < 0.05) the duodenal, jejunal, and ileal villus height/crypt depth (VH/CD) on d 28 and the jejunal VH, jejunal and ileal villus surface area, and VH/CD on d 35. Furthermore, Zn deficiency decreased (p < 0.0001) the number of proliferating cell nuclear antigen-positive cells and downregulated (p < 0.01) the mRNA or protein expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K, phosphorylated serine-threonine kinase (AKT), phosphorylated mechanistic target of rapamycin (mTOR), G protein-coupled receptor 39 (GPR39), and extracellular-regulated protein kinase, but upregulated (p < 0.05) the mRNA or protein expression levels of P38 mitogen-activated protein kinase, c-jun N-terminal kinase (JNK) 1 and JNK2, and phosphorylated protein kinase C in the jejunum of the broilers on d 42. It was concluded that dietary Zn deficiency inhibited cell proliferation possibly via the GPR39-mediated suppression of the PI3K/AKT/mTOR signaling pathway in the jejunum of broilers.

Research progress on the biological regulatory mechanisms of selenium on skeletal muscle in broilers.

As one of the indispensable trace elements for both humans and animals, selenium widely participates in multiple physiological processes and facilitates strong anti-inflammatory, antioxidant, and immune enhancing abilities. The biological functions of selenium are primarily driven by its presence in selenoproteins as a form of selenocysteine. Broilers are highly sensitive to selenium intake. Recent reports have demonstrated that selenium deficiency can adversely affect the quality of skeletal muscles and the economic value of broilers; the regulatory roles of several key selenoproteins (e.g., GPX1, GPX4, TXNRD1, TXNRD3, SelK, SelT, and SelW) have been identified. Starting from the selenium metabolism and its biological utilization in the skeletal muscle, the effect of the selenium antioxidant function on broiler meat quality is discussed in detail. The progress of research into the prevention of skeletal muscle injury by selenium and selenoproteins is also summarized. The findings emphasize the necessity of in vivo and in vitro research, and certain mechanism problems are identified, which aids their further examination. This mini-review will be helpful to provide a theoretical basis for the further study of regulatory mechanisms of selenium nutrition in edible poultry.

Function of autophagy genes in innate immune defense against mucosal pathogens.

Mucosal immunity is posed to constantly interact with commensal microbes and invading pathogens. As a fundamental cell biological pathway affecting immune response, autophagy regulates the interaction between mucosal immunity and microbes through multiple mechanisms, including direct elimination of microbes, control of inflammation, antigen presentation and lymphocyte homeostasis, and secretion of immune mediators. Some of these physiologically important functions do not involve canonical degradative autophagy but rely on certain autophagy genes and their 'autophagy gene-specific functions.' Here, we review the relationship between autophagy and important mucosal pathogens, including influenza virus, Mycobacterium tuberculosis, Salmonella enterica, Citrobacter rodentium, norovirus, and herpes simplex virus, with a particular focus on distinguishing the canonical versus gene-specific mechanisms of autophagy genes.

Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice.

Although autophagy sequesters Mycobacterium tuberculosis (Mtb) in in vitro cultured macrophages, loss of autophagy in macrophages in vivo does not result in susceptibility to a standard low-dose Mtb infection until late during infection, leaving open questions regarding the protective role of autophagy during Mtb infection. Here we report that loss of autophagy in lung macrophages and dendritic cells results in acute susceptibility of mice to high-dose Mtb infection, a model mimicking active tuberculosis. Rather than observing a role for autophagy in controlling Mtb replication in macrophages, we find that autophagy suppresses macrophage responses to Mtb that otherwise result in accumulation of myeloid-derived suppressor cells and subsequent defects in T cell responses. Our finding that the pathogen-plus-susceptibility gene interaction is dependent on dose has important implications both for understanding how Mtb infections in humans lead to a spectrum of outcomes and for the potential use of autophagy modulators in clinical medicine.

Dietary copper requirement of broilers fed a corn-soybean meal diet during 22-42 d of age.

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22-42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P < 0.05) by supplemental Cu levels, and the above indices varied linearly and quadratically (P < 0.05) with increasing Cu levels. Dietary Cu requirements assessed according to the best fitted broken-line models (P < 0.05) of the above indexes were 10.45-13.81 mg/kg. It was concluded that mRNA expression levels of CuZnSOD in liver and MAO B in heart, as well as liver CuZnSOD protein expression level were new specific sensitive biomarkers for estimating dietary Cu requirements, and the dietary Cu requirement was recommended to be 14 mg/kg to support Cu metabolic needs related to key Cu-containing enzymes in broilers fed the corn-soybean meal diet during 22-42 d of age, which was higher than the dietary Cu requirement (8 mg/kg) for broilers at the corresponding stage suggested by the Chinese Feeding Standard of Chicken.

BODIPY-Based NIR Trackers with Acidity-Driven Amphiphilicity for STED Super-Resolution Imaging of Lysosomal Membranes.

Although super-resolution imaging provides a great opportunity to disclose the structures of living cells at the nanoscale level, resolving the structural details of organelles is highly dependent on the targeting accuracy and photophysical properties of fluorescence trackers. Herein, we report a series of ultrabright and photostable trackers of lysosomal membranes for super-resolution imaging using stimulated emission depletion microscopy (STED). These trackers are composed of lipophilic NIR BODIPY derivatives and ionizable tertiary amines. This structural feature enables accurate targeting of the lysosomal membrane through the formation of transient amphiphilicity driven by the acidity in the lysosome. As a representative, Lyso-700 is applied for STED-based super-resolution imaging of the lysosomal membrane of living macrophages. By use of Lyso-700, the interaction details between lysosomes of macrophages and fungi are visualized. Overall, these trackers display great potential as advanced lysosome trackers and merit further evaluation for lysosome-related studies.

Interventions for Persons with Young-Onset Dementia and Their Families: A Scoping Review.

Background: Dementia occurring before age 65 is known as young-onset dementia (YOD), with Alzheimer's disease being the most common type. YOD poses unique challenges for persons and families, impacting their working-age years and family responsibilities. Person-centered interventions and services are essential to improve their quality of life and social engagement. Objective: This study aims to synthesize non-pharmacological interventions for persons with YOD and their families to inform future targeted interventions. Methods: We conducted a systematic literature search across four databases: PubMed, PsycINFO, Scopus, and CINAHL. The included articles were carefully screened, categorized, and synthesized by following Arksey and O'Malley's five stages framework. Results: We included 20 studies reported in 24 papers, with 11 studies (14 papers) on persons with YOD and nine studies (10 papers) on families. Quantitative intervention results vary, but qualitative interviews show positive feedback. Stakeholders provided positive evaluations, stating these interventions provided a sense of normalcy, facilitated communication among families, enhanced the independence of persons with YOD, and improved the families' caregiving self-efficacy, thereby reducing care burden and psychological distress. The heterogeneity among the studies posed integration challenges. Conclusions: Interventions for YOD can improve the quality of life for both persons with YOD and their families. More extensive intervention studies are urgently needed, especially in developing countries, with a focus on family-centered and life course perspectives. In future intervention research design, a more extensive incorporation of stakeholder involvement is essential for successful implementation. Moreover, the integration of new technologies shows promise as a potential avenue for intervention advancement.

The chemical characteristics of different sodium iron ethylenediaminetetraacetate sources and their relative bioavailabilities for broilers fed with a conventional corn-soybean meal diet.

BACKGROUND: Our previous studies demonstrated that divalent organic iron (Fe) proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation (Qf) values displayed higher Fe bioavailabilities for broilers. Sodium iron ethylenediaminetetraacetate (NaFeEDTA) is a trivalent organic Fe source with the strongest chelating ligand EDTA. However, the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains untested. Herein, the chemical characteristics of 12 NaFeEDTA products were determined. Of these, one feed grade NaFeEDTA (Qf = 2.07 × 108), one food grade NaFeEDTA (Qf = 3.31 × 108), and one Fe proteinate with an extremely strong chelation strength (Fe-Prot ES, Qf value = 8,590) were selected. Their bioavailabilities relative to Fe sulfate (FeSO4·7H2O) for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance, hematological indices, Fe contents, activities and gene expressions of Fe-containing enzymes in various tissues of broilers. RESULTS: NaFeEDTA sources varied greatly in their chemical characteristics. Plasma Fe concentration (PI), transferrin saturation (TS), liver Fe content, succinate dehydrogenase (SDH) activities in liver, heart, and kidney, catalase (CAT) activity in liver, and SDH mRNA expressions in liver and kidney increased linearly (P < 0.05) with increasing levels of Fe supplementation. However, differences among Fe sources were detected (P < 0.05) only for PI, liver Fe content, CAT activity in liver, SDH activities in heart and kidney, and SDH mRNA expressions in liver and kidney. Based on slope ratios from multiple linear regressions of the above indices on daily dietary analyzed Fe intake, the average bioavailabilities of Fe-Prot ES, feed grade NaFeEDTA, and food grade NaFeEDTA relative to the inorganic FeSO4·7H2O (100%) for broilers were 139%, 155%, and 166%, respectively. CONCLUSIONS: The bioavailabilities of organic Fe sources relative to FeSO4·7H2O were closely related to their Qf values, and NaFeEDTA sources with higher Qf values showed higher Fe bioavailabilities for broilers fed with a conventional corn-soybean meal diet.