SGMS1 facilitates osteogenic differentiation of MSCs and strengthens osteogenesis-angiogenesis coupling by modulating Cer/PP2A/Akt pathway.

Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.

HyperTMO: a trusted multi-omics integration framework based on hypergraph convolutional network for patient classification.

MOTIVATION: The rapid development of high-throughput biomedical technologies can provide researchers with detailed multi-omics data. The multi-omics integrated analysis approach based on machine learning contributes a more comprehensive perspective to human disease research. However, there are still significant challenges in representing single-omics data and integrating multi-omics information. RESULTS: This article presents HyperTMO, a Trusted Multi-Omics integration framework based on Hypergraph convolutional network for patient classification. HyperTMO constructs hypergraph structures to represent the association between samples in single-omics data, then evidence extraction is performed by hypergraph convolutional network, and multi-omics information is integrated at an evidence level. Last, we experimentally demonstrate that HyperTMO outperforms other state-of-the-art methods in breast cancer subtype classification and Alzheimer's disease classification tasks using multi-omics data from TCGA (BRCA) and ROSMAP datasets. Importantly, HyperTMO is the first attempt to integrate hypergraph structure, evidence theory, and multi-omics integration for patient classification. Its accurate and robust properties bring great potential for applications in clinical diagnosis. AVAILABILITY AND IMPLEMENTATION: HyperTMO and datasets are publicly available at https://github.com/ippousyuga/HyperTMO.

Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases.

BACKGROUND: In this study, we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis (LN) who underwent repeated renal biopsy. CASE SUMMARY: Clinical data of three diffuse proliferative LN patients with different pathological characteristics (case 1 was LN IV-G (A), case 2 was LN IV-G (A) + V, and case 3 was LN IV-G (A) + thrombotic microangiopathy) were reviewed. All patients underwent repeated renal biopsies 6 mo later, and renal biopsy specimens were studied. Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining, and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage. After treatment, Case 1 changed to LN III-(A), Case 2 remained as type V LN lesions, and Case 3, which changed to LN IV-S (A), had the worst prognosis. We observed reduced macrophage infiltration after therapy. However, two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium. Before treatment, the three patients showed discontinuous expression of podocin. Notably, the integrity of podocin was restored after treatment in Case 1. CONCLUSION: It may be possible to reverse podocyte damage and decrease the infiltrating macrophages in LN patients through effective treatment.

Plastid genomes provide insights into the phylogeny and chloroplast evolution of the paper daisy tribe Gnaphalieae (Asteraceae).

Chloroplast genomes, as an essential source of phylogenetic information, are increasingly utilized in the evolutionary study of angiosperms. Gnaphalieae is a medium-sized tribe of the sunflower family of Asteraceae, with about 2,100 species in 178 genera distributed in temperate habitats worldwide. There has been considerable progress in our understanding of their phylogenetic evolution using both nuclear and chloroplast sequences, but no focus on chloroplast genomic data. In this study, we performed sequencing, assembly, and annotation of 16 representative chloroplast genomes from all the major lineages of Gnaphalieae. Our results showed that the plastomes exhibited a typical circular tetrad structure with similar genomic structure gene content. But there were differences in genome size, SSRs, and codon usage within the tribe. Phylogenetic analysis revealed Relhania clade is the earliest diverged lineages with the Lasiopogon clade and the Gnaphalium s.s. clade diverged subsequently. The core group includes FLAG clade sister to the HAP and Australasian group. Compared with the outgroup species, chloroplast genome size of the FLAG clade is much reduced whereas those of Australasian, HAP, Gnaphalium s.s., Lasiopogon and Relhania clades are relatively expanded. Insertions and deletions in the intergenic regions associated with repetitive sequence variations are supposed to be the main factor leading to length variations in the chloroplast genomes of Gnaphalieae. The comparative analyses of chloroplast genomes would provide useful implications into understanding the taxonomic and evolutionary history of Gnaphalieae.

Distinctive biochemistry profiles associated with hyperuricemia between Tibetans and Hans in China.

Purpose: We sought to identify distinct risk factors for hyperuricemia in native Tibetan and immigrant Han populations in Tibet, China. Methods: Three cohorts of male participants aged between 20 and 40 years were enrolled in this study. Biochemical parameters including serum uric acid (UA), fasting plasma glucose, insulin, lactate dehydrogenase (LDH), thyroxin, blood cell count, aminotransferase, and lipid profiles were analyzed. The association of risk factors with UA levels was evaluated using a multivariable line regression model. The effect of UA level on the biochemical parameters between the Hans and Tibetans was evaluated by two-way ANOVA. Results: The prevalence of hyperuricemia (≥420 µmol/L) was 24.8% (62/250) in the Hans, similar to 23.8% (29/136) in the Tibetans. In the regression analysis, the risk factors that were significantly associated with UA in Hans did not apply to Tibetans. Tibetans had higher fasting insulin (P<0.05) and LDH (P<0.01) levels, in contrast with lower levels of triglycerides (P<0.05), total cholesterol (P<0.01), and low-density lipoprotein-cholesterol (P<0.01) than Hans in normal UA populations. Biochemistry analysis revealed lower albumin levels (P<0.001) and higher levels of all aminotransaminase and especially alkaline phosphatase (P<0.01) in Tibetans than in Hans in both populations. Compared with Hans, Tibetans had lower serum levels of urea, creatinine, and electrolytes in the normal UA population, which were further exacerbated in the high UA population. Tibetans had comparable white blood cell counts as Hans in both normal and high UA populations. In contrast, the red blood cell count and hemoglobin concentration were much lower in Tibetans than in Hans under high UA conditions. Conclusions: The distinctive biochemistry between Tibetans and Hans may underlie the different etiologies of hyperuricemia in Tibet, China.

Structural variants involved in high-altitude adaptation detected using single-molecule long-read sequencing.

Structural variants (SVs), accounting for a larger fraction of the genome than SNPs/InDels, are an important pool of genetic variation, enabling environmental adaptations. Here, we perform long-read sequencing data of 320 Tibetan and Han samples and show that SVs are highly involved in high-altitude adaptation. We expand the landscape of global SVs, apply robust models of selection and population differentiation combining SVs, SNPs and InDels, and use epigenomic analyses to predict enhancers, target genes and biological functions. We reveal diverse Tibetan-specific SVs affecting the regulatory circuitry of biological functions, including the hypoxia response, energy metabolism and pulmonary function. We find a Tibetan-specific deletion disrupts a super-enhancer and downregulates EPAS1 using enhancer reporter, cellular knock-out and DNA pull-down assays. Our study expands the global SV landscape, reveals the role of gene-regulatory circuitry rewiring in human adaptation, and illustrates the diverse functional roles of SVs in human biology.

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway.

Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

Chitosan Derivative-Based Microspheres Loaded with Fibroblast Growth Factor for the Treatment of Diabetes.

Diabetes mellitus type 2 (T2DM) is a disease caused by genetic and environmental factors, and the main clinical manifestation is hyperglycemia. Currently, insulin injections are still the first-line treatment for diabetes. However, repeated injections may cause insulin resistance, hypoglycemia, and other serious side effects. Thus, it is imperative to develop new diabetes treatments. Protein-based diabetes drugs, such as fibroblast growth factor-21 (FGF-21), have a longer-lasting glycemic modulating effect with high biosafety. However, the instability of these protein drugs limits their applications. In this study, we extract protein hypoglycemic drugs with oral and injectable functions. The FGF-21 analog (NA-FGF) was loaded into the chitosan derivative-based nanomaterials, N-2-Hydroxypropyl trimethyl ammonium chloride chitosan/carboxymethyl chitosan (N-2-HACC/CMCS), to prepare NA-FGF-loaded N-2-HACC/CMCS microspheres (NA-FGF-N-2-HACC/CMCS MPs). It was well demonstrated that NA-FGF-N-2-HACC/CMCS MPs have great biocompatibility, biostability, and durable drug-release ability. In addition to injectable drug delivery, our prepared microspheres were highly advantageous for oral administration. The in vitro and in vivo experimental results suggested that NA-FGF-N-2-HACC/CMCS MPs could be used as a promising candidate and universal nano-delivery system for both oral and injectable hypoglycemic regulation.

Specific dilation pattern in placental circulation and the NO/sGC role in preeclampsia placental vessels.

Objective: Endothelial functions in controlling blood flow in placental circulation are still unclear. The present study compares vascular dilations between placental circulation and other vessels, as well as between normal and preeclampsia placental vessels. Methods: Placental, umbilical, and other vessels (cerebral and mesenteric arteries) were collected from humans, sheep, and rats. Vasodilation was tested by JZ101 and DMT. Q-PCR, Western blot, and Elisa were used for molecular experiments. Results: Endothelium-dependent/derived vasodilators, including acetylcholine, bradykinin, prostacyclin, and histamine, mediated no or minimal dilation in placental circulation, which was different from that in other vessels in sheep and rats. There were lower mRNA expressions of muscarinic receptors, histamine receptors, bradykinin receptor 2, endothelial nitric oxide synthesis (eNOS), and less nitric oxide (NO) in human umbilical vessels when compared with placental vessels. Exogenous NO donors (sodium nitroprusside, SNP) and soluble guanylate cyclase (sGC) activators (Bay41-2272) decreased the baseline of vessel tone in placental circulation in humans, sheep, and rats, but not in other arteries. The sGC inhibitor ODQ suppressed the reduced baseline caused by the SNP. The decreased baseline by SNP or Bay41-2272 was higher in placental vessels than in umbilical vessels, suggesting that the role of NO/sGC is more important in the placenta. NO concentrations in preeclampsia placental vessels were lower than those in control, while no significant change was found in umbilical plasma between the two groups. eNOS expression was similar between normal and preeclampsia placental vessels, but phosphorylated eNOS levels were significantly lower in preeclampsia. Following serotonin, SNP or Bay41-2272-mediated dilations were weaker in preeclampsia placental vessels. The decreased amplitude of SNP- or Bay41-2272 at baseline was smaller in preeclampsia. The decreased amplitudes of ODQ + SNP were comparable between the two groups. Despite higher beta sGC expression, sGC activity in the preeclampsia placenta was lower. Conclusion: This study demonstrated that receptor-mediated endothelium-dependent dilation in placental circulation was significantly weaker than other vessels in various species. The results, showed firstly, that exogenous NO played a role in regulating the baseline tone of placental circulation via sGC. Lower NO production and decreased NO/sGC could be one of the reasons for preeclampsia. The findings contribute to understanding specific features of placental circulation and provide information about preeclampsia in placental vessels.

Preparation and Properties of Self-Cross-Linking Hydrogels Based on Chitosan Derivatives and Oxidized Sodium Alginate.

A self-cross-linking and biocompatible hydrogel has wide application potential in the field of tissue engineering. In this work, an easily available, biodegradable, and resilient hydrogel was prepared using a self-cross-linking method. This hydrogel was composed of N-2-hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and oxidized sodium alginate (OSA). A stable and reversible cross-linking network was formed by the Schiff base self-cross-linked and hydrogen bonding. The addition of a shielding agent (NaCl) may weaken the intense electrostatic effect between HACC and OSA and solve the problem of flocculation caused by the rapid formation of ionic bonds, which provided an extended time for the Schiff base self-cross-linked reaction for forming a homogeneous hydrogel. Interestingly, the shortest time for the formation of the HACC/OSA hydrogel was within 74 s and the hydrogel had a uniform porous structure and enhanced mechanical properties. The HACC/OSA hydrogel withstood large compression deformation due to improved elasticity. What's more, this hydrogel possessed favorable swelling property, biodegradation, and water retention. The HACC/OSA hydrogels have great antibacterial properties against Staphylococcus aureus and Escherichia coli and demonstrated good cytocompatibility as well. The HACC/OSA hydrogels have a good sustained release effect on rhodamine (model drug). Thus, the obtained self-cross-linked HACC/OSA hydrogels in this study have potential applications in the field of biomedical carriers.

Estrogen ameliorates sepsis-induced vascular hyporeactivity in thoracic aorta of female rats via permissive effect of GRα expression.

OBJECTIVE: Estrogen is correlated to the lower mortality and disease severity of female than that of male, which indicates the potential therapeutic role of estrogen supplement therapy in sepsis. The structure of Daidzein is similar to that of 17ß estradiol (E2), an estrogen in human body, causing the exogenous Daidzein can interact with estrogen receptor as well as E2 in the body. We aim to explore the therapeutic role of estrogen in sepsis-induced vascular dysfunction. Also, we wonder if estrogen regulates blood pressure via glucocorticoid-mediated vascular reactivity. METHODS: Female SD rats received ovariectomy (OVX) to induce estrogen deficiency. After 12 weeks of administration, cecal ligation and puncture (CLP) was used to establish the in vivo model of sepsis. Lipopolysaccharide (LPS) was used to construct the in vitro model of sepsis in vascular smooth muscle cells (VSMCs). E2 and Daidzein were used for estrogen supplement therapy. RESULTS: E2 and Daidzein significantly inhibited inflammation infiltration and histopathological injury in thoracic aorta in the rat model with CLP. E2 and Daidzein improved carotid pressure and vascular hyporeactivity in sepsis rats with OVX. Importantly, E2 and Daidzein promoted glucocorticoid permissive action and increased glucocorticoid receptor α (GRα) expression in thoracic aorta smooth muscle cells. E2 and Daidzein upregulated GRα, and inhibits cytokine production, proliferative phenotype and cell migration in LPS-induced VSMCs. CONCLUSION: Estrogen improved vascular hyporeactivity in thoracic aorta induced by sepsis via permissive effect of GRα expression.

Detection and classification of volatile compounds emitted by three fungi-infected citrus fruit using gas chromatography-mass spectrometry.

Citrus fruit produced some characteristic volatile compounds when infected by fungi compared with the healthy fruit. In the present study, volatile metabolites of postharvest citrus fruit with three different diseases including stem-end rot, blue mold and green mold were detected. Multivariate analysis such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to classify the volatile compounds between the infected and non-infected citrus fruit. The results indicated that volatile compounds of unrotten, unrotten-rotten junction, and rotten tissues were successfully classified. Importantly, eight volatile compounds as biomarkers for stem-end rot and one biomarker for green mold of citrus were screened to discriminate the infected citrus fruit. This study offers the application potential of odor profiling of volatile compounds for detecting the fungi infection in postharvest citrus fruit.

Gas induced formation of inactive Li in rechargeable lithium metal batteries.

The formation of inactive lithium by side reactions with liquid electrolyte contributes to cell failure of lithium metal batteries. To inhibit the formation and growth of inactive lithium, further understanding of the formation mechanisms and composition of inactive lithium are needed. Here we study the impact of gas producing reactions on the formation of inactive lithium using ethylene carbonate as a case study. Ethylene carbonate is a common electrolyte component used with graphite-based anodes but is incompatible with Li metal anodes. Using mass spectrometry titrations combined with 13C and 2H isotopic labeling, we reveal that ethylene carbonate decomposition continuously releases ethylene gas, which further reacts with lithium metal to form the electrochemically inactive species LiH and Li2C2. In addition, phase-field simulations suggest the non-ionically conducting gaseous species could result in an uneven distribution of lithium ions, detrimentally enhancing the formation of dendrites and dead Li. By optimizing the electrolyte composition, we selectively suppress the formation of ethylene gas to limit the formation of LiH and Li2C2 for both Li metal and graphite-based anodes.

Effect of Structural Design on the Pore Structure, Water Resistance, and Mechanical Properties of Engineered Wood/Bamboo Laminated Composites.

An important principle in rational manufacturing design is matching the properties of composites to their intended uses. Herein, six laminated composites (LCs) were manufactured using fibrous moso bamboo and poplar veneer units, and their pore structure, water resistance, and mechanical properties were evaluated. The LC density (640-1290 kg/m3) increased significantly with increasing bamboo veneer unit content. The LC surface texture and roughness depended on the density and type of surface layer. With increasing LC density, the water absorption rate (WAR), width swelling rate (WSR), and thickness swelling rate (TSR) decreased exponentially and the mechanical properties increased linearly. This behavior was closely related to the changes in pore structure caused by density. Notably, the water resistance and mechanical properties of the LCs with densities higher than 910 kg/m3 were superior to the highest levels specified in GB/T 20241-2006 for ''laminated veneer lumber'' and GB/T 30364-2013 for "bamboo scrimber flooring". Thus, these engineered materials are promising for outdoor structures and flooring.

The Potential Role of PPARs in the Fetal Origins of Adult Disease.

The fetal origins of adult disease (FOAD) hypothesis holds that events during early development have a profound impact on one's risk for the development of future adult disease. Studies from humans and animals have demonstrated that many diseases can begin in childhood and are caused by a variety of early life traumas, including maternal malnutrition, maternal disease conditions, lifestyle changes, exposure to toxins/chemicals, improper medication during pregnancy, and so on. Recently, the roles of Peroxisome proliferator-activated receptors (PPARs) in FOAD have been increasingly appreciated due to their wide variety of biological actions. PPARs are members of the nuclear hormone receptor subfamily, consisting of three distinct subtypes: PPARα, ß/δ, and γ, highly expressed in the reproductive tissues. By controlling the maturation of the oocyte, ovulation, implantation of the embryo, development of the placenta, and male fertility, the PPARs play a crucial role in the transition from embryo to fetus in developing mammals. Exposure to adverse events in early life exerts a profound influence on the methylation pattern of PPARs in offspring organs, which can affect development and health throughout the life course, and even across generations. In this review, we summarize the latest research on PPARs in the area of FOAD, highlight the important role of PPARs in FOAD, and provide a potential strategy for early prevention of FOAD.

Prenatal Cases Reflect the Complexity of the COL1A1/2 Associated Osteogenesis Imperfecta.

INTRODUCTION: Osteogenesis imperfecta (OI) is a rare mendelian skeletal dysplasia with autosomal dominant or recessive inheritance pattern, and almost the most common primary osteoporosis in prenatal settings. The diversity of clinical presentation and genetic etiology in prenatal OI cases presents a challenge to counseling yet has seldom been discussed in previous studies. METHODS: Ten cases with suspected fetal OI were enrolled and submitted to a genetic detection using conventional karyotyping, chromosomal microarray analysis (CMA), and whole-exome sequencing (WES). Sanger sequencing was used as the validation method for potential diagnostic variants. In silico analysis of specific missense variants was also performed. RESULTS: The karyotyping and CMA results of these cases were normal, while WES identified OI-associated variants in the COL1A1/2 genes in all ten cases. Six of these variants were novel. Additionally, four cases here exhibited distinctive clinical and/or genetic characteristics, including the situations of intrafamilial phenotypic variability, parental mosaicism, and "dual nosogenesis" (mutations in collagen I and another gene). CONCLUSION: Our study not only expands the spectrum of COL1A1/2-related OI, but also highlights the complexity that occurs in prenatal OI and the importance of clarifying its pathogenic mechanisms.

Investigation of an inherited PCGF2: p.Pro65Leu mutation causing Turnpenny-Fry syndrome.

BACKGROUND: Turnpenny-Fry syndrome (TPFS) has recently been defined as an uncommon monogenic disease and is characterized by global developmental delay (GDD), intellectualdisability (ID), facial dysmorphology, and skeletal abnormality. PCGF2 is the only known causative gene for TPFS, which is a component of polycomb repressive complex 1 (PRC1). PRC1 is a multi-protein complex controlling the knockdown of gene expression. METHODS: The present study included the clinical evaluation of a 2.5-year-old boy with GDD and ID using cerebral MRI and the genetic testing with whole-exome sequencing. Additionally, the in silico molecular dynamic (MD) simulation was carried out on the identified variant. RESULTS: A recurrent missense variant, namely PCGF2: c.194C > T (p.Pro65Leu), was identified and suggested to be inherited from a mosaic father based on Sanger sequencing validation. MD results suggested a deleterious effect on the intramolecular structural flexibility and stability of PCGF2 protein by this variant. CONCLUSION: Our results indicated that PCGF2: p.Pro65Leu might be a hotspot for GDD and highlighted the effect of this variant on protein function.

Association between spiritual care competency and perceived professional benefit among nurses: A cross-sectional study.

AIMS: This study aimed to investigate the status quo of nurses' spiritual care competency and their relationship with perceived professional benefit. BACKGROUND: Spiritual care has always been considered a vitally important part of holistic nursing. Understanding the spiritual care competency of nurses during the COVID-19 pandemic can help nursing managers understand the weak links in spiritual care practice and improve the quality of nursing service. As a positive emotional experience and cognitive evaluation of the profession, perceived professional benefit can serve to adjust work pressure, relieve job burnout and promote an individual's overall growth. However, the relationship between perceived professional benefit among nurses and spiritual care competency remains unclear. METHODS: A total of 372 nurses were recruited from 15 separate Chinese hospitals. An online questionnaire was used to assess nurses' sociodemographic, spiritual care competency and perceived professional benefit. Statistical analyses were performed using Pearson's correlation analysis, t test, analysis of variance (ANOVA) and multiple stepwise linear regression analysis. RESULTS: The total mean score of spiritual care competency (99.43 ± 21.10) among nurses was found to be moderate. Nurses' spiritual care competency was positively correlated with perceived professional benefit (P < .01). The multiple stepwise linear regression model (n = 372) had an explained variance (R2 = 0.218) and showed that perceived professional benefit and the manner of receiving spiritual training were the main influencing factors of nurses' spiritual care competency (P < .001). CONCLUSION: The study findings indicated that nurses need to improve their spiritual care competency by improving their perceived professional benefit. IMPLICATION FOR NURSING MANAGERS: Our study evaluated the spiritual care competency of nurses and explored the correlation between perceived professional benefit and spiritual care competency among nurses. The results of this study can help nursing managers to carry out relevant interventions, thus improving nurses' spiritual care competency and optimizing the quality of nursing.

Locally generated C3 regulates the clearance of Toxoplasma gondii by IFN-γ-primed macrophage through regulation of xenophagy.

Exogenous pathogen infection can induce autophagy in cells. Autophagy is essential for cell survival, development, and homeostasis. It not only regulates cell defense and stress, but also has a close relationship with innate and adaptive immunity. Complement is an important part of innate immunity, which could be activated by three approaches, including classic, alternative, and lectin pathways. All the three pathways result in the activation of C3, and generate anaphylatoxin fragments C3a and C5a, and formation of the membrane attack complex. Either C3a or C5a induces the inflammatory cytokines through binding to C3aR or C5aR, respectively. However, it is still unknown whether the complement could regulate the autophagy of intracellular microorganisms or not. In this study, we constructed a Toxoplasma gondii (T. gondii) and macrophages co-culture experimental model using T. gondii expressing enhanced green fluorescence protein (EGFP) fluorescence and C3-/-C57BL/6 J mice for that T. gondii invaded peritoneal macrophages in mice. Western blot, laser confocal microscopy (LCM), and transmission electron microscopy (TEM) were used to observe the changes of autophagy between the macrophages from wild-type (WT) and C3-/- mice. Flow cytometry and LCM were used to investigate the effect of autophagy on the killing ability of macrophages against T. gondii. Here, we found that local C3 could suppress not only the canonical autophagy of macrophage, but also the xenophagy to T. gondii. Interestingly, the inhibition of C3 on host cell autophagy could significantly suppress the clearance of T. gondii by the IFN-γ-primed macrophage. Finally, we investigated the mechanism of the autophagy regulation of C3 that the effect of C3 on the macrophage-specific autophagy against T. gondii depends on mTOR. And, there is C3a but not C5a/C5aR involved in regulating macrophage xenophagy against T. gondii. Collectively, our findings suggest locally generated C3 regulates the clearance of T. gondii by Macrophage through the regulation of the non-canonical IFN-γ-dependent autophagy pathway, and paint a clearer picture in the regulation of autophagy by innate immune components.

Hybrid recommendation algorithm based on real-valued RBM and CNN.

With the unprecedented development of big data, it is becoming hard to get the valuable information hence, the recommendation system is becoming more and more popular. When the limited Boltzmann machine is used for collaborative filtering, only the scoring matrix is considered, and the influence of the item content, the user characteristics and the user evaluation content on the predicted score is not considered. To solve this problem, the modified hybrid recommendation algorithm based on Gaussian restricted Boltzmann machine is proposed in the paper. The user text information and the item text information are input to the embedding layer to change the text information into numerical vector. The convolutional neural network is used to get the latent feature vector of the text information. The latent vector is connected to rating vector to get the item and the user vector. The user vector and the item vector are fused together to get the user-item matrix which is input to the visual layer of Gaussian restricted Boltzmann Machine to predict the ratings. Some simulation experiments have been performed on the algorithm, and the results of the experiments proved that the algorithm is feasible.