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This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d'). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (β, O hit /O false alarm ). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: None.

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., 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 © 2024 Elsevier B.V. All rights reserved.)

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., (© The Author(s) 2024. Published by Oxford University Press.)

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., Competing Interests: The authors declare that they have no conflict of interests., (© 2024 The Author(s).)

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., (© 2023. The Author(s).)

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., 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., (Copyright © 2023 Ren, Chen, Wu, Yang, Ji and Zhang.)

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., (© 2023. The Author(s).)

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.

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., 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.)

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., 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., (Copyright © 2023 Tang, Zhang, Zhang, Tao, Wu, Zheng, Xu, Li and Xu.)

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 17β estradiol (E 2 ), an estrogen in human body, causing the exogenous Daidzein can interact with estrogen receptor as well as E 2 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). E 2 and Daidzein were used for estrogen supplement therapy., Results: E 2 and Daidzein significantly inhibited inflammation infiltration and histopathological injury in thoracic aorta in the rat model with CLP. E 2 and Daidzein improved carotid pressure and vascular hyporeactivity in sepsis rats with OVX. Importantly, E 2 and Daidzein promoted glucocorticoid permissive action and increased glucocorticoid receptor α (GRα) expression in thoracic aorta smooth muscle cells. E 2 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., 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 Inc. All rights reserved.)

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., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

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 13 C and 2 H 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 Li 2 C 2 . 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 Li 2 C 2 for both Li metal and graphite-based anodes., (© 2023. The Author(s).)

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/m 3 ) 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/m 3 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 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, β/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.

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 (R 2  = 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., (© 2022 John Wiley & Sons Ltd.)

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.

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., Competing Interests: None., (AJTR Copyright © 2022.)

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., 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., (Copyright © 2022 Liu, Yan, Wang, Chen and Wu.)

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.

In this study, the inclusion complex (IC) of thymol with 2-hydroxypropyl-β-cyclodextrin (HPβCD) was fast synthetized by ultrasonic technology and its antifungal activities were evaluated. The thymol/HPβCD-IC was characterized by UV-vis absorption spectroscopy, fluorescence emission spectroscopy, powder X-ray diffraction, FT-IR, 1 H-NMR, TGA and DSC. The phase solubility studies proved that the aqueous solubility of thymol was significantly improved by forming the inclusion complex with HPβCD, and the thermal stability analysis showed that thymol/HPβCD-IC had a better thermal stability than pure thymol. The in vitro antifungal activities of thymol/HPβCD-IC against Botrytis cinerea, Penicillium digitatum and Alternaria alternata were significantly improved compared with pure thymol. Furthermore, the gray mold rot of tomatoes was evidently inhibited by thymol/HPβCD-IC treatment in vivo study. Therefore, the complexation with HPβCD assisted by ultrasound is a promising approach to solubilize and stabilize thymol for application as an antifungal agent in fruit preservation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Gastric cancer (GC) is a common malignancy around the world with a poor prognosis. Aldo-keto reductase family 1 member B10 (AKR1B10) is indispensable to cancer development and progression, which has served as a diagnostic biomarker for tumors. In our study, we demonstrated that the expression of AKR1B10 in GC tissues was significantly lower compared with normal gastric tissues. Subgroup analysis showed that, according to the clinic-pathological factors, the effect of the AKR1B10 expression level on the prognosis of GC patients was significantly different. Moreover, reduced expression of AKR1B10 promoted the ability of GC cells in proliferation and migration. Furthermore, increased AKR1B10 levels resulted in the opposite trend in vitro . Moreover, AKR1B10 was correlated with epithelial-mesenchymal transition (EMT) in a significant way. In vivo experiment, knockdown of AKR1B10 promoted the growth of tumor, increased Vimentin, and E-cadherin significantly. In summary, AKR1B10 is considered as a tumor suppressor in GC and is a promising therapeutic target.

Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well-recognized. ROR2 plays an important role in aging-related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self-renewal capacity, while its overexpression in aged DPSCs restores their self-renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4-FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging., (© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

The study aimed to explore the opinions of multi-field Chinese experts on mental health literacy and further build a comprehensive picture of mental health literacy based on these opinions. Semi-structured interviews were conducted with ten Chinese experts from the fields of psychiatry, clinical psychology, mental health education, and social work. A mixed deductive-inductive thematic analysis was used in the analysis of the qualitative data. The experts noted that mental health literacy applies both to persons with mental illness and the people who help them. The comprehensive view of mental health literacy that emerged from the interviews included knowledge about mental illness, an attitude of acceptance, respectful behavior, and recognition of the importance of getting help. Characteristically, Chinese components of mental health literacy included living in harmony with others and achieving balance in all aspects of life. To the best of our knowledge, this is the first qualitative study of experts' views of the concept of mental health literacy in the context of Chinese culture. The experts' responses to the interviews generated a comprehensive view of mental health literacy, including several elements that may be especially salient in Chinese culture. The results have implications for researchers and clinicians.

Replacing coenzyme F 430 , an Ni(i) F 430 -like cofactor derived from vitamin B 12 (F 430-B12 ) is revealed by DFT calculations to be able to catalyze methane formation in methyl-coenzyme M reductase with a barrier of 13.3 kcal mol -1 , demonstrating the correctness of the route starting from vitamin B 12 . The structure-activity relationships of F 430 and F 430-B12 (especially the roles of the F ring) are discovered and several sources of inspiration promoting the application of F 430-B12 are also obtained, coming closer to using F 430 chemistry in man-made catalysis.

Redox (reduction and oxidation) chemistry provides the fundamental basis for numerous energy-related electrochemical devices. Detecting the electrochemical redox chemistry is pivotal but challenging because it requires independent probes of the cationic and anionic redox states at different electrochemical states. The synchrotron-based soft X-ray mapping of resonant inelastic X-ray scattering (mRIXS) has recently emerged as a powerful tool for exploring such states in electrochemical devices, especially batteries. High-efficiency mRIXS covers the energy range of the absorption edge with the extra dimension of information on the emitted photon energies. In this frontier article, we review recent representative demonstrations of utilizing soft X-ray mRIXS for detecting the novel chemical state during electrochemical operation and for quantifying the cationic redox reactions through inverse partial fluorescence yield analysis (mRIXS-iPFY). More importantly, the non-divalent states of oxygen in electrodes involving oxygen redox reactions could be reliably captured by mRIXS, with its reversibility quantified by the intensity variation of the characteristic mRIXS feature through a super-partial fluorescence yield analysis (mRIXS-sPFY). These recent demonstrations inspire future perspectives on using mRIXS for studying the complex phenomena in energy materials, with both technical and scientific challenges in RIXS theory, in situ/operando experiments, and spatially resolved RIXS imaging.

Previous studies have suggested that pathogenic variants in interferon regulatoryse factor 6 (IRF6) can account for almost 70% of familial Van der Woude Syndrome (VWS) cases. However, gene modifiers that account for the phenotypic variability of IRF6 in the context of VWS remain poorly characterized. The aim of this study was to report a family with VWS with variable expressivity and to identify the genetic cause. A 4‑month‑old boy initially presented with cleft palate and bilateral lower lip pits. Examination of his family history identified similar, albeit milder, clinical features in another four family members, including bilateral lower lip pits and/or hypodontia. Peripheral blood samples of eight members in this three‑generation family were subsequently collected, and whole‑exome sequencing was performed to detect pathogenic variants. A heterozygous missense IRF6 variant with a c.1198C>T change in exon 9 (resulting in an R400W change at the amino acid level) was detected in five affected subjects, but not in the other three unaffected subjects. Moreover, subsequent structural analysis was indicative of damaged stability to the structure in the mutant IRF protein. Whole‑transcriptome sequencing, expression analysis and Gene Ontology enrichment analysis were conducted on two groups of patients with phenotypic diversity from the same family. These analyses identified significant differentially expressed genes and enriched pathways in these two groups. Altogether, these findings provide insight into the mechanism underlying the variable expressivity of VWS.

In this work, Li-rich Li 1.2 Mn 0.4 3+ Mn x 4+ Ti 0.4- x O 2 (LMM x TO, 0 ≤ x ≤ 0.4) oxides have been studied for the first time. X-ray diffraction (XRD) patterns show a cation-disordered rocksalt structure when x ranges from 0 to 0.2. After Mn 4+ substitution, LMM 0.2 TO delivers a high specific capacity of 322 mAh g -1 at room temperature (30 °C, 30 mA g -1 ) and even 352 mAh g -1 (45 °C, 30 mA g -1 ) with an energy density of 1041 Wh kg -1 . The reason for such a high capacity of LMM 0.2 TO is ascribed to the increase of both cationic (Mn) and anionic (O) redox after Mn 4+ substitution, which is proved by d Q /d V curves, X-ray absorption near edge structure, DFT calculations, and in situ XRD results. In addition, the roles of Mn 3+ and Ti 4+ in LMM 0.2 TO are also discussed in detail. A ternary phase diagram is established to comprehend and further optimize the earth-abundant Mn 3+ -Mn 4+ -Ti 4+ system. This work gives an innovative strategy to improve the energy density, broadening the ideas of designing Li-rich materials with better performance.

Layered Li-rich Ni, Mn, Co (NMC) oxide cathodes in Li-ion batteries provide high specific capacities (>250 mAh/g) via O-redox at high voltages. However, associated high-voltage interfacial degradation processes require strategies for effective electrode surface passivation. Here, we show that an acidic surface treatment of a Li-rich NMC layered oxide cathode material leads to a substantial suppression of CO 2 and O 2 evolution, ∼90% and ∼100% respectively, during the first charge up to 4.8 V vs Li +/0 . CO 2 suppression is related to Li 2 CO 3 removal as well as effective surface passivation against electrolyte degradation. This treatment does not result in any loss of discharge capacity and provides superior long-term cycling and rate performance in comparison to as-received, untreated materials. We also quantify the extent of lattice oxygen participation in charge compensation ("O-redox") during Li + removal by a novel ex situ acid titration. Our results indicate that the peroxo-like species resulting from O-redox originate on the surface at least 300 mV earlier than the activation plateau region at around 4.5 V. X-ray photoelectron spectra and Mn L-edge X-ray absorption spectra of the cathode powders reveal a Li + deficiency and a partial reduction of Mn ions on the surface of the acid-treated material. More interestingly, although the irreversible oxygen evolution is greatly suppressed through the surface treatment, O K-edge resonant inelastic X-ray scattering shows that the lattice O-redox behavior is largely sustained. The acidic treatment, therefore, only optimizes the surface of the Li-rich material and almost eliminates the irreversible gas evolution, leading to improved cycling and rate performance. This work therefore presents a simple yet effective approach to passivate cathode surfaces against interfacial instabilities during high-voltage battery operation.

As a parent compound of Li-rich electrodes, Li 2 MnO 3 exhibits high capacity during the initial charge; however, it suffers notoriously low Coulombic efficiency due to oxygen and surface activities. Here, we successfully optimize the oxygen activities toward reversible oxygen redox reactions by intentionally introducing protons into lithium octahedral vacancies in the Li 2 MnO 3 system with its original structural integrity maintained. Combining structural probes, theoretical calculations, and resonant inelastic X-ray scattering results, a moderate coupling between the introduced protons and lattice oxygen at the oxidized state is revealed, which stabilizes the oxygen activities during charging. Such a coupling leads to an unprecedented initial Coulombic efficiency (99.2%) with a greatly improved discharge capacity of 302 mAh g -1 in the protonated Li 2 MnO 3 electrodes. These findings directly demonstrate an effective concept for controlling oxygen activities in Li-rich systems, which is critical for developing high-energy cathodes in batteries.

Binuclear Mg ketol-acid reductoisomerase (KARI), which converts (S)-2-acetolactate into (R)-2,3-dihydroxyisovalerate, is responsible for the second step of the biosynthesis of branched-chain amino acids in plants and microorganisms and thus serves as a key inhibition target potentially without effects on mammals. Here, through the use of density functional calculations and a chemical model, the KARI-catalyzed reaction has been demonstrated to include the initial deprotonation of the substrate C2 hydroxy group, bridged by the two Mg ions, alkyl migration from the C2-alkoxide carbon atom to the C3-carbonyl carbon atom, and hydride transfer from a nicotinamide adenine dinucleotide phosphate [NAD(P)H] cofactor to C2. A dead-end mechanism with a hydride transferred to the C3 carbonyl group has been ruled out. The nucleophilicity (migratory aptitude) of the migrating carbon atom and the provision of additional negative charge to the di-Mg coordination sphere have significant effects on the steps of alkyl migration and hydride transfer, respectively. Other important mechanistic characteristics are also revealed. Inspired by the mechanism, an inhibitor (2-carboxylate-lactic acid) was designed and predicted by barrier analysis to be effective in inactivating KARI, hence probably enriching the antifungal and antibacterial library. Two types of slow substrate analogues (2-trihalomethyl acetolactic acids and 2-glutaryl lactic acid) were also found., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous research indicates that kaempferol (Kae) promotes osteogenesis, but its underlying mechanism of action remains unclear. The present study hypothesized that the osteogenic effects of Kae were mediated through mammalian target of rapamycin (mTOR). To validate this hypothesis, bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) rats were differentiated into osteoblasts. The bone mineral density and bone microarchitecture of the OVX rats was measured in vivo, while osteogenesis was evaluated in vitro via Alizarin Red S staining and alkaline phosphatase activity measurements in cultured BMSCs. The levels of phosphorylated eukaryotic translation initiation factor 4E‑binding protein 1 (p‑4E/BP1) and phosphorylated ribosomal protein S6 kinase B1 (p‑S6K), and the expression of Runt‑related transcription factor 2 and Osterix, were concurrently quantified by western blot analysis. The data suggested that Kae prevented OVX‑induced osteoporosis in rats by promoting osteoblastogenesis. Furthermore, treatment with Kae in rat BMSCs enhanced mineralization, elevated ALP activity, increased the expression levels of Runx‑2 and Osterix and increased the levels of p‑S6K and decreased the levels of p‑4E/BP1 and, consistent with its ability to promote osteoblast differentiation. In contrast, treatment with rapamycin, an mTOR inhibitor, produced the opposite phenotype. Taken together, these data suggested that the protective effects of Kae in BMSCs and in the OVX rat model resulted from the induction of osteogenesis via mTOR signaling, or at least partially via the regulation of downstream effectors of the mTOR pathway.

Reactivation renders consolidated memory labile again, and the ensuing temporary reconsolidation process is highly susceptible to mnemonic modification. Here, we show that memories in such an unstable state could be influenced by sheer behavioral means, bypassing the need for pharmacological intervention. Across several experiments using a "face-location association" paradigm in which participants experienced a "Learning - New-learning - Final-test" procedure, we demonstrate that reactivated memory traces were hampered when the new learning was strategically administered at between 0-min and 20-min delay. Using fMRI, we further advance our theoretical understanding that this lability can be mechanistically explained by the differential activation in the hippocampal-amygdala memory system implicated by the post-activation new-learning whereas the mnemonic intrusion caused by newly learned memories is efficaciously reconciled by the left inferior frontal gyrus., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Accurate protein binding structure determination presents a great challenge to both experiment and theory. Here, in this work, we propose a new DOX protocol which combines the ensemble molecular Docking as the coarse-level, structure Optimization with the semiempirical quantum mechanics methods as the medium level, and the eXtended ONIOM ( XO) calculations as the fine level. The fundamental of the DOX protocol relies on the Conformation Search Across Multiple-level Potential-energy surfaces (CSAMP) strategy, where the conformation spaces of a funnel-like structure are searched from the coarse level with hundreds of candidates to the medium level with around 10 top candidates to the fine level with the final top 1 or 2 binding modes. An in-depth test for the protocol set up against 28 crystallographic data consisting of HMGR-statins, SDase-inhibitors, 3HNRase-inhibitors, and NA-inhibitors yielded a satisfactory result with ∼0.5 Å root-mean-square deviations (RMSDs) on geometries and ∼0.8 kcal/mol absolute error of relative binding energies on average. A further larger scale validation on the Astex test set (including 85 diverse structures) revealed an impressive performance with a RMSD < 2 Å success rate of 99%, suggesting DOX is a promising computational route toward accurate prediction of the protein-ligand binding structures.

Skeletal dysplasias (SDs) comprise a series of severe congenital disorders that have strong clinical heterogeneity and usually attribute to diverse genetic variations. The pathogenesis of more than half of SDs remains unclear. Additionally, the clinical manifestations of fetal SDs are ambiguous, which poses a big challenge for accurate diagnosis. In this study, eight unrelated families with fetal SD were recruited and subjected to sequential tests including chromosomal karyotyping, chromosomal microarray analysis (CMA), and trio whole-exome sequencing (WES). Sanger sequencing and quantitative fluorescence PCR (QF-PCR) were performed as affirmative experiments. In six families, a total of six pathogenic/likely pathogenic variations were identified in four genes including SLC26A2, FGFR3, FLNB, and TMEM38B . These variations caused disorders following autosomal dominant or autosomal recessive inheritance patterns, respectively. The results provided reliable evidence for the subsequent genetic counseling and reproductive options to these families. With its advantage in variation calling and interpreting, trio WES is a promising strategy for the investigation of fetal SDs in cases with normal karyotyping and CMA results. It has considerable prospects to be utilized in prenatal diagnosis.

This study investigated the effects of milk solution or milk proteins (casein and whey protein) on the bioaccessibility and antioxidant activity of oat phenolics during in vitro gastric and pancreatic digestion. During digestion, most of oat phenolics were partially degraded by alkaline pH of pancreatic fluid (pH 7.5). For phenolic acids, both milk solution and milk protein only had a slight influence on their bioaccessibility, while exhibited a significant effect on antioxidant activity of oat phenolic extracts and bioaccessibility of avenanthramides (AVs), a kind of bioactive phenols exclusively found in oats. The antioxidant activity and bioaccessibility of AVs were decreased by adding milk and casein, while significantly improved when mixed with milk whey protein. Remarkably, the bioaccessibility of AV 2c, which had the highest antioxidant activity among all phenolic compounds detected in oats, increased above 360% after intestinal digestion by mixing with whey protein. This result suggested the possibility of protecting AVs against digestive alteration and oxidation by milk whey protein. PRACTICAL APPLICATION: In recent years, oats are often consumed with milk under different conditions of preparation, and there have been many oat milk products manufactured by food companies all over the world. The results of this paper showed that the adding of milk may reduce the absorption and antioxidant activity of phenolic compounds from oat. However, the antioxidant activity and bioaccessibility of oat phenolics were significantly increased when mixed with milk whey protein, suggesting that oats could be consumed with milk whey protein to improve their functional properties., (© 2019 Institute of Food Technologists®.)

Aims: High-salt diet is linked to hypertension, and prenatal high-salt diet increases the risk of cardiovascular diseases in the offspring. The present study investigated whether and how prenatal high-salt diet influenced nitric oxide-mediated vasodilatation in the offspring., Methods and Results: Pregnant rats were fed either normal-salt (1% sodium chloride) or high-salt (8% sodium chloride) diet during gestation. Experiments were conducted in 5-month-old male offspring. Sodium nitroprusside (SNP, nitric oxide donor)-induced hypotensive responses (in vivo) and vascular dilatation (in vitro) was significantly attenuated (Emax: 84 ± 2 vs. 51 ± 2, high-salt vs. control, P < 0.001) in the high-salt offspring, indicating reduced vascular relaxations. Pretreatment with Tempol (reactive oxygen species scavenger) alleviated this attenuation. The high-salt offspring showed an increased level of oxidative stress markers in both mesenteric arteries and plasma samples. The antioxidant activity, serum superoxide dismutase and catalase were significantly reduced, whereas malondialdehyde was increased in the high-salt offspring. O2 production, and protein expression of Nox2 and Nox4 in mesenteric arteries was significantly increased in the high-salt offspring whereas Nox1 showed no changes. The local renin-angiotensin system in mesenteric arteries was activated, associated with an increased NADPH oxidase. DNA methylation at the proximal promoter of angiotensin-converting enzyme gene in the lung was significantly increased in the high-salt offspring (P = 0.004)., Conclusion: The results suggest that prenatal high-salt diet impairs nitric oxide-mediated vasodilatation because of the increased oxidative stress-affected renin-angiotensin system in the high-salt offspring, providing new information for understanding, and early prevention of cardiovascular diseases in fetal origins.

Addicted drugs like nicotine affect autonomic nervous system that results in arrhythmia and other cardiovascular diseases. Notable effects of Zen meditation on autonomic nervous system have been reported during the past decade. Holistic Detox Association (HDA) in Taiwan offered Zen-meditation program to drug addicts as the core scheme among a variety of drug addiction treatments. This paper reports the results of quantifying the cardiorespiratory interactions and autonomic nervous system function to evaluate the on-site effect of Zen meditation on drug rehab. Methods and schemes for quantifying time-domain heart rate variability were employed to electrocardiograph and respiratory signals. Peak-valley method was developed to quantify the respiratory sinus arrhythmia (RSA) behavior. Poincaré Plot Analysis was adopted to evaluate the cardiorespiratory functioning. Among 18 voluntary drug addicts during the 10-minute Zen meditation session, about two-third subjects have significant improvement in autonomic nervous system function characterized by heart rate variability (SDNN, RMSSD and pNN50). Group average of RSA increases from 33.43 ms(Rest) to 69.14 ms(AR Zen meditation). Poincaré-plot analysis reveals the improvement of SD1, SD2 and SD2/SD1 by respectively 14.7%, 19.8% and 8.8%. The group averages of all the parameters exhibit significantly positive changes in the 10-minute session of abdominal-respiration Zen meditation. Even the subject with heart transplant showed the improvement of all the quantitative indicators during the AR Zen meditation.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis and limited effective treatment. The rise in immunotherapeutic strategies prompted the establishment of a genetic vaccine against TNBC in vitro using a possible biological marker of TNBC. In the present study, different detection methods were used to evaluate the distribution and expression of runt-associated transcription factor 2 (Runx2) in various breast cancer cell lines. Following the development of the Runx2-dendritic cell (DC) vaccine using a lentivirus, the transfection efficacy was recorded. The T lymphocytes co-cultured with the vaccine were collected to assess the antitumor potency. Increased levels of Runx2 were expressed in breast cancer cells; however, different breast cancer cell lines expressed various levels of Runx2. Runx2 demonstrated particularly high expression in TNBC cells, compared with non-TNBC cells. A Runx2 lentivirus transfection system was successfully engineered, and Runx2 was transduced into dendritic cells whilst maintaining stable expression. The sustained and stable cytotoxic T cells induced in the transfected group had higher and more specific antitumor efficacy against TNBC, compared with the other cell lines. Runx2 may be a novel target for TNBC treatment. The Runx2-DC vaccine may induce specific and efficient antitumor effects in TNBC in vitro .

Insoluble dietary fiber from rice bran (RBIDF) was treated with dynamic high-pressure microfluidization (DHPM). The influence of pressure on the adsorption of Pb(II) capacity of RBIDF was explored in a simulation of the gastrointestinal environment. RBIDF (pH 7.0) displayed the maximal binding capacity (420.74 ± 13.12 μmol/g), at the level of 150 MPa, which was as 1.36 times as the untreated sample. DHPM-treated RBIDF demonstrated a higher ability to adsorb cholesterol and sodium cholate. Meanwhile, the treatment changed the morphology but did not alter the primary structure. The adsorption capacity is linear to the physicochemical properties of the total negative charges. The adsorption kinetics fit the pseudo-second-order model, Pb(II) adsorption mainly occur on the surface of the fiber particulate, this process includes natural physical adsorption and chemical reaction. This study provides a feasible approach for improving the adsorption capacity of RBIDF, especially the adsorption of Pb(II)., Practical Application: Dynamic high-pressure microfluidization can modify biomass adsorption materials effectively as a physically modification. The pretreatment dietary fiber can be used as a low-cost absorbing heavy metal biosorbent, and can be develop the functional food ingredients in the food industry., (© 2018 Institute of Food Technologists®.)

This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%). The self microemulsion formed by the SMEDDS upon aqueous media had spherical droplets with a hydrodynamic size of 46.0±3.2nm. The dissolution of tacrolimus from SD and SMEDDS was performed in sink and non-sink conditions with various pH. As revealed by the DSC and FT-IR, the tacrolimus was molecularly or amorphously dispersed in the SMEDDS and SD. The in vivo intestinal absorption study in rats showed that both SMEDDS and SD improved the absorption of tacrolimus over the raw tacrolimus while the SMEDDS exhibited lower absorption rate constant (K a ) and apparent permeability coefficients (P app ) than the SD. The self-prepared SD with poloxamer 188 or HPMC had comparable intestinal absorption as compared with Prograf®. The tacrolimus-loaded SMEDDS and SD would be further compared by in vivo pharmacokinetic study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background/aims: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK) channels in offspring mesenteric arteries following prenatal hypoxia., Methods: Pregnant rats were exposed to normoxic control (21% O2, Con) or hypoxic (10.5% O2, Hy) conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR., Results: Prenatal hypoxia increased pressor responses and vasoconstrictions to phenylephrine in the offspring. Whole-cell currents density of BK channels and amplitude of spontaneous transient outward currents (STOCs), not the frequency, were significantly reduced in Hy vascular myocytes. The sensitivity of BK channels to voltage, Ca2+, and tamoxifen were reduced in Hy myocytes, whereas the number of channels per patch and the single-channel conductance were unchanged. Prenatal hypoxia impaired NS1102- and tamoxifen-mediated relaxation in mesenteric arteries precontracted with phenylephrine in the presence of Nω-nitro-L-arginine methyl ester. The mRNA and protein expression of BK channel β1, not the α-subunit, was decreased in Hy mesenteric arteries., Conclusions: Impaired BK channel β1-subunits in vascular smooth muscle cells contributed to vascular dysfunction in the offspring exposed to prenatal hypoxia., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Several studies have shown that long non-coding RNAs (lncRNAs) may play an essential role in Epithelial-Mesenchymal Transition (EMT), which is an important step in tumor metastasis; however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alterations contribute to EMT progression regulation, we deep-sequenced the whole-transcriptome of MCF10A as the cells underwent TGF-β-induced EMT., Results: Deep-sequencing results showed that the long RNA transcriptome of MCF10A had undergone global changes as early as 8h after treatment with TGF-β. The expression of 3403 known and novel lncRNAs, and 570 known and novel circRNAs were altered during EMT. To identify the key lncRNA-regulator, we constructed the co-expression network and found all junction nodes in the network are lncRNAs. One junction node, RP6-65G23.5, was further verified as a key regulator of EMT. Intriguingly, we identified 216 clusters containing lncRNAs which were located in "gene desert" regions. The expressions of all lncRNAs in these clusters changed concurrently during EMT, strongly suggesting that these clusters might play important roles in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome during EMT and provides clues for the future study of the molecular mechanism of EMT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Scope: High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via protein kinase A (PKA) pathway in coronary arteries., Methods and Results: Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K + channels and Adenosine signal pathways. Adenosine-mediated vasodilatation was reduced in coronary arteries in HS. There was no difference in gene expression of A 2A receptors between the two groups. After pretreatment with PKA inhibitor, vasodilatation to Adenosine was decreased to a smaller extent in HS than that in control. Forskolin (activator of adenylate cyclase)-mediated vasodilatation was decreased in HS. Iberiotoxin (large-conductance Ca 2+ -activated K + channel [BK channel] inhibitor) attenuated Forskolin-induced vasodilatation in control, not in HS group. Currents of BK channels decreased in coronary artery smooth muscle cells, and PKA-modulated BK channel functions were declined. Protein levels of BK β1 and PKA C-subunits in coronary arteries of HS offspring were reduced., Conclusions: Prenatal HS diets altered Adenosine-mediated coronary artery vasodilatation in the offspring, which was linked to downregulation of cAMP/PKA/BK channel pathway., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Prenatal insults have been shown to affect vascular functions, leading to increased risks of cardiovascular diseases in offspring. The present study determined whether high sucrose (HS) intake in pregnancy affected central vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley rats were fed a standard food and tap water with normal or high (20%) sucrose content during pregnancy. Offspring were maintained with normal diets and tap water. Central vascular functions and related ion channels were assessed in male offspring at 5 months old. Compared with the control, angiotensin II (AII)-induced vasoconstrictions were significantly higher in the MCA of the offspring exposed to prenatal HS. In the MCA, large conductance Ca 2+ -activated K + channels (BKCa) currents were decreased with a reduction of opening frequency, sensitivity to intracellular Ca 2+ /membrane voltage, and BKβ1 expression. mRNA levels of AT1α and AT2, as well as AT1/AT2 ratio, were significantly increased in the MCA of offspring following exposure to prenatal HS diets. The data suggested that prenatal HS diets could alter microvascular activities in the MCA, probably via changes of BKCa channels in the brain., (© 2017 The Author(s).)

The present study tested the hypothesis that angiotensin II plays a role in the regulation of placental vascular tone, which contributes to hypertension in preeclampsia. Functional and molecular assays were performed in large and micro placental and non-placental vessels from humans and animals. In human placental vessels, angiotensin II induced vasoconstrictions in 78.7% vessels in 155 tests, as referenced to KCl-induced contractions. In contrast, phenylephrine only produced contractions in 3.0% of 133 tests. In non-placental vessels, phenylephrine induced contractions in 76.0% of 67 tests, whereas angiotensin II failed to produce contractions in 75 tests. Similar results were obtained in animal placental and non-placental vessels. Compared with non-placental vessels, angiotensin II receptors and β-adrenoceptors were significantly increased in placental vessels. Compared to the vessels from normal pregnancy, angiotensin II-induced vasoconstrictions were significantly reduced in preeclamptic placentas, which was associated with a decrease in angiotensin II receptors. In addition, angiotensin II and angiotensin converting enzyme in the maternal-placenta circulation in preeclampsia were increased, whereas angiotensin I and angiotensin1-7 concentrations were unchanged. The study demonstrates a selective effect of angiotensin II in maintaining placental vessel tension, which may play an important role in development of hypertension in preeclampsia.

Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway., (© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.)