Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

Optimizing the Use of Personal Values to Promote Medication Adherence: A Randomized Controlled Trial Comparing Affective and Behavioral Responses to Theory-Driven Domain Congruent Versus Incongruent Values Approaches.

BACKGROUND: Self-affirmation theory (SAT) and acceptance and commitment therapy (ACT) embody competing approaches to leveraging personal values to motivate behavior change but are rarely compared in the domain of health behavior. This study compares these theory-driven values-based interventions for promoting medication adherence. PURPOSE: To compare affective and behavioral responses to competing values-based medication adherence interventions. METHODS: In this three-armed randomized trial, participants with cancer (n = 95) or diabetes (n = 97) recruited online using Prolific and prescribed daily oral medication for that disease completed a one-session online writing intervention leveraging (1) a domain incongruent (DI) value, where the value was not connected to medication adherence; (2) a domain congruent (DC) value, where the value was connected to adherence; or (3) a control condition, focused on medication adherence procedures. RESULTS: There were no main effects of conditions on reported medication adherence at the 1-month follow-up. During the intervention, positive affect was higher in the values conditions than control (p < .001), and trended higher in DI versus DC (p = .054). Negative affect did not vary between the values and control groups (p = .093) but was lower in DI versus DC (p = .006). Improvements in positive affect over the course of the intervention were associated with increased adherence behavior for individuals who started with low levels of positive affect (p = .003). Disease type did not moderate findings. CONCLUSIONS: Consistent with SAT, focusing on DI values led to more positive and less negative affect than connecting values directly to behavior in a threatening domain such as chronic illness. For some participants, increases in positive affect predicted greater adherence.

This study compared different methods to boost medication adherence in patients with cancer or diabetes. We tested competing theory-driven, brief, online, values-based writing interventions to better understand how values motivate behavior. Participants were randomized to either write about (1) personal values as they relate to medication adherence, (2) personal values without connecting them to medication adherence, or (3) their medication regimen without commenting on personal values. One month later, there were no significant differences in reported medication adherence across the groups. However, participants in the values-based groups reported higher positive affect over the course of intervention compared to the group that did not write about personal values. This pattern was especially strong for participants who wrote about values without connecting them to medication adherence. Importantly, participants who started with lower positive affect but experienced improvements during the intervention tended to show better adherence 1 month following the intervention.

A retrospective analysis of 1600 infertility patients with azoospermia and severe oligozoospermia.

OBJECTIVE: This study aimed to investigate the genetic etiology of male infertility patients. METHOD: A total of 1600 male patients with infertility, including 1300 cases of azoospermia and 300 cases of severe oligozoospermia, underwent routine semen analysis, chromosomal karyotype analysis and sex hormone level testing. The Azoospermia factor (AZF) on the Y chromosome was detected using the multiple fluorescence quantitative PCR technique. Additionally, copy number variation (CNV) analysis was performed on patients with Sertoli-cell-only syndrome who had a normal karyotype and AZF. RESULT: Chromosomal abnormalities were found in 334 cases (20.88 %) of the 1600 male infertility patients. The most common type of abnormality was sex chromosome abnormalities (18.94 %), with 47, XXY being the most frequent abnormal karyotype. The rates of chromosomal abnormalities were significantly different between the azoospermia group and the severe oligospermia group (23.69 % and 8.67 %, respectively; P<0.05). AZF microdeletions were detected in 155 cases (9.69 %), with various deletion types and AZFc region microdeletion being the most prevalent. The rates of AZF microdeletions were not significantly different between the azoospermia group and the severe oligospermia group (9.15 % and 12 %, respectively; P=0.133). In 92 patients with Sertoli-cell-only syndrome who had a normal karyotype and AZF, the detection rate of CNV was 16.3 %. Compared to the severe oligospermia group, the azoospermia group had higher levels of FSH and LH and lower levels of T and E2, and the differences were statistically significant (P<0.05). CONCLUSIONS: Male infertility is a complex multifactorial disease, with chromosomal abnormalities and Y chromosome microdeletions being important genetic factors leading to the disease. Initial genetic testing of infertile men should include karyotyping and Y chromosome microdeletions. If necessary, CNV testing should be performed to establish a clinical diagnosis and provide individualized treatment for male infertility.

Ferrostatin-1 alleviates skin inflammation and inhibits ferroptosis of neutrophils and CD8+ T cells in allergic contact dermatitis.

BACKGROUND: Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown. OBJECTIVE: To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD. METHODS: We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD. RESULTS: Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8+ T cells both of which contribute to development of ACD. CONCLUSION: Ferroptosis was activated in immune cells, especially neutrophils and CD8+ T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8+ T cells and relieved skin damage in ACD mice.

Analysis of the Aging-Related AP2/ERF Transcription Factor Gene Family in Osmanthus fragrans.

Ethylene-Responsive Factor (ERF) is a key element found in the middle and lower reaches of the ethylene signal transduction pathway. It is widely distributed in plants and plays important roles in plant growth and development, hormone signal transduction, and various stress processes. Although there is research on AP/ERF family members, research on AP2/ERF in Osmanthus fragrans is lacking. Thus, in this work, AP2/ERF in O. fragrans was extensively and comprehensively analyzed. A total of 298 genes encoding OfAP2/ERF proteins with complete AP2/ERF domains were identified. Based on the number of AP2/ERF domains and the similarity among amino acid sequences between AP2/ERF proteins from A. thaliana and O. fragrans, the 298 putative OfAP2/ERF proteins were divided into four different families, including AP2 (45), ERF (247), RAV (5), and SOLOIST (1). In addition, the exon-intron structure characteristics of these putative OfAP2/ERF genes and the conserved protein motifs of their encoded OfAP2/ERF proteins were analyzed, and the results were found to be consistent with those of the population classification. A tissue-specific analysis showed the spatiotemporal expression of OfAP2/ERF in the stems and leaves of O. fragrans at different developmental stages. Specifically, 21 genes were not expressed in any tissue, while high levels of expression were found for 25 OfAP2/ERF genes in several tissues, 60 genes in the roots, 34 genes in the stems, 37 genes in young leaves, 34 genes in old leaves, 32 genes in the early flowering stage, 18 genes in the full flowering stage, and 37 genes in the late flowering stage. Quantitative RT-PCR experiments showed that OfERF110a and OfERF110b had the highest expression levels at the full-bloom stage (S4), and this gradually decreased with the senescence of petals. The expression of OfERF119c decreased first and then increased, while the expression levels of OfERF4c and OfERF5a increased constantly. This indicated that these genes may play roles in flower senescence and the ethylene response. In the subsequent subcellular localization experiments, we found that ERF1-4 was localized in the nucleus, indicating that it was expressed in the nucleus. In yeast self-activation experiments, we found that OfERF112, OfERF228, and OfERF23 had self-activation activity. Overall, these results suggest that OfERFs may have the function of regulating petal senescence in O. fragrans.

Spatial-Frequency Characteristics of EEG Associated With the Mental Stress in Human-Machine Systems.

Accurate assessment of user mental stress in human-machine system plays a crucial role in ensuring task performance and system safety. However, the underlying neural mechanisms of stress in human-machine tasks and assessment methods based on physiological indicators remain fundamental challenges. In this paper, we employ a virtual unmanned aerial vehicle (UAV) control experiment to explore the reorganization of functional brain network patterns under stress conditions. The results indicate enhanced functional connectivity in the frontal theta band and central beta band, as well as reduced functional connectivity in the left parieto-occipital alpha band, which is associated with increased mental stress. Evaluation of network metrics reveals that decreased global efficiency in the theta and beta bands is linked to elevated stress levels. Subsequently, inspired by the frequency-specific patterns in the stress brain network, a cross-band graph convolutional network (CBGCN) model is constructed for mental stress brain state recognition. The proposed method captures the spatial-frequency topological relationships of cross-band brain networks through multiple branches, with the aim of integrating complex dynamic patterns hidden in the brain network and learning discriminative cognitive features. Experimental results demonstrate that the neuro-inspired CBGCN model improves classification performance and enhances model interpretability. The study suggests that the proposed approach provides a potentially viable solution for recognizing stress states in human-machine system by using EEG signals.

SERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-Type Palmoplantar Keratoderma.

Nagashima-type palmoplantar keratoderma is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for Nagashima-type palmoplantar keratoderma because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. In addition, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a 3-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a protease-substrate manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in Nagashima-type palmoplantar keratoderma. These findings may lead to the development of therapeutic strategies for Nagashima-type palmoplantar keratoderma.

ATG5-mediated keratinocyte ferroptosis promotes M1 polarization of macrophages to aggravate UVB-induced skin inflammation.

Autophagy participates in the regulation of ferroptosis. Among numerous autophagy-related genes (ATGs), ATG5 plays a pivotal role in ferroptosis. However, how ATG5-mediated ferroptosis functions in UVB-induced skin inflammation is still unclear. In this study, we unveil that the core ferroptosis inhibitor GPX4 is significantly decreased in human skin tissue exposed to sunlight. We report that ATG5 deletion in mouse keratinocytes strongly protects against UVB-induced keratinocyte ferroptosis and skin inflammation. Mechanistically, ATG5 promotes the autophagy-dependent degradation of GPX4 in UVB-exposed keratinocytes, which leads to UVB-induced keratinocyte ferroptosis. Furthermore, we find that IFN-γ secreted by ferroptotic keratinocytes facilitates the M1 polarization of macrophages, which results in the exacerbation of UVB-induced skin inflammation. Together, our data indicate that ATG5 exacerbates UVB-induced keratinocyte ferroptosis in the epidermis, which subsequently gives rise to the secretion of IFN-γ and M1 polarization. Our study provides novel evidence that targeting ATG5 may serve as a potential therapeutic strategy for the amelioration of UVB-caused skin damage.

Immune micro-environment analysis and drug screening for ovarian endometriosis.

BACKGROUND: Patients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions. OBJECTIVE: This study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis. METHOD: In this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic. RESULTS: Seven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment. CONCLUSION: The decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.

Identification of a pathogenic SMCHD1 variant in a Chinese patient with bosma arhinia microphthalmia syndrome: a case report.

BACKGROUND: Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation. CASE PRESENTATION: In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS. CONCLUSION: This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.

Identification of a novel MYO1D variant associated with laterality defects, congenital heart diseases, and sperm defects in humans.

The establishment of left-right asymmetry is a fundamental process in animal development. Interference with this process leads to a range of disorders collectively known as laterality defects, which manifest as abnormal arrangements of visceral organs. Among patients with laterality defects, congenital heart diseases (CHD) are prevalent. Through multiple model organisms, extant research has established that myosin-Id (MYO1D) deficiency causes laterality defects. This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D (NM_015194: c.1531G>A; p.D511N) in a consanguineous family with complex CHD and laterality defects. Further examination of the proband revealed asthenoteratozoospermia and shortened sperm. Afterward, the effects of the D511N variant and another known MYO1D variant (NM_015194: c.2293C>T; p.P765S) were assessed. The assessment showed that both enhance the interaction with ß-actin and SPAG6. Overall, this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans. Furthermore, this research established a connection between sperm defects and MYO1D variants. It offers guidance for exploring infertility and reproductive health concerns. The findings provide a critical basis for advancing personalized medicine and genetic counseling.

Gasdermin E promotes translocation of p65 and c-jun into nucleus in keratinocytes for progression of psoriatic skin inflammation.

Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme-/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1ß, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

METTL14 affects UVB-induced human dermal fibroblasts photoaging via miR-100-3p biogenesis in an m6A-dependent manner.

Exposure to ultraviolet radiation can lead to skin photoaging, which increases the risk of skin tumors. This study aims to investigate how microRNA m6A modification contributes to skin photoaging. This study found that skin fibroblasts exposed to a single UVB dose of 30 mJ/cm2 exhibited characteristics of photoaging. The m6A level of total RNA decreased in photoaged cells with a down-regulated level of METTL14, and overexpression of METTL14 displayed a photoprotective function. Moreover, miR-100-3p was a downstream target of METTL14. And METTL14 could affect pri-miR-100 processing to mature miR-100-3p in an m6A-dependent manner via DGCR8. Furthermore, miR-100-3p targeted at 3' end untranslated region of ERRFI1 mRNA with an inhibitory effect on translation. Additionally, photoprotective effects of overexpression of METTL14 were reversed by miR-100-3p inhibitor or overexpression of ERRFI1. In UVB-induced photoaging of human skin fibroblasts, METTL14-dependent m6A can regulate miR-100-3p maturation via DGCR8 and affect skin fibroblasts photoaging through miR-100-3p/ERRFI1 axis.

hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility.

Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.

Integration of hydrothermal liquefaction of Cyanophyta and supercritical water oxidation of its aqueous phase products: Biocrude production and nutrient removal.

Cyanophyta has the potential to produce biocrude via hydrothermal liquefaction (HTL). However, aqueous phase products (APs), as by-products of HTL, pose a risk of eutrophication for the high levels of carbon, nitrogen, and phosphorus. Supercritical water oxidation (SCWO) can efficiently convert organics into small molecules, offering a technique for the harmless treatment of APs. Effects of holding time, pressure, and moisture content on the biocrude yields from isothermal HTL (300 °C) and fast HTL (salt bath temperature of 500 °C) were comprehensively investigated. Biocrude properties were characterized by elemental analysis, FT-IR and GC-MS. Subsequently, the APs obtained under the conditions producing the highest biocrude yield were subjected to SCWO at 550 °C with different oxidation coefficients (n) from 0 to 2. Removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and total phosphorus (TP) were further explored. The results show that the highest biocrude yields from isothermal HTL and fast HTL were 24.2 wt% (300 °C, 1800 s, 25 MPa, and 80 wt% moisture content) and 21.9 wt% (500 °C, 40 s, 25 MPa, and 80 wt% moisture content), respectively. The biocrude primarily consisted of N-containing heterocyclic compounds, amides, and acids. SCWO effectively degraded the COD and TP in APs, while the NH3-N required further degradation. At n = 2, the highest removal rates of COD, NH3-N and TP were 98.5 %, 22.6 % and 89.1 %, respectively.

Association between single nucleotide polymorphisms, TGF-ß1 promoter methylation, and polycystic ovary syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine and metabolic disease in women. Hyperandrogenaemia (HA) and insulin resistance (IR) are the basic pathophysiological characteristics of PCOS. The aetiology of PCOS has not been fully identified and is generally believed to be related to the combined effects of genetic, metabolic, internal, and external factors. Current studies have not screened for PCOS susceptibility genes in a large population. Here, we aimed to study the effect of TGF-ß1 methylation on the clinical PCOS phenotype. METHODS: In this study, three generations of family members with PCOS with IR as the main characteristic were selected as research subjects. Through whole exome sequencing and bioinformatic analysis, TGF-ß1 was screened as the PCOS susceptibility gene in this family. The epigenetic DNA methylation level of TGF-ß1 in peripheral blood was detected by heavy sulfite sequencing in patients with PCOS clinically characterised by IR, and the correlation between the DNA methylation level of the TGF-ß1 gene and IR was analysed. We explored whether the degree of methylation of this gene affects IR and whether it participates in the occurrence and development of PCOS. RESULTS: The results of this study suggest that the hypomethylation of the CpG4 and CpG7 sites in the TGF-ß1 gene promoter may be involved in the pathogenesis of PCOS IR by affecting the expression of the TGF-ß1 gene. CONCLUSIONS: This study provides new insights into the aetiology and pathogenesis of PCOS.

Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS).

OBJECTIVE: The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. METHODS: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. RESULTS: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). CONCLUSION: The relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease.

Parkinson's disease can affect not only motor functions but also cognitive abilities, leading to cognitive impairment. One common issue in Parkinson's disease with cognitive dysfunction is the difficulty in executive functioning. Executive functions help us plan, organize, and control our actions based on our goals. The brain area responsible for executive functions is called the prefrontal cortex. It acts as the command center for the brain, especially when it comes to regulating executive functions. The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine. However, little is known about how dopamine affects the cognitive functions of patients with Parkinson's disease. In this article, the authors review the latest research on this topic. They start by looking at how the dopaminergic system, is altered in Parkinson's disease with executive dysfunction. Then, they explore how these changes in dopamine impact the synaptic structure, electrical activity, and connection components of the prefrontal cortex. The authors also summarize the relationship between Parkinson's disease and dopamine-related cognitive issues. This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson's disease.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Temporal segmentation of EEG based on functional connectivity network structure.

In the study of brain functional connectivity networks, it is assumed that a network is built from a data window in which activity is stationary. However, brain activity is non-stationary over sufficiently large time periods. Addressing the analysis electroencephalograph (EEG) data, we propose a data segmentation method based on functional connectivity network structure. The goal of segmentation is to ensure that within a window of analysis, there is similar network structure. We designed an intuitive and flexible graph distance measure to quantify the difference in network structure between two analysis windows. This measure is modular: a variety of node importance indices can be plugged into it. We use a reference window versus sliding window comparison approach to detect changes, as indicated by outliers in the distribution of graph distance values. Performance of our segmentation method was tested in simulated EEG data and real EEG data from a drone piloting experiment (using correlation or phase-locking value as the functional connectivity strength metric). We compared our method under various node importance measures and against matrix-based dissimilarity metrics that use singular value decomposition on the connectivity matrix. The results show the graph distance approach worked better than matrix-based approaches; graph distance based on partial node centrality was most sensitive to network structural changes, especially when connectivity matrix values change little. The proposed method provides EEG data segmentation tailored for detecting changes in terms of functional connectivity networks. Our study provides a new perspective on EEG segmentation, one that is based on functional connectivity network structure differences.