Altered functional connectivity of primary olfactory cortex-hippocampus-frontal cortex in subjective cognitive decline during odor stimulation.

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD.

The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer: biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial.

BACKGROUND: Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown. METHODS: In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated. RESULTS: No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis. CONCLUSION: sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.

Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice.

BACKGROUND: Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. METHODS: Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. CONCLUSIONS: Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

In vitro regeneration of triploid from mature endosperm culture of Passiflora edulis "Mantianxing".

The regeneration of shoots from endosperm tissue is a highly effective method to obtain triploid plants. In this study, we elucidated the establishment of an in vitro regeneration system from endosperm culture for the production of Passiflora edulis "Mantianxing." The highest callus induction rate (83.33%) was obtained on the media supplemented with 1.0 mg/L TDZ. Meanwhile, the MS medium containing 1.0 mg/L 6-BA and 0.4 mg/L IBA gave the optimum 75% shoot bud induction. Chromosome analysis revealed that the chromosomal count of P. edulis "Mantianxing" regenerated from endosperm tissues was 27 (2n = 3x = 27), which indicated that shoots regenerated from endosperm tissues were triploids. Triploid P. edulis had more drought resistance than diploid plants. Our study provided a method for breeding of passion fruit by means of a stable and reproducible regeneration system from endosperm culture, leading to the generation of triploid plants.

The relationship between psychological distress and the nursing humanistic care demands in postoperative cancer inpatients: a cross-sectional study.

PURPOSE: We aimed to investigate cancer patients' experiences of psychological distress after surgery and the factors that influence it, and to analyze the relationship between this and the nursing humanistic care demands. METHODS: This study used a convenience sampling method to survey 432 cancer patients undergoing surgical treatment in the specialized cancer hospital in Beijing. The survey used socio-demographic information, the Distress Management Screening Measures, and the Nursing Humanistic Care Demands questionnaire. Questionnaire Star was used to collect data online. SPSS24.0 software was used to test the relationship between psychological distress and nursing humanistic care demands. RESULTS: The mean scores for psychological distress and nursing humanistic care demands were 3.95 ± 2.71 and 147.02 ± 19.88, respectively, and showed a moderately positive correlation. The main issues that caused psychological distress in patients were: worry, financial problems, surroundings, nervousness, sleep, and pain. Regression analysis showed that gender, financial burden, personality trait, and need for humanistic care in nursing explained 24.5% of the total variance in the model and were independent predictors of psychological distress. CONCLUSION: Cancer inpatients have significant psychological distress after surgery and exhibit high levels of nursing humanistic care demands. This study fills the research gap on humanistic care for psychological distress management, nursing humanistic care demands positively predicted psychological distress. Nursing staff should pay attention to the psychological suffering of patients and develop individualized care measures to alleviate their psychological suffering by accurately identifying their nursing humanistic care demands.

Identification and analysis of lipid metabolism-related genes in allergic rhinitis.

BACKGROUND: Studies have shown that the lipid metabolism mediator leukotriene and prostaglandins are associated with the pathogenesis of allergic rhinitis (AR). The aim of this study was to identify key lipid metabolism-related genes (LMRGs) related to the diagnosis and treatment of AR. MATERIALS AND METHODS: AR-related expression datasets (GSE75011, GSE46171) were downloaded through the Gene Expression Omnibus (GEO) database. First, weighted gene co-expression network analysis (WGCNA) was used to get AR-related genes (ARRGs). Next, between control and AR groups in GSE75011, differentially expressed genes (DEGs) were screened, and DEGs were intersected with LMRGs to obtain lipid metabolism-related differentially expressed genes (LMR DEGs). Protein-protein interaction (PPI) networks were constructed for these LMR DEGs. Hub genes were then identified through stress, radiality, closeness and edge percolated component (EPC) analysis and intersected with the ARRGs to obtain candidate genes. Biomarkers with diagnostic value were screened via receiver operating characteristic (ROC) curves. Differential immune cells screened between control and AR groups were then assessed for correlation with the diagnostic genes, and clinical correlation analysis and enrichment analysis were performed. Finally, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was made on blood samples from control and AR patients to validate these identified diagnostic genes. RESULTS: 73 LMR DEGs were obtained, which were involved in biological processes such as metabolism of lipids and lipid biosynthetic processes. 66 ARRGs and 22 hub genes were intersected to obtain four candidate genes. Three diagnostic genes (LPCAT1, SGPP1, SMARCD3) with diagnostic value were screened according to the AUC > 0.7, with markedly variant between control and AR groups. In addition, two immune cells, regulatory T cells (Treg) and T follicular helper cells (TFH), were marked variations between control and AR groups, and SMARCD3 was significantly associated with TFH. Moreover, SMARCD3 was relevant to immune-related pathways, and correlated significantly with clinical characteristics (age and sex). Finally, RT-qPCR results indicated that changes in the expression of LPCAT1 and SMARCD3 between control and AR groups were consistent with the GSE75011 and GSE46171. CONCLUSION: LPCAT1, SGPP1 and SMARCD3 might be used as biomarkers for AR.

Long-term maintenance rituximab for ANCA-associated vasculitis: relapse and infection prediction models.

OBJECTIVES: Following a maintenance course of rituximab (RTX) for ANCA-associated vasculitis (AAV), relapses occur on cessation of therapy, and further dosing is considered. This study aimed to develop relapse and infection risk prediction models to help guide decision making regarding extended RTX maintenance therapy. METHODS: Patients with a diagnosis of AAV who received 4-8 grams of RTX as maintenance treatment between 2002 and 2018 were included. Both induction and maintenance doses were included; most patients received standard departmental protocol consisting of 2× 1000 mg 2 weeks apart, followed by 1000 mg every 6 months for 2 years. Patients who continued on repeat RTX dosing long-term were excluded. Separate risk prediction models were derived for the outcomes of relapse and infection. RESULTS: A total of 147 patients were included in this study with a median follow-up of 63 months [interquartile range (IQR): 34-93]. Relapse: At time of last RTX, the model comprised seven predictors, with a corresponding C-index of 0.54. Discrimination between individuals using this model was not possible; however, discrimination could be achieved by grouping patients into low- and high-risk groups. When the model was applied 12 months post last RTX, the ability to discriminate relapse risk between individuals improved (C-index 0.65), and once again, clear discrimination was observed between patients from low- and high-risk groups. Infection: At time of last RTX, five predictors were retained in the model. The C-index was 0.64 allowing discrimination between low and high risk of infection groups. At 12 months post RTX, the C-index for the model was 0.63. Again, clear separation of patients from two risk groups was observed. CONCLUSION: While our models had insufficient power to discriminate risk between individual patients they were able to assign patients into risk groups for both relapse and infection. The ability to identify risk groups may help in decisions regarding the potential benefit of ongoing RTX treatment. However, we caution the use of these prediction models until prospective multi-centre validation studies have been performed.

Quantitative proteomic, physiological and biochemical analysis of cotyledon, embryo, leaf and pod reveals the effects of high temperature and humidity stress on seed vigor formation in soybean.

BACKGROUND: Soybean developing seed is susceptible to high temperature and humidity (HTH) stress in the field, resulting in vigor reduction. Actually, the HTH in the field during soybean seed growth and development would also stress the whole plant, especially on leaf and pod, which in turn affect seed growth and development as well as vigor formation through nutrient supply and protection. RESULTS: In the present study, using a pair of pre-harvest seed deterioration-sensitive and -resistant cultivars Ningzhen No. 1 and Xiangdou No. 3, the comprehensive effects of HTH stress on seed vigor formation during physiological maturity were investigated by analyzing cotyledon, embryo, leaf, and pod at the levels of protein, ultrastructure, and physiology and biochemistry. There were 247, 179, and 517 differentially abundant proteins (DAPs) identified in cotyledon, embryo, and leaf of cv. Xiangdou No. 3 under HTH stress, while 235, 366, and 479 DAPs were identified in cotyledon, embryo, and leaf of cv. Ningzhen No. 1. Moreover, 120, 144, and 438 DAPs between the two cultivars were identified in cotyledon, embryo, and leaf under HTH stress, respectively. Moreover, 120, 144, and 438 DAPs between the two cultivars were identified in cotyledon, embryo, and leaf under HTH stress, respectively. Most of the DAPs identified were found to be involved in major metabolic pathways and cellular processes, including signal transduction, tricarboxylic acid cycle, fatty acid metabolism, photosynthesis, protein processing, folding and assembly, protein biosynthesis or degradation, plant-pathogen interaction, starch and sucrose metabolism, and oxidative stress response. The HTH stress had less negative effects on metabolic pathways, cell ultrastructure, and physiology and biochemistry in the four organs of Xiangdou No. 3 than in those of Ningzhen No. 1, leading to produce higher vigor seeds in the former. CONCLUSION: High seed vigor formation is enhanced by increasing protein biosynthesis and nutrient storage in cotyledon, stronger stability and viability in embryo, more powerful photosynthetic capacity and nutrient supply in leaf, and stronger protection in pod under HTH stress. These results provide comprehensive characteristics of leaf, pod and seed (cotyledon and embryo) under HTH stress, and some of them can be used as selection index in high seed vigor breeding program in soybean.

Characteristics, service use and mortality of clusters of multimorbid patients in England: a population-based study.

BACKGROUND: Multimorbidity is associated with mortality and service use, with specific types of multimorbidity having differential effects. Additionally, multimorbidity is often negatively associated with participation in research cohorts. Therefore, we set out to identify clusters of multimorbidity patients and how they are differentially associated with mortality and service use across age groups in a population-representative sample. METHODS: Linked primary and secondary care electronic health records contributed by 382 general practices in England to the Clinical Practice Research Datalink (CPRD) were used. The study included a representative set of multimorbid adults (18 years old or more, N = 113,211) with two or more long-term conditions (a total of 38 conditions were included). A random set of 80% of the multimorbid patients (N = 90,571) were stratified by age groups and clustered using latent class analysis. Consistency between obtained multimorbidity phenotypes, classification quality and associations with demographic characteristics and primary outcomes (GP consultations, hospitalisations, regular medications and mortality) was validated in the remaining 20% of multimorbid patients (N = 22,640). RESULTS: We identified 20 patient clusters across four age strata. The clusters with the highest mortality comprised psychoactive substance and alcohol misuse (aged 18-64); coronary heart disease, depression and pain (aged 65-84); and coronary heart disease, heart failure and atrial fibrillation (aged 85+). The clusters with the highest service use coincided with those with the highest mortality for people aged over 65. For people aged 18-64, the cluster with the highest service use comprised depression, anxiety and pain. The majority of 85+-year-old multimorbid patients belonged to the cluster with the lowest service use and mortality for that age range. Pain featured in 13 clusters. CONCLUSIONS: This work has highlighted patterns of multimorbidity that have implications for health services. These include the importance of psychoactive substance and alcohol misuse in people under the age of 65, of co-morbid depression and coronary heart disease in people aged 65-84 and of cardiovascular disease in people aged 85+.

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice.

BACKGROUND: Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. METHODS: Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. RESULTS: AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1ß, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. CONCLUSIONS: Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.

NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression. METHODS: Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. RESULTS: Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1ß, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus. CONCLUSIONS: NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.

Gender differences in the relationship of sexual partnership characteristics and inconsistent condom use among people living with HIV in China.

Few studies have examined the relationship between inconsistent condom use and sexual partnership characteristics among people living with HIV (PLWH). The current study focused on such association and its gender differences. The study was conducted in a large hospital in South China in 2013. A total of 320 dyads (PLWH indexes and their sexual partners) were recruited from an outpatient clinic using convenience sampling. The proportion of inconsistent condom use in the last six months among female indexes was higher than that among male indexes (52.4% vs. 43.6%). Of sexual partnership characteristics, HIV seropositive status was a risk factor for inconsistent condom use for both male and female indexes (aOR = 2.32, 95%CI = 1.15∼4.66, aOR = 3.09, 95%CI = 1.10∼8.67, respectively). For male indexes, lower educational level was also a risk factor (aOR = 2.39, 95%CI = 1.23∼4.67); while having had emotionally intimate relationships was a protective factor (aOR = 0.40, 95%CI = 0.21∼0.77). For female indexes, receiving material support was a risk factor (aOR = 10.17, 95%CI = 2.13∼48.61) and receiving health-related advice was a protective factor (aOR = 0.11, 95%CI = 0.02∼0.55). Future HIV interventions for PLWH need to be gender-sensitive and include their sexual partners.

The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive-compulsive disorder: A combined fMRI and 1H-MRS study.

OBJECTIVE: The imbalance in neurotransmitter and neuronal metabolite concentration within cortico-striato-thalamo-cortical (CSTC) circuit contributes to obsessive-compulsive disorder's (OCD) onset. Previous studies showed that glutamate mediated upregulation of resting-state activity in healthy people. However, there have been few studies investigating the correlational features between functional and neurochemical alterations in OCD. METHODS: We utilize a combined resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) approach to investigate the altered functional connectivity (FC) in association with glutamatergic dysfunction in OCD pathophysiology. Three regions of interest are investigated, i.e., medial prefrontal cortex and bilateral thalamus, for seed-based whole-brain FC analysis as well as MRS data acquisition. There are 23 unmedicated adult OCD patients and 23 healthy controls recruited for brain FC analysis. Among them, 12 OCD and 8 controls are performed MRS data acquisition. RESULTS: Besides abnormal FC within CSTC circuit, we also find altered FCs in large-scale networks outside CSTC circuit, including occipital area and limbic and motor systems. The decreased FC between right thalamus and right middle occipital gyrus (MOG) is correlated with glutamatergic signal within right thalamus in OCD patients. Moreover, the FC between right thalamus and right dorsal anterior cingulate cortex (dACC) is associated with glutamate level in right thalamus, specifically in patient's group. Finally, the FC between right thalamus and right MOG is correlated with patient's Yale-Brown Obsessive Compulsive Scale (YBOCS) compulsion and total scores, while the right thalamic glutamatergic signal is associated with YBOCS-compulsion score. CONCLUSION: Our findings showed that the coupled intrinsic functional-biochemical alterations existed both within CSTC circuit and from CSTC to occipital lobe in OCD pathophysiology.

Enhanced Immunological Tolerance by HLA-G1 from Neural Progenitor Cells (NPCs) Derived from Human Embryonic Stem Cells (hESCs).

BACKGROUND: Despite the great potential of utilizing human embryonic stem cells (hESCs)-derived cells as cell source for transplantation, these cells were often rejected during engraftment by the immune system due to adaptive immune response. METHODS: We first evaluated HLA-G expression level in both hESCs and differentiated progenitor cells. After that, we generated modified hESC lines that over-express HLA-G1 using lentiviral infection with the construct contains both HLA-G1 and GFP tag. The lentivirus was first produced by co-transfecting HLA-G1 expressing lentiviral vector together with packaging vectors into packaging cell line 293T. Then the produced virus was used for the infection of selected hESC lines. We characterized the generated cell lines phenotype, including pluripotency and self-renewal abilities, as well as immune tolerance ability by mixed lymphocyte reaction (MLR) and cytotoxicity assays. RESULTS: Although the hESCs do not express high levels of HLA-G1, over-expression of HLA-G1 in hESCs still retains their stem cell characteristics as determined by retaining the expression levels of OCT4 and SOX2, two critical transcriptional factors for stem cell function. Furthermore, the HLA-G1 overexpressing hESCs retain the self-renewal and pluripotency characteristics of stem cells, which can differentiate into different types of cells, including pigment cells, smooth muscle cells, epithelia-like cells, and NPCs. After differentiation, the differentiated cells including NPCs retain the high levels of HLA-G1 protein. In comparison with conventional NPCs, these HLA-G1 positive NPCs have enhanced immune tolerance ability. CONCLUSIONS: Ectopic expression of HLA-G1, a non-classical major histocompatibility complex class I (MHC I) antigen that was originally discovered involving in engraftment tolerance during pregnancy, can enhance the immunological tolerance in differentiated neural progenitor cells (NPCs). Our study shows that stably overexpressing HLA-G1 in hESCs might be a feasible strategy for enhancing the engraftment of NPCs during transplantation.

Association between perceived social norm and condom use among people living with HIV/AIDS in Guangzhou, China.

The number of people living with HIV/AIDS (PLWHA) has been increasing in China. Previous studies have examined the association between social norms and risk behaviors among high-risk populations for HIV infection. However, little is known about social norms and condom use among people living with HIV/AIDS (PLWHA). This study sought to investigate the relationship between perceived social norms on condom use and inconsistent condom use among PLWHA. A cross-sectional survey was conducted through convenience sampling among 412 PLWHA between March and June 2013 in Guangzhou, China. Descriptive norm of condom use was measured as perception of number of friends thinking it necessary to use condoms when having sex. About three-fourths (n = 301, 73.1%) of the PLWHA were sexually active since HIV diagnosis. Among the sexually active PLWHA, the average age was 36.5 years; about two-thirds were male; the majority was Han ethnic (92.7%); 55.5% discussed condom use with their friends and the rate of inconsistent condom use in the last three sexual encounters was 29.2%. In the multivariate logistic regression, PLWHA who perceived more of their friends' approval of condom use were less likely to engage in unprotected sex than their counterparts (aOR = 0.25, p = .001). Those whose family members were aware of their HIV infection status were less likely to engage in unprotected sex than their counterparts (aOR = 0.17, p < .001). Those who lived with family members were more likely to have unprotected sex than those who lived with friends (aOR = 8.47, p = .007). The results underscore the importance of developing culturally appropriate social norm-based HIV interventions among PLWHA. Future interventions focused on changing social norms on risk behaviors in the social network of PLWHA have the potential to reduce risk behaviors and to promote condom use among PLWHA.

Altered intrinsic insular activity predicts symptom severity in unmedicated obsessive-compulsive disorder patients: a resting state functional magnetic resonance imaging study.

BACKGROUND: Previous neuroimaging data indicated that the dysfunction in cortico-striato-thalamo-cortical (CSTC) circuit contributed to the neuropathological mechanism of obsessive-compulsive disorder (OCD). Whereas, emerging work has shown that the pathophysiology of OCD might be related to more widely distributed large-scale brain systems including limbic system and the salience network. This study aims to investigate the aberrant spontaneous neuronal activity within the whole brain, and its association with the symptom severity for unmedicated OCD patients. METHOD: Twenty-eight unmedicated OCD adults and twenty-eight matched healthy controls were recruited for a resting state functional magnetic resonance imaging (fMRI) study. The amplitude of low-frequency fluctuation (ALFF) analysis over whole brain was performed to examine the intrinsic cerebral activity of subjects. In addition, we conducted the voxel-based Pearson's correlative analysis to probe into the relationship between ALFF values and symptom severity for OCD patients. RESULTS: Our results showed that OCD patients had increased ALFF measures in the left frontopolar cortex and left orbital frontal cortex (OFC), with decreased ALFF values in the right insula. Moreover, the right insular intrinsic activity was significantly correlated with total YBOCS score (r = 0.611, p = 0.002) and compulsion score (r = 0.640, p = 0.001) for OCD patients. CONCLUSION: The results showed abnormal intrinsic neuronal activity within CSTC circuit and salience network of OCD patients. Our finding of aberrant insular activity advanced the understanding of OCD pathophysiology beyond the traditional CSTC circuit. To the best of our knowledge, it is the first finding about a reduced insular activity at the resting state for unmedicated OCD patients, which might serve as an informative biomarker for OCD pathophysiology.

Construction of N-doped carbon encapsulated CoP hollow nanofibers as multifunctional electrode materials for potassium-ion and lithium-sulfur batteries.

Herein, a composite of N-doped carbon coated phosphating cobalt hollow nanofibers (N/C@CoP-HNFs) was synthesized by electrospinning, phosphating, and carbon coating processes. When employed as multifunctional electrode materials for potassium-ion batteries (PIBs) and lithium-sulfur (Li-S) batteries, the N/C@CoP-HNFs demonstrated notable electrochemical properties. Specifically, it delivered an initial specific capacity of 420.4 mA h g-1 at a current density of 100 mA g-1, with a sustained capacity of 190.8 mA h g-1 after 200 cycles in PIBs, and a specific capacity of 1448 mA h g-1 at a current density of 0.5C in Li-S batteries, which is considered relatively high for these types of battery technology. This good performance may due to the combination of the carbon nitrogen layer and cobalt phosphide bilayer hollow tube structure, which is conducive to telescoping the diffusion length of ions and electrons and buffer volume variation, and effectively inhibits the shuttle effect. Density functional theory (DFT) calculations were also used to explore the energy storage mechanism of the material. The possible adsorption sites and corresponding adsorption energy of K+ were analyzed, and the advantages of the material were explored by calculating the diffusion barrier and state density. The theoretical simulations further validated the strong adsorption capability of CoP for polysulfides. This work is expected to provide new ideas for new energy storage materials.

Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum.

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Mediating effects of core competence between the transition shock and work readiness of newly graduated nurses in cancer hospitals: A cross-sectional study.

BACKGROUND: Newly graduated nurses face a dilemma of transitioning from student to clinical nurse roles, resulting in a low level of work readiness. The special professional environment of oncology hospitals requires newly graduated nurses to have specialized and novel theoretical knowledge and nursing skills. Therefore, they are constantly expected to develop better core competence. However, whether the core competence of newly graduated nurses mediates the relationship between transition shock and work readiness has not been investigated. OBJECTIVE: This study examined the relationship among transition shock, core competence, and work readiness of newly graduated nurses in cancer hospitals. DESIGN: A descriptive, cross-sectional study design. SETTING: This study was conducted at a tertiary cancer hospital in Beijing. PARTICIPATIONS: A convenience sample of 188 newly graduated nurses was studied from July to August 2022. METHODS: Sociodemographic data and Transition Shock Scale for Newly Graduated Nurses, Work Readiness Scale for Newly Graduated Nurses, and Core Competence Scale scores were collected using the online Questionnaire Star support platform. Pearson correlation and multiple regression analysis were applied using the Statistical Package for the Social Sciences version 24 to test the relationship among transition shock, core competencies, and work readiness. The Analysis of Moment Structures version 24.0 software was used to construct structural equation models. This report followed the Strengthening the Reporting of Observational studies in Epidemiology checklist. RESULTS: The transition shock of newly graduated nurses was negatively correlated with work readiness and core competence, whereas core competence was positively correlated with work readiness. Core competence partially mediated the effect between transition shock and work readiness, accounting for 19 % of the total effect. CONCLUSION: Core competence is the mediating variable between transition shock and work readiness of newly graduated nurses in oncology hospitals. During the transition period of newly graduated nurses, clinical nursing managers and teachers should pay attention to cultivating the core competence of newly graduated nurses to improve their work readiness.