Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation.

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.

[Association between dietary patterns and depressive symptom based on reduced rank regression in people aged 55 and above in 4 provinces of China].

OBJECTIVE: To investigate the dietary patterns related to depressive symptoms based on reduced rank regression in people aged 55 and above in 4 provinces of China and the degree of association between this dietary pattern and depressive symptoms. METHODS: Stratified, multi-stage, cluster and random sampling method was used to collect personal information such as demographic characteristics, behavioral lifestyles, disease history and medicine use in Chinese aged 55 and above who participated in the baseline survey of "Community-based Cohort Study on Nervous System Diseases" project conducted in 2018 and 2019 in Hebei, Zhejiang, Shaanxi and Hunan Provinces. Food frequency questionnaire was used to obtain dietary data. Depressive symptom was assessed by geriatric depression scale with a cut-off of 11. Participants who have incomplete demographic information, dietary data or scores of geriatric depression scale, and those whose intake frequency of each food-group >99. 5% were excluded. A total of 11 497 participants, 43. 1% of whom were male, were involved in this study with average age of(67. 3±7. 6) years. The reduced rank regression method was used to extract depressive symptoms-related dietary patterns by gender, and the degree of association between dietary patterns and depressive symptom was analyzed by logistic regression. RESULTS: Among males, the depressive symptoms-related dietary pattern was characterized by the higher intake frequency of fried flour-made food, meat, processed meat, animal offal, and preserved eggs, and the lower intake frequency of liquid milk/milk power/cheese, fresh eggs(except preserved eggs) and nut. Among females, the depressive symptoms-related dietary pattern was characterized by the higher intake frequency of fried flour-made food, meat, processed meat, animal offal and preserved eggs, and the lower intake frequency of coarse cereals, fruits, liquid milk/milk power/cheese and fresh eggs(except preserved eggs). The highest quartile group of the dietary pattern score had a significantly higher risk of depressive symptom than the lowest quartile group(OR=3. 498, 95% CI 2. 624-4. 663, P<0. 001 for males; OR=3. 853, 95% CI 3. 002-4. 944, P<0. 001 for females). CONCLUSION: The depressive symptoms-related dietary pattern is characterized by the higher intake frequency of fried flour-made food, meat, processed meat, animal offal and preserved eggs, and the lower intake frequency of liquid milk/milk power/cheese and fresh eggs(except preserved eggs) in the Chinese aged 55 and above. The score of this dietary pattern is significantly positively correlated with depressive symptom.

[Determination of vitamin A and vitamin E in human serum by high performance liquid chromatography with fluorescence detection].

OBJECTIVE: To establish a method for the simultaneous and rapid determination of vitamin A and vitamin E of different configurations in human serum by high performance liquid chromatography(HPLC) with multi-wavelength fluorescence detector. METHODS: The serum was mixed after adding internal standard, and acetonitrile was added for protein precipitation. The mixture was centrifuged after extraction with n-hexane. The n-hexane layer was dried by N_2 flow, the residue was dissolved with methanol. The HPLC system was consisted of WATERS Symmetry C_(18) column(4. 6 mm × 250 mm, 5 µm) and the mobile phase was methanol. The column temperature was 30 ℃ and fluorescence detector with online wavelength conversion method was carried out for the quantitative detection. RESULTS: The liner range of determination of vitamin A, α-vitamin E, ß-vitamin E and δ-vitamin E were 0. 050-2. 0 µg/mL, 0. 50-50 µg/mL, 0. 050-5. 0 µg/mL and 0. 050-5. 0 µg/mL, respectively(r≥0. 996). The minimum detection limits of the method for vitamin A and vitamin E were all 0. 02 µg/mL. The intraday and interday relative standard deviations(RSDs) were less than 3% at high, medium and low concentrations. The recoveries of the samples at the three concentrations were 91. 2%-107. 5%, and the RSDs were less than 10%. CONCLUSION: This method is simple and accurate, with higher sensitivity than using UV detector and can be used for the simultaneous determination of vitamin A and vitamin E of different configurations in serum, and is suitable for rapid detection of batch serum samples.

[Simultaneous determination of 25-hydroxyvitamin D and vitamin K_1 in serum by ultra-performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a method for analysis of 25-hydroxylvitamin D_2(25(OH)D_2), 25-hydroxylvitamin D_3(25(OH)D_3)and vitamin K_1 in serum by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS), which can be applied in diagnosis of vitamin deficiency and estimation on the nutritional status of people. METHODS: Serum samples mixed with d_6-25(OH)D_3, d_7-vitamin K_1(internal standard)were precipitated with acetonitrile and extracted with n-hexane. The sample solution was separated using BEH C_(18) column(2. 1 mm×100 mm, 1. 7 µm) with gradient elution using methanol-water containing 0. 1% formic acid as mobile phase. The target molecule was detected in positive electrospray ionization(ESI~+) and multiple reaction monitoring. RESULTS: The concentration of 25(OH)D_2, 25(OH)D_3 and vitamin K_1 showed good linearity in the range 5. 0-75. 0 ng/mL, 2. 0-81. 5 ng/mL and 0. 3-12. 0 ng/mL, respectively, with the correlation coefficients greater than 0. 995. The limits of detection(LOD) of 25(OH)D_2, 25(OH)D_3 and vitamin K_1 were 1, 0. 25 and 0. 1 ng/mL, and the limits of quantification(LOQ) for 25(OH)D_2, 25(OH)D_3 and vitamin K_1were 3, 0. 75 and 0. 3 ng/mL, respectively. The recoveries of three levels in the matrix were 98. 5%-104. 3%, the relative standard deviation(RSD) were all less than 5. 0%(n=6). CONCLUSION: An UPLC-MS/MS method for analysis of 25(OH)D_2, 25(OH)D_3 and vitamin K_1 in serum is sensitive, rapid, accurate and suitable for the nutritional surveillance of vitamin D and K_1 in the population.

[Genetic analysis of a pedigree affected with tuberous sclerosis complex caused by a novel mutation of TSC1].

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with Tuberous sclerosis complex (TSC) and explore pathogenic mutations of TSC1 and TSC2 gene. METHODS: Unique clinical phenotypes，the results of imaging, examination of the proband and special family history, collectively, made the constellation of features of TSC. Genomic DNA was obtained from six affected and eight unaffected members of the family and potential mutations of the TSC1 and TSC2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing. A total of 150 normal unrelated individuals were used as controls. RESULTS: Genetic analysis documented the presence of a heterozygous mutation, c.1781_1782delTG (p.Val594GlyfsX11), in the exon 15 of TSC1 gene within all the patients of the family. This mutation was not observed in the eight unaffected family members or in the 150 unrelated control subjects from the same population , or the Human Gene Mutation Database (HGMD) and had completely co-segregated with the disease phenotype in the family. CONCLUSION: The c.1781_1782delTG mutation of TSC1 gene may be responsible for the tuberous sclerosis complex in this family. The data presented in the present study are of significance to clinicians, as well as genetic counselors, and may provide new clues for molecular diagnosis of this disease．.

Elevated MIC Values of Imidazole Drugs against Aspergillus fumigatus Isolates with TR34/L98H/S297T/F495I Mutation.

The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Aspergillus fumigatus Though widely used in agriculture, imidazole fungicides have not been linked to resistance in A. fumigatus This study showed that elevated MIC values of imidazole drugs were observed against A. fumigatus isolates with TR34/L98H/S297T/F495I mutation, but not among isolates with TR34/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 A. fumigatus isolates from 20 countries suggested that the majority of TR34/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14α-demethylase sequences suggested that F495I in A. fumigatus was orthologous to F506I in Penicillium digitatum and F489L in Pyrenophora teres, which have been reported to be associated with imidazole resistance. In vitro antifungal susceptibility testing of different recombinants with cyp51A mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in A. fumigatus.

Oxidative stress markers in blood in systemic sclerosis: A meta-analysis.

OBJECTIVES: The purpose of this study is to clarify the relationship between systemic sclerosis (SSC) and oxidative stress markers in blood. METHODS: We conducted a systematic literature search of databases, including PubMed and Embase, for studies reporting circulating oxidative stress markers in patients with SSC and controls published from 1980 to December 2015. Standardized mean differences (SMDs) and 95% confidence intervals (95%CI) were calculated. RESULTS: Of the 1076 articles initially retrieved, 47 were included in our meta-analysis including 12 oxidative stress markers. The concentrations of nitric oxide (SMD = 0.77; 95%CI: 0.18, 1.36; p = 0.01), malondialdehyde (SMD =1.63; 95%CI: 1.03, 2.24; p = 0.000), asymmetric dimethylarginine (SMD = 0.51; 95%CI: 0.12, 0.91; p = 0.011), and ROOH (SMD = 3.37; 95%CI: 0.28, 6.46; p = 0.033) in the blood of patients with SSC were higher than those of the control group, whereas the concentrations of superoxide dismutase (SMD = -1.11; 95%CI: -1.57, -0.65; p = 0.000) and vitamin C (SMD = -1.12; 95%CI: -1.51, -0.73; p = 0.000) were lower than in the control group. CONCLUSIONS: The oxidative stress markers in blood for patients with SSC were aberrant, indicating the imbalanced states of oxidation and antioxidation in SSC.

Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China.

Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR34/L98H mutation, whereas four carry the TR34/L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR34/L98H isolates, while the TR34/L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azole-susceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.

Natural nitric oxide (NO) inhibitors from Chloranthus japonicus.

Eight new lindenane sesquiterpenoid dimers, chlojapolides A-H (1-8), along with 11 known analogues were isolated from the whole plant of Chloranthus japonicus. Their structures including absolute configurations were elucidated by spectral and chemical methods. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1, 11, 13, and 17 exhibited pronounced inhibition with IC50 values in the range of 6.91-15.75µM, being more active than the positive control, quercetin (IC50=15.90µM).

Eremophilane-Type Sesquiterpenoids from an Acremonium sp. Fungus Isolated from Deep-Sea Sediments.

Chemical examination of an EtOAc extract of a cultured Acremonium sp. fungus from deep-sea sediments resulted in the isolation of 15 new eremophilane-type sesquiterpenoids, namely, acremeremophilanes A-O (1-15), together with seven known analogues. The structures of new compounds were determined through extensive spectroscopic analyses, in association with chemical conversions and ECD calculations for configurational assignments. The PKS-derived 4-hexenoic acid unit in 2-6 is rarely found in nature. All compounds were evaluated for inhibitory effects toward nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophage cells. Compounds 2-6 and 14 exhibited inhibitory effects with IC50 values ranging from 8 to 45 µM.

Chlojaponilactone B from Chloranthus japonicus: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway.

Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators, such as iNOS, TNF-α, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-κB signaling pathway, which inhibited NF-κB-dependent transcriptional activity, IκBα phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.

Multiple cyp51A-based mechanisms identified in azole-resistant isolates of Aspergillus fumigatus from China.

Seventy-two A. fumigatus clinical isolates from China were investigated for azole resistance based on mutations of cyp51A. We identified four azole-resistant strains, among which we found three strains highly resistant to itraconazole, two of which exhibit the TR34/L98H/S297T/F495I mutation, while one carries only the TR34/L98H mutation. To our knowledge, the latter has not been found previously in China. The fourth multiazole-resistant isolate (with only moderate itraconazole resistance) carries a new G432A mutation.

An ESIPT + AIE based dual-response fluorescent probe for continuous detection of PhSH and HClO and visualization of PhSH-induced oxidative stress in living cells.

As a valuable industrial chemical, thiophenol (PhSH) is poisonous, which can be easily absorbed by the human body, leading to many serious health issues. In addition, PhSH-triggered oxidative stress is considered to be related with the pathogenesis and toxicity of PhSH. Therefore, efficient methods for monitoring PhSH and ROS production induced by PhSH in living systems are very meaningful and desired. Herein, we reasonably developed a facile dual-response fluorescent probe (HDB-DNP) by incorporating the dinitrophenyl (DNP) group into a novel methylthio-substituted salicylaldehyde azine (HDB) with AIE and ESIPT features. The probe itself was non-fluorescent owing to the strong quenching effect of DNP group. In the presence of PhSH, HDB-DNP gave an intense red fluorescence (610 nm), which can rapidly switch to green fluorescence (510 nm) upon further addition of HClO, allowing the successive detection of PhSH and HClO in two well-separated channels. HDB-DNP proved to be a very promising dual-functional probe for rapid (PhSH: < 17 min; HClO: 10 s) and selective detection of PhSH and HClO in physiological conditions with low detection limit (PhSH: 13.8 nM; HClO: 88.6 nM). Inspired by its excellent recognition properties and low cytotoxicity, HDB-DNP was successfully applied for monitoring PhSH and PhSH-induced HClO generation in living cells with satisfactory results, which may help to better understand the pathogenesis of PhSH-related diseases.

OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome.

PURPOSE: In this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism. METHODS: Exome sequencing and Sanger sequencing was conducted in affected and unaffected family members. A variety of human and cell studies were performed to explore the pathogenic process of keratosis. RESULTS: Our finding indicated that DIDA syndrome was caused by compound heterozygous variants in the oxysterol-binding protein-related protein 2 (OSBPL2) gene. Furthermore, our findings revealed a direct interaction between OSBPL2 and Phosphoinositide phospholipase C-beta-3 (PLCB3), a key player in hyperkeratosis. OSBPL2 effectively inhibits the ubiquitylation of PLCB3, thereby stabilizing PLCB3. Conversely, OSBPL2 variants lead to enhanced ubiquitination and subsequent degradation of PLCB3, leading to epidermal hyperkeratosis, characterized by aberrant proliferation and delayed terminal differentiation of keratinocytes. CONCLUSIONS: Our study not only unveiled the association between OSBPL2 variants and the newly identified DIDA syndrome but also shed light on the underlying mechanism.

Evaluation of Psychiatric Comorbidities and Quality of Life As Well As Brain-Derived Neurotrophic Factor (BDNF) Concentrations Among Patients Suffering From Acne Vulgaris: A Systematic Review and Meta-Analysis.

Acne vulgaris usually affects the dermal layer of the skin and is revealed frequently in young adulthood and adolescence. It has serious psychosocial comorbidities. We conducted the present systematic review and meta-analysis to elucidate the association of acne vulgaris with psychiatric comorbidities and quality of life as well as the brain-derived neurotrophic factor (BDNF) level. A systematic review and meta-analysis of the published articles were carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We investigated diverse databases: Web of Science, PubMed, the Cochrane Library, Embase, PsycINFO, and CINAHL to search for articles reporting the prevalence of psychosocial comorbidities among patients with acne vulgaris from database inception through June 2022. The outcomes were depression, anxiety, symptom checklist-90-R (SCL-90-R), quality of life, self-esteem, stress, loneliness, and BDNF concentrations. Of 3647 articles identified, 23 met the inclusion criteria. Patients with acne vulgaris have a significantly higher level of anxiety, depression, and stress (P<0.05). Yet, the reported findings of the SCL-90-R, self-esteem, loneliness, and BDNF scores among patients suffering from acne vulgaris were variable and did not differ significantly compared to healthy participants (P>0.05), hampering any conclusive findings on absolute prevalence. Subgroup analysis and comparison showed that heterogeneity between studies was likely due to factors, including country, study design, and assessment tools. This comprehensive review and meta-analysis revealed that anxiety, depression, and stress are significantly more frequent among patients suffering from acne vulgaris. These findings confirm that acne vulgaris has both psychiatric and medical characteristics and requires a multidisciplinary approach.

Construction of a novel ESIPT and AIE-based fluorescent sensor for sequentially detecting Cu2+ and H2S in both living cells and zebrafish.

The development of effective methods for tracking Cu2+ and H2S in living organisms is urgently required due to their vital function in a variety of pathophysiological processes. In this work, a new fluorescent sensor BDF with excited-state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) features for the successive detection of Cu2+ and H2S was constructed by introducing 3,5-bis(trifluoromethyl)phenylacetonitrile into the benzothiazole skeleton. BDF showed a fast, selective and sensitive fluorescence "turn off" response to Cu2+ in physiological media, and the situ-formed complex can serve as a fluorescence "turn on" sensor for highly selective detection of H2S through the Cu2+ displacement approach. In addition, the detection limits of BDF for Cu2+ and H2S were determined to be 0.05 and 1.95 µM, respectively. Encouraged by its favourable features, including strong red fluorescence from the AIE effect, large Stokes shift (285 nm), high anti-interference ability and good function at physiological pH as well as a low toxicity, BDF was successfully applied for the consequent imaging of Cu2+ and H2S in both living cells and zebrafish, making it an ideal candidate for detecting and imaging of Cu2+ and H2S in live systems.

Clinical efficacy and safety of targeted injection of PRP with skin booster in the treatment of aging face.

Platelet-rich plasma (PRP) with skin booster is a popular treatment for improving skin quality and reducing the signs of aging. However, few studies have evaluated its clinical efficacy in patients with aging face. This study aimed to evaluate the clinical efficacy, adverse reactions, and follow-up results of targeted injection of PRP with skin booster in treating patients with aging face. The study included 80 patients treated with targeted injection of PRP with skin booster from July 2022 to February 2023. The doctors compared the changes of the patients' facial skin indicators, quality of life, and satisfaction with their appearance before and after treatment, and analyzed the clinical efficacy, adverse reactions, and follow-up results of the patients after treatment. After one course of treatment, the patients' facial skin indicators, quality of life, and satisfaction with their appearance improved significantly, with P < 0.05. The total clinical effective rate was 88.75%, and the incidence of adverse reactions was 6.25%. After half a year of follow-up, 48.75% of the patients were willing to receive further treatment, and their facial soft feel, natural expression, and self-feeling comfort had significantly improved. Targeted injection of PRP with skin booster is an effective and safe treatment for improving facial skin symptoms such as coarse pores and wrinkles in patients with aging face. The results of this study provide evidence for the clinical use of PRP with skin booster in aesthetic medicine.

Dietary supplementation of n-3 PUFAs ameliorates LL37-induced rosacea-like skin inflammation via inhibition of TLR2/MyD88/NF-κB pathway.

Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and neurovascular system and treatments for rosacea are challenging. N-3 polyunsaturated fatty acids (PUFAs), one of essential fatty acids, are needed for health maintenance and exert anti-inflammation and immunomodulatory effects in a series of cutaneous diseases such as atopic dermatitis and photoaging through dietary supplementation. However, the role of n-3 PUFAs on rosacea remains to be elucidated. In this study, KEGG enrichment analysis and GO analysis indicated that the biological process and signaling pathways, including chemokine signaling pathway, regulated by n-3 PUFAs highly overlapped with those in the pathogenic biological process of rosacea, especially the erythema telangiectasia type. Next, mice were randomized to fed with a customized n-3 PUFAs diet. We showed that n-3 PUFAs ameliorated skin erythema, inhibited dermal inflammatory cell infiltration (mast cells, neutrophils, and CD4 +T cells) and suppressed elevated pro-inflammatory cytokines in LL37-induced rosacea-like mice. Besides, n-3 PUFAs were also verified to repress angiogenesis in LL37-induced mice skin. Further investigation revealed that n-3 PUFAs attenuated LL37-induced inflammation via TLR2/ MyD88/ NF-κB pathway both in mice and in keratinocytes. In conclusion, our findings underscore that dietary supplementation of n-3 PUFAs have the potential to become an efficient and safe clinical therapeutic candidate for rosacea.

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets.

Background: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by extensive skin fibrosis. There are no effective treatments due to the severity, multiorgan presentation, and variable outcomes of the disease. Here, integrated bioinformatics was employed to discover tissue-specific expressed hub genes associated with SSc, determine potential competing endogenous RNAs (ceRNA) regulatory networks, and identify potential targeted drugs. Methods: In this study, four datasets of SSc were acquired. To identify the genes specific to tissues or organs, the BioGPS web database was used. For differentially expressed genes (DEGs), functional and enrichment analyses were carried out, and hub genes were screened and shown in a network of protein-protein interactions (PPI). The potential lncRNA-miRNA-mRNA ceRNA network was constructed using the online databases. The specifically expressed hub genes and ceRNA network were validated in the SSc mouse and in normal mice. We also used the receiver operating characteristic (ROC) curve to determine the diagnostic values of effective biomarkers in SSc. Finally, the Drug-Gene Interaction Database (DGIdb) identified specific medicines linked to hub genes. Results: The pooled datasets identified a total of 254 DEGs. The tissue/organ-specifically expressed genes involved in this analysis are commonly found in the hematologic/immune system and bone/muscle tissue. The enrichment analysis of DEGs revealed the significant terms such as regulation of actin cytoskeleton, immune-related processes, the VEGF signaling pathway, and metabolism. Cytoscape identified six gene cluster modules and 23 hub genes. And 4 hub genes were identified, including Serpine1, CCL2, IL6, and ISG15. Consistently, the expression of Serpine1, CCL2, IL6, and ISG15 was significantly higher in the SSc mouse model than in normal mice. Eventually, we found that MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1 may be promising RNA regulatory pathways in SSc. Besides, ten potential therapeutic drugs associated with the hub gene were identified. Conclusions: This study revealed tissue-specific expressed genes, SERPINE1, CCL2, IL6, and ISG15, as effective biomarkers and provided new insight into the mechanisms of SSc. Potential RNA regulatory pathways, including MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1, contribute to our knowledge of SSc. Furthermore, the analysis of drug-hub gene interactions predicted TIPLASININ, CARLUMAB and BINDARIT as candidate drugs for SSc.

Neural signatures for the n-back task with different loads: An event-related potential study.

The n-back task is widely used in working memory (WM) research. However, it remains unclear how the electrophysiological correlates of WM processes, the P2, N2, P300, and negative slow wave (NSW), are affected by differences in load. Specifically, while previous work has examined the P300, less attention has been paid to the other components assessing the load of the n-back paradigm. The present study aims to investigate whether other sub-processes in WM (such as inhibitory control) are as sensitive to n-back load changes as the update process by observing changes in the above event-related potential (ERP) components. The results showed poorer behavioral performance with increasing WM load. Greater NSW and smaller P300 amplitudes were elicited by n-back task with a higher load compared to that with lower load. In contrast, there was no significant effect of the n-back load on the amplitudes of P2 and N2. These findings suggest that the updating process and the maintenance process are sensitive to the n-back load change. Therefore, changes in the updating and maintenance processes should be considered when using the n-back task to manipulate the WM load in experiments. The present study may contribute to the understanding of the complexity of WM loads. Additionally, a theoretical basis for follow-up research to explore ways of improving WM performance with high load is provided.