SABA prescriptions and asthma management practices in Singapore: results from a cross-sectional, observational SABINA III study.

OBJECTIVES: To evaluate asthma characteristics and treatment patterns, including short-acting ß2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study. DESIGN: Cross-sectional, observational study. SETTING: Multicentre study conducted at five sites across Singapore. METHODS: In patients with asthma (aged ≥12 years), data on demographics, disease characteristics and asthma treatment prescriptions were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by 2017 Global Initiative for Asthma recommendations) and practice type (primary/specialist care). RESULTS: Of the 205 patients analysed (mean (SD) age, 53.6 (16.8) years; female, 62%), 55.9% were enrolled by specialists and 44.1% by primary care physicians. Most study patients (80.5%) had moderate-to-severe asthma (86.0% in specialist care and 74.4% in primary care). In the 12 months before study enrolment, 18.0% of patients experienced ≥1 severe exacerbation. Asthma was well or partly controlled in 78.0% of patients. Overall, 17.1% of all patients were overprescribed SABA (≥3 SABA canisters/year) in the preceding 12 months, and overprescription was greater in specialist versus primary care (26.3% vs 5.6%). Only 2.9% of patients were prescribed SABA monotherapy, while 41.0% received SABA in addition to maintenance therapy. Among the latter, 40.5% were overprescribed SABA. Overall, a higher percentage of patients prescribed ≥3 SABA canisters (vs 0-2 SABA canisters) were assessed as having uncontrolled asthma during the study visit (42.9% vs 17.6%). Maintenance therapy in the form of inhaled corticosteroids (ICS) or ICS/long-acting ß2 agonist fixed-dose combinations were prescribed to 14.1% and 84.9% of patients, respectively, in the 12 months before enrolment. CONCLUSIONS: In this Singapore cohort, ~17% of all patients and more than 40% of patients prescribed SABA in addition to maintenance therapy were overprescribed SABA. These findings emphasise the need to align clinical practices with the latest evidence-based treatment recommendations. TRIAL REGISTRATION: NCT03857178.

The effect of different times of day for exercise on blood glucose fluctuations.

AIMS: This study aims to explore blood glucose variations before and after short-term intensive exercise in the morning or afternoon of a day and the trend of blood glucose fluctuations during exercise in patients with T2DM (type 2 diabetes, T2DM). METHODS: Blood glucose variations of Fouty during morning exercise 8:00-12:00 hours and twenty during afternoon exercise 14:30-18:30 hours). Patients with T2DM discharged from the hospital were analyzed retrospectively, with the baseline data checked through the medical record system before intervention. We were asked to perform seven times of treadmill aerobic exercise, which lasted for 30 minutes with incremental intensity for each time, for two weeks under the supervision of the Continuous Glucose Monitor (CGM) and the heart rate armband. The exercise intensity has been adjusted by the clinicians and specialist nurses from the Department of Diabetes Mellitus according to the blood glucose levels and heart rate curves during exercise; data including the height, weight, body mass index (BMI), waist-to-hip ratio, fasting blood glucose, glycosylated hemoglobin, in-exercise CGM-measured blood glucose value/min, and after-exercise fingertip blood glucose value of patients with T2DM were collected after the intensive exercise (2 weeks). SPSS 22.0 and GraphPad Prism 7 were adopted for statistical analysis using the T-test and ANOVA. RESULT: No difference was observed in the baseline data between the morning and afternoon exercise groups before intervention; compared to the morning exercise group, the fasting C-peptide value (2.15±0.97 vs. 1.53±0.46) in the afternoon exercise group was higher than that in the morning exercise group, with a superior (p=0.029) effect after two weeks of intervention, exhibiting a significant difference in the results. According to the results of repeated variance ANOVA analysis, the time for the appearance of significant improvement in blood glucose in the afternoon exercise group was 5 minutes earlier (11th minute vs 1 minute)than that in the morning exercise group (15th minute vs 1 min); significant differences were observed in both time (p=0.048 vs p<0.01) between the two groups on exercise days, as revealed by the results of bivariate ANOVA; in comparison to the morning exercise group (7.42±1.68), there was a significant difference (p=0.049)in the mean blood glucose between the two groups 25 min after patients with T2DM in the afternoon exercise group (6.25±1.53) started to exercise; in addition, a significant statistical difference (p=0.021) was revealed in the CGM-measured hourly the mean blood glucose on exercise days between the morning(8.18±1.88) and afternoon exercise (6.75±1.40)groups at 4:00 pm in week one and two w. CONCLUSIONS: Glycaemic improvement in the short-term intensive afternoon exercise group may be superior to that of the morning exercise group, which may be related to greater fasting C-peptide secretion and longer effective exercise duration. The time to exercise is a factor affecting blood glucose variations during exercise. However, significant variations in the level of blood glucose during exercise must be further observed through exercise intervention over a more extended period.

LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to suppress colorectal cancer metastasis and chemoresistance.

Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC). Metastatic CRC frequently develops resistance to chemotherapeutic agents. This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance. Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models. Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain- and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L-CHEK2. RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance. An oxaliplatin-resistant CRC cell line was established by in vivo selection. WST-1, colony formation, invasion, migration, Biacore technology, gain- and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results: The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor. The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients. Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2, resulting in the formation of long CHEK2 (L-CHEK2), subsequently promoting E-cadherin secretion. PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion. Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance. Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC. Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance.

DNA nanoassembly based turn-on amplification probe for sensitive colorimetric CRISPR/Cas12a-mediated detection of pathogen DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR) system has been explored as an efficient tool for nucleic acid diagnostics. However, it normally needs instrumentation or produces turn-off signals. Herein, a bulged Y-shape DNA (Y-DNA) nanoassembly was designed and synthesized as a novel turn-on probe. A CRISPR/Cas12a and Y-DNA probe mediated colorimetric assay (named as CYMCOA) strategy was developed for visual detection of pathogen DNA. Upon activating Cas12a with pathogen DNA, the Y-DNA bulge is catalytically trans-cleaved, releasing the G-quadruplex sequence embedded in the Y-DNA nanoassembly as a peroxidase-like DNAzyme. Visible signals with chromogen substrates are thus produced. The CYMCOA strategy was combined with recombinase polymerase amplification (RPA), an isothermal amplification technique, in detecting Helicobacter pylori (Hp) bacteria and SARS-CoV-2 N plasmids as two model pathogens. The bioassay has very excellent detection sensitivity and specificity, owing to the triple cascade amplification reactions and the very low mismatch tolerance. The lower limit of detection values were 0.16 cfu⋅mL-1, 1.5 copies⋅µL-1, and 0.17 copies⋅µL-1 for Hp bacteria, Hp plasmids, and SARS-CoV-2 N plasmids respectively. The detection is fast and accurate. The colorimetric bioassay strategy provides to be a simple, accurate, fast and instrumentation-free platform for nucleic acids detections in various settings, including crude and emergent situations.

Moonlighting glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus gasseri inhibits keratinocyte apoptosis and skin inflammation in experimental atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. OBJECTIVE: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. METHODS: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. RESULTS: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. CONCLUSION: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice.

Introduction: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR. Methods: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition. Results: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group. Discussion: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

High salt diet inhibits the expression of Bmal1 and promotes atrial fibrosis and vulnerability to atrial fibrillation in Dahl salt sensitive rats.

BACKGROUND: Hypertension is a risk factor for atrial fibrillation (AF), and brain and muscle arnt-like protein 1 (Bmal1) regulate circadian blood pressure and is implicated in several fibrotic disorders. Our hypothesis that Bmal1 inhibits atrial fibrosis and susceptibility to AF in salt-sensitive hypertension (SSHT) and our study provide a new target for the pathogenesis of AF induced by hypertension. METHODS: The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). An experimental model was used to measure systolic blood pressure (SBP), left atrial ejection fraction (LAEF), left atrial end-volume index (LAEVI), left atrial index (LAFI), AF inducibility, AF duration, and atrial fibrosis pathological examination and the expression of Baml1 and fibrosis-related proteins (TNF-α and α-SMA) in left atrial tissue. RESULTS: DSH increased TNF-α and α-SMA expression in atrial tissue, level of SBP and LAESVI, atrial fibrosis, AF induction rate and AF duration, and decreased Bmal1 expression in atrial tissue, circadian rhythm of hypertension and level of LAEF and LAFI. Our results also showed that the degree of atrial fibrosis was negatively correlated with Bmal1 expression, but positively correlated with the expression of TNF-α and α-SMA. CONCLUSIONS: We demonstrated that a high-salt diet leads to circadian changes in hypertension due to reduction Bmal1 expression, which plays a crucial role in atrial fibrosis and increased susceptibility to AF in SSHT rats.

Optimization and mechanisms of proteolytic enzyme immobilization onto large-pore mesoporous silica nanoparticles: Enhanced tumor penetration.

Immobilization of proteolytic enzymes onto nanocarriers is effective to improve drug diffusion in tumors through degrading the dense extracellular matrix (ECM). Herein, immobilization and release behaviors of hyaluronidase, bromelain, and collagenase (Coll) on mesoporous silica nanoparticles (MSNs) were explored. A series of cationic MSNs (CMSNs) with large and adjustable pore sizes were synthesized, and investigated together with two anionic MSNs of different pore sizes. CMSNs4.0 exhibited the highest enzyme loading capacity for hyaluronidase and bromelain, and CMSNs4.5 was the best for Coll. High electrostatic interaction, matched pore size, and large pore volume and surface area favor the immobilization. Changes of the enzyme conformations and surface charges with pH, existence of a space around the immobilized enzymes, and the depth of the pore structures, affect the release ratio and tunability. The optimal CMSNs-enzyme complexes exhibited deep and homogeneous penetration into pancreatic tumors, a tumor model with the densest ECM, with CMSNs4.5-Coll as the best. Upon loading with doxorubicin (DOX), the CMSNs-enzyme complexes induced high anti-tumor efficiencies. Conceivably, the DOX/CMSNs4.5-NH2-Coll nanodrug exhibited the most effective tumor therapy, with a tumor growth inhibition ratio of 86.1 %. The study provides excellent nanocarrier-enzyme complexes, and offers instructive theories for enhanced tumor penetration and therapy.

Relationship between Circulating 25-Hydroxyvitamin D and Metabolic Syndrome in Chinese Adults: A Large Nationwide Longitudinal Study.

OBJECTIVE: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. METHODS: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). CONCLUSIONS: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.

Lithium Exposure and Risk of Major Neurocognitive Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). CONCLUSION: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

A novel bispecific antibody drug conjugate targeting HER2 and HER3 with potent therapeutic efficacy against breast cancer.

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

Glioblastoma U-87 cell electrotaxis is hindered by doxycycline with a concomitant reduction in the matrix metallopeptidase-9 expression.

Electric fields (EF) play an essential role in cancer cell migration. Numerous cancer cell types exhibit electrotaxis under direct current electric fields (dcEF) of physiological electric field strength (EFs). This study investigated the effects of doxycycline on the electrotactic responses of U87 cells. After EF stimulation, U87 cells migrated toward the cathode, whereas doxycycline-treated U87 cells exhibited enhanced cell mobility but hindered cathodal migration. We further investigated the expression of the metastasis-correlated proteins matrix metallopeptidase-2 (MMP-2) and MMP-9 in U87 cells. The levels of MMP-2 in the cells were not altered under EF or doxycycline stimulation. In contrast, the EF stimulation greatly enhanced the levels of MMP-9 and then repressed in doxycycline-cotreated cells, accompanied by reduced cathodal migration. Our results demonstrated that an antibiotic at a non-toxic concentration could suppress the enhanced cell migration accelerated by EF of physiological strength. This finding may be applied as an anti-metastatic treatment for cancers.

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

Evaluating serum CXCL12, sCD22, Lp-PLA2 levels and ratios as biomarkers for diagnosis of Alzheimer's disease.

BACKGROUND: Grasping the underlying mechanisms of Alzheimer's disease (AD) is still a work in progress, and existing diagnostic techniques encounter various obstacles. Therefore, the discovery of dependable biomarkers is essential for early detection, tracking the disease's advancement, and steering treatment strategies. AIM: To explore the diagnostic potential of serum CXCL12, sCD22, Lp-PLA2, and their ratios in AD, aiming to enhance early detection and inform targeted treatment strategies. METHODS: The study was conducted in Dongying people's Hospital from January 2021 to December 2022. Participants included 60 AD patients (AD group) and 60 healthy people (control group). Using a prospective case-control design, the levels of CXCL12, sCD22 and Lp-PLA2 and their ratios were detected by enzyme-linked immunosorbent assay kit in the diagnosis of AD. The differences between the two groups were analyzed by statistical methods, and the corresponding ratio was constructed to improve the specificity and sensitivity of diagnosis. RESULTS: Serum CXCL12 levels were higher in the AD group (47.2 ± 8.5 ng/mL) than the control group (32.8 ± 5.7 ng/mL, P < 0.001), while sCD22 levels were lower (14.3 ± 2.1 ng/mL vs 18.9 ± 3.4 ng/mL, P < 0.01). Lp-PLA2 levels were also higher in the AD group (112.5 ± 20.6 ng/mL vs 89.7 ± 15.2 ng/mL, P < 0.05). Significant differences were noted in CXCL12/sCD22 (3.3 vs 1.7, P < 0.001) and Lp-PLA2/sCD22 ratios (8.0 vs 5.2, P < 0.05) between the groups. Receiver operating characteristic analysis confirmed high sensitivity and specificity of these markers and their ratios in distinguishing AD, with area under the curves ranging from 0.568 to 0.787. CONCLUSION: Serum CXCL12 and Lp-PLA2 levels were significantly increased, while sCD22 were significantly decreased, as well as increases in the ratios of CXCL12/sCD22 and Lp-PLA2/sCD22, are closely related to the onset of AD. These biomarkers and their ratios can be used as potential diagnostic indicators for AD, providing an important clinical reference for early intervention and treatment.

Ethnic disparities in the prevalence of diabetes and its association with sleep disorder among older adults in rural southwest China.

OBJECTIVES: This study aimed to examine ethnic disparities in the prevalence of diabetes and its association with sleep disorders among the older adults Han and ethnic minority (Bai, Ha Ni, and Dai) population in rural southwest China. METHODS: A cross-sectional survey of 5,642 was conducted among the rural southwest population aged ≥60 years, consisting of a structured interview and measurement of fasting blood glucose, height, weight, and waist circumference. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. RESULTS: The overall prevalence of diabetes and sleep disorder was 10.2% and 40.1%, respectively. Bai participants had the highest prevalence of diabetes (15.9%) and obesity (9.9%)(P < 0.01), while Ha Ni participants had the lowest prevalence of diabetes (5.1%) and obesity (3.4%)(P < 0.01). The highest prevalence of sleep disorder (48.4%) was recorded in Bai participants, while Dai participants had the lowest prevalence of sleep disorder (25.6%)(P < 0.01). In all four studied ethnicities, females had a higher prevalence of sleep disorder than males (P < 0.01), and the prevalence of sleep disorder increased with age (P < 0.01). The results of multivariate logistic regression analysis indicated older adults with sleep disorder had a risk of developing diabetes (P < 0.05). Moreover, the higher educational level, family history of diabetes, and obesity were the main risk factors for diabetes in participants (P < 0.01). CONCLUSION: There are stark ethnic disparities in the prevalence of diabetes and sleep disorders in southwest China. Future diabetes prevention and control strategies should be tailored to address ethnicity, and improving sleep quality may reduce the prevalence of diabetes.

Investigation of Structures, Stabilities, and Electronic and Magnetic Properties of Niobium Carbon Clusters Nb7Cn (n = 1-7).

The geometrical structures, relative stabilities, and electronic and magnetic properties of niobium carbon clusters, Nb7Cn (n = 1-7), are investigated in this study. Density functional theory (DFT) calculations, coupled with the Saunders Kick global search, are conducted to explore the structural properties of Nb7Cn (n = 1-7). The results regarding the average binding energy, second-order difference energy, dissociation energy, HOMO-LUMO gap, and chemical hardness highlight the robust stability of Nb7C3. Analysis of the density of states suggests that the molecular orbitals of Nb7Cn primarily consist of orbitals from the transition metal Nb, with minimal involvement of C atoms. Spin density and natural population analysis reveal that the total magnetic moment of Nb7Cn predominantly resides on the Nb atoms. The contribution of Nb atoms to the total magnetic moment stems mainly from the 4d orbital, followed by the 5p, 5s, and 6s orbitals.

TGF-ß downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

The integrated bioinformatic analysis identifies immune microenvironment-related potential biomarkers for patients with gestational diabetes mellitus.

Background: Gestational diabetes mellitus (GDM), a transient disease, may lead to short- or long-term adverse influences on maternal and fetal health. Therefore, its potential functions, mechanisms and related molecular biomarkers must be comprehended for the control, diagnosis and treatment of GDM. Methods: The differentially expressed genes (DEGs) were identified using GSE49524 and GSE87295 associated with GDM from the Gene Expression Omnibus database, followed by function enrichment analysis, protein-protein interactions network construction, hub DEGs mining, diagnostic value evaluation and immune infiltration analysis. Finally, hub DEGs, the strongest related to immune infiltration, were screened as immune-related biomarkers. Results: A hundred and seven DEGs were identified between patients with GDM and healthy individuals. Six hub genes with high diagnostic values, including ALDH1A1, BMP4, EFNB2, MME, PLAUR and SLIT2, were identified. Among these, two immune-related genes (PLAUR and SLIT2) with the highest absolute correlation coefficient were considered immune-related biomarkers in GDM. Conclusion: Our study provides a comprehensive analysis of GDM, which would provide a foundation for the development of diagnosis and treatment of GDM.