Amphiphilic Janus Graphene Oxide Acts as a Corrosion Inhibitor to Mitigate the Corrosion Caused by a 1 M HCl Solution on Mild Steel.

Great aqueous dispersibility, a large specific surface area, and high impermeability make graphene oxide (GO) the ideal candidate for a high-performance corrosion inhibitor. Numerous symmetrical modification methods have been reported to enhance the adsorption of GO on metal surfaces in various corrosive media. This work aims to investigate the enhancement and mechanism of unilateral hydrophobic modification on the corrosion inhibition performance of GO. In this study, amphiphilic Janus GO (JGO) was prepared by grafting hydrophobic alkyl chains on one side of GO, and its anticorrosion performance was evaluated via weight loss experiments and electrochemical tests. The results revealed that the corrosion inhibition efficiency for Q235 mild steel (MS) in a 1 M HCl aqueous solution of 25 ppm JGO (81.08%) was much higher than that of GO at the same concentration (22.12%). Furthermore, the Langmuir adsorption isotherm and computational study demonstrated that the synergistic effect of physical adsorption and chemical adsorption promoted the hydrophilic side of JGO close to the surface of the metal, and the dense protective layer was formed by the hydrophobic chains toward the corrosive medium, which effectively hindered the corrosion of MS by the acidic liquid. This study emphasizes the significant role of asymmetrically modified hydrophobic alkyl chains in improving the corrosion prevention performance of GO and provides a perspective for the structural design of GO-based corrosion inhibitors.

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1.

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.

New Insights into TRP Ion Channels in Stem Cells.

Transient receptor potential (TRP) ion channels are cationic permeable proteins located on the plasma membrane. TRPs are cellular sensors for perceiving diverse physical and/or chemical stimuli; thus, serving various critical physiological functions, including chemo-sensation, hearing, homeostasis, mechano-sensation, pain, taste, thermoregulation, vision, and even carcinogenesis. Dysregulated TRPs are found to be linked to many human hereditary diseases. Recent studies indicate that TRP ion channels are not only involved in sensory functions but are also implicated in regulating the biological characteristics of stem cells. In the present review, we summarize the expressions and functions of TRP ion channels in stem cells, including cancer stem cells. It offers an overview of the current understanding of TRP ion channels in stem cells.

An Elaborate Supramolecular Assembly for a Smart Nanodevice for Ratiometric Molecular Recognition and Logic Gates.

Ingenious approaches to supramolecular assembly for fabricating smart nanodevices is one of the more significant topics in nanomaterials research. Herein, by using surface quaternized cationic carbon dots (CDots) as the assembly and fluorescence platform, anionic sulfonatocalix[4]arene with modifiable lower and upper rims as a connector, as well as in situ coordination of Tb(3+) ions, we propose an elaborate supramolecular assembly strategy for the facile fabrication of a multifunctional nanodevice. The dynamic equilibrium characteristics of the supramolecular interaction can eventually endow this nanodevice with functions of fluorescent ratiometric molecular recognition and as a nano-logic gate with two output channels.

The difference in antioxidant capacity of four alfalfa cultivars in response to Zn.

The aim of this study was to evaluate antioxidative responses in roots, stem and leaves of four alfalfa cultivars to different concentrations of zinc (Zn) (0, 300, 600 and 900 µM) for 23 days. Among the four cultivars, Aohan displayed the highest Zn concentrations in tissues and the largest Zn amount in aerial parts. Zn stress induced the production of H2O2 and increased the content of free proline and activities of antioxidative enzymes in roots, stem and leaves of Aohan. Based on the above results, we concluded that Aohan is superior to other three cultivars for Zn phyto-remediation, which indicated that Aohan is a novel Zn accumulator and able to tolerate Zn-induced toxicity by activating the antioxidative defense system.

Exploring the association between parental rearing styles and medical students' critical thinking disposition in China.

BACKGROUND: Critical thinking is an essential ability for medical students. However, the relationship between parental rearing styles and medical students' critical thinking disposition has rarely been considered. The aim of this study was to investigate whether parental rearing styles were significant predictors of critical thinking disposition among Chinese medical students. METHODS: 1,075 medical students from the first year to the fifth year attending one of three medical schools in China were recruited via multistage stratified cluster sampling. The Chinese Critical Thinking Disposition Inventory(CTDI-CV) and The Egna Minnen av Barndoms Uppfostran (EMBU) questionnaire were applied to collect data and to conduct descriptive analysis. Stepwise multiple linear regression was used to analyze the data. RESULTS: The critical thinking disposition average mean score was 287.44 with 632 participants (58.79%) demonstrating positive critical thinking disposition. Stepwise multiple linear regression analysis revealed that the rearing styles of fathers, including "overprotection", "emotional warmth and understanding", "rejection" and "over-interference" were significant predictors of medical students' critical thinking disposition that explained 79.0% of the variance in critical thinking ability. Rearing styles of mothers including "emotional warmth and understanding", "punishing" and "rejection" were also found to be significant predictors, and explained 77.0% of the variance. CONCLUSIONS: Meaningful association has been evidenced between parental rearing styles and Chinese medical students' critical thinking disposition. Parental rearing styles should be considered as one of the many potential determinant factors that contribute to the cultivation of medical students' critical thinking capability. Positive parental rearing styles should be encouraged in the cultivation of children's critical thinking skills.

Cardiovascular adverse events associated with targeted therapies for multiple myeloma: a pharmacovigilance study.

Introduction: Multiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated. Objective: This study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs). Methods: Disproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs). Results: A total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after 1 year. This trend was observed for all cardiovascular AEs. The Kaplan-Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab (p < 0.001). Conclusions: MM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management.

Causal effect of blood osteocalcin on the risk of Alzheimer's disease and the mediating role of energy metabolism.

Growing evidence suggests an association between osteocalcin (OCN), a peptide derived from bone and involved in regulating glucose and lipid metabolism, and the risk of Alzheimer's disease (AD). However, the causality of these associations and the underlying mechanisms remain uncertain. We utilized a Mendelian randomization (MR) approach to investigate the causal effects of blood OCN levels on AD and to assess the potential involvement of glucose and lipid metabolism. Independent instrumental variables strongly associated (P < 5E-08) with blood OCN levels were obtained from three independent genome-wide association studies (GWAS) on the human blood proteome (N = 3301 to 35,892). Two distinct summary statistics datasets on AD from the International Genomics of Alzheimer's Project (IGAP, N = 63,926) and a recent study including familial-proxy AD patients (FPAD, N = 472,868) were used. Summary-level data for fasting glucose (FG), 2h-glucose post-challenge, fasting insulin, HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol (TC), and triglycerides were incorporated to evaluate the potential role of glucose and lipid metabolism in mediating the impact of OCN on AD risk. Our findings consistently demonstrate a significantly negative correlation between genetically determined blood OCN levels and the risk of AD (IGAP: odds ratio [OR, 95%CI] = 0.83[0.72-0.96], P = 0.013; FPAD: OR = 0.81 [0.70-0.93], P = 0.002). Similar estimates with the same trend direction were obtained using other statistical approaches. Furthermore, employing multivariable MR analysis, we found that the causal relationship between OCN levels and AD was disappeared after adjustment of FG and TC (IGAP: OR = 0.97[0.80-1.17], P = 0.753; FPAD: OR = 0.98 [0.84-1.15], P = 0.831). There were no apparent instances of horizontal pleiotropy, and leave-one-out analysis showed good stability of the estimates. Our study provides evidence supporting a protective effect of blood OCN levels on AD, which is primarily mediated through regulating FG and TC levels. Further studies are warranted to elucidate the underlying physio-pathological mechanisms.

Association of Fat Mass and Skeletal Muscle Mass with Cardiometabolic Risk Varied in Distinct PCOS Subtypes: A Propensity Score-Matched Case-Control Study.

(1) Background: polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome with a constellation of cardiometabolic risk factors. We aimed to investigate if the association of body fat mass (BFM) and skeletal muscle mass (SMM) with cardiometabolic risk differed in PCOS subtypes. (2) Methods: 401 participants (245 PCOS and 156 controls) were assessed for anthropometric measurements, glucose-lipid profiles, reproductive hormones and body composition with propensity score-matched (PSM) analysis. The association of the cardiometabolic risk score (z score, calculated based on levels of obesity and gluco-lipid measurements) with BFM (estimated by trunk BFM/Height2) and SMM (estimated by SMM/Height2) was calculated. (3) Results: Trunk BFM/Height2 and SMM/Height2 were both positively associated with cardiometabolic risk in PCOS (trunk BFM/Height2, OR 2.33, 95% CI 1.49-3.65; SMM/Height2, OR 2.05, 95% CI 1.12-3.76). SMM/Height2 associated with increased cardiometabolic risk in obese PCOS (BMI ≥ 28 kg/m2, OR 2.27, 95% CI 1.15-4.47). For those with lower BMI (<28 kg/m2), trunk BFM/Height2 showed a higher OR in both groups (PCOS, OR 2.12, 95% CI 1.06-4.24; control 2.04, 95% CI 1.04-4.02). Moreover, distinct associations among BMI-stratified groups were validated in hierarchical clustering identifying metabolic and reproductive clusters. (4) Conclusions: BFM and SMM are synergistically associated with higher cardiometabolic risk in PCOS women. Although BFM contributes to increased cardiometabolic risk, SMM also plays a primary role in obese PCOS. Our results highlight the importance of body composition in the management of PCOS.

Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81.

PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.

Mitochondrial translocation of cofilin is required for allyl isothiocyanate-mediated cell death via ROCK1/PTEN/PI3K signaling pathway.

BACKGROUND: Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family, which regulates actin dynamics. Increasing evidence suggests that mitochondrial translocation of cofilin appears necessary for the regulation of apoptosis. RESULTS: We report that allyl isothiocyanate (AITC) potently induces mitochondria injury and apoptosis. These events were accompanied by a loss of polymerized filamentous actin (F-actin) and increase in unpolymerized globular actin (G-actin). AITC also induces dephosphorylation of cofilin through activation of PP1 and PP2A. Only dephosphorylated cofilin binds to G-actin and translocates to mitochondria during AITC-mediated apoptosis. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K signaling pathway plays a critical role in AITC-mediated dephosphorylation and mitochondrial translocation of cofilin and apoptosis. Our in vivo study also showed that AITC-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with dephosphorylation of cofilin. CONCLUSIONS: These findings support a model in which induction of apoptosis by AITC stems primarily from activation of ROCK1 and PTEN, and inactivation of PI3K, leading in turn to activation of PP1 and PP2A, resulting in dephosphorylation of cofilin, which binds to G-actin and translocates to mitochondria, culminating in the dysfunction of mitochondria, release of cytochrome c and apoptosis.

Synthesis, characterization, and antibacterial activity of cross-linked chitosan-glutaraldehyde.

This present study deals with synthesis, characterization and antibacterial activity of cross-linked chitosan-glutaraldehyde. Results from this study indicated that cross-linked chitosan-glutaraldehyde markedly inhibited the growth of antibiotic-resistant Burkholderia cepacia complex regardless of bacterial species and incubation time while bacterial growth was unaffected by solid chitosan. Furthermore, high temperature treated cross-linked chitosan-glutaraldehyde showed strong antibacterial activity against the selected strain 0901 although the inhibitory effects varied with different temperatures. In addition, physical-chemical and structural characterization revealed that the cross-linking of chitosan with glutaraldehyde resulted in a rougher surface morphology, a characteristic Fourier transform infrared (FTIR) band at 1559 cm⁻¹, a specific X-ray diffraction peak centered at 2θ = 15°, a lower contents of carbon, hydrogen and nitrogen, and a higher stability of glucose units compared to chitosan based on scanning electron microscopic observation, FTIR spectra, X-ray diffraction pattern, as well as elemental and thermo gravimetric analysis. Overall, this study indicated that cross-linked chitosan-glutaraldehyde is promising to be developed as a new antibacterial drug.

Bevacizumab rescue therapy extends the survival in patients with recurrent malignant glioma.

OBJECTIVE: We retrospectively studied the efficacy of bevacizumab as salvage therapy for recurrent malignant glioma with a focus on the overall survival (OS). METHODS: Patients who received a therapy other than surgery for recurrent malignant glioma were included. Efficacy was evaluated using MRI. Neurological function was evaluated using the Response Assessment in Neuro-Oncology (RANO). The survival rate was calculated using the Kaplan-Meier method. RESULTS: Fifty-one patients with recurrent glioma (31 grade III, 20 grade IV) were included. Among them, 22 subjects (43.1%) received bevacizumab. The median OS was 10.2 months (range, 1 to 27 months). Patients receiving bevacizumab had comparable OS (a median of 9.9 vs. 10.0 months) and similar 6-month survival rate (43% vs. 34%) to those who did not receive bevacizumab. A subgroup analysis failed to notice any significant difference in grade III glioma patients receiving bevacizumab vs. those who did not. The median survival was significantly longer at 8.9 months (range, 4 to 13 months) in grade IV glioma patients receiving bevacizumab than in those who did not (5.6 months, range, 2 to 7 months, P=0.042). The 6-month survival rate was higher (83%) in those who received bevacizumab than in those who did not (47%, P=0.046). No grade 3/4 adverse events were observed in any patient. CONCLUSIONS: Bevacizumab, as a rescue therapy, provides a survival benefit for recurrent grade IV glioma.

The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP are supported only by correlative evidence in vitro. Thus, it remains unclear whether the circulating levels of activin A, BMP4 and BMP6 correlate with flare-ups in FOP patients. Hence, we investigated the protein levels of activin A, BMP4 and BMP6 in the serum of FOP patients. RESULTS: We recruited 16 untreated FOP patients and 16 age- and sex- matched healthy control subjects in this study. The 16 FOP patients were retrospectively divided into the flare-up group (n = 8) and remission group (n = 8) depending on whether they had flare-ups or worsening of any joint movement in the last 6 months. The serum activin A, BMP4 and BMP6 levels were detected by enzyme-linked immunosorbent assay. The serum activin A, BMP4 and BMP6 levels were slightly higher in FOP patients (median: 434.05 pg/mL, 459.48 pg/mL and 67.84 pg/mL) versus healthy control subjects (median: 364.14 pg/mL, 450.39 pg/mL and 55.36 pg/mL). However, there were no statistically significant differences between the two groups (p > 0.05 for all items), nor were there significant differences between the flare-up and remission groups of FOP (p > 0.05 for all items). Univariate and multivariate logistic regression analyses showed that age, sex, and serum activin A, BMP4 and BMP6 levels were not related to flare-up in FOP patients. CONCLUSIONS: There were no significant differences in the serum levels of activin A, BMP4 and BMP6 in FOP patients compared with healthy control subjects. Serum activin A, BMP4 and BMP6 proteins might not be the stimulators for FOP flare-up, and may not be biomarkers for FOP diagnosis.

Tyrosine metabolic reprogramming coordinated with the tricarboxylic acid cycle to drive glioma immune evasion by regulating PD-L1 expression.

Due to the existence of the blood-brain barrier in glioma, traditional drug therapy has a poor therapeutic outcome. Emerging immunotherapy has been shown to have satisfactory therapeutic effects in solid tumors, and it is clinically instructive to explore the possibility of immunotherapy in glioma. We performed a retrospective analysis of RNA-seq data and clinical information in 1027 glioma patients, utilizing machine learning to explore the relationship between tyrosine metabolizing enzymes and clinical characteristics. In addition, we also assessed the role of tyrosine metabolizing enzymes in the immune microenvironment including immune infiltration and immune evasion. Highly expressed tyrosine metabolizing enzymes 4-hydroxyphenylpyruvate dioxygenase, homogentisate 1,2-dioxygenase, and fumarylacetoacetate hydrolase not only promote the malignant phenotype of glioma but are also closely related to poor prognosis. The expression of tyrosine metabolizing enzymes could distinguish the malignancy degree of glioma. More importantly, tyrosine metabolizing enzymes regulate the adaptive immune process in glioma. Mechanistically, multiple metabolic enzymes remodel fumarate metabolism, promote α-ketoglutarate production, induce programmed death-ligand 1 expression, and help glioma evade immune surveillance. Our data suggest that the metabolic subclass driven by tyrosine metabolism provides promising targets for the immunotherapy of glioma.

RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study.

Women with polycystic ovarian syndrome (PCOS) are more likely to have non-alcoholic fatty liver disease (NAFLD) than non-PCOS women; however, the exact mechanism underlying this trend is unknown. The receptor activator of NF-κB ligand (RANKL) is strongly involved in bone metabolism and has multiple functions. Recent studies suggest that RANKL is implicated in hepatic insulin resistance (IR), which is the highest risk factor for NAFLD. This study aimed to assess the role of RANKL in NAFLD in Chinese women with PCOS. A cross-sectional observational study was conducted on women newly diagnosed with PCOS, which included 146 patients with NAFLD and 142 patients without NAFLD. Sex hormones, glucose, insulin, and lipids were measured, and anthropometric data were collected. The concentration of serum total RANKL was measured using commercial ELISA kits. PCOS patients with NAFLD had a significantly higher mean age, body mass index (BMI), waist circumference (WC), and worsened metabolic profile than non-NAFLD subjects. The concentrations of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol increased with the RANKL tertile (p for trend = 0.023, 0.026, and 0.035, respectively). A significantly positive association was found between RANKL (per SD change) and the risks of NAFLD (OR = 1.545, 95% CI = 1.086−2.199) after adjusting for confounders, including demographic factors, metabolic markers, and sex hormones. Subgroup multivariate logistic analyses stratified by age, BMI, and WC showed the same tendency. In addition, the positive association between RANKL and NAFLD seemed more prominent in lean patients with a BMI < 24 kg/m2 (OR = 1.70, 95% CI = 1.06−2.75) when compared to overweight/obesity subjects. Therefore, this study suggests that RANKL is positively associated with the increased risk of NAFLD in Chinese women with PCOS, independent of metabolic and reproductive factors.

Osteocalcin ameliorates cognitive dysfunctions in a mouse model of Alzheimer's Disease by reducing amyloid ß burden and upregulating glycolysis in neuroglia.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by the accumulation of amyloid ß peptides (Aß) and impaired glucose metabolism in the brain. Osteocalcin (OCN), an osteoblast-derived protein, has been shown to modulate brain functions but whether it has any effect on AD is undetermined. In this study, daily intraperitoneal injection of OCN for 4 weeks ameliorated the anxiety-like behaviors and cognitive dysfunctions in the APP/PS1 transgenic AD mice model, as shown in the increased entries into the central area in open field test, the increased time and entries into open arms in elevated plus maze test, the increased time spent in the light chamber in light-dark transition test, as well as the reduced escape latency and the increased preference for target quadrant in Morris water maze test. Aß burden in the hippocampus and cortex of AD mice was ameliorated by OCN. Besides, OCN improved the neural network function of the brain, mainly in the enhanced power of high gamma band in the medial prefrontal cortex of AD mice. The proliferation of astrocytes in the hippocampus in AD mice was also inhibited by OCN as demonstrated by immunofluorescence. Furthermore, OCN enhanced glycolysis in astrocytes and microglia, as evidenced by elevated glucose consumption, lactate production, and increased extracellular acidification rate. Such an effect was abolished when the receptor of OCN - Gpr158 was knockdown in astrocytes. Our study revealed OCN as a novel therapeutic factor for AD potentially through reducing Aß burden and upregulation of glycolysis in neuroglia.

Effects of different modified starches and gums on the physicochemical, functional, and microstructural properties of tapioca pearls.

The effects of different modified starch and gums on the physicochemical, functional, and microstructural properties of tapioca pearls were investigated. The addition of starch acetate (SA) and carboxymethylcellulose (CMC) improved the springiness, hardness, cooking properties, and overall acceptability of pearls. Samples added with CMC presented higher peak viscosities, breakdown viscosities, onset gelatinization temperature, and lower enthalpy of gelatinization values compared to control pearls. Furthermore, Rheology and LF-NMR results indicated that all five kinds of modifiers promoted the formation of tighter network structures in products. SEM showed that the addition of SA and hydroxypropyl distarch phosphate (HDP) could fill the voids in the internal gel network of the pearls, thus promoting the formation of a continuous phase network. This study proved SA, HDP, and CMC as modifiers could have tremendous potential to improve the quality of pearls before and after cooking.

Low Serum 25-Hydroxyvitamin D Levels Are Associated With Hyperandrogenemia in Polycystic Ovary Syndrome: A Cross-Sectional Study.

Background: Increasing evidence suggests a link between vitamin D and polycystic ovary syndrome (PCOS). However, whether vitamin D is related to hyperandrogenemia in PCOS is still inconclusive. The aim of our study is to elucidate the relationship between vitamin D and hyperandrogenemia in women with PCOS in China. Methods: This is a cross-sectional study including 625 Chinese women with PCOS and 217 controls from January 2016 to June 2020. The anthropometric and biochemical parameters related to 25(OH)D, sex steroids, glucose and lipid profiles were measured. Results: Serum 25(OH)D levels were lower in women with PCOS than controls (33.99 ± 15.05 vs 36.58 ± 16.49 nmol/L, P = 0.034), especially lower in hyperandrogenic women with PCOS (32.79 ± 14.24 vs 36.21 ± 16.27 nmol/L, P = 0.007). Higher 25(OH)D levels were independently associated with lower risks of hyperandrogenemia after adjusting demographic, metabolic and hormonal confounders (OR = 0.982, 95% CI: 0.969 - 0.995, P = 0.006). Consistent results were observed in subgroup analyses. Among PCOS women with vitamin D deficiency, females with age ≥ 26 years had lower risks of hyperandrogenemia (OR = 0.611, 95% CI = 0.389 - 0.958, P = 0.032), while overweight patients had higher risks of hyperandrogenemia (OR = 2.202, 95% CI = 1.130 - 4.293, P = 0.020) after adjusting multiple confounders. Conclusions: Our study reported lower vitamin D levels in Chinese women with PCOS, especially in those with hyperandrogenemia. An independent negative correlation between 25(OH)D and hyperandrogenemia was noted in PCOS. For PCOS women with vitamin D deficiency, females that have higher BMI with age < 26 years may be prioritized for hyperandrogenemia assessment.

Hepatitis B virus X protein promotes hepatoma cell proliferation via upregulation of MEKK2.

AIM: To investigate the mechanism underlying the increase of hepatoma cell proliferation by hepatitis B virus X protein (HBx). METHODS: HepG2, H7402 and HepG2.2.15 cells, which constitutively replicated hepatitis B virus were used. The effects of HBx on hepatoma cell proliferation were examined using 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and MTT assay. The expression level of MEKK2 was measured using RT-PCR, Western blot and luciferase reporter gene assay. The activity of activator protein 1 (AP-1) was detected using luciferase reporter gene assay. The phosphorylation levels of JNK and c-Jun were measured using Western blot. The expression levels of HBx and MEKK2 in 11 clinical hepatocellular carcinoma (HCC) tissues were measured using real time PCR and Western blot. In addition, the expression of MEKK2 in 95 clinical HCC tissues was examined using immunohistochemistry. RESULTS: HBx significantly enhanced HepG2-X cell proliferation. In HepG2-X, H7402-X and HepG2.2.15 cells, the expression level of MEKK2 was remarkably increased. In HepG2.2.15 cells, HBx was found to activate JNK and AP-1, which were the downstream effectors of MEKK2 in HepG2-X and HepG2.2.15 cells. In 11 clinical HCC tissues, both HBx and MEKK2 expression levels were remarkably increased, as compared to those in the corresponding peritumor tissues. In 95 clinical HCC tissues, the rate of detection of MEKK2 was 85.3%. CONCLUSION: HBx promotes hepatoma cell proliferation via upregulating MEKK2, which may be involved in hepatocarcinogenesis.