Revealing the BroÌ·nsted Acidic Nature of Penta-Coordinated Aluminum Species in Dealuminated Zeolite Y with Solid-State NMR Spectroscopy.

The inevitable dealumination process of zeolite Y is closely related to ultrastabilization, enhanced BroÌ·nsted acidity, and deactivation throughout its life cycle, producing complex aluminum and acidic hydroxyl species. Most investigations on dehydrated zeolites have focused on the BroÌ·nsted acidity of tetra-coordinated Al (Al(IV)) and Lewis acidity associated with tricoordinated Al (Al(III)) sites, which has left the penta-coordinated Al (Al(V)) in dealuminated zeolites scarcely discussed. This is largely due to the oversimplified view of detectable Al(V) as an exclusively extra-framework species with Lewis acidity. Here we report the formation of BroÌ·nsted acidic penta-coordinated Al species (Al(V)-BAS) in the dealumination process. Two-dimensional (2D) through-bond and multiquantum 1H-{27Al} correlation solid-state NMR experiments demonstrate the presence of a bridging Si-OH-Al(V) structure in dealuminated Y zeolites. Different from the conventional belief that water attack leads to the breaking of zeolite framework Al-O bonds in the initial stage of zeolite dealumination, the observed Al(V) as a dealumination intermediate is directly correlated with a BAS pair because of the direct dissociation of water on the framework tetrahedral aluminum (Al(IV)), thus bypassing the cleavage of Al-O bonds. 1H double-quantum solid-state NMR experiments and theoretical calculations provide further evidence for this mechanism, whereas pyridine adsorption experiments confirm stronger acidity of Al(V)-BASs than the traditional bridging hydroxyl groups associated with Al(IV). We were also able to detect the Al(V)-BAS site from dealuminated SSZ-13 zeolite with CHA topology, suggesting that its creation is not specific to the framework structure of zeolites.

Association of lifestyle with sleep health in general population in China: a cross-sectional study.

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Association of polygenic risk scores with Alzheimer's disease and plasma biomarkers among Chinese older adults: A community-based study.

INTRODUCTION: We examined the associations of polygenic risk score (PRS) with Alzheimer's disease (AD) and plasma biomarkers in the Chinese population. METHODS: This population-based study used baseline data from MIND-China (2018; n = 4873) and follow-up data from dementia-free individuals (2014-2018; n = 2117). We measured AD-related plasma biomarkers in a subsample (n = 1256). Data were analyzed using logistic and Cox regression models. RESULTS: We developed PRS with (PRSAPOE) and without (PRSnon- APOE) apolipoprotein E (APOE) gene. In the longitudinal analysis, PRSAPOE was associated with a multivariable-adjusted hazards ratio of 1.91 (95% CI = 1.13-3.23) for AD. PRSAPOE in combination with demographics yielded discriminative (area under the curve [AUC]) and predictive(C-statistic) accuracy of 0.80 (95% confidence interval [CI] = 0.77-0.84) and 0.80 (0.77-0.82), respectively. PRSnon- APOE showed an association with AD risk similar to PRSAPOE. PRSAPOE, but not PRSnon- APOE, was associated with reduced plasma Aß42/Aß40 ratio and increased Neurofilament light chain (NfL) (p < 0.05). DISCUSSION: The PRS with and without APOE gene, in combination with demographics, shows good discriminative and predictive ability for AD. The AD-related pathologies underlie AD risk associated with PRSAPOE. HIGHLIGHTS: The PRSAPOE and PRSnon- APOE were associated with AD risk in the Chinese population. The PRSAPOE and PRSnon- APOE, in combination with demographics, showed good discriminative and predictive ability for AD. The AD-related pathologies underlie the AD risk associated with PRSAPOE but not PRSnon- APOE.

SUBSTANDARD STARCH GRAIN7 regulates starch grain size and endosperm development in rice.

Starch is synthesized as insoluble, semicrystalline particles within plant chloroplast and amyloplast, which are referred to as starch grains (SGs). The size and morphology of SGs in the cereal endosperm are diverse and species-specific, representing a key determinant of the suitability of starch for industrial applications. However, the molecular mechanisms modulating SG size in cereal endosperm remain elusive. Here, we functionally characterized the rice (Oryza sativa) mutant substandard starch grain7 (ssg7), which exhibits enlarged SGs and defective endosperm development. SSG7 encodes a plant-specific DUF1001 domain-containing protein homologous to Arabidopsis (Arabidopsis thaliana) CRUMPLED LEAF (AtCRL). SSG7 localizes to the amyloplast membrane in developing endosperm. Several lines of evidence suggest that SSG7 functions together with SSG4 and SSG6, known as two regulators essential for SG development, to control SG size, by interacting with translocon-associated components, which unveils a molecular link between SG development and protein import. Genetically, SSG7 acts synergistically with SSG4 and appears to be functional redundancy with SSG6 in modulating SG size and endosperm development. Collectively, our findings uncover a multimeric functional protein complex involved in SG development in rice. SSG7 represents a promising target gene for the biotechnological modification of SG size, particularly for breeding programs aimed at improving starch quality.

Synergistic associations of CD33 variants and hypertension with brain and cognitive aging among dementia-free older adults: A population-based study.

INTRODUCTION: CD33 rs3865444 and hypertension (HTN) are related to cognitive impairment, individually. However, little is known about their combined effects on cognitive function in older adults. METHODS: This population-based study included 4368 dementia-free participants (age ≥65 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND-China), with data available in 1044 persons for gray matter volume and 85 persons for cerebral blood flow (CBF). We used general linear regression and mediation models to examine the associations of rs3865444 and HTN with cognition, brain atrophy, and CBF. RESULTS: Among rs3865444 CC carriers, HTN and late-life HTN were significantly associated with impaired cognition. Midlife and late-life HTN were correlated with brain atrophy. CD33 rs3865444 CC moderated the mediation effect of gray matter volume on the association between HTN and global cognition. HTN was correlated with low CBF in rs3865444 CC carriers. DISCUSSION: There are synergistic associations of CD33 rs3865444 and HTN with brain and cognitive aging in dementia-free older adults.

Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment.

With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research in this area tends to develop functional microcarriers for stem cell and Exo delivery to improve the therapeutic effect. Herein, we develop a novel system of Exo-encapsulated stem cell-recruitment hydrogel microcarriers from liquid nitrogen-assisted microfluidic electrospray for OA treatment. Benefited from the advanced droplet generation capability of microfluidics and mild cryogelation procedure, the resultant particles show uniform size dispersion and excellent biocompatibility. Moreover, acryloylated stem cell recruitment peptides SKPPGTSS are directly crosslinked within the particles by ultraviolet irradiation, thus simplifying the peptide coupling process and preventing its premature release. The SKPPGTSS-modified particles can recruit endogenous stem cells to promote cartilage repair and the released Exo from the particles further enhances the cartilage repair performance through synergistic effects. These features suggest that the proposed hydrogel microcarrier delivery system is a promising candidate for OA treatment.

High-Frequency Hearing Loss, Hippocampal Volume, and Motoric Cognitive Risk Syndrome in Older Adults in China: A Population-Based Study.

Background: Little is known about the associations of hearing loss, hippocampal volume, and motoric cognitive risk syndrome (MCR) in older adults. Objective: We aimed to investigate the associations of hearing loss with MCR and hippocampal volume; and the interaction of hearing loss with hippocampal volume on MCR. Methods: This population-based cross-sectional study included 2,540 dementia-free participants (age≥60 years; 56.5% women) in the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China. Data were collected through face-to-face interviews, clinical examination, and laboratory tests. Hearing function was assessed using pure tone audiometry test. In the subsample (n = 661), hippocampal volume was assessed on structural magnetic resonance images. Data were analyzed with logistic regression models. Results: In the total sample, MCR was diagnosed in 246 persons (9.7%). High-frequency hearing loss was significantly associated with an increased likelihood of MCR and slow gait. In the subsample, the restricted cubic spline plots indicated an inverted U-shaped nonlinear relationship between high-frequency hearing performance and hippocampal volume. Moreover, greater hippocampal volume was significantly associated with a deduced likelihood of MCR and subjective cognitive decline (SCD). In addition, there were statistical interactions of high-frequency hearing loss with hippocampal volume on MCR and slow gait (p for interaction < 0.05), such that the associations were statistically significant only among participants free of high-frequency hearing loss. Conclusions: High-frequency hearing loss was associated with an increased likelihood of MCR in older adults. The hippocampus might play a part in the relationship of high-frequency hearing loss and MCR.

Short time-series expression transcriptome data reveal the gene expression patterns and potential biomarkers of blood infection with LPS and poly (I:C) in Mandarin fish (Siniperca chuatsi).

Blood transcriptomics has emerged as a vital tool for tracking the immune system and supporting disease diagnosis, prognosis, treatment, and research. The present study was conducted to analyze the gene expression profile and potential biomarker candidates using the whole blood of mandarin fish (Siniperca chuatsi) infected with LPS or poly (I:C) at 0 h, 3 h, 6 h, and 12 h. Our data suggest that 310 shared differentially expressed genes (DEGs) were identified among each comparison group after LPS infection, and 137 shared DEGs were identified after poly (I:C) infection. A total of 62 shared DEGs were differentially expressed in all compared groups after LPS or poly (I:C) infection. Pathways analysis for DEGs in all different compared groups showed that cytokine-cytokine receptor interaction was the most enrichment pathway. The expression levels of genes C-X-C chemokine receptor type 2-like (cxcr2), chemokine (C-C motif) receptor 9a (ccr9a), chemokine (C-C motif) receptor 9b (ccr9b), chemokine (C-X-C motif) receptor 4b (cxcr4b), and interleukin 10 receptor alpha (il10ra) were significantly different in all compared groups and most enriched in cytokine-cytokine receptor interaction pathway. The protein-protein interactions analysis among all shared DEGs showed that cxcr4 was the hub gene with the highest degree. The biomarker candidates discovered in this study may, following validation, prove effective as diagnostic tools in monitoring mandarin fish diseases.

Associations of 24-hour movement behaviors with depressive symptoms in rural-dwelling older adults: a compositional data analysis.

BACKGROUND: We aimed to explore the association of sleep duration with depressive symptoms among rural-dwelling older adults in China, and to estimate the impact of substituting sleep with sedentary behavior (SB) and physical activity (PA) on the association with depressive symptoms. METHODS: This population-based cross-sectional study included 2001 rural-dwelling older adults (age ≥ 60 years, 59.2% female). Sleep duration was assessed using the Pittsburgh Sleep Quality Index. We used accelerometers to assess SB and PA, and the 15-item Geriatric Depression Scale to assess depressive symptoms. Data were analyzed using restricted cubic splines, compositional logistic regression, and isotemporal substitution models. RESULTS: Restricted cubic spline curves showed a U-shaped association between daily sleep duration and the likelihood of depressive symptoms (P-nonlinear < 0.001). Among older adults with sleep duration < 7 h/day, reallocating 60 min/day spent on SB and PA to sleep were associated with multivariable-adjusted odds ratio (OR) of 0.81 (95% confidence interval [CI] = 0.78-0.84) and 0.79 (0.76-0.82), respectively, for depressive symptoms. Among older adults with sleep duration ≥ 7 h/day, reallocating 60 min/day spent in sleep to SB and PA, and reallocating 60 min/day spent on SB to PA were associated with multivariable-adjusted OR of 0.78 (0.74-0.84), 0.73 (0.69-0.78), and 0.94 (0.92-0.96), respectively, for depressive symptoms. CONCLUSIONS: Our study reveals a U-shaped association of sleep duration with depressive symptoms in rural older adults and further shows that replacing SB and PA with sleep or vice versa is associated with reduced likelihoods of depressive symptoms depending on sleep duration.

Both middle and large envelope proteins can mediate neutralization of hepatitis B virus infectivity by anti-preS2 antibodies: escape by naturally occurring preS2 deletions.

Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins containing preS1/preS2/S, preS2/S, and S domain alone, respectively. S and preS1 domains mediate sequential virion attachment to heparan sulfate proteoglycans and sodium taurocholate cotransporting polypeptide (NTCP), respectively, which can be blocked by anti-S and anti-preS1 antibodies. How anti-preS2 antibodies neutralize HBV infectivity remains enigmatic. The late stage of chronic HBV infection often selects for mutated preS2 translation initiation codon to prevent M protein expression, or in-frame preS2 deletions to shorten both L and M proteins. When introduced to infectious clone of genotype C or D, both M-minus mutations and most 5' preS2 deletions sustained virion production. Such mutant progeny viral particles were infectious in NTCP-reconstituted HepG2 cells. Neutralization experiments were performed on the genotype D clone. Although remaining susceptible to anti-preS1 and anti-S neutralizing antibodies, M-minus mutants were only partially neutralized by two anti-preS2 antibodies tested while preS2 deletion mutants were resistant. By infection experiments using viral particles with lost versus increased M protein expression, or a neutralization escaping preS2 deletion only present on L or M protein, we found that both full-length L and M proteins contributed to virus neutralization by the two anti-preS2 antibodies. Thus, immune escape could be a driving force for the selection of M-minus mutations, and especially preS2 deletions. The fact that both L and M proteins could mediate neutralization by anti-preS2 antibodies may shed light on the underlying molecular mechanism.IMPORTANCEThe large (L), middle (M), and small (S) envelope proteins of hepatitis B virus (HBV) contain preS1/preS2/S, preS2/S, and S domain alone, respectively. The discovery of heparan sulfate proteoglycans and sodium taurocholate cotransporting polypeptide (NTCP) as the low- and high-affinity HBV receptors could explain neutralizing potential of anti-S and anti-preS1 antibodies, respectively, but how anti-preS2 neutralizing antibodies work remains enigmatic. In this study, we found two M-minus mutants in the context of genotype D partially escaped two anti-preS2 neutralizing antibodies in NTCP-reconstituted HepG2 cells, while several naturally occurring preS2 deletion mutants escaped both antibodies. By point mutations to eliminate or enhance M protein expression, and by introducing preS2 deletion selectively to L or M protein, we found binding of anti-preS2 antibodies to both L and M proteins contributed to neutralization of wild-type HBV infectivity. Our finding may shed light on the possible mechanism(s) whereby anti-preS2 antibodies neutralize HBV infectivity.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

[Regulatory effect of Tingli Dazao Xiefei Decoction on asthmatic rats by urine metabolomics].

Urine metabolomics based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was utilized to investigate the metabolic regulation mechanism of Tingli Dazao Xiefei Decoction(TLDZ) in rats with allergic asthma. SD male rats were divided into a normal group, a model group, a dexamethasone group, and a TLDZ group. The allergic asthma model was established by intraperitoneal injection of ovalbumin(OVA) to induce allergy, combined with atomization excitation. Urine metabolites from all rats were collected by UHPLC-Q-TOF-MS. The metabolic profiles of rats in each group were built by principal component analysis(PCA). Besides, the differential metabolites between the model group and the TLDZ group were selected by orthogonal partial least squares discriminant analysis(OPLS-DA), t-test(P<0.05), and variable importance in the projection(VIP) values of more than 3. The differential metabolites were identified through HMDB, METLIN, and other online databa-ses. Heat maps and clustering analysis for relative quantitative information of biomarkers in each group were drawn by MeV 4.8.0 software. Finally, MetaboAnalyst, MBRole, and KEGG databases were used to enrich related metabolic pathways and construct metabolic networks. The result demonstrated that TLDZ could effectively regulate the disordered urine metabolic profiles of asthmatic rats. Combined with multivariate statistical analysis and online databases, a total of 45 differential metabolites with significant changes(P<0.05) between the model group and the TLDZ group were screened out. Metabolic pathways including histidine metabolism, tryptophan metabolism, and arginine and proline metabolism were enriched. TLDZ could improve asthma by regulating related metabolic pathways and interfering with pathological processes such as immune homeostasis airway inflammation. The study investigates the molecular mechanism of anti-asthma of TLDZ from the perspective of urine metabolomics, and combined with previous pharmacological studies, it provides a scientific basis for the clinical development and application of TLDZ in the treatment of asthma.

Development and validation of a diagnostic model for cerebral small vessel disease among rural older adults in China.

Objectives: Cerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults. Methods: This study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis. Results: The model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67-0.76) in the training set and 0.69 (95% CI, 0.63-0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50-90% in the training set, and 65-98% in the validation set. Conclusion: A model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

Association of enlarged perivascular spaces with cognitive function in dementia-free older adults: A population-based study.

Introduction: We sought to characterize cognitive profiles associated with enlarged perivascular spaces (EPVS) among Chinese older adults. Methods: This population-based study included 1191 dementia-free participants (age ≥60 years) in the MIND-China MRI Substudy (2018-2020). We visually evaluated EPVS in basal ganglia (BG) and centrum semiovale (CSO), white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and cortical superficial siderosis. We used a neuropsychological test battery to assess cognitive function. Data were analyzed using general linear models. Results: Greater BG-EPVS load was associated with lower z-scores in memory, verbal fluency, and global cognition (p < 0.05); these associations became non-significant when controlling for other cerebral small vessel disease (CSVD) markers (e.g., WMHs, lacunes, and mixed CMBs). Overall, CSO-EPVS load was not associated with cognitive z-scores (p > 0.05); among apolipoprotein E (APOE) -ε4 carriers, greater CSO-EPVS load was associated with lower verbal fluency z-score, even when controlling for other CSVD markers (p < 0.05). Discussion: The associations of BG-EPVS with poor cognitive function in older adults are largely attributable to other CSVD markers. HIGHLIGHTS: The association of enlarged perivascular spaces (EPVS) with cognitive function in older people is poorly defined.The association of basal ganglia (BG)-EPVS with poor cognition is attributed to other cerebral small vessel disease (CSVD) markers.In apolipoprotein E (APOE) ε4 carriers, a higher centrum semiovale (CSO)-EPVS load is associated with poorer verbal fluency.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study.

Background: Clinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis. Methods: Data of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups' clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients' prognosis. Results: There was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70-0.87; CSS: AUC 0.74-0.89). Conclusion: Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.

Macrophage GIT1 promotes oligodendrocyte precursor cell differentiation and remyelination after spinal cord injury.

Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.

Epigallocatechin gallate protects MC3T3-E1 cells from cadmium-induced apoptosis and dysfunction via modulating PI3K/AKT/mTOR and Nrf2/HO-1 pathways.

Epigallocatechin gallate (EGCG), an active constituent of tea, is recognized for its anticancer and anti-inflammatory properties. However, the specific mechanism by which EGCG protects osteoblasts from cadmium-induced damage remains incompletely understood. Here, the action of EGCG was investigated by exposing MC3T3-E1 osteoblasts to EGCG and CdCl2 and examining their growth, apoptosis, and differentiation. It was found that EGCG promoted the viability of cadmium-exposed MC3T3-E1 cells, mitigated apoptosis, and promoted both maturation and mineralization. Additionally, CdCl2 has been reported to inhibit both the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathways. EGCG treatment attenuated cadmium-induced apoptosis in osteoblasts and restored their function by upregulating both signaling pathways. The findings provide compelling evidence for EGCG's role in attenuating cadmium-induced osteoblast apoptosis and dysfunction through activating the PI3K/AKT/mTOR and Nrf2/HO-1 pathways. This suggests the potential of using EGCG for treating cadmium-induced osteoblast dysfunction.

Untargeted serum and gastric metabolomics and network pharmacology analysis reveal the superior efficacy of zingiberis rhizoma recens-/euodiae fructus-processed Coptidis Rhizoma on gastric ulcer rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. AIM OF THE STUDY: To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. MATERIAL AND METHODS: First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. RESULTS: zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. CONCLUSION: zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.

The lifestyle for brain health index, the cluster of differentiation 33 (CD33) gene, and cognitive function among rural Chinese older adults: A population-based study.

BACKGROUND: We sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. METHODS: This population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33(rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. RESULTS: A higher LIBRA index was associated with multivariable-adjusted ß-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33(rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: ß-coefficient=0.042; 95 %CI=0.008-0.077), the dominant (CA+AA vs. CC: 0.040; 0.007-0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009-0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (Pinteraction<0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). CONCLUSIONS: This population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association.