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Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD.

Mutations in AT‐rich interactive domain‐containing protein 1A (ARID1A) cause Coffin‐Siris syndrome (CSS), a rare genetic disorder that results in mild to severe intellectual disabilities. However, the biological role of ARID1A in the brain remains unclear. In this study, we report that the haploinsufficiency of ARID1A in excitatory neurons causes cognitive impairment and defects in hippocampal synaptic transmission and dendritic morphology in mice. Similarly, human embryonic stem cell‐derived excitatory neurons with deleted ARID1A exhibit fewer dendritic branches and spines, and abnormal electrophysiological activity. Importantly, supplementation of acetate, an epigenetic metabolite, can ameliorate the morphological and electrophysiological deficits observed in mice with Arid1a haploinsufficiency, as well as in ARID1A ‐null human excitatory neurons. Mechanistically, transcriptomic and ChIP‐seq analyses demonstrate that acetate supplementation can increase the levels of H3K27 acetylation at the promoters of key regulatory genes associated with neural development and synaptic transmission. Collectively, these findings support the essential roles of ARID1A in the excitatory neurons and cognition and suggest that acetate supplementation could be a potential therapeutic intervention for CSS. Synopsis Mutations in ARID1A cause Coffin‐Siris syndrome (CSS), a rare genetic disorder with severe neurodevelopmental deficits. This study investigates the genetic basis of the pathophysiological role of ARID1A in CSS and proposes a potential therapeutic intervention. Arid1a haploinsufficiency in mouse excitatory neurons leads to spatial memory defects. ARID1A is required for neuron dendritic and synapse growth in mice and humans. Acetate supplementation rescues the neuronal deficits by increasing H3K27 acetylation levels at the promoters of neuronal genes in both Arid1a haploinsufficient mice and ARID1A KO hESC‐derived neurons. Graphical Abstract Mutations in ARID1A cause Coffin‐Siris syndrome (CSS), a rare genetic disorder with severe neurodevelopmental deficits. This study investigates the genetic basis of the pathophysiological role of ARID1A in CSS and proposes a potential therapeutic intervention.

Salvia miltiorrhiza Burge (Danshen) is an eminent medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries. Accumulating evidence suggests that Danshen and its components prevent vascular diseases, in particular, atherosclerosis and cardiac diseases, including myocardial infarction, myocardial ischemia/reperfusion injury, arrhythmia, cardiac hypertrophy and cardiac fibrosis. The published literature indicates that lipophilic constituents (tanshinone I, tanshinone IIa, tanshinone IIb, cryptotanshinone, dihydrotanshinone, etc) as well as hydrophilic constituents (danshensu, salvianolic acid A and B, protocatechuic aldehyde, etc) contribute to the cardiovascular protective actions of Danshen, suggesting a potential synergism among these constituents. Herein, we provide a systematic up-to-date review on the cardiovascular actions and therapeutic potential of major pharmacologically active constituents of Danshen. These bioactive compounds will serve as excellent drug candidates in small-molecule cardiovascular drug discovery. This article also provides a scientific rationale for understanding the traditional use of Danshen in cardiovascular therapeutics.

Papillary thyroid carcinoma (PTC) represents a malignant epithelial tumor characterized with a preference for younger individuals. Despite its generally favorable prognosis, PTC still poses considerable challenges, particularly in regards to the propensity for distant metastasis. As a key enzyme in the glycolytic pathway, phosphoglycerate kinase 1 (PGK1) has been linked to the progression of various cancer types. However, its role in PTC remains to be elucidated. This study aimed to investigate the association between PGK1 expression in thyroid cancer tissues and clinicopathological features, postoperative recurrence, and prognosis to provide clinical assessment and intervention reference. We investigated the correlation between PGK1 expression and the clinicopathological characteristics, recurrence, and prognosis in 97 PTC patients who underwent surgical treatments between 1 January 2020, and 31 December 2020 in Zhengzhou University First Affiliated Hospital. Besides, we also analysed the correlation of PGK1 expression with the 10-year survival rate of patients with thyroid carcinoma (THCA) in UALCAN database. PGK1 expression was higher in cancerous tissues than that in adjacent non-cancerous tissues. Further analysis of PGK1 expression across clinicopathological characteristics revealed that patients with poorly differentiated tumors, TNM stages III-IV, lymph node metastasis, and tumor diameter ≥1.0 cm exhibited higher PGK1 expression levels in cancerous tissues. A subsequent 3-year postoperative follow-up was conducted to evaluate the correlation between PGK1 expression and recurrence. During this period, 31.96% of patients experienced recurrence, with higher PGK1 expression correlating with increased recurrence rates. Moreover, patients with higher PGK1 expression in cancerous tissue exhibited a significantly lower survival rate of 79.20% compared to the PGK1-low/medium group. Lastly, age, lymph node metastasis, differentiation degree, TNM stage, and tumor diameter were identified as risk factors for poor prognosis in patients with PTC analyzed by Cox regression. Our study demonstrated that PGK1 expression may serve as a potential prognostic biomarker of PTC.

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide, and novel therapeutic targets still need to be investigated to alleviate myocardial injury and the ensuing maladaptive cardiac remodelling. Accumulating studies have indicated that lncRNA H19 might exert a crucial regulatory effect on cardiovascular disease. In this study, we aimed to explore the biological function and molecular mechanism of H19 in MI. To investigate the biological functions of H19, miRNA‐22‐3p and KDM3A, gain‐ and loss‐of‐function experiments were performed. In addition, bioinformatics analysis, dual‐luciferase reporter assays, RNA immunoprecipitation (RIP) assays, RNA pull‐down assays, quantitative RT‐PCR and Western blot analyses as well as rescue experiments were conducted to reveal an underlying competitive endogenous RNA (ceRNA) mechanism. We found that H19 was significantly down‐regulated after MI. Functionally, enforced H19 expression dramatically reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating myocardial apoptosis and decreasing inflammation. However, H19 knockdown resulted in the opposite effects. Bioinformatics analysis and dual‐luciferase assays revealed that, mechanistically, miR‐22‐3p was a direct target of H19, which was also confirmed by RIP and RNA pull‐down assays in primary cardiomyocytes. In addition, bioinformatics analysis and dual‐luciferase reporter assays also demonstrated that miRNA‐22‐3p directly targeted the KDM3A gene. Moreover, subsequent rescue experiments further verified that H19 regulated the expression of KDM3A to ameliorate MI‐induced myocardial injury in a miR‐22‐3p‐dependent manner. The present study revealed the critical role of the lncRNAH19/miR‐22‐3p/KDM3A pathway in MI. These findings suggest that H19 may act as a potential biomarker and therapeutic target for MI.

•NIR methods for qualitative and quantitative analysis of drugs have been established.•1118 samples were used for the model building and validation purposes.•The RMSEC, RMSECV, and RMSEP for all models were less than 1.6%, 2.9%, and 3.6%, respectively. Rapid and nondestructive near infrared spectroscopy (NIR) methods have been developed for simultaneous qualitative and quantitative analysis of methamphetamine, ketamine, heroin, and cocaine in seized samples. This is the first systematic report regarding a qualitative and quantitative procedure of applying NIR for drug analysis. A total of 282 calibration samples and 836 prediction samples were used for the building and validating of qualitative and quantitative models. Two qualitative analysis modeling methods for soft independent modeling by class analogy (SIMCA) and supporting vector machine (SVM) were compared. From its excellent performance in rejecting false positive results, SIMCA was chosen. The drug concentrations in the calibration and validation sample sets were analyzed using high-performance liquid chromatography. Based on the use of first-order derivative spectral data after standard normal variate (SNV) transformation correction, in the wavelength range from 10,000 to 4000cm−1, four partial least squares quantitative-analysis models were built. The coefficients of determination for all calibration models were >99.3, and the RMSEC, RMSECV, and RMSEP were all less than 1.6, 2.9, and 3.6%, respectively. The results obtained here indicated that NIR with chemometric methods was accurate for qualitative and quantitative analysis of drug samples. This methodology provided a potentially useful alternative to time-consuming gas chromatography–mass spectroscopy and high-performance liquid chromatography methods.

This study was to investigate the effects of Tai Chi (TC) and whole-body vibration (WBV) exercise in sarcopenic men in advanced old age. Ninety sarcopenic men (mean age 88.6 years; age range 85–101 years) were divided into three groups: TC group, WBV group, and control (CON) group. Patients in the two treatment groups received 8 weeks of training in either TC or WBV, while the control group received reminders not to change their level of physical exercise or lifestyle. Patients in all groups also received health information related to sarcopenia. Muscle mass, muscle strength, and physical performance [balance, gait speed, timed-up-and-go test (TUGT), and five-times-sit-to-stand test (FTSST)] were analyzed and compared among the three groups. Finally, seventy-nine subjects completed the study (TC n  = 24; WBV n  = 28; and CON 27). Muscle strength was significantly increased in the TC and WBV groups compared to the control group ( P  < 0.01). Following 8 weeks of exercise, improvements were observed in all physical performance tests for the TC and WBV groups ( P  < 0.05). The improvement in balance was greater in the TC group than the WBV group. Time × Group effects revealed significant improvements in muscle strength in the lower extremities ( P  < 0.05) and physical performance ( P  < 0.01) in both the TC and WBV groups. Changes in muscle mass, as measured by dual-energy X-ray absorptiometry, did not significantly differ between groups. These findings indicate that TC and WBV are effective treatments for improving muscle strength and physical performance in sarcopenic men in advanced old age.

Oxidative stress is mainly caused by intracellular reactive oxygen species (ROS) production, which is highly associated with normal physiological homeostasis and the pathogenesis of diseases, particularly ocular diseases. Autophagy is a self-clearance pathway that removes oxidized cellular components and regulates cellular ROS levels. ROS can modulate autophagy activity through transcriptional and posttranslational mechanisms. Autophagy further triggers transcription factor activation and degrades impaired organelles and proteins to eliminate excessive ROS in cells. Thus, autophagy may play an antioxidant role in protecting ocular cells from oxidative stress. Nevertheless, excessive autophagy may cause autophagic cell death. In this review, we summarize the mechanisms of interaction between ROS and autophagy and their roles in the pathogenesis of several ocular diseases, including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and optic nerve atrophy, which are major causes of blindness. The autophagy modulators used to treat ocular diseases are further discussed. The findings of the studies reviewed here might shed light on the development and use of autophagy modulators for the future treatment of ocular diseases.

Objective Previous observational studies on the association between aspirin use, bone mineral density (BMD), and fracture risk have yielded controversial results. This study explored the causal relationship between aspirin use, BMD, and fracture risk using Mendelian randomization (MR). Methods Summary data for aspirin use and BMD of five different body parts (femoral neck, lumbar spine, forearm, heel, and ultra distal forearm) and fractures were obtained from the integrative epidemiology unit open genome-wide association studies database for bidirectional MR analysis. An appropriate model was chosen based on Cochran's Q test, with inverse variance-weighted as the primary method for MR analysis, supplemented by the weighted-median and MR-Egger methods. MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy and exclude significant outliers that could bias the results. Various sensitivity analyses, including leave-one-out analysis, were conducted to ensure the robustness of the findings. Results Aspirin use significantly increased lumbar spine BMD (odds ratio [OR] = 4.660; 95% confidence interval [CI]: 1.365–15.906; P  = 0.014). No significant causal association was found between aspirin use and fracture risk (beta = 59.951; 95% CI: -265.189–385.091; P  = 0.718). No significant reverse causality was observed. Conclusion This study indicates that aspirin use does not significantly affect fracture risk but has a significant protective effect on lumbar spine BMD, revealing a potential benefit of aspirin against osteoporosis.

ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.