Crossmodal to unimodal transfer of temporal perceptual learning.

Subsecond temporal processing is crucial for activities requiring precise timing. Here, we investigated perceptual learning of crossmodal (auditory-visual or visual-auditory) temporal interval discrimination (TID) and its impacts on unimodal (visual or auditory) TID performance. The research purpose was to test whether learning is based on a more abstract and conceptual representation of subsecond time, which would predict crossmodal to unimodal learning transfer. The experiments revealed that learning to discriminate a 200-ms crossmodal temporal interval, defined by a pair of visual and auditory stimuli, significantly reduced crossmodal TID thresholds. Moreover, the crossmodal TID training also minimized unimodal TID thresholds with a pair of visual or auditory stimuli at the same interval, even if crossmodal TID thresholds are multiple times higher than unimodal TID thresholds. Subsequent training on unimodal TID failed to reduce unimodal TID thresholds further. These results indicate that learning of high-threshold crossmodal TID tasks can benefit low-threshold unimodal temporal processing, which may be achieved through training-induced improvement of a conceptual representation of subsecond time in the brain.

Muscle Mass Adjusted by Body Height is not Correlated with Mobility of Middle-Aged and Older Adults.

Background: Low muscle mass and obesity are associated with mobility disability, cardiometabolic diseases, and loss of independence. Three skeletal muscle indices (SMIs) are proposed to adjust the body size of individuals. However, it is unknown which index is better correlated with mobility. Additionally, it remains unclear whether low muscle mass or abdominal obesity has a greater impact on the mobility and cardiometabolic health of older adults. Objectives: This study explored the association between different SMIs {appendicular skeletal muscle mass [ASM] adjusted by body height [Ht], body weight [Wt], or body mass index [BMI (kg/m2)]} and mobility/cardiometabolic health. The roles of low muscle mass and abdominal obesity in the mobility and cardiometabolic health of individuals were also identified. Methods: Four-hundred and twenty-seven community-dwelling middle-aged and older adults underwent body composition assessments [dual-energy x-ray absorptiometry and waist circumference (WC)], grip strength, and mobility (timed up-and-go test and chair stand test). Spearman's rank correlation coefficient and regression models were used to examine research questions. This study was registered in the Thai Clinical Trials Registry (registration number: TCTR20210521007). Results: All SMIs were positively correlated with the grip strength (ASM/Ht2: r = 0.392; ASM/Wt: r = 0.439; ASM/BMI: r = 0.569). Regarding mobility, only ASM/Ht2 wasn't relevant. After adjusting for age, sex, and WC, ASM/BMI was the only SMI associated with grip strength (ß = 0.274). When age and sex were controlled, WC, but not SMI, was associated with mobility and cardiometabolic health. Conclusions: ASM/Ht2 did not correlate with mobility in middle-aged and older adults, whereas ASM/Wt and ASM/BMI did. Abdominal obesity has a greater impact on mobility and cardiometabolic health than low muscle mass in middle-aged and older adults. We recommend using ASM/BMI to identify the low muscle mass of individuals. In addition, clinicians should note the important role of abdominal obesity when considering mobility in middle-aged and older adults.

Age Differences in Prosociality Across the Adult Lifespan: A Meta-Analysis.

Lifespan developmental theories and research suggest a positive effect of adult age on prosociality. However, this effect lacks consistency, with many studies excluding the period of midlife. This study summarized cross-sectional studies on adult age and prosociality, combining 120 (independent) samples (n = 103,829) in a lifespan meta-analysis approach. Linear and quadratic age effects on prosociality were analyzed, as well as comparisons between younger, middle-aged, and older adults. Prosociality was assessed via behavioral measures and self-reports. In both these domains, results indicated small linear age effects and higher prosociality in older compared to younger adults, supporting the hypothesis of increased prosociality in older age. Additionally, leveraging open data sets (64/120 independent samples), predominantly unpublished, we found some evidence for potential quadratic age effects on behavioral prosociality: Middle-aged adults exhibited higher behavioral and self-reported prosociality than younger adults, but no differences between middle-aged and older adults were observed. This meta-analysis offers new perspectives on age trajectories of prosociality, suggesting midlife as a potentially important phase of pronounced prosociality.

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Crohn's disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study.

Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation. Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments. Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland. Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

Associations Between Obstructive Sleep Apnea Syndrome, Dry Eye Disease, and CPAP Usage Among Taiwanese Patients: A Retrospective Analysis.

Study Objectives: To evaluate the association between obstructive sleep apnea (OSA) and dry eye disease (DED) and analyze the impact of Continuous Positive Airway Pressure (CPAP) on DED. Methods: This is a retrospective population-based case-control study. Patients who underwent polysomnography in Taiwan from March 1, 2009, to March 1, 2020, were identified from the database of a sleep center. Patients who were diagnosed with keratoconjunctivitis sicca or tear film insufficiency were included. Patients without data from Schirmer's test, lacking tear break-up time values, or with a history of refractive surgery, Sjögren's syndrome, ocular injuries, or a disability in eyelid closure were excluded. All patients with DED enrolled had DED in both eyes. OSA severity between patients with and without DED was compared. Results: In total, 86 patients with DED and 86 age-matched patients without DED were enrolled. Significant differences in apnea-hypopnea index values (patients with DED: 29.1 ± 23.4, patients without DED: 17.9 ± 20.2, P < 0.001), OSA severity (P < 0.001), and lowest oxygen saturation (P = 0.040) between patients with and without DED were observed. A multivariate logistic regression model indicated that the use of CPAP was independently associated with DED after adjustments for OSA severity. Patients undergoing CPAP were at greater risk of developing DED than those not undergoing CPAP (Odds ratio: 3.93, 95% confidence interval: 1.47-10.49, P = 0.006). Conclusion: OSA severity is associated with DED and might be attributed to the use of CPAP.

Clonal expansion of Tn1546-like transposon-carrying vancomycin-resistant Enterococcus faecium, a nationwide study in Taiwan, 2004-2018.

OBJECTIVES: The prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased significantly in Taiwan. We investigated the molecular epidemiology of clinical VREfm isolates to increase our understanding on their spread and changes in population structure over a 14-year span. METHODS: A total of 1113 E. faecium isolates were collected biennially from 2004 to 2018 in Taiwan. MICs were determined by broth microdilution. Whole-genome sequencing (WGS) was performed on 229 VREfm isolates to characterize their genetic environment of vancomycin resistance and wgMLST was used to investigate their clonal relationship. RESULTS: Among the 229 isolates, ST17 and ST78 predominated, especially during the later years, and their prevalences increased from 14.6% (7/48) and 25.0% (12/48) in 2004-2010 to 47.5% (87/181) and 29.8% (54/181) in 2012-2018, respectively. Four types of vanA-carrying Tn1546 variants were detected, with type 1 and type 2 predominated. Type 1 Tn1546 contained an addition of IS1251, while type 2 resembled type 1 but had an addition of IS1678. wgMLST revealed several distinct clusters of ST17 and ST78 isolates, with type 1 Tn1546-harbouring ST17-Cluster 16 being the largest and most widespread clones throughout the study years. Type 2 Tn1546-carrying ST78 became a predominant clone (Cluster 21) after 2012. Isolates within these clusters are highly similar despite being from different hospitals, regions, and study year. CONCLUSION: The increase of VREfm in Taiwan was attributed to horizontal transfer of vanA-carrying Tn1546 variants between different STs and spread of persistent clones. This study highlights the importance of integrating WGS into surveillance to combat antimicrobial resistance.

Cortical processes of multisensory plausibility modulation of vibrotactile perception in virtual environments in middled-aged and older adults.

Digital technologies, such as virtual or augmented reality, can potentially support neurocognitive functions of the aging populations worldwide and complement existing intervention methods. However, aging-related declines in the frontal-parietal network and dopaminergic modulation which progress gradually across the later periods of the adult lifespan may affect the processing of multisensory congruence and expectancy based contextual plausibility. We assessed hemodynamic brain responses while middle-aged and old adults experienced car-riding virtual-reality scenarios where the plausibility of vibrotactile stimulations was manipulated by delivering stimulus intensities that were either congruent or incongruent with the digitalized audio-visual contexts of the respective scenarios. Relative to previous findings observed in young adults, although highly plausible vibrotactile stimulations confirming with contextual expectations also elicited higher brain hemodynamic responses in middle-aged and old adults, this effect was limited to virtual scenarios with extreme expectancy violations. Moreover, individual differences in plausibility-related frontal activity did not correlate with plausibility violation costs in the sensorimotor cortex, indicating less systematic frontal context-based sensory filtering in older ages. These findings have practical implications for advancing digital technologies to support aging societies.

Imipenem reduces the efficacy of vancomycin against Elizabethkingia species.

BACKGROUND: Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion. METHODS: Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions. RESULTS: Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin. CONCLUSIONS: Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.

Changing epidemiology and antimicrobial resistance of bacteria causing bacteremia in Taiwan: 2002-2020.

Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July-September as part of the TSAR program. The three most common bacteremia agents were Escherichia coli (31%), Staphylococcus aureus (13.6%), and Klebsiella pneumoniae (12.7%) overall. However, there was a steady increase in the proportions of E. coli and Enterococcus faecium isolated from bacteremia cases (both P < 0.001), while the proportions of Acinetobacter spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among E. coli and K. pneumoniae, while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in E. coli. Of concern is the alarming increase in vancomycin resistance among E. faecium, rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant S. aureus has remained stable at 51.2% overall. In conclusion, E. coli, with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of E. faecium in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade. IMPORTANCE: AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002-2020 TSAR program. The study highlights an alarming increase in the proportion of E. faecium causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions.

[Environmental regulation of water use efficiency in Artemisia ordosica in Mu Us Sandy Land: From leaf to ecosystem]. / æ¯›ä¹Œç´ æ²™åœ°é»‘æ²™è’¿æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡çŽ¯å¢ƒè°ƒæŽ§:从叶片到生态系统.

Water use efficiency (WUE) is a key indicator for predicting the impacts of climate change on ecosystem carbon and water cycles. Most studies have explored the changes in the response environment of WUE at a particular scale. Few studies have examined how WUE responds to environments at multiple scales, thus limiting our in-depth understanding of the cross-scale carbon and water cycles. In this study, we measured photosynthesis and transpiration in situ periodically and continuously from June to October 2022 in a community dominated by Artemisia ordosica in Mu Us Sandy Land, and analyzed the seasonal variations in WUE at leaf, canopy, and ecosystem scales. The results showed there were significant seasonal variations in leaf water use efficiency (WUEL), canopy water use efficiency (WUET), and ecosystem water use efficiency (WUEE). WUEL was large in June and small in both August and September, ranging from 0.73-2.98 µmol·mmol-1. Both WUET and WUEE were lowest in June and highest in July and August, ranging from 0.10-7.00 and 0.06-6.25 µmol·mmol-1. WUEL was significantly negatively correlated with stomatal conductance. WUET was significantly positively correlated with canopy conduc-tance and soil water content, and negatively correlated with vapor pressure deficit (VPD). There was a significant positive correlation between WUEE and soil water content (SWC10) in 10 cm soil depth. The structural equation model showed that SWC10 and air temperature affected net photosynthetic rate and transpiration rate by modifying stomatal conductance, and thus affecting WUEL. VPD and SWC10 affected WUET by altering transpiration. SWC10, air temperature, and VPD affected WUEE by regulating ecosystem gross primary productivity. The modelling of carbon and water cycles should thoroughly consider the path and intensity of the effect of environmental factors on WUE at multiple scales.

Discovery of novel EGFR-PROTACs capable of degradation of multiple EGFR-mutated proteins.

Although three generations of Epidermal growth factor receptor (EGFR) - TK inhibitors have been approved for the treatment of Non-small-cell lung cancers (NSCLC), their clinical application is still largely hindered by acquired drug resistance mediated new EGFR mutations and side effects. The Proteolysis targeting chimera (PROTAC) technology has the potential to overcome acquired resistance from mutant EGFR through a novel mechanism of action. In this study, we developed the candidate degrader IV-3 by structural modifications of the lead compound 13, which exhibited limited antiproliferative activity against HCC-827 cells. Compared to compound 13, IV-3 exhibited remarkable anti-proliferative activity against HCC-827 cells, NCI-H1975 cells, and NCI-H1975-TM cells (IC50 = 0.009 µM, 0.49 µM and 3.24 µM, respectively), as well as significantly inducing degradation of EGFR protein in these cell lines (DC50 = 17.93 nM, 0.25 µM and 0.63 µM, respectively). Further investigations confirmed that IV-3 exhibited superior anti-tumor activity in all xenograft tumor models through the degradation of mutant EGFR protein. Moreover, IV-3 showed no inhibitory activity against A431 and A549 cells expressing wild-type EGFR, thereby eliminating potential toxic side effects emerging from wild-type EGFR inhibition. Overall, our study provides promising insights into EGFR-PROTACs as a potential therapeutic strategy against EGFR-acquired mutation.

The individual contributions of blaB, blaGOB and blaCME on MICs of ß-lactams in Elizabethkingia anophelis.

BACKGROUND: The blaB, blaGOB and blaCME genes are thought to confer ß-lactam resistance to Elizabethkingia anophelis, based on experiments conducted primarily on Escherichia coli. OBJECTIVES: To determine the individual contributions of ß-lactamase genes to increased MICs in E. anophelis and to assess their impact on the in vivo efficacy of carbapenem therapy. METHODS: Scarless gene deletion of one or more ß-lactamase gene(s) was performed in three clinical E. anophelis isolates. MICs were determined by broth microdilution. Hydrolytic activity and expressions of ß-lactamase genes were measured by an enzymatic assay and quantitative RT-PCR, respectively. In vivo efficacy was determined using Galleria mellonella and murine thigh infection models. RESULTS: The presence of blaB resulted in >16-fold increases, while blaGOB caused 4-16-fold increases of carbapenem MICs. Hydrolysis of carbapenems was highest in lysates of blaB-positive strains, possibly due to the constitutionally higher expression of blaB. Imipenem was ineffective against blaB-positive isolates in vivo in terms of improvement of the survival of wax moth larvae and reduction of murine bacterial load. The deletion of blaB restored the efficacy of imipenem. The blaB gene was also responsible for a >4-fold increase of ampicillin/sulbactam and piperacillin/tazobactam MICs. The presence of blaCME, but not blaB or blaGOB, increased the MICs of ceftazidime and cefepime by 8-16- and 4-8-fold, respectively. CONCLUSIONS: The constitutionally and highly expressed blaB gene in E. anophelis was responsible for increased MICs of carbapenems and led to their poor in vivo efficacy. blaCME increased the MICs of ceftazidime and cefepime.

Cost-effectiveness of diabetic retinopathy screening for newly diagnosed type 2 diabetic patients: A nationwide population-based propensity score-matched cohort study.

AIMS: This study investigated the association between the frequency of screening for diabetic retinopathy (DR) versus the development of DR and corresponding medical expenses among patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS: This longitudinal, population-based study used the Taiwan National Health Insurance Research Database (2004 to 2020) as a data source. Propensity score matching (PSM) (sex, age, comorbidities and concurrent medication use) was employed in the grouping of T2DM patients according to different frequency of DR screening. Outcome measures included the proportion of patients who developed DR, who received DR treatment, and the associated medical expenses and hospitalizations. RESULTS: The 17-year cohort included 337,046 patients. After PSM, three groups each containing 35,739 patients were assembled and analyzed. Compared to low-frequency screening, high-frequency screening was more effective in detecting patients requiring treatment; however, the net cost for treatment was significantly lower. Standard-frequency screening appears to provide the best balance in terms of DR detection, diagnosis interval, the risk of DR-related hospitalization, and DR treatment costs. CONCLUSIONS: In this real-world cohort study covering all levels of the healthcare system, infrequent screening was associated with delayed diagnosis and elevated treatment costs, while a fundus screening interval of 1-2 years proved optimal in terms of detection and medical expenditures.

Licochalcone D ameliorates lipid metabolism in hepatocytes by modulating lipogenesis and autophagy.

Metabolic dysfunction-associated fatty liver disease is a metabolic disease caused by abnormal lipid accumulation in the liver. Excessive lipid accumulation results in liver inflammation and fibrosis. Previous studies have demonstrated that the chalcone licochalcone D, which is isolated from Glycyrrhiza inflata Batal, has anti-tumor and anti-inflammatory effects. The present study explored whether licochalcone D can regulate lipid accumulation in fatty liver cells. FL83B hepatocytes were incubated with oleic acid to establish a fatty liver cell model, and then treated with licochalcone D to evaluate the molecular mechanisms underlying the regulation of lipid metabolism. In addition, male C57BL/6 mice were fed a methionine/choline-deficient diet to induce an animal model of metabolic dysfunction-associated steatohepatitis (MASH) and given 5 mg/kg licochalcone D by intraperitoneal injection. In cell experiments, licochalcone D significantly reduced lipid accumulation in fatty liver cells and reduced sterol regulatory element-binding protein 1c expression, blocking fatty acid synthase production. Licochalcone D increased adipose triglyceride lipase and carnitine palmitoyltransferase 1 expression, enhancing lipolysis and fatty acid ß-oxidation, respectively. Licochalcone D also significantly increased SIRT-1 and AMPK phosphorylation, reducing acetyl-CoA carboxylase phosphorylation and inhibiting fatty acid synthesis. Licochalcone D also increased the fusion of autophagosomes and lysosomes to promote autophagy, reducing oil droplet accumulation in fatty liver cells. In the animal experiments, licochalcone D effectively reduced the number of lipid vacuoles and degree of fibrosis in liver tissue and inhibited liver inflammation. Thus, licochalcone D can improve MASH by reducing lipid accumulation, inhibiting inflammation, and increasing autophagy.

A review on triterpenoid and triterpenoid saponins from Xanthoceras sorbifolium Bung.

Xanthoceras sorbifolium Bunge, also known as Tu-Mu-Gua and Wen-Dan-Ge-Zi, has several applications. Clinical data and experimental studies have shown anti-tumor, anti-inflammatory, anti-bacterial, and anti-oxidant properties of Xanthoceras sorbifolium Bunge that inhibits prostate hyperplasia, lowers blood pressure and lipid level, and treats enuresis and urinary incontinence. It also has neuroprotective effects and can treat Alzheimer's disease and Parkinson's syndrome. The research on the chemical composition and pharmacological effects of Xanthoceras sorbifolium Bunge has been increasing. Triterpenoid and triterpenoid saponins are the main constituents in Xanthoceras sorbifolium Bunge and exhibit biological activities. In this review, we summarized the research progress on triterpenoids and their glycosides in Xanthoceras sorbifolia, including the chemical constituents, pharmacological activities, and biogenic pathways of triterpenoid mother nucleus. The results would provide a reference for further research and development of triterpenoids and their glycosides in Xanthoceras sorbifolia.

Development and characterization of discontinuous atmospheric pressure interface - Dual pressure chamber miniature mass spectrometer.

Miniaturized mass spectrometers have become increasingly prevalent for real-time detection and analysis, owing to their compact size and portability. The pursuit of performance enhancement in these instruments is a pivotal objective within the domain of mass spectrometry miniaturization. This study introduces a novel miniature mass spectrometer featuring a discontinuous atmospheric pressure interface and a dual pressure chamber. Compared to conventional single-chamber, discontinuous sampling interface mass spectrometers, the newly developed instrument demonstrates a more than tenfold improvement in detection efficiency. This significant enhancement is achieved without the need for complex control of switch coupling time series, thereby streamlining the circuit design and improving the instrument's fault tolerance. Furthermore, by capitalizing on the benefits of discontinuous sampling, the instrument reduces the operational pressure relative to traditional continuous sampling in differential pressure vacuum chambers. It accommodates larger inlet capillary (0.38 mm) and skimmer (0.5 mm) diameters, leading to a ninefold increase in response strength for risperidone and lowering the detection limit to 0.5 ppb. The instrument's capacity for rapid drug detection, along with enhanced resolution and detection limits, underscores its potential utility. Additionally, it facilitates the use of smaller mechanical pumps, significantly diminishing both the instrument's volume and power consumption. This presents a promising avenue for further miniaturization of mass spectrometers.

Microstructural Characteristics and Properties of Laser-Welded Diamond Saw Blade with 30CrMo Steel.

In order to enhance the quality of diamond composite materials, this work employs a Cu-Co-Fe and Ni-Cr-Cu pre-alloyed powder mixture as a transition layer, and utilizes laser-welding technology for saw blade fabrication. By adjusting the laser-welding process parameters, including welding speed and welding power, well-formed welded joints were achieved, and the microstructure and mechanical properties of the welded joints were investigated. The results demonstrate that the best welding performance was achieved at a laser power of 1600 W and a welding speed of 1400 mm/min, with a remarkable tooth engagement strength of up to 819 MPa. The fusion zone can be divided into rich Cu phase and rich Fe phase regions, characterized by coarse grains without apparent preferred orientation. The microstructure of the heat-affected zone primarily consists of high-hardness brittle quenched needle-like martensite, exhibiting a sharp increase in microhardness up to 550 HV. Fracture occurred at the boundary between the fusion zone and the heat-affected zone of the base material, where stress concentration was observed. By adjusting the welding parameters and transition layer materials, the mechanical properties of the joints were improved, thereby achieving a reliable connection between diamond composite materials and the metal substrate.