Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Carbon emissions in China's steel industry from a life cycle perspective: Carbon footprint insights.

China is the most important steel producer in the world, and its steel industry is one of the most carbon-intensive industries in China. Consequently, research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals. We constructed a carbon dioxide (CO2) emission model for China's iron and steel industry from a life cycle perspective, conducted an empirical analysis based on data from 2019, and calculated the CO2 emissions of the industry throughout its life cycle. Key emission reduction factors were identified using sensitivity analysis. The results demonstrated that the CO2 emission intensity of the steel industry was 2.33 ton CO2/ton, and the production and manufacturing stages were the main sources of CO2 emissions, accounting for 89.84% of the total steel life-cycle emissions. Notably, fossil fuel combustion had the highest sensitivity to steel CO2 emissions, with a sensitivity coefficient of 0.68, reducing the amount of fossil fuel combustion by 20% and carbon emissions by 13.60%. The sensitivities of power structure optimization and scrap consumption were similar, while that of the transportation structure adjustment was the lowest, with a sensitivity coefficient of less than 0.1. Given the current strategic goals of peak carbon and carbon neutrality, it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies, increase the ratio of scrap steel to steelmaking, and build a new power system.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Graphitic carbon @ silver nanoparticle @ porous silicon Bragg mirror composite SERS substrate for gallic acid detection.

Graphite carbon (G) @ silver (Ag) @ porous silicon Bragg mirror (PSB) composite SERS substrate was successfully synthesized using electrochemical etching (ec) and hydrothermal carbonization (HTC) techniques with silver nitrate as the source of silver and glucose as the source of carbon. The PSB was used as a functional scaffold for the synthesis of graphite-carbon and silver composite nanoparticles (G@AgNPs) on its surface, thereby combining SERS activity and antioxidant properties. To our knowledge, this is the first time that G@AgNPs has been synthesized on the PSB using glucose as a carbon source. The synthesized G@Ag@PSB was utilized as a SERS platform for the detection of gallic acid (GA). Test results demonstrated that the substrate exhibited a remarkable SERS enhancement capability for GA, with the enhancement factor (EF) reaching 2 × 105. The reproducibility of the SERS spectral signal was excellent, with a relative standard deviation (RSD) of 7.5 %. The sensitivity test results showed that the linear range of GA detection based on G@Ag@PSB composite SERS substrate was 2 × 10-3-2 × 10-12M. The relationship between GA concentration and SERS signal intensity exhibited a strong linear correlation, with a linear correlation coefficient (R2) of 0.97634. Moreover, even with an extended storage period, only a marginal decline in the signal intensity of GA on the substrate was observed. The results of this study demonstrate that the prepared G@Ag@PSB composite SERS substrate had good potential application performance as a low-cost SERS detection platform suitable for commercial use. In addition, this advance facilitates the further exploration of more nanomaterials with ultra-high sensitivity in SERS technology.

Retroreflective optical ISAC using OFDM: channel modeling and performance analysis.

In this Letter, we propose and investigate a retroreflective optical integrated sensing and communication (RO-ISAC) system using orthogonal frequency division multiplexing (OFDM) and corner cube reflector (CCR). To accurately model the reflected sensing channel of the RO-ISAC system, both a point source model and an area source model are proposed according to the two main types of light sources that are widely used. Detailed theoretical and experimental results are presented to verify the accuracy of the proposed channel models and evaluate the communication and sensing performance of the considered RO-ISAC system.

Electron Deficiency is More Important than Conductivity in C-N Coupling for Electrocatalytic Urea Synthesis.

The electrocatalytic C-N coupling from CO2 and nitrate emerges as one of the solutions for waste upgrading and urea synthesis. In this work, we constructed electron-deficient Cu sites by the strong metal-polymer semiconductor interaction, to boost efficient and durable urea synthesis. In situ Raman spectroscopy identified the existence of electron-deficient Cu sites and was able to withstand electrochemical reduction conditions. Operando synchrotron-radiation Fourier transform infrared spectroscopy and theoretical calculations disclosed the vital role of electron-deficient Cu in adsorption and C-N coupling of oxygen-containing species. The electron-deficient Cu displayed a high urea yield rate of 255.0 mmol h-1 g-1 at -1.4 V versus the reversible hydrogen electrode and excellent electrochemical durability, superior than that of non-electron-deficient counterpart with conductive carbon material as the support. It can be concluded that the regulation of site electronic structure is more important than the optimization of catalyst conductive properties in the C-N coupling reactions.

Recent racial/ethnic disparities in cancer-specific mortality among patients diagnosed with rectal cancer.

Background: African American patients frequently receive nonstandard treatment and demonstrate poorer overall survival (OS) outcomes compared to White patients. Our objective was to analysis whether racial/ethnic disparities in rectal cancer-specific mortality remain after accounting for clinical characteristics, treatment, and access-to-care-related factors. Methods: Individuals diagnosed with rectal cancer between 2011 and 2020 were identified using the Surveillance, Epidemiology, and End Results Database. The cumulative incidence of rectal cancer-specific mortality was computed. Sub-distribution hazard ratios (sdHRs) and 95% confidence intervals (CIs) for rectal cancer-specific mortality associated with race/ethnicity were estimated using Fine and Gray model with stepwise adjustments for clinical characteristics, treatment modalities, and factors related to access-to-care. Results: Among 54,370 patients, non-Hispanic (NH) Black individuals exhibited the highest cumulative incidence of rectal cancer-specific mortality (39%), followed by American Indian/Alaska Native (AI/AN) (35%), Hispanics (32%), NH-White (31%), and Asian/Pacific Islander (API) (30%). After adjusting for clinical characteristics, NH-Black patients had a 28% increased risk of rectal cancer mortality (sdHR, 1.28; 95% CI: 1.20-1.35) compared to NH-White patients. In contrast, mortality disparities between Hispanic-White, AI/AN-White, and API-White groups were not significant. The Black-White mortality differences persisted even after adjustments for treatment and access-to-care-related factors. In stratified analyses, among patients with a median household income below $59,999, AI/AN patients showed higher mortality than NH-Whites when adjusted for clinical characteristics (sdHR, 1.32; 95% CI: 1.03-1.70). Conclusions: Overall, the racial/ethnic disparities in rectal cancer-specific mortality were largely attributable to differences in clinical characteristics, treatment modalities, and factors related to access-to-care. These findings emphasize the critical need for equitable healthcare to effectively address and reduce the significant racial/ethnic disparities in rectal cancer outcomes.

Impact of patent foramen ovale with left-to-right shunt on atrial fibrillation ablation in young patients.

OBJECTIVE: The CABANA study shows that atrial fibrillation (AF) paitents younger than 65 years benefit more from the AF radiofrequency catheter ablation (RFCA) procedure. The aim of this study is to investigate the impact of inherent patent foramen ovale (PFO) with a Left-to-Right Shunt on the RFCA procedure in young AF patients. METHODS: Based on the presence or absence of inherent PFO, the AF patients were divided into the PFO groups and the non-PFO group. Clinical follow-up was also investigated. RESULTS: A total of 285 AF patients were enrolled. PFO was detected by TEE in 42 patients. The age of patients at initial AF onset was younger in the PFO group than in the non-PFO group (58.3 ± 8.9 vs. 62.3 ± 9.6 years, P = 0.012). There were more AF patients aged <55 years in the PFO group than in the non-PFO group. For the 9 AF patients with PFO who experienced AF recurrence and the left-to-right shunts decreased in size in 5 of the patients aged <65 years. The LAD decreased in those patients. In the PeAF patients, 53/64 patients aged <65 years and 23/40 patients aged older than 65 years were free of AF (82.8 % vs. 57.5 %, respectively; P = 0.005). CONCLUSION: Success is not affected when AF is combined PFO compared with AF without PFO. Young patients have better PeAF RFCA outcomes. AF in young patients with left atria enlargement and a serious AF burden, may lead to reduced EF and render PFO easy to detect.

Mangiferin alleviates cisplatin-induced ototoxicity in sensorineural hearing loss.

Mangiferin(MGF) exhibits crucial biological roles, including antioxidant and anti-inflammatory functions. However, how to clearly elucidate the functioning mechanism of MGF for inhibiting cisplatin-induced hearing loss requires in-depth investigation. In this work, we aimed at gaining insight into how MGF functions as the protective agent against cisplatin-triggered ototoxicity using various assays. The variation for reactive oxygen species (ROS) concentrations was determined with MitoSOX-Red and 2',7'-Dichlorodihydrofluorescein diacetate staining (DCFH-DA). The protective function and corresponding mechanism of MGF in hair cell survival in the House Ear Institute-Organ of Corti (HEI-OC1) cell line were assessed using RNA sequencing (RNA-Seq). Our findings demonstrated that MGF significantly alleviated cisplatin-induced injury to hair cells in vitro, encompassing cell lines and cochlear explants, as well as in vivo models, including C57BL/6 J mice and zebrafish larvae. Mechanistic studies revealed that MGF reversed the increased accumulation of ROS and inhibited cell apoptosis through mitochondrial-mediated intrinsic pathway. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting data indicated MGF protected against cisplatin-mediated ototoxicity via the mitogen-activated protein kinase pathway (MAPK). These findings demonstrated MGF has significant potential promise in combating cisplatin-induced ototoxicity, offering a foundation for expanded investigation into therapeutic approaches for auditory protection.

Rectal adenocarcinoma: Ex vivo 9.4T MRI-correlation with histopathologic treatment response to neoadjuvant chemoradiotherapy.

OBJECTIVES: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. METHODS: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. RESULTS: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. CONCLUSION: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma.

BACKGROUND: Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes. METHODS: Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP. RESULTS: TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus. CONCLUSIONS: Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.

Epidemiological features of suicidal ideation among the elderly in China based meta-analysis.

BACKGROUND: Studies on the prevalence of suicidal ideation (SI) and its associated factors among the elderly in China show considerable variability. This meta-analysis aims to clarify the epidemiological features of SI in this population. METHODS: We systematically searched English and Chinese databases for relevant literature up to September 15, 2022. The extracted data facilitated the calculation of prevalence and odds ratios (ORs) for factors associated with SI among China's elderly. RESULTS: We analyzed 31 cross-sectional studies, comprising a total of 79,861 participants from over 20 provinces and municipalities. The pooled prevalence of SI was found to be 11.47% [95% confidence interval (CI): 7.82-15.71%]. Significant variations in prevalence were influenced by residence, physical health (including chronic diseases and daily living capabilities), mental health (depressive symptoms and life satisfaction), economic status, and time-specific assessment tools. Notably, the prevalence from 2011-2020 (15.59%, 95% CI: 9.08-23.44%) was almost double that of 2001-2010 (7.85%, 95% CI: 5.08-11.16%). The SI prevalence in the eastern region (8.06%, 95% CI 5.59-10.94%) was significantly lower than in the central and western regions (16.97%, 95% CI 12.04-22.53%). Fourteen factors exhibited a significant pooled OR greater than 1 (p < 0.05), and two factors had ORs less than 1 (p < 0.05), indicating notable association with SI among the elderly. CONCLUSION: SI among China's elderly showed relatively high prevalence and considerable heterogeneity across different characteristics and associated factors. This underscores the need for targeted intervention strategies and standardized temporal assessments of SI to effectively address suicide risk in this population.

Characterization of the tumor microenvironment in breast cancer brain metastasis.

Objective: The difference in the tumor microenvironment (TME) between primary breast cancer (PBC) and breast cancer brain metastasis (BCBM) is still unknown. Herein, we present the landscape of the TME in PBC and BCBM to better understand the process of BCBM. Methods: The Gene Expression Omnibus (GEO) database was used to obtain suitable PBC and BCBM data. Hub genes that were differentially expressed between the two groups were searched. Gene Ontology (GO) and KEGG were used to define the gene's function. Single-cell data were also analyzed to determine the difference between PBC and BCBM. Results: Two datasets (GSE100534 and GSE125989) were used to search for hub genes, and 79 genes were either upregulated or downregulated between the two groups. Four hub genes (COL1A1, PDGFR, MMP3 and FZD7) were related to prognosis. GO and KEGG analyses showed that extracellular matrix and focal adhesion play major roles in the metastasis process. Another two datasets (GSE176078 and GSE186344) were enrolled for single-cell analysis. Single-cell analysis demonstrated that immune cells (66.6 %) form the main part of PBC, while cancer-associated fibroblasts (CAFs) (21.7 %) are the main component of BCBM. Immune cell proportion analysis showed that CD4+/CD8+ T cells (28.9 % and 14.3 %, respectively) and macrophages(M2) accounted for the majority of cells in PBC and BCBM, respectively. Further analysis of the classification of CAFs showed that apCAFs were significantly higher in PBC. Conclusions: This study presents the landscape of BCBM with hub gene searching and single-cell analysis. Showing the difference in the tumor/immune microenvironment of PBC and BCBM, would be beneficial to explore immunotherapy and targeted therapy for BCBM.

Esterase-Activated Hydrogen Sulfide Donors with Self-Reporting Fluorescence Properties and Highly Tunable Rates of Delivery.

Hydrogen sulfide (H2S) has emerged as a significant biomolecule with diverse activities, akin to other gaseous signaling molecules such as nitric oxide (NO) and carbon monoxide (CO). In the present study, we report on the development of esterase-activated donors that track their direct cellular donation of H2S by enlisting a cyclization reaction onto a thioamide that forms a fluorogenic byproduct. This simple donor design provides a noninvasive method for monitoring the biological delivery and activity of H2S, along with access to a library of compounds with highly variable rates of H2S delivery. These studies culminated with the identification of a slow-release, yet highly efficient, donor (ZL-DMA-Ph) that was shown to self-report its gradual and continuous cellular donation of H2S for up to 24 h which, in addition to better mimicking the natural biosynthesis of H2S, provided impressive cytoprotection in a cellular cardiotoxicity model, even at submicromolar concentrations. In total, these findings indicate that the esterase-triggered fluorogenic donors identified in this study will offer new opportunities for exploring the chemical biology and therapeutic potential of exogenous H2S supplementation.

Bio-inspired Mechanically Responsive Smart Windows for Visible and Near-Infrared Multiwavelength Spectral Modulation.

Mechanochromic light control technology that can dynamically regulate solar irradiation is recognized as one of the leading candidates for energy-saving windows. However, the lack of spectrally selective modulation ability still hinders its application for different scenarios or individual needs. Here, inspired by the generation of structure color and color change of living organisms, a simple layer-by-layer assembly approach toward large-area fabricating mechanically responsive film for visible and near-infrared multiwavelength spectral modulation smart windows is reported here. The assembled SiO2 nanoparticles and W18O49 nanowires enable the film with an optical modulation rate of up to 42.4% at the wavelength of 550 nm and 18.4% for the near-infrared region, separately, and the typical composite film under 50% stretching shows ≈41.6% modulation rate at the wavelength of 550 nm with NIR modulation rate less than 2.7%. More importantly, the introduction of the multilayer assembly structure not only optimizes the film's optical modulation but also enables the film with high stability during 100 000 stretching cycles. A cooling effect of 21.3 and 6.9 °C for the blackbody and air inside a model house in the real environmental application is achieved. This approach provides theoretical and technical support for the new mechanochromic energy-saving windows.

Chromosome-specific painting reveals the Y genome origin and chromosome rearrangements of the St genome in Triticeae.

Karyotypes provide key cytogenetic information on phylogenetic relationships and evolutionary origins in related plant species. The St genome of Pseudoroegneria contributes to eight alloploid genera, representing over half of the species that are highly valuable for wheat (Triticum aestivum) breeding and for understanding Triticeae species evolution. However, St chromosome characterization is challenging due to limited cytogenetic markers and DNA information. We developed a complete set of St genome-specific chromosome painting probes for identification of the individual chromosomes 1St to 7St based on the genome sequences of Pse. libanotica and wheat. We revealed the conservation of St chromosomes in St-containing species by chromosome painting, including Pseudoroegneria, Roegneria, Elymus, and Campeiostachys. Notably, the Y genome showed hybridization signals, albeit weaker than those of the St genome. The awnless species harboring the Y genome exhibited more intense hybridization signals compare to the awned species in Roegneria and Campeiostachys, yet weaker than the hybridization signals of the St genome in autotetraploid Pse. strigosa. Although awnless species were morphologically more similar to each other, phenotypic divergence progressively increased from awnless to awned species. Our results indicate that the Y genome originated from the St genome and shed light on the possible origin of the Roegneria and Campeiostachys species, enhancing our understanding of St-genome-containing species evolution.

Association Between Remnant Cholesterol and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-Analysis.

Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.

Evaluation of glucose-lowering medications in older people: a comprehensive systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is increasingly being diagnosed in older adults. Our objective is to assess the advantages and potential drawbacks of different glucose-lowering medications in this specific population. METHODS: A network meta-analysis was conducted to identify randomized controlled trials that examined patient-centered outcomes in adults aged ≥65 years with T2DM. We searched PubMed, Cochrane CENTRAL, and Embase up to September 23, 2023. Quality of eligible studies were assessed using the Cochrane RoB 2.0 tool. RESULTS: A total of 22 trials that involved 41 654 participants were included, incorporating sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, sulfonylureas (SU) and acarbose. Our findings reveal that GLP-1RAs reduce the risk of major adverse cardiovascular events (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.97) and body weight (mean difference [MD], -3.87 kg; 95% CI, -5.54 to -2.21). SGLT2 inhibitors prevent hospitalization for heart failure (RR, 0.66; 95% CI, 0.57 to 0.77), renal composite outcome (RR, 0.69; 95% CI, 0.53 to 0.89), and reduce body weights (MD, -1.85 kg; 95% CI, -2.42 to -1.27). SU treatment increases the risk of any hypoglycaemia (RR, 4.19; 95% CI, 3.52 to 4.99) and severe hypoglycaemia (RR, 7.06; 95% CI, 3.03 to 16.43). GLP-1RAs, SGLT2 inhibitors, metformin, SU and DPP-4 inhibitors are effective in reducing glycaemic parameters. Notably, the number of treatments needed decreases in most cases as age increases. CONCLUSIONS: Novel glucose-lowering medications with benefits that outweigh risks should be prioritized for older patients with diabetes.