Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy.

JOURNAL/nrgr/04.03/01300535-202506000-00027/figure1/v/2024-08-05T133530Z/r/image-tiff Degenerative cervical myelopathy is a common cause of spinal cord injury, with longer symptom duration and higher myelopathy severity indicating a worse prognosis. While numerous studies have investigated serological biomarkers for acute spinal cord injury, few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy. This study involved 30 patients with degenerative cervical myelopathy (51.3 ± 7.3 years old, 12 women and 18 men), seven healthy controls (25.7 ± 1.7 years old, one woman and six men), and nine patients with cervical spondylotic radiculopathy (51.9 ± 8.6 years old, three women and six men). Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics. Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities. Using least absolute shrinkage and selection operator analysis, we constructed a five-gene model (TBCD, TPM2, PNKD, EIF4G2, and AP5Z1) to diagnose degenerative cervical myelopathy with an accuracy of 93.5%. One-gene models (TCAP and SDHA) identified mild and severe degenerative cervical myelopathy with accuracies of 83.3% and 76.7%, respectively. Signatures of two immune cell types (memory B cells and memory-activated CD4+ T cells) predicted levels of lesions in degenerative cervical myelopathy with 80% accuracy. Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Detecting biomarkers by dynamic nuclear polarization enhanced magnetic resonance.

Hyperpolarization stands out as a technique capable of significantly enhancing the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Dynamic nuclear polarization (DNP), among various hyperpolarization methods, has gained prominence for its efficacy in real-time monitoring of metabolism and physiology. By administering a hyperpolarized substrate through dissolution DNP (dDNP), the biodistribution and metabolic changes of the DNP agent can be visualized spatiotemporally. This approach proves to be a distinctive and invaluable tool for non-invasively studying cellular metabolism in vivo, particularly in animal models. Biomarkers play a pivotal role in influencing the growth and metastasis of tumor cells by closely interacting with them, and accordingly detecting pathological alterations of these biomarkers is crucial for disease diagnosis and therapy. In recent years, a range of hyperpolarized DNP molecular bioresponsive agents utilizing various nuclei, such as 13C, 15N, 31P, 89Y, etc., have been developed. In this context, we explore how these magnetic resonance signals of nuclear spins enhanced by DNP respond to biomarkers, including pH, metal ions, enzymes, or redox processes. This review aims to offer insights into the design principles of responsive DNP agents, target selection, and the mechanisms of action for imaging. Such discussions aim to propel the future development and application of DNP-based biomedical imaging agents.

First-principles calculations to investigate the impact of fluorine doping on electrochemical properties of Li-rich Li2MnO3 layered cathode materials.

Li-rich layered oxides are promising candidates for high-capacity Li-ion battery cathode materials. In this study, we employ first-principles calculations to investigate the effect of F doping on Li-rich Li2MnO3 layered cathode materials. Our findings reveal that both Li2MnO3 and Li2MnO2.75F0.25 exhibit significant volume changes (greater than 10%) during deep delithiation, which could hinder the cycling of more Li ions from these two materials. For Li2MnO3, it is observed that oxygen ions lose electrons to compensate for charge during the delithiation process, leading to a relatively high voltage plateau. After F doping, oxidation occurs in both the cationic (Mn) and anionic (O) components, resulting in a lower voltage plateau at the beginning of the charge, which can be attributed to the oxidation of Mn3+ to Mn4+. Additionally, F doping can somewhat suppress the release of oxygen in Li2MnO3, improving the stability of anionic oxidation. However, the increase of the activation barriers for Li diffusion can be observed after F doping, due to stronger electrostatic interactions between F- and Li+, which adversely affects the cycling kinetics of Li2MnO2.75F0.25. This study enhances our understanding of the impact of F doping in Li2MnO3 based on theoretical calculations.

The impact and mechanism study of Sijunzi decoction and Rg1 on proliferation and differentiation of human umbilical cord mesenchymal stem cells: An experimental study.

BACKGROUND: Previous researches have demonstrated that the traditional Chinese medicine could therapeutically treat inflammatory and hypoxic diseases by enhancing the functionality of mesenchymal stem cells. However, its mechanism was not yet clear. This research aimed to investigate the impact of the traditional Chinese medicine Sijunzi decoction and its herb monomer ginsenoside Rg1 on the proliferation and differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and explore the underlying mechanisms. METHODS: Different concentrations of Sijunzi decoction and Rg1 were applied to differentiating induced hUC-MSCs. The CCK-8 test was utilized to evaluate cell proliferation activity and identify suitable drug concentrations. Alizarin Red staining was employed to detect the formation of calcium nodules, and Oil Red O staining was used to assess the formation of lipid droplets. PCR was utilized to examine gene expression related to osteogenic differentiation, adipogenic differentiation, and the HIF-1α signaling pathway in hUC-MSCs. Western blot analysis was conducted to evaluate protein expression in osteogenic differentiation and HIF-1α. ELISA was performed to measure HIF-1α signaling factors and inflammatory cytokine expression. Biochemical assays were used to assess changes in oxidative stress indicators. RESULTS: The Sijunzi decoction and Rg1 both demonstrated a dose-dependent promotion of hUC-MSC proliferation. The Sijunzi decoction significantly increased the expression of genes and proteins relevant to osteogenesis, such as osterix, osteocalcin, RUNX2, and osteopontin, and activated the HIF-1α pathway in hUC-MSCs. (P < .05). Similar effects were observed at the gene level after treatment with Rg1. Simultaneously, Sijunzi decoction significantly reduced the secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, while increasing the secretion of the anti-inflammatory cytokine IL-10 during osteogenic differentiation (P < .05). Moreover, Sijunzi decoction lowered oxidative stress levels and enhanced the antioxidant capacity of hUC-MSCs during osteogenic differentiation (P < .05). However, the impact of Sijunzi decoction on hUC-MSCs toward adipogenic differentiation was not significant (P > .05). CONCLUSION: Sijunzi decoction promotes the proliferation and osteogenic differentiation of hUC-MSCs, potentially through the activation of the HIF-1α signaling pathway and by modulating the microenvironment via reducing inflammation and oxidative stress levels. Rg1 might be involved in this process.

Trimetazidine attenuates Ischemia/Reperfusion-Induced myocardial ferroptosis by modulating the Sirt3/Nrf2-GSH system and reducing Oxidative/Nitrative stress.

Ferroptosis is a newly defined mode of cellular demise. The increasing investigation supports that ferroptosis is a crucial factor in the complex mechanisms of myocardial ischemia-reperfusion (I/R) injury. Hence, targeting ferroptosis is a novel strategy for treating myocardial injury. Although evidence suggests that trimetazidine (TMZ) is potentially efficacious against myocardial injury, the exact mechanism of this efficacy is yet to be fully elucidated. This study aimed to determine whether TMZ can act as a ferroptosis resistor and affect I/R-mediated myocardial injury. To this end, researchers have constructed in vitro and in vivo models of I/R using H9C2 cardiomyocytes, primary cardiomyocytes, and SD rats. Here, I/R mediated the onset of ferroptosis in vitro and in vivo, as reflected by excessive iron aggregation, GSH depletion, and the increase in lipid peroxidation. TMZ largely reversed this alteration and attenuated cardiomyocyte injury. Mechanistically, we found that TMZ upregulated the expression of Sirt3. Therefore, we used si-Sirt3 and 3-TYP to interfere with Sirt3 action in vitro and in vivo, respectively. Both si-Sirt3 and 3-TYP partly mitigated the inhibitory effect of TMZ on I/R-mediated ferroptosis and upregulated the expression of Nrf2 and its downstream target, GPX4-SLC7A11. These results indicate that TMZ attenuates I/R-mediated ferroptosis by activating the Sirt3-Nrf2/GPX4/SLC7A11 signaling pathway. Our study offers insights into the mechanism underlying the cardioprotective benefits of TMZ and establishes a groundwork for expanding its potential applications.

Intercomparison of measured and modelled photochemical ozone production rates: Suggestion of chemistry hypothesis regarding unmeasured VOCs.

Ozone (O3) pollution is a severe environmental problem in China. The incomplete understanding of atmospheric photochemical reaction mechanisms prevents us from accurately understanding the chemistry of O3 production. Here, we used an improved dual-channel reaction chamber technique to measure net photochemical O3 production rate (P(O3)net) directly in Dongguan, a typical industrial city in China. The maximum P(O3)net was 46.3 ppbv h-1 during the observation period, which is at a relatively high level compared to previous observations under different environment worldwide. We employed an observation-based box model coupled with the state-of-the-art atmospheric chemical mechanism (MCM v3.3.1) to investigate the chemistry of O3 production. Under the base scenario, the modelling underestimates P(O3)net by ~30 %. Additionally considering HO2 uptake by ambient aerosols, inorganic deposition, and Cl chemistry only caused a small change (< 13 %) in the simulation of P(O3)net. Further analysis indicates that unmeasured reactive volatile organic compounds (VOCs), such as oxygenated VOCs and branched alkenes are potential contributors to the underestimation of P(O3)net. This study underscores the underestimation of P(O3)net in conventional atmospheric modelling setups, providing a crucial scientific foundation for further investigation aimed at promoting our understanding of photochemical O3 formation.

Structures and genetic information of control region in mitogenomes of Odonata.

Mitogenome data of Odonata is accumulating and widely used in phylogenetic analysis. However, noncoding regions, especially control region, were usually omitted from the phylogenetic reconstruction. In an effort to uncover the phylogenetic insights offered by the control region, we have amassed 65 Odonata mitogenomes and conducted an examination of their control regions. Our analysis discovered that species belonging to Anisoptera and Anisozygoptera exhibited a stem-loop structure, which was formed by a conserved polyC-polyG stretch located near the rrns gene (encoding 12S rRNA). Conversely, the polyC-polyG region was not a conserved fragment in Zygoptera. The length and number of repetitions within the control region were identified as the primary determinants of its overall length. Further, sibling species within Odonata, particularly those in the genus Euphaea, displayed similar patterns of repetition in their control region. Collectively, our research delineates the structural variations within the control region of Odonata and suggests the potential utility of this region in elucidating phylogenetic relationships among closely related species.

Influence of network latency and bandwidth on robot-assisted laparoscopic telesurgery: A pre-clinical experiment.

BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS: This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.

Downregulation of C1R promotes hepatocellular carcinoma development by activating HIF-1α-regulated glycolysis.

C1R has been identified to have a distinct function in cutaneous squamous cell carcinoma that goes beyond its role in the complement system. However, it is currently unknown whether C1R is involved in the progression of hepatocellular carcinoma (HCC). HCC tissues were used to examine C1R expression in relation to clinical and pathological factors. Malignant characteristics of HCC cells were assessed through in vitro and in vivo experiments. The mechanism underlying the role of C1R in HCC was explored through RNA-seq, methylation-specific PCR, immuno-precipitation, and dual-luciferase reporter assays. This study found that the expression of C1R decreased as the malignancy of HCC increased and was associated with poor prognosis. C1R promoter was highly methylated through DNMT1 and DNMT3a, resulting in a decrease in C1R expression. Downregulation of C1R expression resulted in heightened malignant characteristics of HCC cells through the activation of HIF-1α-mediated glycolysis. Additionally, decreased C1R expression was found to promote xenograft tumor formation. We found that C-reactive protein (CRP) binds to C1R, and the free CRP activates the NF-κB signaling pathway, which in turn boosts the expression of HIF-1α. This increase in HIF-1α leads to higher glycolysis levels, ultimately promoting aggressive behavior in HCC. Methylation of the C1R promoter region results in the downregulation of C1R expression in HCC. C1R inhibits aggressive behavior in HCC in vitro and in vivo by inhibiting HIF-1α-regulated glycolysis. These findings indicate that C1R acts as a tumor suppressor gene during HCC progression, opening up new possibilities for innovative therapeutic approaches.

Curcumin Induces Autophagy-mediated Ferroptosis by Targeting the PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer.

As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 µM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Biointerfacial supramolecular self-assembly of whey protein isolate nanofibrils on probiotic surface to enhance survival and application to 3D printing dysphagia foods.

Personalized three-dimensional (3D) printed foods rich in probiotics were investigated. Lactiplantibacillus plantarum (Lp), as a representative of probiotics, was used to investigate the 3D printing of probiotic-rich dysphagia foods. Here, whey protein isolate nanofibrils (WPNFs) were coated and anchored on bacterial surfaces via biointerfacial supramolecular self-assembly, providing protection against environmental stress and the 3D printing process. The optimized composite gels consisting of High acyl gellan gum (0.25 g), whey protein isolate (1.25 g), fructooligosaccharides (0.75 g), Lp-WPNFs-Glyceryl tributyrate emulsion (Φ = 40%, 3.75 mL) can realize 3D printing, and exhibit high resolution, and stable shape. The viable cell count is higher than 8.0 log CFU/g. They are particularly suitable for people with dysphagia and are classified as level 5-minced & moist in the international dysphagia diet standardization initiative framework. The results provide new insights into the development of WPNFs-coating on bacterial surfaces to deliver probiotics and 3D printed food rich in probiotics.

Ultralow Power In-Sensor Neuronal Computing with Oscillatory Retinal Neurons for Frequency-Multiplexed, Parallel Machine Vision.

In-sensor and near-sensor computing architectures enable multiply accumulate operations to be carried out directly at the point of sensing. In-sensor architectures offer dramatic power and speed improvements over traditional von Neumann architectures by eliminating multiple analog-to-digital conversions, data storage, and data movement operations. Current in-sensor processing approaches rely on tunable sensors or additional weighting elements to perform linear functions such as multiply accumulate operations as the sensor acquires data. This work implements in-sensor computing with an oscillatory retinal neuron device that converts incident optical signals into voltage oscillations. A computing scheme is introduced based on the frequency shift of coupled oscillators that enables parallel, frequency multiplexed, nonlinear operations on the inputs. An experimentally implemented 3 × 3 focal plane array of coupled neurons shows that functions approximating edge detection, thresholding, and segmentation occur in parallel. An example of inference on handwritten digits from the MNIST database is also experimentally demonstrated with a 3 × 3 array of coupled neurons feeding into a single hidden layer neural network, approximating a liquid-state machine. Finally, the equivalent energy consumption to carry out image processing operations, including peripherals such as the Fourier transform circuits, is projected to be <20 fJ/OP, possibly reaching as low as 15 aJ/OP.

Advances in the treatment of axillary bromhidrosis.

BACKGROUND: Bromhidrosis, characterized by foul-smelling sweat, is a prevalent condition that significantly affects patients' social and psychological well-being. METHODS: This review presents novel treatment approaches and discusses the pros and cons of various treatment options for axillary bromhidrosis. RESULTS: Extensive research has explored numerous treatment modalities for bromhidrosis. This article systematically reviews both surgical and nonsurgical interventions utilized in clinical practice. CONCLUSION: By synthesizing available evidence, this review aims to offer evidence-based recommendations for effectively managing bromhidrosis, considering factors such as treatment efficacy, safety profiles, patient preferences, and clinical outcomes.

First-Principles Nonadiabatic Dynamics of Molecules at Metal Surfaces with Vibrationally Coupled Electron Transfer.

Accurate description of nonadiabatic dynamics of molecules at metal surfaces involving electron transfer has been a long-standing challenge for theory. Here, we tackle this problem by first constructing high-dimensional neural network diabatic potentials including state crossings determined by constrained density functional theory, then applying mixed quantum-classical surface hopping simulations to evolve coupled electron-nuclear motion. Our approach accurately describes the nonadiabatic effects in CO scattering from Au(111) without empirical parameters and yields results agreeing well with experiments under various conditions for this benchmark system. We find that both adiabatic and nonadiabatic energy loss channels have important contributions to the vibrational relaxation of highly vibrationally excited CO(v_{i}=17), whereas relaxation of low vibrationally excited states of CO(v_{i}=2) is weak and dominated by nonadiabatic energy loss. The presented approach paves the way for accurate first-principles simulations of electron transfer mediated nonadiabatic dynamics at metal surfaces.

Tailoring vinegar residue-derived all-carbon electrodes for efficient electrocatalytic carbon dioxide reduction to formate through heteroatom doping and defect enrichment.

Electrocatalytic carbon dioxide reduction (ECO2R) to formate is the most technically and economically feasible approach to achieve electrochemical CO2 value addition. Here, a few-layer graphene is prepared from vinegar residue. Then a series of heteroatom-doped vertical graphene electrodes (X-rGO, X=P/S/N/B/, NS/NP/NB, NSP/NSB/NPB/NSPB) are prepared. The NS-rGO has improved ECO2R to formate selectivity (Faraday Efficiency (FEHCOO-) = 78.7 %) thanks to the synergistic effect between N and S. Carbon quantum dots (CQDs) are introduced into the electrode, the doped heteroatoms are further removed by high-temperature to form the defects-rich electrode (NS-CQDs-rGO-1100), which has better catalytic performance (FEHCOO-=90 %, stability over 10 h) with electrochemical double layer capacitance of 12.5 mF cm-2. The intrinsic effect of heteroatom doping and defects on the ECO2R activity of the electrodes are explored by density functional theory calculation. This work broadens the field of preparation of graphene and opens the door to the development of cost-effective electrocatalysts for efficient ECO2R.

Research Progress on Immune Evasion of Mycoplasma hyopneumoniae.

As the main pathogen associated with enzootic pneumonia (EP), Mycoplasma hyopneumoniae (Mhp) is globally prevalent and inflicts huge financial losses on the worldwide swine industry each year. However, the pathogenicity of Mhp has not been fully explained to date. Mhp invasion usually leads to long-term chronic infection and persistent lung colonization, suggesting that Mhp has developed effective immune evasion strategies. In this review, we offer more detailed information than was previously available about its immune evasion mechanisms through a systematic summary of the extant findings. Genetic mutation and post-translational protein processing confer Mhp the ability to alter its surface antigens. With the help of adhesins, Mhp can achieve cell invasion. And Mhp can modulate the host immune system through the induction of inflammation, incomplete autophagy, apoptosis, and the suppression of immune cell or immune effector activity. Furthermore, we offer the latest views on how we may treat Mhp infections and develop novel vaccines.

Latilactobacillus sakei QC9 alleviates hyperglycaemia in high-fat diet and streptozotocin-induced type 2 diabetes mellitus mice via the microbiota-gut-liver axis.

Probiotics have been considered a promising option for mitigating the progression of type 2 diabetes mellitus (T2DM). Here, Latilactobacillus sakei QC9 (L. sakei QC9) with a hypoglycemic effect was screened out from 30 food-derived strains through α-glucosidase and α-amylase activity inhibition tests in vitro and a 4-week in vivo preliminary animal experiment. To further understand its alleviating effect on long-term hyperglycaemia occurring in T2DM, we conducted an experiment that lasted for 8 weeks. The results showed that taking L. sakei QC9 can regulate glucose and lipid metabolism while improving the antioxidant capacity and alleviating chronic inflammation. In addition, our results demonstrated that L. sakei QC9 may mediate the microbiota-gut-liver axis by regulating the composition of intestinal flora (increasing the abundance of butyrate-producing bacteria) and increasing the content of short-chain fatty acids (especially butyrate), affecting the PI3K/Akt signalling pathway in the liver, thereby achieving the purpose of alleviating the development of T2DM. In summary, our work is the first to prove the long-term hypoglycemic effect of L. sakei in high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mice and supports the possibility of L. sakei QC9 being used as a new treatment for alleviating T2DM.

Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer.

BACKGROUND: Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration. METHODS: To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients. RESULTS: We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer. CONCLUSIONS: Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME.

Tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease: a systematic review and meta-analysis of cohort studies.

Background: Limited and conflicting evidence exists for the associations between tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease (AD). This meta-analysis aimed to elucidate these associations and quantify potential dose-response relationships. Methods: PubMed, EMBASE, and Web of Science were searched up to 11 June 2024 for cohort studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs), with the dose-response relationship assessed using restricted cubic splines. The Grading of Recommendations Assessment Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: Our analysis encompassed 38 cohorts, totalling 751 824 participants and 13 017 dementia and 17 341 AD cases. For dementia, compared with the lowest category, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine were 0.84 (0.74-0.96, n = 6), 0.95 (0.87-1.02, n = 9), and 0.94 (0.70-1.25, n = 5), with all rated as low certainty in GRADE. For AD, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine compared to the lowest category were 0.93 (0.87-1.00, n = 6), 1.01 (0.90-1.12, n = 10), and 1.34 (1.04-1.74, n = 2), with certainty ratings of low, low, and very low, respectively. Dose-response analysis indicated a non-linear relationship between coffee intake (Poverall = 0.04 and Pnonlinear = 0.01) and dementia risk, showing the protective association of risk of dementia with 1 to 3 cups per day of coffee intake. There is a linear association between tea intake and risk of dementia, with a significantly decreased risk of dementia for each 1 cup per day increase in tea consumption (0.96, 95% CI 0.94-0.99, Poverall = 0.01 and Pnonlinear = 0.68). Conclusion: Increased tea consumption was associated with a decreased risk of dementia and AD, and a non-linear relationship was found between coffee and dementia, supporting public health recommendations for dementia prevention.