Dendrite-Free Li5.5PS4.5Cl1.5-Based All-Solid-State Lithium Battery Enabled by Grain Boundary Electronic Insulation Strategy through In Situ Polymer Encapsulation.

Sulfide-based all-solid-state lithium batteries (ASSLBs) have attracted unprecedented attention in the past decade due to their excellent safety performance and high energy storage density. However, the sulfide solid-state electrolytes (SSEs) as the core component of ASSLBs have a certain stiffness, which inevitably leads to the formation of pores and cracks during the production process. In addition, although sulfide SSEs have high ionic conductivity, the electrolytes are unstable to lithium metal and have non-negligible electronic conductivity, which severely limits their practical applications. Herein, a grain boundary electronic insulation strategy through in situ polymer encapsulation is proposed for this purpose. A polymer layer with insulating properties is applied to the surface of the Li5.5PS4.5Cl1.5 (LPSC) electrolyte particles by simple ball milling. In this way, we can not only achieve a dense electrolyte pellet but also improve the stability of the Li metal anode and reduce the electronic conductivity of LPSC. This strategy of electronic isolation of the grain boundaries enables stable deposition/stripping of the modified electrolyte for more than 2000 h at a current density of 0.5 mA cm-1 in a symmetrical Li/Li cell. With this strategy, a full cell with Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) as the cathode shows high performance including high specific capacity, improved high-rate capability, and long-term stability. Therefore, this study presents a new strategy to achieve high-performance sulfide SSEs.

BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in MI/R induced myocyte apoptosis.

BACKGROUND: Cardiomyocyte apoptosis plays a vital role in myocardial ischemia-reperfusion (MI/R) injury; however, the role of beclin1 (BECN1) remains unclear. This study aimed at revealing the function of BECN1 during cardiomyocyte apoptosis after MI/R injury. METHODS: In vivo, TTC and Evan's blue double staining was applied to verify the gross morphological alteration in both wild type (WT) mice and BECN1 transgene mice (BECN1-TG), and TUNEL staining and western blot were adopted to evaluate the cardiomyocyte apoptosis. In vitro, a hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate MI/R injury. Proteomics analysis was preformed to verify if apoptosis occurs in the H/R cellular model. And apoptosis factors, RIPK1, Caspase-1, Caspase-3, and cleaved Caspase-3, were investigated using western bolting. In addition, the mRNA level were verified using RT-PCR. To further investigate the protein interactions small interfering RNA and lentiviral transfection were used. To continue investigate the protein interactions, immunofluorescence and coimmunoprecipitation were applied. RESULTS: Morphologically, BECN1 significantly attenuated the apoptosis from TTC-Evan's staining, TUNEL, and cardiac tissue western blot. After H/R, a RIPK1-induced complex (complex II) containing RIPK1, Caspase-8, and FADD was formed. Thereafter, cleaved Caspase-3 was activated, and myocyte apoptosis occurred. However, BECN1 decreased the expression of RIPK1, Caspase-8, and FADD. Nevertheless, BECN1 overexpression increased RIPK1 ubiquitination before apoptosis by inhibiting OTUD1. CONCLUSIONS: BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in C-Caspase-3-induced myocyte apoptosis after MI/R injury. Therefore, BECN1 can function as a cardioprotective candidate.

Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank.

BACKGROUND: Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths. METHODS: This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. RESULTS: During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. CONCLUSION: Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.

Inflammation-based lung adenocarcinoma molecular subtype identification and construction of an inflammation-related signature with bulk and single-cell RNA-seq data.

The role of inflammation is increasingly understood to have a central influence on therapeutic outcomes and prognosis in lung adenocarcinoma (LUAD). However, the detailed molecular divisions involved in inflammatory responses are yet to be fully elucidated. Our study identified two main inflammation-oriented LUAD grades: the inflammation-low (INF-low) and the inflammation-high (INF-high) subtypes. Both presented with unique clinicopathological features, implications for prognosis, and distinctive tumor microenvironment profiles. Broadly, the INF-low grade, marked by its dominant immunosuppressive tumor microenvironment, was accompanied by less favorable prognostic outcomes and a heightened prevalence of oncogenic mutations. In contrast, the INF-high grade exhibited more optimistic clinical trajectories, underscored by its immune-active environment. In addition, our efforts led to the conceptualization and empirical validation of an inflammation-centric predictive model with considerable predictive potency. Our study paves the way for a refined inflammation-centric LUAD classification and fosters a deeper understanding of tumor microenvironment intricacies.

Study of the collagen tissue nanostructure by analyzing the echo decay obtained using the MRI technique.

The multicomponent relaxation observed in nuclear magnetic resonance experiments in biological tissues makes it difficult to establish a correlation between specific relaxation times and tissue structural parameters. The analysis of a nanostructure (the characteristic size of 10-1000 nm) is usually based on formulas for relaxation times which depend on structural parameters at the atomic or molecular levels in the size range of 0.1-5 nm. We have recently developed an analysis method in which relaxation times' anisotropy in a sample is explicitly related to its structure of nanocavities containing a liquid or gas. However, the method is based on the analysis of experimental data on the anisotropy of relaxation times obtained by using the standard NMR technique and rotating the sample relative to a magnetic field and requires a series of experiments. In the present study, to address this challenge, we develop a new method of analysis of a multi-exponential magnetic resonance signal that does not require determining relaxation times and eliminates the sample rotation and the necessity of a series of experiments. Using the magnetic resonance imaging (MRI) technique, the total signal from the whole sample was obtained as a sum of the signals (echo decays) from all voxels. In contrast to previous research, the volumes of nanocavities and their angular distribution can be obtained by analyzing a single total signal for the entire cartilage. In addition, within the framework of this approach, it is possible to identify the reason for the multicomponent nature of relaxation. The proposed method for analyzing a single multi-exponential signal (transverse relaxation) was implemented on cartilage. Using the signal, three anatomical zones of cartilage were studied, revealing significant structural differences between them. The proposed method not only avoids the need for sample rotation but also enables repeated application of layer-by-layer magnetic resonance imaging with micron resolution. The study results allow us to suggest that water molecules contributing to the echo decay are more likely located in nanocavities formed by the fibrillar structure rather than inside the fibrils.

Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease.

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).

Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant healthcare problem within both developed and developing countries, has been associated with genetic risk factors. As well, an association between physical activity and KSD risk has been hypothesized but studies have yielded inconsistent findings. This study aimed to investigate the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURES: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOMES: Individuals with KSD were identified using the International Classification of Diseases 10th Edition, and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential non-linear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared to those in the lowest quartiles: HRs (95% confidence interval) of 0.50 (0.44, 0.56), 0.57 (0.51, 0.64), and 0.66 (0.59, 0.74), respectively. TPA, MVPA, and LPA were associated with lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSION: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations.

The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Ultrafast-Loaded Nickel Sulfide on Vertical Graphene Enabled by Joule Heating for Enhanced Lithium Metal Batteries.

The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).

Li5.5PS4.5Cl1.5-Based All-Solid-State Battery with a Silver Nanoparticle-Modified Graphite Anode for Improved Resistance to Overcharging and Increased Energy Density.

All-solid-state lithium batteries (ASSLBs) are attracting tremendous attention due to their improved safety and higher energy density. However, the use of a metallic lithium anode poses a major challenge due to its low stability and processability. Instead, the graphite anode exhibits high reversibility for the insertion/deinsertion of lithium ions, giving ASSLBs excellent cyclic stability but a lower energy density. To increase the energy density of ASSLBs with the graphite anode, it is necessary to lower the negative/positive (N/P) capacity ratio and to increase the charging voltage. These strategies bring new challenges to lithium metal plating and dendrite growth. Here, a nano-Ag-modified graphite composite electrode (Ag@Gr) is developed to overcome these shortcomings for Li5.5PS4.5Cl1.5-based ASSLBs. The Ag@Gr composite exhibits a strong ability to inhibit lithium metal plating and fast lithium-ion transport kinetics. Ag nanoparticles can accommodate excess Li, and the as-obtained Li-Ag alloy enhances the kinetics of the composite electrode. The ASSLB with the Li(Ni0.8Co0.1Mn0.1)O2 cathode and Ag@Gr anode achieves an energy density of 349 W h kg-1. The full cell using Ag@Gr with an N/P ratio of 0.6 also highlights the rate performance. This work provides a simple and effective method to regulate the charge transport kinetics of graphite anodes and improve the cyclic performance and energy density of ASSLBs.

Effectiveness and safety of immune response to SARS­CoV­2 vaccine in patients with chronic kidney disease and dialysis: A systematic review and meta­analysis.

The coronavirus disease 2019 (COVID-19) vaccination is the most effective way to prevent COVID-19. However, for chronic kidney disease patients on long-term dialysis, there is a lack of evidence regarding the efficacy and safety of the immune response to the vaccine. The present meta-analysis explores the efficacy and safety of COVID-19 vaccine in the immune response of patients with chronic kidney disease (CKD) undergoing dialysis. PubMed, Web of Science, Science Direct, and Cochrane Library databases were systematically searched from January 1, 2020, to December 31, 2022. Data analysis was performed using REVMAN 5.1s and Stata14 software. Baseline data and endpoint events were extracted, mainly including age, sex, dialysis vintage, body mass index (BMI), vaccine type and dose, history of COVID-19 infection, seropositivity rate, antibody titer, pain at injection site, headache and other safety events. The meta-analysis included 33 trials involving 81,348 patients. The immune efficacy of patients with CKD and dialysis was 80% (95 CI, 73-87%). The seropositivity rate of individuals without COVID-19 infection was 76.48% (3,824/5,000), while the seropositivity rate of individuals with COVID-19 infection was 80.82% (1,858/2,299). The standard mean difference of antibody titers in CKD and dialysis patients with or without COVID-19 infection was 27.73 (95% CI, -19.58-75.04). A total of nine studies reported the most common adverse events: Pain at the injection site, accounting for 18% (95 CI, 6-29%), followed by fatigue and headache, accounting for 8 (95 CI, 4-13%) and 6% (95 CI, 2-9%), respectively. COVID-19 vaccine benefitted patients with CKD undergoing dialysis with seropositivity rate ≥80%. Adverse events such as fatigue, headache, and pain at the injection site may occur after COVID-19 vaccination but the incidence is low.

Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome.

The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T cell recruitment. circDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging the IGF2BP3 half-life, which in turn sustains mRNA levels of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators. Production of CXCL10 and interleukin-9 by CRC cells is elicited through JAK-STAT1 signaling, in turn promoting the chemotactic and cytolytic activities of CD8+ T cells. Clinical evidence associates increased circDNA2v expression in CRC tissues with reductions in CD8+ T cell infiltration and worse outcomes. The regulatory relationship between circDNA2v, cellular senescence, and tumor-infiltrating lymphocytes thus provides a rational approach for improving immunotherapy in CRC.

A Stable Lithium Metal Anode Enabled by the Site-Directed Lithium Deposition of ZnO-Nanosheet-Modified Carbon Cloth.

Uneven lithium (Li) metal deposition typically results in uncontrollable dendrite growth, which renders an unsatisfactory cycling stability and coulombic efficiency (CE) of Li metal batteries (LMBs), preventing their practical application. Herein, a novel carbon cloth with the modification of ZnO nanosheets (ZnO@CC) is fabricated for LMBs. The as-prepared ZnO@CC with a cross-linked network significantly reduces the local current density, and the design of ZnO nanosheets can promote the uniform deposition of Li metal as lithiophilic sites. As a result, the Li metal anodes (LMAs) based on ZnO@CC (ZnO@CC@Li) enables a long cycle life over 640 hours with a low overpotential of 65 mV at a current density of 4 mA cm-2 with a capacity of 1 mAh cm-2 in the symmetric cell. Moreover, when coupling the ZnO@CC@Li with a LiFePO4 cathode, the assembled full cell exhibits excellent long cycle and rate performance, highlighting its promising practical application prospect.

Ultra-processed food consumption, genetic susceptibility, and the risk of hip/knee osteoarthritis.

BACKGROUND: The associations between ultra-processed food (UPF) consumption, genetic susceptibility, and the risk of osteoarthritis (OA) remain unknown. This study was to examine the effect of UPF consumption, genetic susceptibility, and their interactions on hip/knee OA. METHODS: Cohort analyses included 163,987 participants from the UK Biobank. Participants' UPF consumption was derived from their 24-h dietary recall using a questionnaire. Genetic risk scores (GRSs) of 70 and 83 single nucleotide polymorphisms (SNPs) for hip and knee OA were constructed. FINDINGS: After 1,461,447 person-years of follow-up, 11,540 patients developed OA. After adjustments, compared to participants in the low quartile of UPF consumption, those in the high quartile had a 10 % (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.18) increased risk of knee OA. No significant association was found between UPF consumption and hip OA. Replacing 20% of UPF diet weight with an equivalent proportion of unprocessed or minimally processed food caused a 6% (HR, 0.94; 95% CI, 0.89-0.98) decreased risk of knee OA, respectively. A significant interaction was found between UPF consumption, genetic predisposition, and the risk of knee OA (P = 0.01). Participants with lower OA-GRS scores experienced higher knee OA risks due to UPF consumption. INTERPRETATION: UPF consumption was associated with a higher risk of knee OA but not hip OA, particularly in those with lower genetic susceptibility. These results highlight the importance of reducing UPF consumption to prevent knee OA.

Metagenomic Analyses Reveal Gut Microbial Profiles of Cnaphalocrocis medinalis Driven by the Infection of Baculovirus CnmeGV.

The composition of microbiota in the digestive tract gut is essential for insect physiology, homeostasis, and pathogen infection. Little is known about the interactions between microbiota load and oral infection with baculoviruses. CnmeGV is an obligative baculovirus to Cnaphalocrocis medinalis. We investigated the impact of CnmeGV infection on the structure of intestinal microbes of C. medinalis during the initial infection stage. The results revealed that the gut microbiota profiles were dynamically driven by pathogen infection of CnmeGV. The numbers of all the OTU counts were relatively higher at the early and later stages, while the microbial diversity significantly increased early but dropped sharply following the infection. The compositional abundance of domain bacteria Firmicutes developed substantially higher. The significantly enriched and depleted species can be divided into four groups at the species level. Fifteen of these species were ultimately predicted as the biomarkers of CnmeGV infection. CnmeGV infection induces significant enrichment of alterations in functional genes related to metabolism and the immune system, encompassing processes such as carbohydrate, amino acid, cofactor, and vitamin metabolism. Finally, the study may provide an in-depth analysis of the relationship between host microbiota, baculovirus infection, and pest control of C. medinalis.

Sugar types, genetic predictors of the gut microbiome, and the risk of chronic kidney disease: a prospective cohort study.

Background: Emerging studies suggest that focusing on the intake of specific types or sources of sugars may yield greater benefits in preventing chronic kidney disease (CKD). Objective: We aimed to investigate the associations between free and non-free sugar intakes and CKD risk as well as the potential sugar type-gut microbiome interactions. Methods: A total of 138 064 participants from the UK Biobank were included in this prospective study. The free and non-free sugar intakes were assessed using repeated web-based 24-hour dietary recalls. A cause-specific competing risk model was used to estimate hazard ratios (HRs) and the corresponding confidence intervals (CIs) of incident CKD, treating deaths before incident CKD as competing events. Results: During a median follow-up of 10.5 years, 2,923 participants (2.1%) developed CKD. The free sugar intake was positively associated with the risk of CKD (HRquartile 4 vs. quartile 1 = 1.32, 95% CI = 1.18, 1.47), with a nonlinear relationship (P for nonlinearity = 0.01, the risk increased rapidly after free sugars made up 10% of the total energy). The non-free sugar intake was inversely associated with CKD risk (HRquartile 4 vs. quartile 1 = 0.68, 95% CI = 0.60, 0.77), with an L-shaped nonlinear curve (p for nonlinearity = 0.01, the turning point was at 13.5% of the total energy). We found that the associations between free sugar and non-free sugar intakes and CKD risk were more pronounced in participants with high genetically predicted gut microbial abundance. Furthermore, a significant interaction was observed between the genetically predicted gut microbial abundance and non-free sugar intake (P for interaction = 0.04). Conclusion: A higher intake of free sugars was associated with an elevated risk of CKD, whereas a higher intake of non-free sugars was associated with a reduced risk of CKD. The impact of free sugar intake and non-free sugar intake may be modified by the gut microbial abundance.

Intake of the different types of dairy products, genetic predisposition, and the risks of nonalcoholic fatty liver disease and cirrhosis: a prospective cohort study.

Background: The association of dairy product consumption with nonalcoholic fatty liver disease (NAFLD) and cirrhosis remains controversial. This study aimed to prospectively investigate the associations between the consumption of the different types of dairy products, genetic predisposition, and the risks of NAFLD and cirrhosis. Methods: This cohort study included 190 145 participants from the UK Biobank Study. The consumption of the different types of dairy products was assessed based on the Oxford WebQ at baseline and defined as the sum of milk, yogurt, and cheese. NAFLD and cirrhosis were evaluated using hospital inpatient records and death data in the UK Biobank. The weighted genetic risk score (GRS) for NAFLD and cirrhosis was constructed using 5 and 6 single-nucleotide variants (SNVs), respectively. Cox proportional hazards regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between genetic factors and different types of dairy products with the incidence of NAFLD and cirrhosis. Results: During a median follow-up of 11.6 years, 1512 NAFLD and 556 cirrhosis cases were ascertained. After adjusting for several potential confounders, the HRs (95% CIs) (Q4 vs. Q1) of NAFLD were 0.86 (0.74, 0.995) for total dairy products, 0.96 (0.84, 1.09) for high-fat dairy products, 0.78 (0.67, 0.92) for low-fat dairy products, 0.86 (0.74, 0.99) for unfermented dairy products, and 0.79 (0.68, 0.91) for fermented dairy products. The multivariable-adjusted HRs (95% CIs) (Q4 vs. Q1) of cirrhosis were 0.75 (0.59, 0.96) for total dairy products, 0.97 (0.78, 1.19) for high-fat dairy products, 0.67 (0.51, 0.89) for low-fat dairy products, 0.75 (0.59, 0.96) for unfermented dairy products, and 0.71 (0.56, 0.90) for fermented dairy products. The associations of high-fat dairy products and fermented dairy products with NAFLD and cirrhosis were found to be nonlinear (P for nonlinear <0.05). No interaction was observed between dairy product consumption and NAFLD or cirrhosis genetic susceptibility. Conclusions: Higher consumption of dairy products, except for high-fat dairy, was correlated with lower risks of NAFLD and cirrhosis, regardless of their differences in genetic susceptibility.

Joint association of serum urate and healthy diet with chronic obstructive pulmonary disease incidence: results from the UK Biobank study.

Background: The role of serum urate (SU) levels in the development of chronic obstructive pulmonary disease (COPD) remains a topic of debate, and it is unclear whether a healthy diet can mitigate the impact of SU on COPD risk. The objective of this study is to examine whether and to what extent a healthy diet can reduce the risk of COPD in relation to SU levels. Methods: The cohort analysis included 155 403 participants from the UK Biobank. SU levels were measured at the time of recruitment. A healthy diet score was calculated based on the consumption of vegetables, fruits, fish, processed meats, unprocessed red meat, whole grains, and refined grains. The Cox proportional hazards model was used to analyze the associations between SU levels, a healthy diet score, and the risk of COPD. Results: During a follow-up period of 1 409 969 person-years, 2918 incident cases of COPD were identified. Compared with the lowest SU level group, the hazard ratio (HR) and 95% confidence interval (CI) for COPD were 1.17 (1.03, 1.34) for participants with the highest SU level (hyperuricemia), indicating a positive association. Additionally, a dose-response relationship was observed between SU levels and the incidence of COPD (P-value for overall <0.0001). In the combined effect analysis, compared to individuals with high SU (hyperuricemia) + a low diet score (diet score <4), those with normal SU + a high diet score (diet score ≥4) had a HR (95% CI) of 0.75 (0.65, 0.87) for COPD. Conclusions: In summary, there is a positive association between SU levels and the risk of COPD. Furthermore, a healthier diet can mitigate the risk of COPD associated with high SU levels.