Synergistically Engineering Grains and Grain Boundaries toward Li Dendrite-Free Li7La3Zr2O12.

Cation-doped cubic Li7La3Zr2O12 is regarded as a promising solid electrolyte for safe and energy-dense solid-state lithium batteries. However, it suffers from the formation of Li2CO3 and high electronic conductivity, which give rise to an unconformable Li/Li7La3Zr2O12 interface and lithium dendrites. Herein, composite AlF3-Li6.4La3Zr1.4Ta0.6O12 solid electrolytes were created based on thermal AlF3 decomposition and F/O displacement reactions under a high-temperature sintering process. When the AlF3 is thermally decomposed, it leaves Al2O3/AlF3 meliorating the grain boundaries and F- ions partially displacing O2- ions in the grains. Due to the higher electronegativity of F- in the grains and the grain-boundary modification, these AlF3-Li6.4La3Zr1.4Ta0.6O12 deliver optimized electronic conduction and chemical stability against the formation of Li2CO3. The Li/AlF3-Li6.4La3Zr1.4Ta0.6O12/Li cell exhibits a low interfacial resistance of ∼16 Ω cm2 and an ultrastable long-term cycling behavior for 800 h under a current density of 200 µA/cm2, leading to Li//LiCoO2 solid-state batteries with good rate performance and cycling stability.

Integrative and comprehensive pan-cancer analysis of ubiquitin specific peptidase 11 (USP11) as a prognostic and immunological biomarker.

The significance of USP11 as a critical regulator in cancer has garnered substantial attention, primarily due to its catalytic activity as a deubiquitinating enzyme. Nonetheless, a thorough evaluation of USP11 across various cancer types in pan-cancer studies remains absent. Our analysis integrates data from a variety of sources, including five immunotherapy cohorts, thirty-three cohorts from The Cancer Genome Atlas (TCGA), and sixteen cohorts from the Gene Expression Omnibus (GEO), two of which involve single-cell transcriptomic data. Our findings indicate that aberrant USP11 expression is predictive of survival outcomes across various cancer types. The highest frequency of genomic alterations was observed in uterine corpus endometrial carcinoma (UCEC), with single-cell transcriptome analysis revealing significantly higher USP11 expression in plasmacytoid dendritic cells and mast cells. Notably, USP11 expression was associated with the infiltration levels of CD8+ T cells and natural killer (NK) activated cells. Additionally, in the skin cutaneous melanoma (SKCM) phs000452 cohort, patients with higher USP11 mRNA levels during immunotherapy experienced a significantly shorter median progression-free survival. USP11 emerges as a promising molecular biomarker with significant potential for predicting patient prognosis and immunoreactivity across various cancer types.

Reinforcement learning for individualized lung cancer screening schedules: A nested case-control study.

BACKGROUND: The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking. PURPOSE: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models. METHODS: Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer). RESULTS: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes. CONCLUSIONS: This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.

Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

PURPOSE: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. METHODS: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. RESULTS: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CONCLUSION: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

High Power Factor Flexible Ag2Te Film on Nylon by a Wet Chemical Method for Power Generator.

Herein, we develop a facile wet chemical method for the synthesis of Ag2Te powders at room temperature and flexible Ag2Te/nylon thermoelectric (TE) films are prepared by vacuum-assisted filtration of the synthesized Ag2Te powders and then hot pressing. Because of the good crystallinity of Ag2Te grains and continuous grain boundaries, an optimized film exhibits a power factor of 513 µW m-1 K-2 at 300 K, which stands among the highest values reported for Ag2Te-based films to date. In addition, the film also has good flexibility. A four-leg flexible TE device assembled with the film generates a power density of 5.46 W m-2 at a temperature gradient of 31.8 K. This work provides a facile and environmentally friendly method for preparing flexible Ag2Te films.

Greatly Enhanced Thermoelectric Performance of Flexible Cu2-xS Composite Film on Nylon by Se Doping.

In this work, flexible Cu2-xS films on nylon membranes are prepared by combining a simple hydrothermal synthesis and vacuum filtration followed by hot pressing. The films consist of Cu2S and Cu1.96S two phases with grain sizes from nano to submicron. Doping Se on the S site not only increases the Cu1.96S content in the Cu2-xS to increase carrier concentration but also modifies electronic structure, thereby greatly improves the electrical properties of the Cu2-xS. Specifically, an optimal composite film with a nominal composition of Cu2-xS0.98Se0.02 exhibits a high power factor of ~150.1 µW m-1 K-2 at 300 K, which increases by ~138% compared to that of the pristine Cu2-xS film. Meanwhile, the composite film shows outstanding flexibility (~97.2% of the original electrical conductivity is maintained after 1500 bending cycles with a bending radius of 4 mm). A four-leg flexible thermoelectric (TE) generator assembled with the optimal film generates a maximum power of 329.6 nW (corresponding power density of 1.70 W m-2) at a temperature difference of 31.1 K. This work provides a simple route to the preparation of high TE performance Cu2-xS-based films.

Prognostic and predictive value of interstitial lung abnormalities and EGFR mutation status in patients with non-small cell lung cancer.

BACKGROUND: To determine the predictive value of interstitial lung abnormalities (ILA) for epidermal growth factor receptor (EGFR) mutation status and assess the prognostic significance of EGFR and ILA in patients with non-small cell lung cancer (NSCLC). METHODS: We reviewed 797 consecutive patients with a histologically proven diagnosis of primary NSCLC from January 2013 to October 2018. Of these, 109 patients with NSCLC were found to have concomitant ILA. Multivariate logistic regression analysis was used to identify the significant clinical and computed tomography (CT) findings in predicting EGFR mutations. Cox proportional hazard models were used to identify significant prognostic factors. RESULTS: EGFR mutations were identified in 22 of 109 tumors (20.2%). Multivariate analysis showed that the models incorporating clinical, tumor CT and ILA CT features yielded areas under the receiver operating characteristic curve (AUC) values of 0.749, 0.838, and 0.849, respectively. When combining the three models, the independent predictive factors for EGFR mutations were non-fibrotic ILA, female sex, and small tumor size, with an AUC value of 0.920 (95% confidence interval[CI]: 0.861-0.978, p < 0.001). In the multivariate Cox model, EGFR mutations (hazard ratio = 0.169, 95% CI = 0.042-0.675, p = 0.012; 692 days vs. 301 days) were independently associated with extended overall survival compared to the wild-type. CONCLUSION: Non-fibrotic ILA independently predicts the presence of EGFR mutations, and the presence of EGFR mutations rather than non-fibrotic ILA serves as an independent good prognostic factor for patients with NSCLC.

Largely Enhanced Thermoelectric Performance of Flexible Ag2Se Film by Cationic Doping and Dual-Phase Engineering.

Recent studies have shown that silver selenide is a promising thermoelectric material at room temperature. Herein, flexible films with a nominal composition of (Ag1-xCux)2Se are prepared by a simple and efficient one-pot method combined with vacuum-assisted filtration and hot pressing. The thermoelectric properties of the films are regulated by both cationic doping and a dual-phase strategy via a wet chemical method. As the x increases, not only Cu is doped into the Ag2Se, but different new phases (CuAgSe and/or CuSe2) also appear. The (Ag1-xCux)2Se film with x = 0.02 composed of Cu-doped Ag2Se and CuAgSe shows a high PF of ∼2540 µW m-1 K-2 (ZT ∼ 0.90) and outstanding flexibility at room temperature. The high thermoelectric properties of the film are due to the effect of Cu doping and the CuAgSe phase, including the increase in electrical conductivity caused by doping, the enhanced phonon scattering at the Ag2Se/CuAgSe interface, and the interaction between the energy filtering effect and the doping effect. In addition to the high output performance (PDmax = 28.08 W m-2, ΔT = 32.2 K), the flexible device assembled with the (Ag0.98Cu0.02)2Se film also has potential applications as a temperature sensor.

Prevalence and patterns of multimorbidity in China during 2002-2022: A systematic review and meta-analysis.

BACKGROUND: Multimorbidity is common, particularly among elderly people. Restructuring health service systems to better manage this public health issue requires knowledge regarding disease prevalence and patterns. We quantified the epidemiology characteristics of multimorbidity among adults in China to inform policy-making and resource allocation. METHODS: We searched 10 databases for studies (January 2000-October 2023) reporting primary epidemiological multimorbidity data for adults in China. We included observational studies; we excluded duplicate publications and studies investigating a single comorbidity pattern, focused on specific population categories, using medical insurance reimbursement data, and with unclear/incomplete data. We assessed risk of bias using the STROBE checklist and estimated heterogeneity among studies. The prevalence was pooled using the random-effects method and sample size as weight. FINDINGS: Of 13,998 records retrieved, 67 studies (30 in English, 37 in Chinese) were included. The prevalence (95% confidence interval) of multimorbidity was 25.4% (15.1%, 35.7%) among Chinese adults. Among 42 studies reporting age-specific prevalence, multimorbidity prevalence increased rapidly with age: 3.3% (0%, 15.2%) for age 18-29 years, 5.9% (0%, 12.9%) for 30-44 years, 17.6% (6.1%, 29.1%) for 45-59 years, 32.4% (16.1%, 48.7%) for 60-69 years, 38.5% (23.6%, 53.4%) for 70-79 years, and 40.2% (20.8%, 59.6%) for age ≥ 80 years. Overall prevalence of multimorbidity has increased in recent years, with regional disparity. The most common patterns included hypertension with hearing impairment (10.4% [95% CI: 4.3%, 16.5%]), dyslipidemia (8.9% [4.1%, 13.6%]), and diabetes (8.7% [3.7%, 13.8%]). CONCLUSION: Multimorbidity was present nearly one in four Chinese adults, with hypertensive diseases and other comorbidities being the most-observed pattern; the prevalence increased rapidly with increased age. There is huge variation in the prevalence of multimorbidity across China. Coordinated, comprehensive strategies are urgently needed to control the ongoing impact of multimorbidity.

Sample size calculation for mixture model based on geometric average hazard ratio and its applications to nonproportional hazard.

With the advent of cancer immunotherapy, some special features including delayed treatment effect, cure rate, diminishing treatment effect and crossing survival are often observed in survival analysis. They violate the proportional hazard model assumption and pose a unique challenge for the conventional trial design and analysis strategies. Many methods like cure rate model have been developed based on mixture model to incorporate some of these features. In this work, we extend the mixture model to deal with multiple non-proportional patterns and develop its geometric average hazard ratio (gAHR) to quantify the treatment effect. We further derive a sample size and power formula based on the non-centrality parameter of the log-rank test and conduct a thorough analysis of the impact of each parameter on performance. Simulation studies showed a clear advantage of our new method over the proportional hazard based calculation across different non-proportional hazard scenarios. Moreover, the mixture modeling of two real trials demonstrates how to use the prior information on the survival distribution among patients with different biomarker and early efficacy results in practice. By comparison with a simulation-based design, the new method provided a more efficient way to compute the power and sample size with high accuracy of estimation. Overall, both theoretical derivation and empirical studies demonstrate the promise of the proposed method in powering future innovative trial designs.

Research advances in the therapeutic potential of xanthine oxidoreductase inhibitors for periodontitis / 口腔疾病防治

@#Periodontitis is associated with abnormal purine metabolism, which is manifested by increased uric acid in host blood and increased expression of the purine-degrading enzyme, xanthine oxidoreductase (XOR), in periodontal tissues. Both XOR and uric acid are pro-oxidative and pro-inflammatory mediators under pathological conditions. Animal studies have found that injection of uric acid promotes the progression of periodontitis and that febuxostat (an XOR inhibitor) improves tissue destruction in periodontitis. Therefore, blocking the source of uric acid may be a therapeutic strategy to control the progression of periodontitis. In this article, the rationality of XOR inhibitors as potential therapeutic drugs for periodontitis is reviewed. The literature review results suggest that XOR inhibitors show antioxidative, anti-inflammatory, and anti-osteoclastic effects, and XOR inhibitors show clinical efficacy in the treatment of infectious, inflammatory and osteolytic diseases. Although there is no direct evidence to support the finding that XOR inhibitors can ameliorate periodontal microecological dysbiosis, these drugs can modulate intestinal microflora dysbiosis, and there is indirect evidence to support a beneficial effect of XOR inhibitors on periodontal microecological dysbiosis. In conclusion, XOR inhibitors may be used as immunomodulators for the adjuvant treatment of periodontitis by inhibiting inflammation, oxidative stress and anti-osteoclast effects.