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Nonalcoholic fatty liver disease (NAFLD) has become a common health care burden worldwide. The high heterogeneity of NAFLD remains elusive and impairs outcomes of clinical diagnosis and pharmacotherapy. Several NAFLD classifications have been proposed on the basis of clinical, genetic, alcoholic, or serum metabolic analyses. Yet, accurately predicting the progression of NAFLD to cirrhosis or hepatocellular carcinoma (HCC) in patients remains a challenge. Here, on the basis of a Chinese cohort of patients, we classified NAFLD into three distinct molecular subtypes (NAFLD-mSI, NAFLD-mSII, and NAFLD-mSIII) using integrative multiomics including whole-genome sequencing (WGS), proteomics, phosphoproteomics, lipidomics, and metabolomics across a broad range of liver, blood, and urine specimens. We found that NAFLD-mSI had higher expression of CYP1A2 and CYP3A4, which alleviate hepatic steatosis through mediating free fatty acid/bile acid–mTOR–FXR/PPARα signaling. NAFLD-mSII displayed an elevated risk of liver cirrhosis along with increased hepatic infiltration of M1 and M2 macrophages because of lipid-triggered hepatic CCL2 and CRP production. NAFLD-mSIII exhibited a potential risk for HCC development by increased transcription of CEBPB- and ERCC3-regulated oncogenes because of activation of the EGF-EGFR/CHKA/PI3K-PDK1-AKT cascade. Next, we validated the existence of these three NAFLD molecular subtypes in an external cohort comprising 92 patients with NAFLD across three different Chinese hospitals. These findings may aid in understanding the molecular features underlying NAFLD heterogeneity, thereby facilitating clinical diagnosis and treatment strategies with the aim of preventing the development of liver cirrhosis and HCC. Editor's summary: Nonalcoholic fatty liver disease (NAFLD) is part of a disease spectrum and can progress to cirrhosis (scarring) or hepatocellular carcinoma. However, existing NAFLD classifications are unable to identify patients who are at risk of progressing. Using multiomic profiling, Ding et al. found that two independent cohorts of Chinese patients with NAFLD could be divided into three molecular subtypes broadly characterized by reduced liver steatosis, increased hepatic macrophage infiltration and risk of cirrhosis, or increased risk of hepatocellular carcinoma. Further work will need to determine whether these subtypes could be applied to benefit individual patients in a clinical setting. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Author(s): Shulin Chen 1, Yeates Conwell 2,*, Jiang Xue 1, Lydia Li 3, Tingjie Zhao 4, Wan Tang 4, Hillary Bogner 5, Hengjin Dong 6 Introduction Older adults are the [...], Background Effectiveness of integrated care management for common, comorbid physical and mental disorders has been insufficiently examined in low- and middle-income countries (LMICs). We tested hypotheses that older adults treated in rural Chinese primary care clinics with integrated care management of comorbid depression and hypertension (HTN) would show greater improvements in depression symptom severity and HTN control than those who received usual care. Methods and findings The study, registered with ClinicalTrials.gov as Identifier NCT01938963, was a cluster randomized controlled trial with 12-month follow-up conducted from January 1, 2014 through September 30, 2018, with analyses conducted in 2020 to 2021. Participants were residents of 218 rural villages located in 10 randomly selected townships of Zhejiang Province, China. Each village hosts 1 primary care clinic that serves all residents. Ten townships, each containing approximately 20 villages, were randomly selected to deliver either the Chinese Older Adult Collaborations in Health (COACH) intervention or enhanced care-as-usual (eCAU) to eligible village clinic patients. The COACH intervention consisted of algorithm-driven treatment of depression and HTN by village primary care doctors supported by village lay workers with telephone consultation from centrally located psychiatrists. Participants included clinic patients aged [greater than or equal to]60 years with a diagnosis of HTN and clinically significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score [greater than or equal to]10). Of 2,899 eligible village residents, 2,365 (82%) agreed to participate. They had a mean age of 74.5 years, 67% were women, 55% had no schooling, 59% were married, and 20% lived alone. Observers, older adult participants, and their primary care providers (PCPs) were blinded to study hypotheses but not to group assignment. Primary outcomes were change in depression symptom severity as measured by the Hamilton Depression Rating Scale (HDRS) total score and the proportion with controlled HTN, defined as systolic blood pressure (BP) Sixty-seven of 1,133 participants assigned to eCAU and 85 of 1,232 COACH participants were lost to follow-up over 12 months. Thirty-six participants died of natural causes, 22 in the COACH arm and 14 receiving eCAU. Forty COACH participants discontinued antidepressant medication due to side effects. Compared with participants who received eCAU, COACH participants showed greater reduction in depressive symptoms (Cohen&apos;s d [±SD] = -1.43 [-1.71, -1.15]; p < 0.001) and greater likelihood of achieving HTN control (odds ratio [OR] [95% CI] = 18.24 [8.40, 39.63]; p < 0.001). Limitations of the study include the inability to mask research assessors and participants to which condition a village was assigned, and lack of information about participants&apos; adherence to recommendations for lifestyle and medication management of HTN and depression. Generalizability of the model to other regions of China or other LMICs may be limited. Conclusions The COACH model of integrated care management resulted in greater improvement in both depression symptom severity and HTN control among older adult residents of rural Chinese villages who had both conditions than did eCAU. Trial registration ClinicalTrials.gov Identifier NCT01938963 https://clinicaltrials.gov/ct2/show/NCT01938963.

In this paper, we are concerned with the propagation dynamics of a nonlocal dispersal predator–prey model with one predator and two preys. Accurately, we mainly study the invading phenomenon of an alien predator to the habitat of two aborigine preys, which is depicted by traveling waves connecting the predator-free state to the co-existence state. We characterize the minimal wave speed of this invading process based on an application of Schauder’s fixed point theorem with the help of generalized upper-lower solutions and the Lyapunov argument. Particularly, the discussion of traveling waves with critical wave speed is more involved due to the effect of nonlocal dispersal. Finally, a numerical simulation is given to present the traveling waves and shows the differences between non-local and local dispersals. [ABSTRACT FROM AUTHOR]

Current methods, including ball milling and spray drying, are subject to some restrictions in application for preparing nano 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105), such as too large volume of dangerous goods, unstable temperature as well as discontinuous industrial production. In this study, continuous and safe preparation of nano-LLM-105 was achieved using microfluidic technology. Several influence factors had been studied on the particle size of LLM-105 including supersaturation, microreactor structure, solvent/non-solvent ratio, the total flow rate, reactor temperature, as well as the number of plates. Results showed that supersaturation of solution and structure of the microreactor played a critical role in the formation of nano-scale LLM-105. Further analysis on these nano-particles revealed its D50 was 124.95 nm with a spherical-like narrow shape through scanning electron microscopy and particle size distribution curve. X-ray diffraction results show that the crystal structure of nano-LLM-105 has not changed, and the differential scanning calorimeter test results show that nano-LLM-105 still maintains good thermal stability compared to raw-LLM-105. In short, this protocol provides a new route for continuous and safe preparation of nano-level LLM-105, which could be potentially applied to other nano-energetic materials, such as HMX and CL-20. [ABSTRACT FROM AUTHOR]

Abstract Background Communication about prognosis and treatment choices is essential for informed decision making in advanced cancer. This article describes an investigation designed to facilitate communication and decision making among oncologists, patients with advanced cancer, and their caregivers. Methods/design The Values and Options in Cancer Care (VOICE) Study is a National Cancer Institute sponsored randomized controlled trial conducted in the Rochester/Buffalo, NY and Sacramento, CA regions. A total of 40 oncologists, approximately 400 patients with advanced cancer, and their family/friend caregivers (one per patient, when available) are expected to enroll in the study. Drawing upon ecological theory, the intervention uses a two-pronged approach: oncologists complete a multifaceted tailored educational intervention involving standardized patient instructors (SPIs), and patients and caregivers complete a coaching intervention to facilitate prioritizing and discussing questions and concerns. Follow-up data will be collected approximately quarterly for up to three years. Discussion The intervention is hypothesized to enhance patient-centered communication, quality of care, and patient outcomes. Analyses will examine the effects of the intervention on key elements of physician-patient-caregiver communication (primary outcomes), the physician-patient relationship, shared understanding of prognosis, patient well-being, and health service utilization (secondary outcomes). Trial registration Clinical Trials Identifier: NCT01485627

In this study, 0.015 Eu2+-doped Sr3−xBaxMgSi2O8 (x=0, 0.3, 0.6, 0.9) were used as compositions to find the effect of BaO content on their photoluminescence excitation (PLE) and photoluminescence emission (PL) properties. They were sintered at 1400°C in a reduction atmosphere of 95% N2+5% H2 to form blue phosphors. X-ray diffraction pattern and SEM observation were used to analyze their crystal properties, and a fluorescence spectrophotometer was used to analyze their PLE and PL properties. After conducting a thorough analysis, our research primarily encompasses four significant research themes. First, SEM observations revealed that synthesized Eu2+-doped Sr3−xBaxMgSi2O8 phosphors exhibit the formation of whisker-like structures. Therefore, the whisker-like structures in all the Eu2+-doped Sr3−xBaxMgSi2O8 phosphors were analyzed using the HRTEM and its equipped EDS to find how BaO content influenced both the quantity and fineness of these whiskers. Second, we examined the impact of BaO content on the PLE and PL emission intensities of the Eu2+-doped Sr3−xBaxMgSi2O8 phosphors across a temperature range from room temperature to 210°C. This investigation aimed to uncover the effects of BaO content and temperature on the thermal stability of the Eu2+-doped Sr3−xBaxMgSi2O8 phosphors. Lastly, our fourth important investigation involved reorganizing the PLE spectra of the Eu2+-doped Sr3−xBaxMgSi2O8 phosphors with the energy band as the x-axis. The Gaussian fitting function was applied to analyze the excitation spectra and discern the influence of BaO content on the value of the Stokes shift. [ABSTRACT FROM AUTHOR]

In this paper, based on an Fe-based amorphous alloy, four kinds of RGO/Cu/Fe-based amorphous composite coatings with mass ratios of 5%, 10%, 15%, and 20% of RGO/Cu were prepared on the surface of 45# steel by using high-velocity oxy-fuel (HVOF) spraying. The coatings were immersed in simulated seawater at room temperature and at 90 °C for different lengths of time, and their corrosion resistance was tested using electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and X-ray diffraction (XRD), and the surface morphology and phase distribution of the samples were observed. The results showed that with the increase in the introduction ratio of RGO/Cu, when the addition ratio reached 15%, the composite coating had the best corrosion resistance. After soaking in simulated seawater at 90 °C for 18 days, the surface of the coating showed slight peeling and crack propagation, but no obvious pitting phenomenon occurred. The corrosion mechanism of the RGO/Cu/Fe coating in high-temperature seawater is mainly that high temperature causes the cracking of the coating, which opens up a transport channel for corrosion media. However, due to the addition of RGO, the corrosion has a certain self-limitation effect, which is mainly due to the toughening effect of RGO on the coating and its effect on extending the corrosion channel. [ABSTRACT FROM AUTHOR]