A Perturbed Inverse Gaussian Process Model with Time Varying Variance-To-Mean Ratio

International audienceThe inverse gaussian (IG) process has become a common model for reliability analysis of monotonic degradation processes. The traditional IG process model assumes that the degradation increment follows an IG distribution, and the variance-to-mean ratio (VMR) is constant with time. However, for the degradation paths of some practical applications, e.g., the GaAs laser degradation data that motivated to propose the IG process, the VMR is actually time varying. Confronted with this, we propose an IG process model with measurement errors that depend on the actual degradation level. According to different forms or parameter values of the dependence function, the VMR of the degradation paths can display different time varying patterns. The maximum likelihood estimation method is developed in a step-by-step way, combined with numerical integration method and heuristic optimization method. Finally, the GaAs laser example is revisited to illustrate the effectiveness of the proposed model, which indicates that the introduction of statistically dependent measurement error can provide better fitting results and lifetime evaluation performance

Zhongjing: Enhancing the Chinese Medical Capabilities of Large Language Model through Expert Feedback and Real-world Multi-turn Dialogue

Recent advances in Large Language Models (LLMs) have achieved remarkable breakthroughs in understanding and responding to user intents. However, their performance lag behind general use cases in some expertise domains, such as Chinese medicine. Existing efforts to incorporate Chinese medicine into LLMs rely on Supervised Fine-Tuning (SFT) with single-turn and distilled dialogue data. These models lack the ability for doctor-like proactive inquiry and multi-turn comprehension and cannot always align responses with safety and professionalism experts. In this work, we introduce Zhongjing, the first Chinese medical LLaMA-based LLM that implements an entire training pipeline from pre-training to reinforcement learning with human feedback (RLHF). Additionally, we introduce a Chinese multi-turn medical dialogue dataset of 70,000 authentic doctor-patient dialogues, CMtMedQA, which significantly enhances the model's capability for complex dialogue and proactive inquiry initiation. We define a refined annotation rule and evaluation criteria given the biomedical domain's unique characteristics. Results show that our model outperforms baselines in various capacities and matches the performance of ChatGPT in a few abilities, despite having 50x training data with previous best model and 100x parameters with ChatGPT. RLHF further improves the model's instruction-following ability and safety.We also release our code, datasets and model for further research

Understanding the Habitual Pattern of Concomitant Consumption of Herbs to Alleviate the Symptoms of Ulcerative Colitis by Comparative Proteome Analysis

Anchang decoction is an empirical prescription for the treatment of ulcerative colitis in China. In order to better understand its therapeutic function, large efforts have been made to identify its chemical constituents and to unravel the efficacy of its principal constituents. However, the molecular mechanism of its combinations is still unclear. Proteomics application has yielded some positive results in drug development and the identification of potential drug targets, suggesting the potential of this analytical approach to explore the action of molecular mechanisms of herbal formula by robustly addressing dynamic proteome changes. Label-free quantification and parallel reaction monitoring were used to identify differentially expressed proteins in the colon tissue of ulcerative colitis rats, fed with Anchang decoction and mesalazine, respectively. In this study, a total of 1,182 proteins were identified. From GO and KEGG analyses, the proteins of cytoskeleton and cytochrome P450 changed significantly with the occurrence of ulcerative colitis. In the meantime, antigen binding proteins and antioxidant-related proteins turned out to have drastic fluctuations with mesalazine and Anchang decoction. It has also been confirmed that KRT8, MYH11, FLNA, and LMNA are all related to the formation of ulcerative colitis based on parallel reaction monitoring analysis. The increase in FGG in the ulcerative colitis rat model is due to mesalazine, whereas that in KRT8 is due to Anchang decoction. The results from this study provide insights for the mechanism of action of Anchang decoction, which turns out to be an efficient technical pipeline for understanding worldwide medicinal herbs

Prevalence of non-alcoholic fatty liver disease and its relation to hypoadiponectinaemia in the middle-aged and elderly Chinese population

Introduction: Hypoadiponectinaemia is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, little is known about its role in the Chinese population. This study sought to assess the prevalence of NAFLD and its association with hypoadiponectinaemia in middle-aged and elderly Chinese. Material and methods: We conducted a population-based cross-sectional study in an urban Shanghai sample of 2201 participants age 50 years to 83 years (973 men, 1228 women). Hepatic ultrasonographic examination was performed for all participants. Serum adiponectin concentrations were measured by ELISA methods. Results: The prevalence of NAFLD was 19.8% (16.0% in men, 22.8% in women). Serum adiponectin levels were significantly higher in female than in male subjects (p < 0.001). Serum adiponectin levels were significantly lower in NAFLD subjects than those in control subjects (p < 0.001). The prevalence of NAFLD progressively increased with declining adiponectin levels (p(for) (trend) < 0.001). The participants in the lowest adiponectin quartile had a significantly increased risk for acquiring NAFLD (OR = 2.31, 95% CI 1.72-3.15) after adjustment for potential confounders. Conclusions: Population-based screening suggests that NAFLD is highly prevalent in middle-aged and elderly people in Shanghai, particularly among women. Serum adiponectin level is negatively associated with NAFLD independently of potential cofounders, indicating that hypoadiponectinaemia may contribute to the development of NAFLD

Robust memristors based on layered two-dimensional materials

Van der Waals heterostructures are formed by stacking layers of different two-dimensional materials and offer the possibility to design new materials with atomic-level precision. By combining the valuable properties of different 2D systems, such heterostructures could potentially be used to address existing challenges in the development of electronic devices, particularly those that require vertical multi-layered structures. Here we show that robust memristors with good thermal stability, which is lacking in traditional memristors, can be created from a van der Waals heterostructure composed of graphene/MoS2–xO x/graphene. The devices exhibit excellent switching performance with an endurance of up to 107 and a high operating temperature of up to 340 °C. With the help of in situ electron microscopy, we show that the thermal stability is due to the MoS2–xO x switching layer, as well as the graphene electrodes and the atomically sharp interface between the electrodes and the switching layer. We also show that the devices have a well-defined conduction channel and a switching mechanism that is based on the migration of oxygen ions. Finally, we demonstrate that the memristor devices can be fabricated on a polyimide substrate and exhibit good endurance against over 1,000 bending cycles, illustrating their potential for flexible electronic applications

Inhibition of 26S Protease Regulatory Subunit 7 (MSS1) Suppresses Neuroinflammation

Recently, researchers have focused on immunosuppression induced by rifampicin. Our previous investigation found that rifampicin was neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In this study, using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we discovered that 26S protease regulatory subunit 7 (MSS1) was decreased in rifampicin-treated microglia. Western blot analysis verified the downregulation of MSS1 expression by rifampicin. As it is indicated that the modulation of the ubiquitin-26S proteasome system (UPS) with proteasome inhibitors is efficacious for the treatment of neuro-inflammatory disorders, we next hypothesized that silencing MSS1 gene expression might inhibit microglial inflammation. Using RNA interference (RNAi), we showed significant reduction of IkBα degradation and NF-kB activation. The production of lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide, cyclooxygenase-2, and prostaglandin E2 were also reduced by MSS1 gene knockdown. Taken together, our findings suggested that rifampicin inhibited microglial inflammation by suppressing MSS1 protein production. Silencing MSS1 gene expression decreased neuroinflammation. We concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin, might represent a novel mechanism for the treatment of neuroinflammatory disorders

Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors

Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with antitumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/refractory mature Bcell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase 2 dose (RP2D). Overall, 134 Chinese patients were enrolled (dose escalation, n=27; dose expansion, n=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d. The primary efficacy end point of independent review committee–assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% CI, 37.5–64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the doseexpansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased doseproportionally with ascending dose levels from 200–800 mg, without observed saturation. Sovleplenib showed antitumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted

Environmental Effects on Vertebrate Species Richness: Testing the Energy, Environmental Stability and Habitat Heterogeneity Hypotheses

Background: Explaining species richness patterns is a central issue in biogeography and macroecology. Several hypotheses have been proposed to explain the mechanisms driving biodiversity patterns, but the causes of species richness gradients remain unclear. In this study, we aimed to explain the impacts of energy, environmental stability, and habitat heterogeneity factors on variation of vertebrate species richness (VSR), based on the VSR pattern in China, so as to test the energy hypothesis, the environmental stability hypothesis, and the habitat heterogeneity hypothesis. Methodology/Principal Findings: A dataset was compiled containing the distributions of 2,665 vertebrate species and eleven ecogeographic predictive variables in China. We grouped these variables into categories of energy, environmental stability, and habitat heterogeneity and transformed the data into 1006100 km quadrat systems. To test the three hypotheses, AIC-based model selection was carried out between VSR and the variables in each group and correlation analyses were conducted. There was a decreasing VSR gradient from the southeast to the northwest of China. Our results showed that energy explained 67.6 % of the VSR variation, with the annual mean temperature as the main factor, which was followed by annual precipitation and NDVI. Environmental stability factors explained 69.1 % of the VSR variation and both temperature annual range and precipitation seasonality had important contributions. By contrast, habitat heterogeneity variables explained only 26.3 % of the VSR variation. Significantly positive correlations were detected among VSR, annua

A novel role for cdk5 in the cell cycle

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