Search

This study uses the Multi-Level Perspective (MLP) on socio-technical transitions to develop a theoretical model for analyzing the stable operation of regional innovation ecosystems. Focusing on 30 provinces in China, it employs Necessary Condition Analysis (NCA) and Fuzzy-set Qualitative Comparative Analysis (fsQCA) to systematically examine the configuration paths driving their stability. First, the findings reveal that innovation actors, resources, driving policies, industrial regulations, infrastructures, and the innovation environment are not individually necessary for stability. However, infrastructure is identified as a critical core condition. The study highlights a complex causal relationship and synergistic interplay among the six antecedent conditions. Second, the research identifies two paths to highly stable operation in regional innovation ecosystems: the ‘Innovation Actor + Infrastructure’ path and the ‘Infrastructure’ path. Finally, the results show that configurations for highly and non-highly stable operations exhibit causal asymmetry, indicating ‘different paths to the same destination.’ This study deepens theoretical insights into regional innovation ecosystems and offers actionable strategies for their stable operation. [ABSTRACT FROM AUTHOR]

Diverse clinical observations and basic studies have been conducted to explore the implications of analgesic medications in liver diseases. However, the direct causal relationship between prescription analgesic use (PAU) and the risk of liver cancer and precancerosis remains unclear. Thus, we aimed to reveal the conceivable causal effect of PAU on liver cancer and precancerosis, with immune cells as mediating factors. Two-sample Mendelian randomization (MR) analyses were performed to ascertain the causality of PAU on liver cancer and precancerosis. Sensitivity analysis approaches were employed to assess the heterogeneity and pleiotropy of results. Our findings revealed a causal correlation between different PAUs and the risk of liver cancer and alcoholic liver disease (ALD). Specifically, salicylic acid derivatives (SADs) and anilide medications were found to have a protective effect on liver cancer. And non-steroidal anti-inflammatory drugs (NSAIDs) and anilide medications showed a causal impact on ALD. Finally, mediation analyses found that anilide medications influence liver cancer through different immune cell phenotypes. Our research provides new genetic evidence for the causal impact of PAU on liver cancer and precancerosis, with the mediating role of immune cells demonstrated, offering a valuable foundation for researching analgesic medications in liver cancer and precancerosis treatment. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides (HMOs) are complexes that play a crucial role in shaping the early-life gut microbiota. This study intends to explore whether HMO patterns are associated with the gut microbiota of infants. We included 96 Chinese breastfeeding mother–infant dyads. Breast milk and infant faecal samples were collected and tested. With milk 2′-fucosyllactose, difucosyllactose, and lacto-N-fucopentaose-I as biomarkers, we divided the mothers into secretor and non-secretor groups. HMO patterns were extracted using principal component analysis. The majority (70.7%) of mothers were categorised as secretor and five different HMO patterns were identified. After adjustment, the infants of secretor mothers exhibited a lower relative abundance of Bifidobacterium bifidum (β = −0.245, 95%CI: −0.465~−0.025). An HMO pattern characterised by high levels of 3-fucosyllactose, lacto-N-fucopentaose-III, and lacto-N-neodifucohexaose-II was positively associated with the relative abundance of Bifidobacterium breve (p = 0.014), while the pattern characterised by lacto-N-neotetraose, 6′-sialyllactose, and sialyllacto-N-tetraose-b was negatively associated with Bifidobacterium breve (p = 0.027). The pattern characterised by high levels of monofucosyl-lacto-N-hexaose-III and monofucosyl-lacto-N-neohexaose was positively associated with Bifidobacterium dentium (p = 0.025) and Bifidobacterium bifidum (p < 0.001), respectively. This study suggests that HMO patterns from mature breast milk were associated with certain gut microbiota of breastfed infants. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a heterogeneous disease, causing severe breathing problems and cardiac morbidity. Here, the authors study chromatin marks in pulmonary arterial endothelial cells from PAH patients and controls and find changes in transcription factor and enhancer activity that suggest an aberrant response to signalling in PAH.

Sn-2 palmitate is widely used in infant formula. However, little is known about its effects on metabolism and body composition in middle-aged and elderly adults. In a double-blinded, randomized controlled trial, we enrolled Chinese adults aged 45–75 years with self-reported constipation. Individuals were randomly assigned in a 1:1 ratio to a 1,3-dioleoyl-2-palmitoyl-glycerol (OPO)-enriched oil (66% palmitic acid in the sn-2 position) or a control vegetable oil (24% palmitic acid in the sn-2 position) daily for 24 weeks. Skim milk powder was used as the carrier for both fats. Interviews and body composition were performed at baseline, week 4, week 12 and week 24. A fasting blood draw was taken except at week 4. This study was a secondary analysis and considered exploratory. A total of 111 adults (83 women and 28 men, mean age 64.2 ± 7.0 years) were enrolled, of whom 53 were assigned to the OPO group and 57 to the control group. During the intervention, blood glucose, triglyceride, the triglyceride-glucose index, total cholesterol, low-density lipoprotein cholesterol and remnant cholesterol remained stable, while high-density lipoprotein cholesterol decreased in both groups (p = 0.003). No differences in change were observed between the groups (all p > 0.05). From baseline to week 24, the level of visceral fat increased slightly (p = 0.017), while body weight, total body water, protein, soft lean mass, fat-free mass, skeletal muscle and skeletal muscle mass index (SMI) decreased in two groups (p < 0.01). At weeks 4, 12 and 24, the SMI decreased less in the OPO group than in the control group, with a trend towards significance (p = 0.090). A 24-week daily intake of sn-2-palmitate-enriched oil had no adverse impact on fasting blood glucose, lipids and body composition compared with the control vegetable oil in Chinese adults (funded by Chinese Nutrition Society National Nutrition Science Research Grant, National Key Research and Development Program of China and Wilmar (Shanghai) Biotechnology Research & Development Center Co., Ltd.; ChiCTR1900026480). [ABSTRACT FROM AUTHOR]

Orbital angular momentum (OAM), inherent to light beams characterized by helical phase fronts, represents an alternative spatial degree of freedom for photons. In recent years, OAM-based communication has gained significant attention as a potential solution to increase the capacity and spectral efficiency of optical fiber communication systems. In optical fibers, OAM modes can be generated and manipulated by utilizing specialized optical components and techniques. One approach involves using specially designed optical fibers, such as ring–core fibers, which have the capability to support multiple OAM modes. In the manufacturing process, the ring fiber is hardly made perfectly, especially the doped-cores. The introduced defect breaks the symmetry of the ring–core, which has a serious impact on OAM mode transmission. Using a material with a slightly higher refractive index than the cladding to wrap the ring–core is effective in reducing impairment of defects. After numerical simulation, the proposed method improves the walk-off length by a factor of 2–40. [ABSTRACT FROM AUTHOR]

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death, highlighting the urgent clinical need for effective therapies. Recently, tanshinone IIA has been identified as a promising therapeutic agent for myocardial infarction. However, efficient delivery remains a major issue that limits clinical translation. To address this problem, an injectable thermosensitive poly (lactic acid‐co‐glycolic acid)‐block‐poly (ethylene glycol)‐block‐poly (lactic acid‐co‐glycolic acid) gel (PLGA‐PEG‐PLGA) system encapsulating tanshinone IIA‐loaded reactive oxygen species‐sensitive microspheres (Gel−MS/tanshinone IIA) has been designed and synthesized in this study. The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature. Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species‐triggered release properties in a high‐reactive oxygen species environment after myocardial infarction onset. As a result, encapsulated tanshinone IIA is effectively released into the infarcted myocardium, where it exerts local anti‐pyroptotic and anti‐inflammatory effects. Importantly, the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinone IIA. Therefore, this novel, precision‐guided intra‐tissue therapeutic system allows for customized local release of tanshinone IIA, presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post‐infarct heart. [ABSTRACT FROM AUTHOR]

Background: Tumor metastasis and recurrence are major causes of mortality in patients with hepatocellular carcinoma (HCC) that is still lack of effective therapeutic targets and drugs. Previous reports implied that ras homolog family member C (RhoC) plays a toxic role on metastasis and proliferation of cancer. Methods: In this research, the correlation between RhoC and metastasis ability was confirmed by in vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real‐time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient‐derived xenografts (PDXs) were employed to evaluate the anti‐metastasis effects of quercetin. Results: Clinical relevance and in vitro experiments further confirmed the level of RhoC was positively correlated with invasion and metastasis ability of HCC. Then we uncovered that quercetin could attenuate invasion and metastasis of HCC by downregulating RhoC's level in vitro, in vivo and PDXs. Furthermore, mechanistic investigations displayed quercetin hindered the E3 ligase expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) leading to enhancement of RhoC's ubiquitination and proteasomal degradation. Conclusions: Our research has revealed the novel mechanisms quercetin regulates degradation of RhoC level by targeting SMURF2 and identified quercetin may be a potential compound for HCC therapy. [ABSTRACT FROM AUTHOR]