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In order to study the creep characteristics of concrete under different temperatures, the uniaxial creep test of concrete is carried out. On this basis, the nonlinear creep model of concrete is established by using the fractal order derivative theory. According to the characteristics of the classical creep curve and the creep equation, the calculation method of creep parameters is determined. The variation law of each creep model parameter under different stress and temperature is analyzed. The results showed that the model can well reproduce the change trend of the curve during the creep process of concrete under different temperature conditions and stress levels, indicating that the model has strong adaptability and accuracy in capturing the creep law. In the later stage of concrete creep, the accelerated creep stage is often accompanied by complex situations such as rapid accumulation of internal damage and rapid deterioration of the structure. The traditional model has limitations in the accurate description of this stage, and the new model can effectively solve this problem. Undoubtedly, it enhances its value and advantages in practical applications. The elastic modulus of the elastomer controls the instantaneous strain. The elastic modulus, viscosity coefficient and fractal order of viscoelastic body control the viscoelastic creep and creep rate. Viscosity coefficient and fractal order of viscoplastic body control the viscoplastic creep and creep rate.

In order to measure the impact of the degree of coupling and coordination between logistics and financial industries on the carbon emissions of the logistics industry, a comprehensive evaluation index system for the logistics-financial industry from 2007 to 2017 was constructed, which was calculated using the multi-objective linear weighting method; and a combination of logistics and financial industry was constructed. The panel smooth conversion model of coordination degree and carbon emission of logistics industry. The empirical results show that the coupling coordination degree of logistics and financial industry in China’s 30 provinces is mostly in primary and medium coordination, and only a few provinces are on the verge of imbalance; the coupling coordination degree in the eastern region is overall moderate coordination, and the overall coordination degree in the central and western regions It is the primary coordination; with the growth of GDP per capita, the degree of coupling and coordination between the logistics and financial industries has promoted the increase of carbon emissions in various regions, but the promotion effect is an inverted U-shaped trend that first increases and then decreases.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC 50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use ( n  = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We show levels of Disrupted‐in‐schizophrenia‐1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ‐treated cultured cells. Disrupted‐in‐schizophrenia‐1 contains a canonical LC3‐interacting region (LIR) motif (210FSFI213), through which DISC1 directly binds to LC3‐I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking‐down of DISC1 blocks Aβ‐induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which abolishes the interaction of DISC1 with LC3, rescues Aβ‐induced mitochondrial dysfunction, loss of spines, suppressed long‐term potentiation (LTP). Overexpression of DISC1 via adeno‐associated virus (serotype 8, AAV8) in the hippocampus of 8‐month‐old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aβ plaque accumulation, in a way dependent on the interaction of DISC1 with LC3. These results indicate that DISC1 is a novel mitophagy receptor, which protects synaptic plasticity from Aβ accumulation‐induced toxicity through promoting mitophagy.

Seven previously undescribed prenylated p-hydroxybenzoic acid derivatives, oberoniaensiformisins A–G, were isolated from an EtOH extract of the whole plant Oberonia ensiformis. Their structures were determined through spectroscopic analyses (IR, NMR) and HRESIMS analysis. The isolated compounds were tested for their antimicrobial, antioxidant, and α-glucosidase-inhibitory activity. Among them, compounds 6 and 12 exhibited potential antioxidant activity, while compounds 5, 6, 12, 13, and 15 showed varying degrees of α-glucosidase-inhibitory activity, with IC50 values ranging from 34.03 to 106.10 μg/mL.

Inducing cancer differentiation is a promising approach to treat cancer. Here, we identified chlorogenic acid (CA), a potential differentiation inducer, for cancer therapy, and elucidated the molecular mechanisms underlying its differentiation-inducing effects on cancer cells. Cancer cell differentiation was investigated by measuring malignant behavior, including growth rate, invasion/migration, morphological change, maturation, and ATP production. Gene expression was analyzed by microarray analysis, qRT-PCR, and protein measurement, and molecular biology techniques were employed for mechanistic studies. LC/MS analysis was the method of choice for chemical detection. Finally, the anticancer effect of CA was evaluated both and Results: Cancer cells treated with CA showed reduced proliferation rate, migration/invasion ability, and mitochondrial ATP production. Treating cancer cells with CA resulted in elevated SUMO1 expression through acting on its 3'UTR and stabilizing the mRNA. The increased SUMO1 caused c-Myc sumoylation, miR-17 family downregulation, and p21 upregulation leading to G /G arrest and maturation phenotype. CA altered the expression of differentiation-related genes in cancer cells but not in normal cells. It inhibited hepatoma and lung cancer growth in tumor-bearing mice and prevented new tumor development in naïve mice. In glioma cells, CA increased expression of specific differentiation biomarkers Tuj1 and GFAP inducing differentiation and reducing sphere formation. The therapeutic efficacy of CA in glioma cells was comparable to that of temozolomide. CA was detectable both in the blood and brain when administered intraperitoneally in animals. Most importantly, CA was safe even at very high doses. CA might be a safe and effective differentiation-inducer for cancer therapy. \"Educating\" cancer cells to differentiate, rather than killing them, could be a novel therapeutic strategy for cancer.

While the term interactive marketing often has diverse definitions and usages among marketing professionals and practitioners, it is defined here as the bi-directional value creation and mutual-influence marketing process through active customer connection, engagement, participation and interaction. [...]a definition characterizes interactive marketing in terms of the following aspects, namely, first, it is a two-way communication with mutual influences in social and business ecosystems; second, it focuses on customer responsiveness and often proactive behaviors in value creation and exchange; and third, its interactivity involves customer participation and engagement in controlling and modifying the environment in real-time (Steuer, 1992). The growth of digital platforms has displaced traditional intermedia not only by creating a new type of superpower of omnichannel marketplace spanning online and offline retailers but also changed business models from a linear supply chain pipeline to a complex network of producers and users in an interconnected ecosystem (Parker, VA Alstyne and Choudary, 2016). [...]participants can swap their roles from hosts to customers on Airbnb, from drivers to riders on Uber and Didi, from media content creators to audience on Youtube and Wikipedia.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the ninth member of the proprotein convertase family that regulates lipoprotein homeostasis and altered PCSK9 expression was reportedly associated with tumor development and progression. This study assessed PCSK9 expression and functions in human colon cancer and then explored the underlying molecular events. Methods Colon cancer tissues were utilized for analysis of PCSK9 expression for association with clinicopathological factors from patients by immunohistochemistry assay. Manipulation of PCSK9 expression was assessed in vitro and in vivo for colon cancer cell proliferation, migration, and invasion using cell viability CCK-8, Transwell tumor cell migration and invasion, and wound-healing assays. Next, proteomic analysis, Western blot, qRT-PCR and Flow cytometry were conducted to assess downstream targets and tumor cell-derived PCSK9 action on macrophage polarization. Results PCSK9 expression was upregulated in colon cancer tissues versus the normal tissues, and associated with advanced tumor pathological grade. Knockdown of PCSK9 expression reduced colon cancer cell proliferation, migration, and invasion and suppressed tumor metastasis in vivo. PCSK9 directly or indirectly upregulated Snail 1 and in turn to downregulate E-cadherin expression, but upregulate N-cadherin and MMP9 levels and thereafter, to induce colon cancer cell epithelial-mesenchymal transition (EMT) process and activated PI3K/AKT signaling. However, PCSK9 overexpression showed the inverse effects on colon cancer cells. Knockdown of PCSK9 expression inhibited M2 macrophage polarization, but also promoted M1 macrophage polarization by reduction of lactate, protein lactylation and macrophage migration inhibitory factor (MIF) levels. Conclusion PCSK9 played an important role in the progression and metastasis of colon cancer by regulation of tumor cell EMT and PI3K/AKT signaling and in the phenotypic polarization of macrophages by mediating MIF and lactate levels. Targeting PCSK9 expression or activity could be used to effectively control colon cancer.

Natural pigments, including carotenoids, flavonoids and anthocyanidins, determine the attractive color of fruits. These natural pigments are essential secondary metabolites, which play multiple roles in the whole life cycle of plants and are characterized by powerful antioxidant activity. After decades of research and development, multiple benefits of these natural pigments to human health have been explored and recognized and have shown bright application prospects in food, medicine, cosmetics and other industries. In this paper, the research progress of natural fruit pigments in recent years was reviewed, including the structural characteristics and classification, distribution in fruits and analysis methods, biosynthetic process, antioxidant capacity and mechanism, bioaccessibility and bioavailability, and health benefits. Overall, this paper summarizes the recent advances in antioxidant activity and other biological functions of natural fruit pigments, which aims to provide guidance for future research.

Background Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI). Methods This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes. Results A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 ( p  = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively ( p  < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005–2.804) and MACEs (HR 2.064, 95% CI 1.386–3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM). Conclusion Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status.