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This paper investigated the mutual interaction between two extra-thin line fires under different wind speeds of 0.4, 0.6, 0.8, 1.0 and 1.2 m/s by using a small-scale wind tunnel. The experiments involved the spacing distances of 5, 10, 15, 20, 25, 30, 35 and 40 cm, and the heat release rates of 19.4, 25.7 and 32.7 kW, respectively. The results show that the flame merging probability increase, as the wind speed or the heat release rate increases. Compared with the two rectangular or square fires, the flame height and flame length will be smaller at the same heat release rate for the extra-thin line fires. Meanwhile, the line fires will decrease the flame merging, making the downstream flame temperature smaller than that of the upstream at the relatively larger wind speed or heat release rate. The interesting finding is that, with the increase of the heat release rate, the flame inclination angle will increase in the fully merging stage, which is opposite to that of square fires. Correspondingly, the flame merging model is built on the influences of the buoyancy force and inertial force of the horizontal wind, which can give the good explanation on this behavior.

Summary: Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

Central nervous system (CNS) damage is usually irreversible owing to the limited regenerative capability of neurons. Following CNS injury, astrocytes are reactively activated and are the key cells involved in post-injury repair mechanisms. Consequently, research on the reprogramming of reactive astrocytes into neurons could provide new directions for the restoration of neural function after CNS injury and in the promotion of recovery in various neurodegenerative diseases. This review aims to provide an overview of the means through which reactive astrocytes around lesions can be reprogrammed into neurons, to elucidate the intrinsic connection between the two cell types from a neurogenesis perspective, and to summarize what is known about the neurotranscription factors, small-molecule compounds and MicroRNA that play major roles in astrocyte reprogramming. As the malignant proliferation of astrocytes promotes the development of glioblastoma multiforme (GBM), this review also examines the research advances on and the theoretical basis for the reprogramming of GBM cells into neurons and discusses the advantages of such approaches over traditional treatment modalities. This comprehensive review provides new insights into the field of GBM therapy and theoretical insights into the mechanisms of neurological recovery following neurological injury and in GBM treatment.

Objectives: This study aimed to assess the diagnostic, risk stratification, and prognostic capabilities of apelin-13 and APJ in comparison to procalcitonin (PCT) for septic patients presenting to the emergency department (ED). Methods: Two hundred and thirty-eight patients meeting the Third International Consensus Definition (Sepsis-3) criteria were enrolled from Beijing Chaoyang Hospital's ED, along with a control group of forty healthy individuals. Patients were categorized into two groups based on disease severity: those with sepsis or septic shock. Plasma levels of apelin-13, CD4+ Th cells, and PCT were measured. The expression levels of plasma APJ mRNA were quantified using real-time fluorescence quantitative PCR (RT-qPCR) methodology. The Sequential Organ Failure Assessment (SOFA) score was determined at the time of enrollment. The prognostic values of apelin-13 and APJ was evaluated in comparison to that of PCT and the SOFA score. All patients were followed up for a duration of 28 days. Results: The plasma concentrations of apelin-13 and APJ exhibited a positive correlation with the severity of sepsis, while the number of CD4+ T cells decreased in septic patients. The areas under the receiver operating characteristic (AUC) curves for apelin-13 and APJ in the diagnosis and prediction of 28-day mortality were greater than that of PCT. In non-survivors at the 28-day follow-up, the plasma levels of apelin-13 and APJ were significantly higher compared to survivors. Furthermore, apelin-13 levels were notably higher in cases of sepsis-induced cardiomyopathy (SICM) than in those without SICM. Apelin-13 and APJ emerged as independent predictors of 28-day mortality among septic patients. Conclusions: Apelin-13 and APJ demonstrate value in the assessment of risk stratification, early diagnosis, and prognosis of sepsis in the ED. Apelin-13 also proves to be an effective biomarker for assessing the prognosis of SICM in the ED. Sepsis may lead to immune function suppression.

The biotoxicity and chemotherapeutic resistance of cisplatin (CDDP) pose a challenge for tumor therapy. Practically, the change in the therapeutic response of tumor from resistance to sensitivity are impressive but challenging. To this end, we propose a strategy of “one stone, three birds” by designing a CuPt nanoalloy to simultaneously eliminate GSH, relieve hypoxia, and promote ROS production for effectively reversing the platinum (IV) (Pt(IV), (c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)2)) resistance. Notably, the CuPt nanoalloy exhibits ternary catalytic capabilities including mimicking GSH oxidase, catalase and peroxidase. With the subsequent disguise of tumor cell membrane, the CuPt nanoalloy is conferred with homologous targeting ability, making it actively recognize tumor cells and then effectively internalized by tumor cells. Upon entering tumor cell, it gives rise to GSH depletion, hypoxia relief, and oxidative stress enhancement by catalyzing the reaction of GSH and H2O2, which mitigates the vicious milieu and ultimately reinforces the tumor response to Pt(IV) treatment. In vivo results prove that combination therapy of mCuPt and Pt(IV) realizes the most significant suppression on A549 cisplatin-resistant tumor. This study provides a potential strategy to design novel nanozyme for conquering resistant tumor.

This study aimed to prepare an o/w mitiglinide microemulsion (MTGME) to improve the drug solubility and bioavailability. The formulation of o/w MTGME was optimized by the solubility study of drug, pseudo-ternary phase diagram and Box-Behnken design successively. MTGME was characterized by dynamic laser light scattering (DLS), zeta potential and transmission electron microscopy (TEM), moreover, the storage stability, pharmacodynamics and pharmacokinetics were investigated. The optimal prescription for MTGME consisted of Maisine 35–1 (oil), Cremophor EL (surfactant) and propylene glycol (PG, cosurfactant). MTGME with a spherical dimension of 58.1 ± 5.86 nm was stable when stored at 4 °C for 3 months. The blood glucose levers (BGL) of diabetic mice were uniformly and significantly decreased by intragastric (i.g.) administration of 1–4 mg/kg MTGME, in which BGL (i.g. 4 mg/kg MTGME) was reduced by 69% during 24 h. The pharmacokinetics study of MTGME (i.g., 20 mg/kg) in Wistar rats showed higher plasma drug concentration (Cmax, 2.9 folds), larger area under curve (AUC, 4.6 folds) and oral bioavailability than those of MTG suspensions. Generally, the MTGME (o/w) showed good effect on controlling hyperglycemia. Therefore, microemulsion can be used as an effective oral drug delivery system to improve the bioavailability of MTG.

The skeleton of 2-trifluoromethyl quinoline is the core structure of many natural products and pharmaceutical molecules. The synthesis of this scaffold is limited by metal catalysis, harsh conditions, toxic or hazardous reagents and solvents, and lower atom-economy. Herein, a novel method for the synthesis of 2-trifluoromethyl quinolines via the [4 + 2] cyclization of β-keto esters or 1,3-diketones with various substituted o-aminobenzaldehydes using the metal free catalyst in EtOH is reported. This atom- and step-economical protocol features simple operation, broad substrate scope, and good functional-group compatibility. The synthetic utility of this methodology was highlighted by easy gram-scale synthesis and late-stage functionalization, which would promote the vigorous development of quinoline chemistry. Moreover, the in vitro antifungal activities of the 2-trifluoromethyl quinolines against F. graminearum (from wheat), F. graminearum (from corn), F. moniliforme, F. oxysporum, and R. solani were investigated to further potential utility of these compounds.

Activated pancreatic stellate cells (PSCs) are the main cells involved in chronic pancreatitis and pancreatic intraepithelial neoplasia lesion (PanIN). Fine-tuning the precise molecular targets in PSC activation might help the development of PSC-specific therapeutic strategies to tackle progression of pancreatic cancer-related fibrosis. miR-301a is a pro-inflammatory microRNA known to be activated by multiple inflammatory factors in the tumor stroma. Here, we show that miR-301a is highly expressed in activated PSCs in mice, sustained tissue fibrosis in caerulein-induced chronic pancreatitis, and accelerated PanIN formation. Genetic ablation of miR-301a reduced pancreatic fibrosis in mouse models with chronic pancreatitis and PanIN. Cell proliferation and activation of PSCs was inhibited by downregulation of miR-301a via two of its targets, Tsc1 and Gadd45g. Moreover, aberrant PSC expression of miR-301a and Gadd45g restricted the interplay between PSCs and pancreatic cancer cells in tumorigenesis. Our findings suggest that miR-301a activates two major cell proliferation pathways, Tsc1/mTOR and Gadd45g/Stat3, in vivo, to facilitate development of inflammatory-induced PanIN and maintenance of PSC activation and desmoplasia in pancreatic cancer.

Antisense long noncoding RNAs (AS-lncRNAs), a sub-class of lncRNAs, are transcribed in the opposite direction from their overlapping protein-coding genes and are implicated in various physiological and pathological processes. However, their role in female reproduction remains largely unknown. Here, we report that BRE-AS, an AS-lncRNA transcript from intron 10 of the protein-coding gene BRE, is involved in granulosa cell (GC) apoptosis. Based on our previous RNA sequencing data, we identified 28 AS-lncRNAs as important in the initiation of porcine follicular atresia, with BRE-AS showing the most significant upregulation in early atretic follicles. In this study, gain- and loss-of-function assays demonstrated that BRE-AS induces early apoptosis in GCs. Mechanistically, BRE-AS acts in cis to suppress the expression of BRE, an anti-apoptotic factor, via direct interaction with the pre-mRNA transcript of the latter, inducing increased GC apoptosis. Notably, we also found that BRE-AS was upregulated in SMAD4-silenced GCs. SMAD4 was identified as a transcriptional repressor of BRE-AS because it inhibits BRE-AS expression and BRE-AS-mediated GC apoptosis. In conclusion, we not only identified a novel AS-lncRNA related to the early apoptosis of GCs and initiation of follicular atresia but also described a novel regulatory pathway, SMAD4/BRE-AS/BRE, coordinating GC function and female fertility.

The engineering of devices with various functional molecules in a high-efficient and convenient manner is crucial for biosensors towards biomedical applications. In this study, a multi-channel surface acoustic wave (SAW) device was rapid engineered with bitter receptors prepared from a cell-free protein expression system for the development of biomimetic biosensors for the detection of bitter substances. The novelty of this study mainly attributed to the utilization of DNA-directed immobilization (DDI) method to achieve high-efficient and controllable immobilization of bitter receptors onto sensitive area of SAW device. SAW device is employed as a transducer to monitor the specific interactions between bitter receptors and their ligands, which is a mass-sensitive device that can monitor tiny mass changes by recording the changes in the phase shift of SAW. The obtained results indicated that this biomimetic biosensor was able to respond to different bitter substances by generating various responsive signals, which show good stability. In addition, the distinct responsive patterns could be used to discriminating different bitter substances. It was successfully used to detect and discriminate 10 μM MgSO4, 0.1 μM denatonium, 0.1 μM D-(−)-Salicin, and 0.1 μM quinine. This biomimetic biosensor has great potential to be used as a novel tool for chemical sensing as well as for the research of mechanisms of bitter receptor interacting with their ligands.

Pulmonary fibrosis has been characterized by abnormal proliferation of fibroblasts and massive deposition of the extracellular matrix, which results from a complex interplay of chronic injury and inflammatory responses. MicroRNA-301a (miR-301a) is activated by multiple inflammatory stimulators, contributing to multiple tumorigenesis and autoimmune diseases. This study showed that miR-301a was overexpressed in a bleomycin-induced murine model of pulmonary fibrosis and patients with idiopathic pulmonary fibrosis (IPF). In addition, miR-301a was activated by transforming growth factor β (TGF-β) and interleukin 6 (IL-6) in normal and IPF fibroblasts, which was markedly reversed by the signal transducer and activator of transcription 3 (STAT3) inhibitor. The genetic ablation of miR-301a in mice reduced bleomycin-induced lung fibrosis, and the downregulation of miR-301a restrained proliferation and activation of fibroblasts. Furthermore, this study demonstrated that TSC1 was a functional target of miR-301a in fibroblasts, and the negative regulation of TSC1 by miR-301a promoted the severity of pulmonary fibrosis through the mammalian target of rapamycin (mTOR) signaling pathway. The blocking of miR-301a by the intravenous injection of antagomiR-301a inhibited the proliferation of fibroblasts and the structural destruction of lung tissues in the bleomycin-induced lung fibrosis mouse model. The findings revealed the crucial role of the miR-301a/TSC1/mTOR axis in the pathogenesis of pulmonary fibrosis, suggesting that miR-301a might serve as a potential therapeutic target.

Positive net ecosystem productivity (NEP) extreme represents an extreme carbon sink in the terrestrial ecosystem. Studying positive NEP extremes and their control mechanisms is vital for a better understanding of the carbon cycle and mitigation of global warming. However, there are still challenges and difficulties in quantifying positive NEP extremes and finding optimal climate conditions to form them in China's terrestrial ecosystems. In this study, we used the Boreal Ecosystem Productivity Simulator (BEPS) to detect and reveal the control mechanisms of NEP extremes in China's terrestrial ecosystems. We found the positive NEP extremes occurred in 2002, 2012, and 2015, with the detrended NEP anomalies of 0.15 Pg C yr−1, 0.11 Pg C yr−1, and 0.09 Pg C yr−1, respectively. Also, the three positive NEP extremes contributed 70% of the NEP uptrend during 2000–2016. Evergreen needle-leaf forests and croplands in the subtropical-tropical monsoonal region played dominant roles in the positive NEP extremes, accounting for 34.2% and 32.6% in the positive NEP extremes on average, respectively. The relationship between the anomalies of Gross primary production (GPP) and NEP was significant (P 0.001). These results mean that GPP (rather than Re) played a decisive role in the positive NEP extremes. Also, the best climate conditions for carbon uptake in the subtropical-tropical region have temperature anomalies ranging from −1.0 to 0.5 °C, and precipitation anomalies ranging from 0 to 600 mm. This study provides new knowledge on the potential carbon sink scientific and technological support for mitigating climate warming in China's terrestrial ecosystem.

In this study, simultaneous optimization of ultrasound-assistant extraction (UAE) of four representative groups of Osmanthus fragrans (OF) fruit was firstly performed using the response surface methodology (RSM). Subsequently, qualitative and quantitative analysis of irioid glycosides from the optimized OF fruit extract was performed using UPLC-ESI-Orbitrap-MS/MS. A total of 13 irioid glycosides were tentatively identified, of which six compounds were identified for the first time. Finally, the anti-inflammatory activity of the optimized OF var. aurantiacus Makino (OFA) fruit extract was evaluated based on a CuSO4-induced zebra fish model. The biological results demonstrated that OFA fruit extract at a concentration of 5 μg/mL could significantly reduce the number of macrophages, but no significant activities were observed at high concentrations (10 and 50 μg/mL). These results suggest that OF fruit has the promise as a functional additive in food for health promotion.

The association between internal cadmium exposure and chronic kidney disease (CKD) has been investigated before. However, few studies have shown the association between dietary cadmium intake and CKD. In this study, we show the association between life-time dietary cadmium intake and CKD based on a follow-up study. At baseline, we collected blood and urine samples for assays of cadmium and renal effect biomarkers. A questionnaire and food survey was given to each subject to collect diet and lifestyle information for the estimation of cadmium intake. Dietary cadmium, cadmium in blood and urine were regarded as exposure markers. Life-time dietary cadmium intake was estimated based on an individual’s daily cadmium intake and exposure time. At follow-up, 467 persons (163 men and 304 women) were finally included. CKD at follow-up was considered if the estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m2. The eGFR level in subjects in the highest quartile of total dietary cadmium intake (>9.34 g) was significantly lower than in those with a moderate or low intake (p 2.2 g) was higher than in those with a low intake (odds ratio (OR) = 18.16, 95%CI: 1.75–188.85). A similar association was found between the baseline urinary albumin (UALB) level and CKD incidence. A predictive model based on UALB and life-time dietary cadmium intake showed an acceptable performance (the area under the curve was 0.77 (95%CI: 0.65–0.88)). Our data show that high dietary cadmium exposure was associated with CKD after controlling for renal tubular dysfunction and internal cadmium exposure.

Background: Early pregnancy loss (EPL), a common and severe complication in pregnancy, has a long-term personal and social impact. It was previously reported that follistatin-like 3(FSTL3), an activin A binding protein, contributes to the invasion and migration of trophoblast. Simultaneously, activin A induces the release of FSTL3 and the elevated activin A is found to be associated with pregnancy loss in women. This study aimed to identify the roles of FSTL3 in the establishment and maintenance of pregnancy, and to determine whether FSTL3 is involved in the pathophysiology of EPL. Methods: Endometrial Ishikawa cells and JAR cells were cultured and FSTL3 siRNA was used to silence FSTL3. The trophoblast spheroids mimicking embryos were used in an embryonic adhesion system. The system aimed to investigate the role of FSTL3 silence on embryonic adhesion onto endometrial cell in vitro. The ICR mice model in vivo was used to investigate whether the FSTL3 works in embryonic implantation. The western blotting was used to determine the expression of FSTL3 and activin A. Results: In the in vitro study, silence of FSTL3 in JAR cells significantly reduced the number of trophoblast spheroids adhered onto Ishikawa cells compared with the scramble siRNA. For the in vivo study, the number of embryos implanted in the uterine horn injected with FATL3 siRNA mixture was significantly less than that in control group. In the case control study, both the expression of FSTL3 and activin A in EPL women were significantly higher than that in controls. Conclusions: FSTL3 plays a biological role in the establishment and maintenance of normal pregnancy. Moreover, FSTL3 may be involved in the early pregnancy loss via neutralizing the elevated activin A.

The effect of structural discontinuities on the progressive failure process of anisotropic rocks should be paid particular attention. The crack damage stress σcd, also considered as the yield strength, and the relationship between σcd and the uniaxial peak strength σucs of anisotropic rocks for different orientations θ of the isotropy planes with respect to the loading directions were investigated theoretically and experimentally. A theoretical relation of σcd/σucs with the function of the shape parameter m was established. Additionally, uniaxial compression tests of shale samples were conducted for several inclinations θ. The test result of σcd/σucs was close to the theoretical value for a given orientation. Furthermore, both experimental results and theoretical solutions of σcd/σucs were independent of the inclination θ while σcd and σucs were strongly affected by θ. The strength ratio σcd/σucs may therefore be an intrinsic property of anisotropic rocks and could be used to predict the failure of rock samples. Keywords: Anisotropic rocks, Uniaxial compression test, Brittle failure, Crack damage stress, Stress ratio

The aim of this study was to prepare capsaicin-loaded micelle for oral administration and pharmacokinetic studies in rats. The formulated capsaicin consisted of polyvinylpyrrolidone (PVP)/sodium cholate/phospholipid mixed micellar system. Spherical and physicochemical stable micelles were obtained with a particle size below 50 nm and zeta potential of less than −30 mV. The in vitro release of capsaicin from the micellar system in three different media (pH 7.4 phosphate buffer solution, pH 1.2 HCl solution and double distilled water) was significantly higher than that of free capsaicin. After oral administration, the formulated capsaicin exhibited a prolonged plasma circulation with the oral bioavailability increasing to 2.42-fold as compared with the free capsaicin. Additionally, a reduced irritation of capsaicin-loaded micelle on the gastric mucosa was observed. This novel micellar formulation significantly improved the oral bioavailability of capsaicin and brought a series of notable advantages for its oral delivery.