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Drug resistance is a major hurdle for the effectiveness of tamoxifen (TAM) to provide clinical benefit. Therefore, it is essential to identify a sensitizer that could be used to improve TAM efficacy in treating TAM‐resistant breast cancer. Here, we investigated the ability of baicalein to reverse TAM resistance. We found that baicalein increased the efficacy of TAM in inhibiting proliferation and inducing apoptosis of TAM‐resistant cells. It also enhanced the TAM‐induced growth reduction of resistant cells from NOD/SCID mouse mammary fat pads, without causing obvious systemic toxicity. Analyses using the CellMiner tool and the Kaplan–Meier plotter database showed that HIF‐1α expression was inversely correlated with TAM therapeutic response in NCI‐60 cancer cells and breast cancer patients. HIF‐1α expression was increased in TAM‐resistant cells due to an increase in mRNA levels and reduced ubiquitin‐mediated degradation. Baicalein reduced HIF‐1α expression by promoting its interaction with PHD2 and pVHL, thus facilitating ubiquitin ligase‐mediated proteasomal degradation and thereby suppressing the nuclear translocation, binding to the hypoxia‐response element, and transcriptional activity of HIF‐1α. As a result, baicalein downregulated aerobic glycolysis by restricting glucose uptake, lactate production, ATP generation, lactate/pyruvate ratio and expression of HIF‐1α‐targeted glycolytic genes, thereby enhancing the antiproliferative efficacy of TAM. Furthermore, baicalein interfered with HIF‐1α inhibition of mitochondrial biosynthesis, which increased mitochondrial DNA content and mitochondrial numbers, restored the generation of reactive oxygen species in mitochondria, and thus enhanced the TAM‐induced mitochondrial apoptotic pathway. The HIF‐1α stabilizer dimethyloxallyl glycine prevented the baicalein‐induced downregulation of glycolysis and mitochondrial biosynthesis and reduced the effects of baicalein on reversing TAM resistance. Our results indicate that baicalein is a promising candidate to help overcome TAM resistance by sensitizing resistant cells to TAM‐induced growth inhibition and apoptosis. The mechanism underlying the effects of baicalein consists of inhibition of HIF‐1α–mediated aerobic glycolysis and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

In this letter, a polarization conversion metasurface antenna (PCMA) array for stealth design method is proposed. The array is composed of polarization conversion metasurface (PCM) subarray and their mirror subarray, which simultaneously plays the role of antenna element and PCM. So that, a certain phase cancellation can be produced between subarray and mirror one. The backward scattering is canceled while the radiation performance is maintained. This method has the characteristics of simplicity, low profile and easy to be implemented. Average area occupied by each antenna element can be reduced to 0.15 λ02. Simulation and measured results show that the maximum reduction of monostatic RCS of aforementioned PCMA is 16.3 dB in 8.2–13.6 GHz band, and the relative bandwidth of effective RCS reduction (more than 10 dB) reaches 34%, which verifies the effectiveness of the polarization cancellation design method based on the integration of array elements and PCM. [ABSTRACT FROM AUTHOR]

The study investigated the effects of long‐term glucocorticoid (GC) administration on bone remodelling, microstructure, and biomechanical strength in cortical and cancellous (trabecular) bones. Thirty‐one female Sprague–Dawley rats were randomly divided into three dexamethasone (Dex) dosage groups, 1.0, 2.5, and 5.0 mg/kg twice a week for 8 weeks, and one control group treated with saline. At the end of the experiment, the tibia of one side and the fourth lumbar vertebrae were processed into sections for a histomorphometric analysis, while the femur of the same side and the fifth vertebrae were isolated for a biomechanical test. A dose‐dependent decline in bone formation was observed in both trabecular and cortical (periosteal and endosteal) bones. In contrast, bone resorption was inhibited only in cancellous bone in the two higher dose groups and not dose‐related. The ratio of Node/Termini increased, while marrow star volume (MSV) decreased in all Dex groups in metaphyseal trabecular bones, both of which were dose‐dependent. Subendosteal cortex porosity increased in parallel with non‐uniform trabecular distribution, but cortical thickness remained unchanged. Interestingly, there were no significant changes in microstructure or mechanical strength in lumbar trabecular bone. The cortical elastic load was dose‐independently reduced in all three Dex groups when compared with the control group. In summary, bone remodelling was dose‐dependently inhibited in cancellous bones but enhanced in intracortical bones. The non‐uniform distribution of trabecular bone and increased porosity in the inner edge of cortical bone were both in parallel with GC dosage, and the porosity increase was more likely to occur, leading to reduced cortical mechanical strength. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether the reference formulation and test formulation of acarbose are bioequivalent among healthy Chinese subjects based on evaluation of the pharmacodynamic end point. Two clinical trials with acarbose were conducted: study A, a pilot study (n = 12; 50 and 100 mg), and study B, a pivotal study (n = 60; 50 mg). In study A, there was a dose‐dependent relationship between 50 mg acarbose and 100 mg acarbose and a significant difference compared with sucrose alone. In study B, after logarithmic conversion, a linear mixed‐effects model was used to analyze the maximum serum glucose value and area under the serum glucose‐time curve from 0 to 2 hours. The geometric mean ratios (test formulation/reference formulation) were 92.68% and 95.70%, with 90% confidence intervals of 84.08%‐102.17% and 84.21%‐108.76%, respectively, falling between 80.00% and 125.00%. According to the geometric least‐squares mean, the test formulation (or reference formulation) was statistically significantly different as a single sucrose (P <.001). The effective dose of acarbose in healthy Chinese volunteers was 50 mg. The reference and test formulations were bioequivalent. [ABSTRACT FROM AUTHOR]

For POL-EDM tumors, leukocyte infiltration was comparable to that in POL-WT tumors, whereas CD8+ T-cell infiltration was significantly higher than that in POL-WT tumors. After excluding hypermutant tumors, leukocyte infiltration and CD8+ T-cell infiltration in POL-non-EDM tumors (but not POL-EDM tumors, probably due to the limited sample size) remained higher than those in POL-WT tumors (Figure 4E,F). To the Editor: With the development of immunotherapy, cancer treatment has stepped into a new era.1 Though POLE/POLD1 mutation (POL-MUT) have been proven to be a promising marker in ICI treatment,2-5 the predictive value of different types of POL-MUTs has yet to be fully investigated. Despite the higher neoantigen burden in POL-EDM tumors, neither leukocyte infiltration nor CD8+ T-cell infiltration was found to be different between POL-EDM tumors and POL-non-EDM tumors (Figure 4C,D). [Extracted from the article]

An organocatalyzed asymmetric dearomative [3+2] annulation reaction of electron‐deficient 2‐nitrobenzo heteroarenes including 2‐nitrobenzofurans, 2‐nitrobenzothiophenes and 2‐nitroindoles with 3‐isothiocyanato oxindoles was developed. With a multiple hydrogen‐bonding bifunctional thiourea as the catalyst, the reaction displays broad substrate scope and provides an access to structurally diverse polycyclic spirooxindoles containing three contiguous stereogenic centers in high yields with good diastereo‐ and enantioselectivities (up to 99% yield, 94:6 dr, and 97% ee). This organocatalysis protocol is able to afford the products with complementarily diastereoselectivity versus the previous work with transition metal catalysis. [ABSTRACT FROM AUTHOR]

Summary: The supported Ru/Na‐ZSM‐5 catalyst was prepared by loading Ru on the zeolite support by the impregnation method. X‐ray diffraction (XRD) and transmission electron microscopy (TEM) analysis showed that Ru was successfully supported. The supported catalyst was subjected to supercritical electrocatalytic activation, and the activated catalyst was applied to the isomerisation of safflower seed oil. The effect of activation conditions on the conjugated linoleic acid (CLA) yield was examined. Under the supercritical CO2 condition, the optimal activation conditions were electrocatalytic current of 200 mA, reaction temperature of 70 °C, stirring speed of 300 r.p.m and reaction time of 1.5 h. The CLA yield was 43.10%, the content of c9,t11‐CLA in the product oil was 17.45% and the content of t10,c12‐CLA was 15.86%, significantly higher than the raw oil. The change was not noticeable in terms of physicochemical properties compared with the raw oil, which met edible vegetable oil quality standards. [ABSTRACT FROM AUTHOR]

Objective: To elucidate classification of coiling of the umbilical cord around fetal neck (CUFN) by ultrasound and forming factors of entanglement angle of CUFN.Methods: From January 2006 to December 2012, color Doppler ultrasonic was used to observe the blood flow vector of umbilical artery, and prospective descriptive observation was made for entanglement direction and type of 707 single fetuses taking prenatal examination in our hospital during the middle and late trimester of pregnancy and having umbilical cord echo around the neck. The relationship of position of fetus, position of placenta and entanglement direction of umbilical cord with the entanglement angle of umbilical cord is analyzed.Results: Among the 707 fetuses, 634 had one circle of coiling, 43 had two circles of coiling, two had three circles of coiling, and 28 had CUFN. According to entanglement direction, 361 had entanglement from left to right and 318 had entanglement from right to left According to entanglement type, 305 were C-shaped type (43.14%), 85 were O-shaped type (12.02%), 289 were α-shaped type (40.88%), and 28 were L-shaped type (3.96%).Conclusion: Color Doppler ultrasound was used to detect the entanglement direction of umbilical cord and establish the five-type classification of umbilical cord around the neck, laying the foundation for the feasibility of establishing the normalization of diagnostic standard of umbilical cord around the neck. [ABSTRACT FROM AUTHOR]

The combined use of flue gas waste heat resources and thermoelectric generators (TEGs) is considered to be a relatively reliable method to generate electricity. The focus of this study is on the optimization and improvement of the hot‐end heat collection pipe. This paper aims to increase the temperature difference between hot and cold ends of TEG and enhance uniformity of temperature distribution, thereby improving the output power of the TEG system. To balance the temperature difference between the cold and hot ends of the TEG, the pressure drop from the inlet to the outlet and the mass of TEG hot end pipes, a finite element simulation model is constructed. Meanwhile, a multi‐objective genetic algorithm is applied to optimize the structure of four dimensions: fin bottom length, fin height, fin thickness, and outlet diameter. Three optimization objectives, namely, average temperature difference, total pressure drop from inlet to outlet, and pipeline mass are globally optimized to determine the best size, based on which the accuracy of the simulation model is verified by conducting experiments. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to investigate the feasibility and efficacy of one‐stage surgical resection of thoracic dumbbell tumors using a paravertebral approach and a micro‐tubular technique. Methods: Clinical data of thoracic dumbbell tumors resected using a paravertebral approach and a micro‐tubular technique (14 mm, non‐expandable type) in the Department of Neurosurgery at our hospital from July 2014 to July 2019 were retrospectively analyzed. Tumors were found between T1 and T12 vertebrae. Operation time, blood loss, hospitalization, recovery of neurological function, complications, the Japanese Orthopaedic Association (JOA) score, and the visual analogue scale (VAS) score were used to evaluate clinical efficacy. Results: In all 31 cases, tumors were completely resected in one operation, with a mean blood loss of 53.23 ± 33.08 mL (20–150 mL) and a mean operation time of 95.16 ± 20.31 min (60–180 min). According to the Eden classification, there were four type II cases, 16 type III cases, and 11 type IV cases. The incidence of tumors in the lower thoracic segment (T8–T12) was 51.6% (16/31 cases), while the incidences in the upper thoracic segment (T1–T4) and middle segment (T5–T8) were 25.8% (8/31 cases) and 22.6% (7/31 cases), respectively. Pathological diagnoses were schwannoma (n = 22), gangliocytoma (n = 4), metastatic tumor (n = 2), neurofibroma (n = 1), granuloma (n = 1), and lipoma (n = 1). After surgery, symptoms were relieved in all patients. VAS and JOA scores significantly improved (P < 0.001). There was no pleural or lung injury, and there were no complications, such as cerebrospinal fluid leakage. The average follow‐up duration was 29 months (13–59 months), during which time no tumor recurrence or spinal instability occurred. The group of Eden type II tumors had lower JOA scores at 12 months postoperatively, longer operation times, and more estimated blood loss compared with other groups (P < 0.05). There were no significant influences on VAS scores at 12 months postoperatively and postoperative hospital stay from the different types of tumors. Conclusion: The paravertebral approach with a micro‐tubular technique is a safe and effective minimally invasive surgical approach for thoracic dumbbell tumors that allows one‐stage tumor resection using a single incision. Using this approach significantly reduces intraoperative blood loss and postoperative complications, shortens hospital stay, and reduces the rates of postoperative spinal instability. [ABSTRACT FROM AUTHOR]

Objective: To derive and validate a predictive algorithm integrating clinical and laboratory parameters to stratify a full‐term neonate's risk level of having bacterial meningitis (BM). Methods: A multicentered dataset was categorized into derivation (689 full‐term neonates aged ≤28 days with a lumbar puncture [LP]) and external validation (383 neonates) datasets. A sequential algorithm with risk stratification for neonatal BM was constructed. Results: In the derivation dataset, 102 neonates had BM (14.8%). Using stepwise regression analysis, fever, infection source absence, neurological manifestation, C‐reactive protein (CRP), and procalcitonin were selected as optimal predictive sets for neonatal BM and introduced to a sequential algorithm. Based on the algorithm, 96.1% of BM cases (98 of 102) were identified, and 50.7% of the neonates (349 of 689) were classified as low risk. The algorithm's sensitivity and negative predictive value (NPV) in identifying neonates at low risk of BM were 96.2% (95% CI 91.7%–98.9%) and 98.9% (95% CI 97.6%–99.6%), respectively. In the validation dataset, sensitivity and NPV were 95.9% (95% CI 91.0%–100%) and 98.8% (95% CI 97.7%–100%). Interpretation: The sequential algorithm can risk stratify neonates for BM with excellent predictive performance and prove helpful to clinicians in LP‐related decision‐making. [ABSTRACT FROM AUTHOR]

A rapid, efficient, and environmentally friendly matrix solid‐phase dispersion microextraction was established to determine and quantify terpenoids in Radix Curcumae using ultra‐high‐performance liquid chromatography with a diode array detector. Various parameters affecting the extraction were investigated in detail, such as the grinding time, amount of adsorbent, type and concentration of elution solvent, and pH. The optimization of single‐factor and response surface methodology was performed to confirm the best conditions in this procedure. The final optimized conditions were obtained by applying 70 mg of cucurbituril as adsorbent, 149 s as the optimum grinding time, and 228 mM of 3‐(N,N‐dimethylpalmitylammonio)propanesulfonate aqueous solution (pH 6.5) as the optimal elution solvent. The validated method showed a satisfactory linear range of 0.10–10 µg/mL for curdione and furanodiene, 0.01–10 µg/mL for isocurcumenol and germacrone, and 0.05–10 µg/mL for furanodienone, while the correlation coefficients ranged from 0.9945 to 0.9970. The recoveries of the investigated analytes at two spiked concentration levels (0.1 and 1.0 µg/mL) ranged from 96.53 to 104.60%. In addition, this method displayed acceptable reproducibility (relative standard deviation ≤ 3.66%). The results showed that the newly proposed matrix solid‐phase dispersion microextraction method was successfully applied to analyze curdione, isocurcumenol, furanodienone, germacrone and furanodiene in Radix Curcumae samples. [ABSTRACT FROM AUTHOR]

The Treg/Th17 imbalance is associated with the development of systemic lupus erythematosus (SLE). Dihydroartemisinin (DHA), a semi‐synthetic derivative of artemisinin, is isolated from the traditional Chinese herb Artemisia annua Artemisia annua L. This study aims to evaluate the effects of DHA alone or in combination with prednisone in immunodeficiency of SLE. In vivo, the therapeutical effect of DHA alone or in combination with prednisone was assessed in the pristane‐induced SLE mouse model. Then, the level of serum antibodies, creatinine (Cre), blood urea nitrogen (BUN), urine protein, kidney histopathology, interleukin (IL)‐17, IL‐6, transforming growth factor (TGF)‐β, the expression of RORγt and Foxp3, the percentages of Treg and Th17 in peripheral blood and spleen were assayed. In vitro, the mouse spleen lymphocytes were separated and treated with DHA alone or DHA in combination with prednisone. Then the percentages of Treg and Th17, the concentration of IL‐17, IL‐6, TGF‐β, and the expression of RORγt and Foxp3 were assayed. It was shown that DHA alone or in combination with prednisone treatment significantly alleviated the manifestations of pristane‐induced SLE mice, suppressed inflammation and restored the Treg/Th17 balance. DHA alone or in combination with prednisone significantly inhibited Th17 cell differentiation while induced Treg cell differentiation in vitro. DHA alone or in combination with prednisone also reduced the transcription of RORγt and increased Foxp3 in lymphocytes, as well as IL‐17 and TGF‐β levels. Our data indicated that DHA can produce synergistic effect with prednisone to attenuate the symptoms of SLE by restoring Treg/Th17 balance. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy. [ABSTRACT FROM AUTHOR]

A silver‐catalyzed protocol for [3+1+1] annulation of nitrones and isocyanoacetates is reported. The reaction is proposed to proceed through sequential [3+2] cycloaddition, ring‐opening, cyclization‐oxidation, and dealkylation, allowing access to a broad scope of valuable polysubstituted imidazoles in high yields. [ABSTRACT FROM AUTHOR]

The realization of a controllable transparent conducting system with selective light transparency is crucial for exploring many of the most intriguing effects in top‐illuminated optoelectronic devices. However, the performance is limited by insufficient electrical conductivity, low work function, and vulnerable interface of traditional transparent conducting materials, such as tin‐doped indium oxide. Here, it is reported that two‐dimensional (2D) titanium carbide (Ti3C2Tx) MXene film acts as an efficient transparent conducting electrode for the lead sulfide (PbS) colloidal quantum dots (CQDs) photodiode with controllable near infrared transmittance. The solution‐processed interface engineering of MXene and PbS layers remarkably reduces the interface defects of MXene/PbS CQDs and the carrier concentration in the PbS layer. The stable Ti3C2Tx/PbS CQDs photodiodes give rise to a high specific detectivity of 5.51 × 1012 cm W−1 Hz1/2, a large dynamic response range of 140 dB, and a large bandwidth of 0.76 MHz at 940 nm in the self‐powered state, ranking among the most exceptional in terms of comprehensive performance among reported PbS CQDs photodiodes. In contrast with the traditional photodiode technologies, this efficient and stable approach opens a new horizon to construct widely used infrared photodiodes with CQDs and MXenes. [ABSTRACT FROM AUTHOR]

Unraveling the influence of community assembly processes on soil ecosystem functioning presents a major challenge in the field of theoretical ecology, as it has received limited attention. Here, we used a series of long‐term experiments spanning over 25 years to explore the assembly processes of bacterial, fungal, protist, and nematode communities using high‐throughput sequencing. We characterized the soil microbial functional potential by the abundance of microbial genes associated with carbon, nitrogen, phosphorus, and sulfur cycling using GeoChip‐based functional gene profiling, and determined how the assembly processes of organism groups regulate soil microbial functional potential through community diversity and network stability. Our results indicated that balanced fertilization (NPK) treatment improved the stochastic assembly of bacterial, fungal, and protist communities compared to phosphorus‐deficient fertilization (NK) treatment. However, there was a nonsignificant increase in the normalized stochasticity ratio of the nematode community in response to fertilization across sites. Our findings emphasized that soil environmental factors influenced the assembly processes of the biotic community, which regulated soil microbial functional potential through dual mechanisms. One mechanism indicated that the high phosphorus levels and low soil nutrient stoichiometry may increase the stochasticity of bacterial, fungal, and protist communities and the determinism of the nematode community under NPK treatment, ultimately enhancing soil microbial functional potential by reinforcing the network stability of the biotic community. The other mechanism indicated that the low phosphorus levels and high soil nutrient stoichiometry may increase the stochastic process of the bacterial community and the determinism of the fungal, protist, and nematode communities under NK treatment, thereby enhancing soil microbial functional potential by improving the β‐diversity of the biotic community. Taken together, these results provide valuable insights into the mechanisms underlying the assembly processes of the biotic community that regulate ecosystem functioning. [ABSTRACT FROM AUTHOR]

Purpose: Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. Methods: The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC‐specific processes was investigated. Results: Keratin 18 expression was shown to be up‐regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. Conclusions: Keratin 18 plays a cancer‐promoting role and might be a potential therapeutic target in the treatment of GC. [ABSTRACT FROM AUTHOR]

COVID‐19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID‐19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID‐19‐infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue‐specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN‐I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID‐19‐infected patients experiencing milder disease symptoms showed robust T‐cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS‐CoV‐2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID‐19. SYNOPSIS: Proteomics, metabolomics and RNAseq data map immune responses in COVID‐19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue‐specific proteins. A multi‐omics profiling of the host response to SARS‐CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID‐19 patients and 17 uninfected controls.Significant correlations between multi‐omics data and key clinical parameters.Alteration of tissue‐specific proteins and exRNAs.Enhanced activation of immune responses is associated with COVID‐19 pathogenesis.Biomarkers to predict COVID‐19 clinical outcomes pending clinical validation as prospective marker. [ABSTRACT FROM AUTHOR]

The catalytic activity of cationic NHC‐ZnII and NHC‐AlIII (NHC=N‐heterocyclic carbene) complexes in reactions that require the electrophilic activation of soft C−C π bonds has been studied. The former proved able to act as a soft π‐Lewis acid in a variety of transformations. The benefit of the bulky IPr NHC ligand was demonstrated by comparison with simple ZnX2 salts. The tested NHC‐AlIII catalyst is not able to activate C−C π bonds but simple AlX2+ ions were found potent in some cases. [ABSTRACT FROM AUTHOR]

We presented a new local particle filter named the localized weighted ensemble Kalman filter (LWEnKF), which was tested and verified using a simple high‐dimensional Lorenz 96 model. A revised LWEnKF, the proposal weights calculation of which is modified through localization to prevent filter degeneracy for real geophysical models, is explored further in this article and shows lots of potential in the implementation of real complex models. For geophysical models, the ocean dynamics changes slowly compared with that of the atmosphere. With a relatively low resolution, it is weakly nonlinear in the surface layers of the ocean model used in this article, which fits the linear and Gaussian assumptions of the EnKF but could be a challenge for particle filters in the data assimilation process. With only 50 particles, the LWEnKF assimilates the sea‐surface temperature (SST), sea‐surface height (SSH), temperature, and salinity profiles with affordable computational cost, providing a reasonable forecast. Moreover, the LWEnKF is compared with the ensemble Kalman filter (EnKF) and the local particle filter (PF). For observed variables, the LWEnKF performs comparably to the EnKF, as the observation operator is linear. For unobserved variables, the LWEnKF provides more accurate forecasts than the EnKF, since the latter considers only the correlations, while the former considers higher‐order moments. The local PF ensemble does not converge to the observed solution in an ample amount of time in this study, which needs further investigation. [ABSTRACT FROM AUTHOR]

Objectives: Although the genomic landscape of small‐cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome‐level aberration and immune microenvironment status are unknown. Methods: Using ultra‐deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death‐ligand 1 (PD‐L1) in 62 retrospective SCCE samples with IHC assay. Results: Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG‐3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumor‐free healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD‐L1‐positive rate was 43%. Conclusions: Our study systematically characterized the immune microenvironment in small‐cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy. [ABSTRACT FROM AUTHOR]

Purpose: Transcription co‐activator p300/CBP, a histone acetyltransferase, has a central role in tumours, inflammation and neurodegenerative diseases. We investigated the effect of p300/CBP and its association with various IL‐17‐related indicators and prognosis in patients with acute respiratory distress syndrome (ARDS). Materials and Methods: We enrolled 45 adult ARDS patients who were followed for 28 days and 22 healthy controls. The mRNA expression of p300, CBP, RORγt and Foxp3 and the plasma levels of several cytokines were measured. Result: The mRNA levels of p300, CBP and RORγt, and plasma concentration of IL‐17, IL‐6, were higher in acute ARDS patients (P < 0.05) compared with controls, and the mean levels of p300, CBP and IL‐6 in non‐survivors were higher than in survivors (P < 0.05). The expression of p300 was associated with the level of RORγt, IL‐17 and disease prognosis. Conclusion: The levels of p300, RORγt mRNA and plasma concentration of IL‐6 and IL‐17 in acute ARDS patients were increased compared with controls. Increased p300/CBP expression may be an independent risk factor for 28‐day mortality in ARDS. [ABSTRACT FROM AUTHOR]

Aqueous organic redox flow batteries (AORFBs) have received considerable attention for large‐scale energy storage. Quinone derivatives, such as 9,10‐anthraquinone‐2,7‐disulphonic acid (2,7‐AQDS), have been explored intensively owing to potentially low cost and swift reaction kinetics. However, the low solubility in pH‐neutral electrolytes restricts their application to corrosive acidic or caustic systems. Herein, the single molecule redox‐targeting reactions of 2,7‐AQDS anolyte are presented to circumvent its solubility limit in pH‐neutral electrolytes. Polyimide was employed as a low‐cost high‐capacity solid material to boost the capacity of 2,7‐AQDS electrolyte to 97 Ah L−1. Through in situ FTIR spectroscopy, a hydrogen‐bonding mediated reaction mechanism was disclosed. In conjunction with NaI as catholyte and nickel hexacyanoferrate as the catholyte capacity booster, a single‐molecule redox‐targeting reaction‐based full cell with energy density up to 39 Wh L−1 was demonstrated. [ABSTRACT FROM AUTHOR]

Aqueous organic redox flow batteries (AORFBs) have received considerable attention for large‐scale energy storage. Quinone derivatives, such as 9,10‐anthraquinone‐2,7‐disulphonic acid (2,7‐AQDS), have been explored intensively owing to potentially low cost and swift reaction kinetics. However, the low solubility in pH‐neutral electrolytes restricts their application to corrosive acidic or caustic systems. Herein, the single molecule redox‐targeting reactions of 2,7‐AQDS anolyte are presented to circumvent its solubility limit in pH‐neutral electrolytes. Polyimide was employed as a low‐cost high‐capacity solid material to boost the capacity of 2,7‐AQDS electrolyte to 97 Ah L−1. Through in situ FTIR spectroscopy, a hydrogen‐bonding mediated reaction mechanism was disclosed. In conjunction with NaI as catholyte and nickel hexacyanoferrate as the catholyte capacity booster, a single‐molecule redox‐targeting reaction‐based full cell with energy density up to 39 Wh L−1 was demonstrated. [ABSTRACT FROM AUTHOR]

Background: With several susceptibility single nucleotide polymorphisms identified by case–control association studies, Graves' disease is one of the most common forms of autoimmune thyroid disease. In this study, we aimed to determine whether any observed differences in genetic associations are influenced by sex in Chinese Han populations. Methods: A total of 8,835 patients with Graves' disease and 9,936 sex‐matched healthy controls were enrolled in the study. Confirmed by a two‐staged association analysis, sex‐specific analyses among 20 Graves' disease susceptibility loci were conducted. Results: A significant sex‐gene interaction was detected primarily at rs5912838 on Xq21.1 between the GPR174 and ITM2A genes, whereby male Graves' disease patients possessed a significantly higher frequency of risk alleles than their female counterparts. Interestingly, compared to women, male patients with Graves' disease had a higher cumulative genetic risk and higher persistent thyroid stimulating hormone receptor antibody‐positive rate after receiving antithyroid drug therapy for at least 1 year. Conclusion: The findings of this study suggest the existence of one potential sex‐specific Graves' disease variant on Xq21.1. This could increase our understanding of the pivotal mechanism behind Graves' disease and ultimately aid in identifying possible therapeutic targets. [ABSTRACT FROM AUTHOR]

A protocol involving cooperative silver‐ and base‐catalyzed diastereoselective cycloaddition of nitrones with isocyanides is described, providing access to a wide range of 2‐imidazolinone derivatives with various functional groups as single diastereomers. Varying the base and temperature of the reaction allowed selective access to both diastereomers of the product. A plausible reaction mechanism is proposed and supported by DFT calculations. [ABSTRACT FROM AUTHOR]

Metal halide salts have attracted widespread attention because of their good physical and chemical properties. In this study, lead‐free copper halide salt CsCuCl3 single crystals and photodetectors were prepared. According to the single crystal diffraction data, the CsCuCl3 single crystal has a hexagonal structure with P6522 (179) space group (7.2399 × 7.2399 × 18.3096 Å, 90.000 × 90.000 × 120.000). The crystal structure along the z‐axis is a double‐stranded helix structure. To the best of our knowledge, this is the first study on CsCuCl3 for optoelectronic applications. The CsCuCl3 photodetector exhibits high light response, sensitivity, and selectivity under 369 nm ultraviolet light and invalid response for visible light (511 nm). The device based on CsCuCl3 is highly selective for ultraviolet light (2.43 µA/mW) and feature high anti‐interference of visible light (0.0119 µA/mW). The device has the strongest selectivity at 369 nm light, which is 200 times higher than that at 511 nm. The results will be of interest for applications in photodetectors, LEDs, devices, and metal halide salts. [ABSTRACT FROM AUTHOR]

Mitochondrial aconitase (Aco2) catalyzes the conversion of citrate to isocitrate in the TCA cycle, which produces NADH and FADH2, driving synthesis of ATP through OXPHOS. In this study, to explore the relationship between adipogenesis and mitochondrial energy metabolism, we hypothesize that Aco2 may play a key role in the lipid synthesis. Here, we show that overexpression of Aco2 in 3T3‐L1 cells significantly increased lipogenesis and adipogenesis, accompanied by elevated mitochondrial biogenesis and ATP production. However, when ATP is depleted by rotenone, an inhibitor of the respiratory chain, the promotive role of Aco2 in adipogenesis is abolished. In contrast to Aco2 overexpression, deficiency of Aco2 markedly reduced lipogenesis and adipogenesis, along with the decreased mitochondrial biogenesis and ATP production. Supplementation of isocitrate efficiently rescued the inhibitory effect of Aco2 deficiency. Similarly, the restorative effect of isocitrate was abolished in the presence of rotenone. Together, these results show that Aco2 sustains normal adipogenesis through mediating ATP production, revealing a potential mechanistic link between TCA cycle enzyme and lipid synthesis. Our work suggest that regulation of adipose tissue mitochondria function may be a potential way for combating abnormal adipogenesis related diseases such as obesity and lipodystrophy. [ABSTRACT FROM AUTHOR]

The role of endogenous serotonin (5‐HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real‐time recording of biomolecules, the dynamic monitoring of 5‐HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich‐like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real‐time monitoring of distension‐evoked 5‐HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5‐HT overflow, and 5‐HT level is closely associated with the physiological or pathological states of the intestine. [ABSTRACT FROM AUTHOR]

The role of endogenous serotonin (5‐HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real‐time recording of biomolecules, the dynamic monitoring of 5‐HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich‐like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real‐time monitoring of distension‐evoked 5‐HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5‐HT overflow, and 5‐HT level is closely associated with the physiological or pathological states of the intestine. [ABSTRACT FROM AUTHOR]

To avoid filter collapse, a new localized weighted ensemble Kalman filter (LWEnKF) is presented. This filter is a nonlinear non‐Gaussian filter that combines some of the advantages of the particle filter (PF) and of the ensemble Kalman filter (EnKF). Additionally, the new method can overcome filter degeneracy in high‐dimensional system applications. Based on the weighted ensemble Kalman filter (WEnKF), we extend the scalar weight of each particle to a vector and limit the influence of distant observations through a localization function. According to the results of experiments using the Lorenz '96 model with 40 variables, the LWEnKF with only 10 particles can prevent filter degeneracy. In addition, tests of the new filter are also performed using a two‐layer quasi‐geostrophic model to demonstrate the feasibility of using the new method in high‐dimensional numerical weather prediction models. Comparisons among the LWEnKF, the local particle filter (LPF) and the localized perturbed observation EnKF (LEnKF) reveal that the proposed method can combine the advantages of the latter two in certain aspects, even providing better performance in some situations. This characteristic of the LWEnKF indicates its potential for data assimilation of different types of observations. Moreover, the new filter is compared to the block‐local ensemble Kalman particle filter (LEnKPF). Experiments showed that the LWEnKF has an obvious advantage over the LEnKPF when the number of particles is small, which indicates its potential for realistic applications limited by computing resources. [ABSTRACT FROM AUTHOR]

Background and Purpose: In non-small-cell lung carcinoma (NSCLC) patients, the L858R/T790M mutation of the epithelial growth factor receptor (EGFR) is a major cause of acquired resistance to EGFR-TKIs treatment that limits their therapeutic efficacy. Identification of drugs that can preferentially kill the NSCLC harbouring L858R/T790M mutation is therefore critical. Here, we have evaluated the effects of ursolic acid, an active component isolated from herbal sources, on erlotinib-resistant H1975 cells that harbour the L858R/T790M mutation.Experimental Approach: Gene expression omnibus (GEO) profiles analyses was applied to detect differentially expressed genes in NSCLC cells harbouring EGFR mutation. AnnexinV-FITC/PI, TUNEL staining, MTT, wound healing, RT-PCR, qRT-PCR, western blots, immunostaining, dual-luciferase reporters and ChIP-PCR were utilized to investigate the effects of ursolic acid in vitro and in vivo.Key Results: The cancer/testis antigen family 45 member A2 (CT45A2) was highly expressed in H1975 cells. Ectopic expression of CT45A2 in H1975 cells increased cell proliferation and motility in vitro. Silencing the CT45A2 expression strongly attenuated H1975 cells motility and growth. The anti-cancer effect of ursolic acid was critically dependent on CT45A2 expression in H1975 cells. Ursolic acid suppressed CT45A2 gene transcription mediated by transcriptional factor TCF4 and β-catenin signalling.Conclusions and Implications: CT45A2 is a novel oncogene for NSCLC with an EGFR T790 mutation. Ursolic acid induced apoptosis and inhibited proliferation of H1975 cells by negatively regulating the β-catenin/TCF4/CT45A2 signalling pathway. Therefore, ursolic acid may be a potential candidate treatment for NSCLC harbouring the EGFR-L858R/T790M mutation. [ABSTRACT FROM AUTHOR]

Age structure and seasonality influence the population fluctuations of small rodents. Age determines body weight and social experience, while seasonality regulates the duration of the breeding season and onset of sexual maturity in newborn offspring. Therefore, reproductive success and skew usually occur in different age groups. Brandt's vole (Lasiopodomys brandtii) is a social, short‐lived and seasonal breeding small rodent with a dramatic seasonal population fluctuation, but reproductive skew is not fully understood in this species. In the present study, we determined kinship in semi‐natural enclosure populations using microsatellite markers based on genotyping, analyzed the reproductive skew between sexes and between overwintered and newborn voles, and monitored variation in male reproductive activity by testing fecal testosterone levels throughout the year. Overwintered voles had the most reproductive success along with a striking increase in the population size in the enclosures, with all biological fathers and 77.8% of biological mothers, which had 100% and 87% of the total offspring, respectively. Compared to overwintered voles, reproductive skews were significantly higher in potential overwintered and newborn parents, implying the possible reproductive suppression of newborn voles by dominant overwintered voles. Moreover, both heavier body weight and higher testosterone levels in overwintered males supported their potential social status in the population. Our study provided new evidence for reproductive skew and differentiation of postnatal gonadal development patterns of different age groups in Brandt's vole. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of metformin in high glucose‐induced mesangial cell proliferation, inflammation and extracellular matrix (ECM) accumulation and to elucidate the underlying mechanism of metformin function. An MTT assay was used to examine rat mesangial cell (RMC) proliferation. The levels of TNF‐α, IL‐6 and TGF‐β in RMCs were determined by ELISA. The protein expression of fibronectin, collagen IV and autophagy‐related proteins (Beclin‐1, LC3‐I and LC3‐II) in RMCs was detected using western blot. Fluorescence microscopy analysis was carried out to evaluate RMC autophagy. Our results showed that high glucose‐induced RMC proliferation, inflammation and ECM expression, but these effects were markedly reduced by metformin. We confirmed that metformin suppressed high glucose‐induced RMC proliferation, inflammation and ECM expression via induction of autophagy. Mechanistic investigation demonstrated an axis of SIRT1‐FOXO1 in RMC autophagy. Our data indicated that metformin inhibits high glucose‐induced mesangial cell proliferation, inflammation and ECM expression through a SIRT1‐FOXO1‐autophagy axis. [ABSTRACT FROM AUTHOR]

Slippery liquid‐infused porous surfaces (SLIPS) derived smart windows (SWs) that dynamically fine‐tune the solar spectrum are promising candidates for alleviating the global energy crisis, especially for dim rainy climates. Unfortunately, the inferior durability, high energy‐consumption, and slow tune‐responsivity over SLIPS‐based SWs greatly hinder their practical usage. Reported is an ultrarobust omni‐liquid‐repellent magnetism‐actuated reconfigurable microshutters (OLR‐MARS) via integrating a femtosecond laser ablation and soft‐lithography technique. By alternately loading/discharging a remote magnet, OLR‐MARS can be reversibly switched between a transparent mode and an opaque mode within 0.03 s, which is far sensitive than the previously‐reported SWs. Simultaneously, OLR‐MARS can harness the surface liquids between a slippery state (the sliding angle of ≈15o) and a sticky one (pinning at a tilt angle of 90o). Significantly, owing to its all‐solid‐state merit, OLR‐MARS demonstrates good longevity even when subjected to the raindrops impact above 1000 cycles. Results indicate dual switching over the interfacial hydrodynamics and optics. Last but not least, leveraging the optimized OLR‐MARS, encryption‐decryption, thermal management, and an angle‐dependent privacy‐screen is deployed. Current novel OLR‐MARS with robust durability, fast responsivity, and energy‐free advantages holds promising potential in self‐cleaning smart windows, energy‐saving buildings, antivoyeurism, etc. [ABSTRACT FROM AUTHOR]

This study proposes a space vector pulse width modulation (SVPWM) driving method for the switched reluctance motor (SRM), which enables the use of a standard full‐bridge power converter to drive a three‐phase SRM with a ring structure, in place of the traditional asymmetric H‐bridge (AHB). Based on this driving topology, the SVPWM approach is employed to drive the SRM, and its performance is compared with that of the conventional SRM driving method utilising the AHB. The findings indicate that the SVPWM method can effectively reduce torque ripple in the SRM. Moreover, the experimental validation performed to verify the proposed driving topology and method yields results that closely align with the simulated outcomes. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator‐activated receptor γ (PPARγ) is highly expressed in trophoblast tissues in pregnancy during which the protein participates in diverse events, including embryo implantation and placental formation. However, little is known about the role of PPARγ in embryonic development. This study investigated the function of PPARγ in sheep trophoblast cells. The coding sequence of sheep PPARγ encoded 475 amino acids and included one synonymou mutation compared with the sheep reference sequence for PPARγ. The PPARγ protein was localized in the nucleus and cytoplasm of sheep trophoblasts. The relative expression of PPARγ was elevated in cells treated with rosiglitazone and reduced following administration of GW9662. Activation of PPARγ promoted cell proliferation and mobility, but inhibited apoptosis. In addition, stimulation of PPARγ promoted the expression of lipid metabolism‐related genes FABP4 and PLIN2. The expression of prostaglandin metabolism‐related genes PLA2G4A, PTGS2 and PTGES also was upregulated significantly in trophoblast cells when PPARγ was activated. In contrast, activation of PPARγ did not impact expression of the prostaglandin‐related genes PGFS and SLCO2A1. At the same time, activation of PPARγ activity increased the ratio of PGE2 to PGF2α. Furthermore, fluorescence labelling showed that the numbers of cell lipid droplets increased after stimulation of PPARγ activity, but decreased when PPARγ was inhibited. In conclusion, PPARγ is critical for the regulation of lipid metabolism and prostaglandin synthesis and secretion in sheep trophoblast cells and also has a potent effect on cell proliferation and viability. [ABSTRACT FROM AUTHOR]

Abstraction of iodide from [(η5‐C5iPr5)2UI] (1) produced the cationic uranium(III) metallocene [(η5‐C5iPr5)2U]+ (2) as a salt of [B(C6F5)4]−. The structure of 2 consists of unsymmetrically bonded cyclopentadienyl ligands and a bending angle of 167.82° at uranium. Analysis of the bonding in 2 showed that the uranium 5f orbitals are strongly split and mixed with the ligand orbitals, thus leading to non‐negligible covalent contributions to the bonding. Investigation of the dynamic magnetic properties of 2 revealed that the 5f covalency leads to partially quenched anisotropy and fast magnetic relaxation in zero applied magnetic field. Application of a magnetic field leads to dominant relaxation by a Raman process. [ABSTRACT FROM AUTHOR]

Abstraction of iodide from [(η5‐C5iPr5)2UI] (1) produced the cationic uranium(III) metallocene [(η5‐C5iPr5)2U]+ (2) as a salt of [B(C6F5)4]−. The structure of 2 consists of unsymmetrically bonded cyclopentadienyl ligands and a bending angle of 167.82° at uranium. Analysis of the bonding in 2 showed that the uranium 5f orbitals are strongly split and mixed with the ligand orbitals, thus leading to non‐negligible covalent contributions to the bonding. Investigation of the dynamic magnetic properties of 2 revealed that the 5f covalency leads to partially quenched anisotropy and fast magnetic relaxation in zero applied magnetic field. Application of a magnetic field leads to dominant relaxation by a Raman process. [ABSTRACT FROM AUTHOR]

The generalized method of moments (GMM) and empirical likelihood (EL) are popular methods for combining sample and auxiliary information. These methods are used in very diverse fields of research, where competing theories often suggest variables satisfying different moment conditions. Results in the literature have shown that the efficient‐GMM (GMME) and maximum empirical likelihood (MEL) estimators have the same asymptotic distribution to order n−1/2 and that both estimators are asymptotically semiparametric efficient. In this paper, we demonstrate that when data are missing at random from the sample, the utilization of some well‐known missing‐data handling approaches proposed in the literature can yield GMME and MEL estimators with nonidentical properties; in particular, it is shown that the GMME estimator is semiparametric efficient under all the missing‐data handling approaches considered but that the MEL estimator is not always efficient. A thorough examination of the reason for the nonequivalence of the two estimators is presented. A particularly strong feature of our analysis is that we do not assume smoothness in the underlying moment conditions. Our results are thus relevant to situations involving nonsmooth estimating functions, including quantile and rank regressions, robust estimation, the estimation of receiver operating characteristic (ROC) curves, and so on. [ABSTRACT FROM AUTHOR]

Background and objective: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. Methods: Children (aged 6–11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography–mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma‐related genes. Results: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold‐change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor‐controlled or well‐controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress‐related biological progression of paediatric asthma. Conclusion: Metabolomic analysis of patient urine combined with network‐biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma. [ABSTRACT FROM AUTHOR]

The interior structure of the Qaidam Basin records kinematic information related to the regional deformation of the northern Tibetan Plateau. Based on balanced cross sections and depth structure maps covering two individual anticlines in the western Qaidam Basin, we calculate shortening and strike‐slip amounts on the structures. Strain analyses reveal a complex deformation mechanism for them, comprising ~7°–10° clockwise rotation and oblique convergence, with block rotation having contributed more to the sinistral slip than has oblique convergence. Considering the similarities in geometry, kinematics, and onset time of the pervasive northwest trending structures within the basin, we propose that they were developed during distributed dextral shear that has affected the Qaidam Basin since the early Miocene. The bulk shear strikes at ~N55°E, which is consistent with the northeastward decrease in gravitational potential energy away from the central Tibetan Plateau, and is facilitated by the movement on the Altyn Tagh and eastern Kunlun faults. Plain Language Summary: The conceptual model of distributed strike‐slip shear deformation has been tested in analog experiments and is thought to be relevant to regions affected by major strike‐slip faults. However, whether this phenomenon is taking place on the Tibetan Plateau during continental collision remains uncertain, due mainly to insufficient kinematic constraints on local structures. We examine faults and anticlines in the western Qaidam Basin on the northern Tibetan Plateau. We find that the pervasive northwest trending structures in the basin show similarities in structural architecture and onset time. We retrace the deformation process based on kinematic calculations for the structures using subsurface exploration data. The results reveal that both clockwise rotation and oblique convergence have contributed to deformation of the structures and that block rotation has contributed more to the sinistral slip than has oblique convergence. We infer that this scenario reflects the outward decrease in gravitational potential energy away from the central Tibetan Plateau since the early Miocene, which gives rise to the northeastward dextral distributed strike‐slip shear deformation of the Qaidam Basin. The Altyn Tagh fault acts as a relatively free boundary to the Qaidam Basin, while the eastern Kunlun fault transfers continuous, but laterally changing strain to the Qaidam Basin. Key Points: We calculate the shortening and strike‐slip components of two individual structures within the Qaidam Basin on the northern Tibetan PlateauThe target structures have undergone a complex deformation process comprising clockwise rotation (~7‐10°) and oblique convergenceDistributed dextral shear across the Qaidam Basin has dominated the formation of structures within the basin since the early Miocene [ABSTRACT FROM AUTHOR]

Understanding the factors affecting activities of daily living (ADL) is important in Alzheimer's disease (AD), because decline in ADL contributes to many poor health outcomes. Existing studies often investigate the factors in isolation without a theoretical framework. The purpose of the present study was to provide preliminary results on how cognition, physical performance, and behavioral and psychological symptoms of dementia mediate the relationship of aerobic fitness and ADL in AD. A cross‐sectional analysis was used (n = 28: average age 78 [8] years, education 16 (3) years, Mini‐Mental State Examination scores 20 [4]). The results showed that aerobic fitness is not linked to ADL directly, and its association with ADL was mediated by physical performance and global cognition. Our findings provide preliminary support for aerobic fitness as a potential therapeutic target, as enhanced aerobic fitness could simultaneously modify other factors affecting ADL. Nurses are in a unique position for coordinating exercise safety assessment and prescription and educating older adults with AD about exercise participation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antroquinonol, a ubiquinone derivative that shows anticancer and anti‐inflammatory activities, is produced during solid‐state fermentation of Antrodia camphorata; however, it cannot be biosynthesized via conventional submerged fermentation. RESULTS: A method for enhancing the biosynthesis of antroquinonol by controlling pH and adding an oxygen vector in a 7 L bioreactor was studied. In shake‐flask experiments, a maximum antroquinonol production of 31.39 ± 0.78 mg L−1 was obtained by fermentation with adding 0.2 g L−1 coenzyme Q0 (CoQ0), at the 96th hour. Following kinetic analysis of the fermentation process, pH control strategies were investigated. A maximum antroquinonol production of 86.47 ± 3.65 mg L−1 was achieved when the pH was maintained at 5.0, which exhibited an increase of 348.03% higher than the batch without pH regulation (19.30 ± 0.88 mg L−1). The conversion rate of CoQ0 improved from 1.51% to 20.20%. Further research revealed that the addition of n‐tetradecane could increase the production of antroquinonol to 115.62 ± 4.87 mg L−1 by increasing the dissolved oxygen in the fermentation broth. CONCLUSION: The results demonstrated that pH played an important role in antroquinonol synthesis in the presence of the effective precursor CoQ0. It was a very effective strategy to increase the yield of antroquinonol by controlling pH and adding oxygen vector. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Although it is generally accepted that diabetes is one of the most important risk factors for liver cancer, the underlying mechanism is still not well understood. The purpose of the current study is to further investigate how high concentrations of glucose (HG), a major symptom of diabetes, stimulate the development of liver malignancy. Using data mining, gap junction protein gamma 1 (GJC1) was identified as a critical proto‐oncoprotein that is essential for the HG stimulation of proliferative capacity in liver cancer cells. Furthermore, enhanced transcriptional expression of GJC1 might occur after stimulation by HG. A transcription factor zinc finger protein 410 (APA1)–binding motif was found to be located at the –82 to −77 nt region within the GJC1 promoter. Without APA1, HG was unable to increase GJC1 expression. Interestingly, APA1, but not GJC1, can be O‐GlcNAcylated in liver cancer cells. Moreover, O‐GlcNAcylation is essential for HG‐induced APA1 binding to the GJC1 promoter. Notably, global O‐GlcNAcylation and expression of APA1 and GJC1 were highly elevated in liver cancer patients with diabetes compared to those in patients without diabetes. The HG‐stimulated proliferative capacity was abolished upon decreasing O‐GlcNAcylation, which could be reversed gradually by the simultaneous overexpression of APA1 and GJC1. Therefore, GJC1 could be a potential target for preventing liver cancer in patients with diabetes. High glucose controls GJC1 to induce tumorigenesis. [ABSTRACT FROM AUTHOR]

Background and Aim: Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS. Methods: Illumina high‐throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS‐D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post‐transplant defecation and intra‐epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high‐throughput sequencing technology. Results: Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS. Conclusion: Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Curcumin (Cur), derived from Curcuma species, exhibits anti‐inflammatory, antioxidant, and anticancer effects. Although Cur has some beneficial effects on asthma, its clinical application is limited by its low bioavailability. Tetrahydrocurcumin (THC), the major active metabolite of Cur, has multiple biological functions, similarly to Cur, and importantly, it showed enhanced bioavailability in tissues and plasma. However, the effect of THC on asthma has not been reported. Objective: The current study sought to investigate the efficacy of dietary THC on allergic asthma compared to that of Cur in an animal model. Methods: The anti‐inflammatory effects of Cur and THC were evaluated in an ovalbumin‐induced asthmatic mouse model. The nasal symptoms, pathological alterations of the lung tissues, oxidants and antioxidants, cytokine production, T cell subsets, and Th2‐related signalling pathway activity were assessed. Results: Both THC and Cur had beneficial effects on asthmatic mice with regard to nasal symptoms, pathological changes (eosinophils and mucus hyper‐production), oxidative stress (malondialdehyde), cytokine production (IL‐13), Th17 and cytotoxic T cell subsets, and Th2 signalling pathway (IL‐4Rα‐Jak1‐STAT6 and Jagged1/Jagged2‐Notch1/Notch2 axis) activity. THC was more effective than Cur in suppressing tissue eosinophilia, mucus production, and IL‐4Rα/Jak1/STAT6 pathway activity. Furthermore, only THC inhibited peripheral eosinophil levels, Th2 cytokines (IL‐4 and IL‐5), and Th2 cell subsets and enhanced an antioxidant enzyme (glutathione). Conclusion and Clinical Relevance: The above results demonstrated for the first time that THC was superior to Cur in modulating allergic asthmatic phenotypes, especially attenuating the Th2 response. THC might be a potentially effective agent for asthma treatment. [ABSTRACT FROM AUTHOR]

Abstract: Benefiting from the technique of vertically stacking 2D layered materials (2DLMs), an advanced novel device architecture based on a top‐gated MoS2/WSe2 van der Waals (vdWs) heterostructure is designed. By adopting a self‐aligned metal screening layer (Pd) to the WSe2 channel, a fixed p‐doped state of the WSe2 as well as an independent doping control of the MoS2 channel can be achieved, thus guaranteeing an effective energy‐band offset modulation and large through current. In such a device, under specific top‐gate voltages, a sharp PN junction forms at the edge of the Pd layer and can be effectively manipulated. By varying top‐gate voltages, the device can be operated under both quasi‐Esaki diode and unipolar‐Zener diode modes with tunable current modulations. A maximum gate‐coupling efficiency as high as ≈90% and a subthreshold swing smaller than 60 mV dec−1 can be achieved under the band‐to‐band tunneling regime. The superiority of the proposed device architecture is also confirmed by comparison with a traditional heterostructure device. This work demonstrates the feasibility of a new device structure based on vdWs heterostructures and its potential in future low‐power electronic and optoelectronic device applications. [ABSTRACT FROM AUTHOR]

Gemcitabine (GEM)‐based chemotherapy is a commonly used treatment for pancreatic cancer. However, acquired drug resistance, a major problem in pancreatic cancer treatment, causes a reduction in the survival rate of patients with cancer. In this study, we attempted to reveal the molecular mechanism of GEM resistance. Our data showed that GEM treatment inhibits cell growth, induces apoptosis, and activates autophagy via the AMP‐activated protein kinase (AMPK) pathway. The combination of GEM treatment and AMPK knockdown resulted in a dramatic increase of apoptosis and inhibition of autophagy. Additionally, inhibition of mammalian target of Rapamycin induced autophagy. Our findings show the potential therapeutic implications of the combined treatment with GEM and AMPK inhibitors for pancreatic cancer. [ABSTRACT FROM AUTHOR]