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Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSC regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. This research aimed to compare the therapeutic effectiveness of MSCs pretreated with or without wogonin. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSC therapy in IBDs.

International audience; The Surface Water and Ocean Topography (SWOT) mission will vastly expand measurements of global rivers, providing critical new data sets for both gaged and ungaged basins. SWOT discharge products (available approximately 1 year after launch) will provide discharge for all river that reaches wider than 100 m. In this paper, we describe how SWOT discharge produced and archived by the US and French space agencies will be computed from measurements of river water surface elevation, width, and slope and ancillary data, along with expected discharge accuracy. We present for the first time a complete estimate of the SWOT discharge uncertainty budget, with separate terms for random (standard error) and systematic (bias) uncertainty components in river discharge time series. We expect that discharge uncertainty will be less than 30% for two-thirds of global reaches and will be dominated by bias. Separate river discharge estimates will combine both SWOT and in situ data; these “gage-constrained” discharge estimates can be expected to have lower systematic uncertainty. Temporal variations in river discharge time series will be dominated by random error and are expected to be estimated within 15% for nearly all reaches, allowing accurate inference of event flow dynamics globally, including in ungaged basins. We believe this level of accuracy lays the groundwork for SWOT to enable breakthroughs in global hydrologic science.Plain Language Summary The Surface Water and Ocean Topography (SWOT) satellite mission was launched on 15 December 2022. SWOT is designed to produce estimates of river discharge on many rivers where no in situ discharge measurements are currently available. This paper describes how SWOT discharge estimates will be created, and their expected accuracy. SWOT discharge will be estimated using simple flow laws that combine SWOT measurements of river water elevation above sea level, river width, and river slope, with ancillary data such as river bathymetry. We expect that discharge uncertainty will be less than 30% for two-thirds of global reaches and will be dominated by a systematic bias. Temporal variations in river discharge time series are expected to be estimated within 15% for nearly all reaches, thus capturing the response of river discharge to rainfall and snowmelt events, including in basins that are currently ungaged, and providing a new capability for scientists to better track the flows of freshwater water through the Earth system.

PDF file - 451K, Suppl. Fig. 1 Characterization of BM-MSC surface markers. Suppl. Fig. 2 MSC derived from different donors inhibited LAC cell migration. Suppl. Fig. 3 MSC expresses and secretes OSM. Suppl. Fig. 4 OSM inhibited the proliferation of CL1-5 and A549 LAC cells. Suppl. Fig. 5 OSM inhibited the migratory capability of lung squamous cell carcinoma. Suppl. Fig. 6 STAT3 did not mediate the OSM-dependent inhibition of EMT markers. Suppl. Fig. 7 OSM mediated the MSC-CM-dependent suppression of tumor proliferation and EMT in vivo. Suppl. Table 1 List of antibodies used in the report

Sensors are crucial in the understanding of machines working under high temperatures and high-pressure conditions. Current devices utilize polymeric materials as electrical insulators which pose a challenge in the device’s lifespan. Ceramics, on the other hand, is robust and able to withstand high temperature and pressure. For such applications, a co-fired ceramic device which can provide both electrical conductivity and insulation is beneficial and acts as a superior candidate for sensor devices. In this paper, we propose a novel fabrication technique of complex multi-ceramics structures via 3D printing. This fabrication methodology increases both the geometrical complexity and the device’s shape precision. Structural ceramics (alumina) was employed as the electrical insulator whilst providing mechanical rigidity while a functional ceramic (alumina-doped zinc oxide) was employed as the electrically conductive material. The addition of sintering additives, tailoring the printing pastes’ solid loadings and heat treatment profile resolves multi-materials printing challenges such as shrinkage disparity and densification matching. Through high-temperature co-firing of ceramics (HTCC) technology, dense high quality functional multi-ceramics structures are achieved. The proposed fabrication methodology paves the way for multi-ceramics sensors to be utilized in high temperature and pressure systems in the near future.

Background Lucitanib is a novel multi-target inhibitor of FGFR1-3, VEGFR 1-3, and PDGFR α/β. Here, we evaluated the safety, tolerability, and preliminary efficacy of lucitanib in recurrent and metastatic nasopharyngeal carcinoma (RM-NPC). Methods Patients with pretreated RM-NPC were randomly divided into two treatment arms: continuous or intermittent treatment. The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results One hundred percent of patients in the continuous arm and 90% of patients in the intermittent arm had at least one treatment-related AE (TRAE). Grade ≥3 related TRAEs occurred in 5 patients in the continuous arm (5/10, 50%). No TRAEs grade >3 occurred in the intermittent arm. The ORR and DCR of the continuous arm was 20% and 90%, and the intermittent arm was 10% and 60%, respectively. All responses were observed by the first evaluation. The duration of response was more than 1 year, with two patients still on treatment with sustained response at more than 3 years. Conclusion Lucitanib has promising clinical activity and tolerable safety profile in heavily pretreated patients with NPC. Patients who responded to lucitanib treatment generally achieved a long DoR. Lucitanib is now being evaluated in phase II/III studies. ClinicalTrials.gov identifier NCT03260179

We present Multi-Source Weather (MSWX), a seamless global gridded near-surface meteorological product featuring a high 3-hourly 0.1° resolution, near-real-time updates (∼3-h latency), and bias-corrected medium-range (up to 10 days) and long-range (up to 7 months) forecast ensembles. The product includes 10 meteorological variables: precipitation, air temperature, daily minimum and maximum air temperature, surface pressure, relative and specific humidity, wind speed, and downward shortwave and longwave radiation. The historical part of the record starts 1 January 1979 and is based on ERA5 data bias corrected and downscaled using high-resolution reference climatologies. The data extension to within ∼3 h of real time is based on analysis data from GDAS. The 30-member medium-range forecast ensemble is based on GEFS and updated daily. Finally, the 51-member long-range forecast ensemble is based on SEAS5 and updated monthly. The near-real-time and forecast data are statistically harmonized using running-mean and cumulative distribution function-matching approaches to obtain a seamless record covering 1 January 1979 to 7 months from now. MSWX presents new and unique opportunities for hydrological modeling, climate analysis, impact studies, and monitoring and forecasting of droughts, floods, and heatwaves (within the bounds of the caveats and limitations discussed herein). The product is available at www.gloh2o.org/mswx.

To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI).A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated.The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful.This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

In this paper, molecular dynamics (MD) simulation was used to study the wettability of lithium and tungsten. The surface energy barrier and evaporation control the static contact angle with increasing temperature. The effects of 4 different sizes of droplets and 10 different tungsten sections were evaluated. Moreover, it was found that the different arrangements of atoms on the solid surface will affect the wettability, but the size of the droplet has little effect. In addition, the situation of the droplets driven by six different external forces was evaluated. When the force increases, the two states of the droplet and stream will have different properties. Finally, we studied the phase behavior between lithium and tungsten. For example, lithium overflows from the tungsten plate. The tungsten phase is separated in the lithium plate. Lithium is faster than tungsten when it aggregates in the gas phase, and wettability will drive the effects of engulfing and spitting.

Protein phosphorylation plays key roles in a variety of essential cellular processes. Fasciola gigantica is a tropical liver fluke causing hepatobiliary disease fascioliasis, leading to human health threats and heavy economic losses. Although the genome and protein kinases of F. gigantica provided new insights to understand the molecular biology and etiology of this parasite, there is scant knowledge of protein phosphorylation events in F. gigantica. In this study, we characterized the global phosphoproteomics of adult F. gigantica by phosphopeptide enrichment-based LC–MS/MS, a high-throughput analysis to maximize the detection of a large repertoire of phosphoproteins and phosphosites. A total of 1030 phosphopeptides with 1244 phosphosites representing 635 F. gigantica phosphoproteins were identified. The phosphoproteins were involved in a wide variety of biological processes including cellular, metabolic, and single-organism processes. Meanwhile, these proteins were found predominantly in cellular components like membranes and organelles with molecular functions of binding (51.3%) and catalytic activity (40.6%). The KEGG annotation inferred that the most enriched pathways of the phosphoproteins included tight junction, spliceosome, and RNA transport (each one contains 15 identified proteins). Combining the reports in other protozoa and helminths, the phosphoproteins identified in this work play roles in metabolic regulation and signal transduction. To our knowledge, this work performed the first global phosphoproteomics analysis of adult F. gigantica, which provides valuable information for development of intervention strategies for fascioliasis. Supplementary Information The online version contains supplementary material available at 10.1007/s00436-021-07422-2.

The effect of hold time with 0, 20, and 40 s on in-phase thermomechanical fatigue (TMF) behavior and life of P92 steel is investigated in this study. TMF tests are carried out under mechanical strain control with strain amplitudes of 0.4 0.4 , 0.6 0.6 , and 0.8 % 0.8\text{\%} , and temperature range of 550–650°C which is closely relevant to the operating condition in power plant. TMF tests are performed in a mechanical strain ratio of R = − 1 R=-1 and cycle time of 120 s. The fatigue life variation follows the sequence of N f 0 s < N f 20 s < N f 40 s {N}_{\text{f}}^{0\hspace{.1em}\text{s}}\lt {N}_{\text{f}}^{20\hspace{.1em}\text{s}}\lt {N}_{\text{f}}^{40\hspace{.1em}\text{s}} for the same mechanical strain amplitude. In addition, the influence of hold time on fatigue life decreases with the increasing strain amplitude. A continuous softening can be observed from the cyclic stress response under all test conditions. Fractographic and microstructural tests indicate that the fracture surfaces are characterized by a multi-source cracking initiation and an oxidation phenomenon. Furthermore, a modified Ostergren model is used to predict the fatigue life and achieves a good predicted result.

We reported an electrocatalytic C–H activation method to construct novel highly functionalized tetrasubstituted furan derivatives, which uses allenes and 1,3-dicarbonyl compounds as substrates.

A convenient and practical strategy was developed for the synthesis of carbamo(dithioperoxo)thioates through the simple dehydrogenation coupling of thiols and amines and the insertion of CS2 under mild reaction conditions.

ANKASCIN 568-R is an extract derived from red mold rice (RMR) fermented using

A photocatalytic protocol for the synthesis of β-amino acid ester and β-amino ketone derivatives is developed using simple and easy-to-synthesize oxime oxalate and oxime phenylglyoxylate as difunctionalization reagents.

Spirocyclic compounds have attracted the interest of synthetic chemists because of their unique ring systems and utility in drug discovery. Many natural compounds containing spirocyclic moieties in their skeleton are effective pharmaceuticals. For many redox processes, electroorganic synthesis is considered an environmentally friendly method, since the use of reagents with significant toxicity is replaced by electric current, so the amount of waste is often greatly reduced. Therefore, this review summarizes the construction of compounds with a spirocyclic skeleton via electrochemical synthesis strategies since 2000.1 Introduction2 Electrochemically Mediated Synthesis of Spirocyclopropanes3 Electrochemically Mediated Synthesis of Spirooxindoles4 Electrochemically Mediated Synthesis of Spirodienones5 Electrochemically Mediated Synthesis of Other Heterospirocycles6 Conclusion

This study aimed to investigate compounds that has anti-Toxoplasma gondii with the possible advantage of limiting drug resistance. Artemether has potential anti-T. gondii activity, however the detail information is not clear. To evaluate the Specific effect and potential mechanism, in this study, the cytotoxicity of artemether was Firstly evaluated using MTT assay. Secondly, the anti-T. gondii activities was determined using plaque assay, and then the invasion and intracellular proliferation were evaluated. Finally, the mitochondrial membrane potential and reactive oxygen species (ROS) of T. gondii were detected by the JC-1 probe and automatic microplate reader. The safe concentration of artemether is below 7.042 mM on HFF cells, and artemether exhibited good anti-T. gondii activity with the IC50 = 0.905 mM, it can inhibit T. gondii intracellular proliferation by decreasing T. gondii mitochondrial membrane integrity and increasing ROS production.

Uncontrolled studies suggest that the addition of high dose rate intraluminal brachytherapy (HDRIB) to external beam radiotherapy (EBR) may improve palliation for patients with advanced non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the potential clinical benefit of adding HDRIB to EBR in a multicenter randomized trial.Patients with symptomatic stage III or IV NSCLC with endobronchial disease were randomized to EBR (20Gy in 5 daily fractions or 30Gy in 10 daily fractions) or the same EBR+HDRIB (14Gy in 2 fractions over two weeks). The primary outcome was the proportion of patients who achieved symptomatic improvement in patient-reported overall lung cancer symptoms on the Lung Cancer Symptom Scale (LCSS) at 6 weeks following randomization. Secondary outcomes included improvement in individual symptoms, symptom progression free survival, overall survival and toxicity. The planned sample size was 250 patients based on detection of symptomatic improvement from 40 to 60% with a two-sided α of 0.05 and 80% power.134 patients were randomized over 4.5 years: 67 to each arm. The study closed early due to slow accrual. The mean age was 69.8 years, and 67% had metastatic disease. At six weeks 19 patients (28.4%) in the EBR arm and 20 patients (29.9%) in the EBR+HDRIB arm experienced an improvement in lung cancer symptoms (p=0.84). When limited to patients who completed the LCSS percentages were 40.4% vs 47.6%, respectively, p=0.49. Between group differences in mean change scores (0.3-0.5 standard deviations) in favor of EBR+HDRIB were observed for overall symptoms, but only hemoptysis was significantly improved (p=0.03). No significant differences were observed in progression free or overall survival. Grade 3/4 toxicity was similar between groups.Small to moderate improvements were seen in symptom relief with the combined therapy, but they did not reach statistical significance. Further research is necessary before recommending HDRIB in addition to EBR for palliation of lung cancer symptoms.

Heat transfer can be intensified in shell-and-tube heat exchangers for improved heat transfer performance. Such intensification has been widely studied from the point of view of individual heat exchangers (HEs). The use of heat transfer enhancement in Process Integration has many benefits. First, enhanced heat exchangers require less heat transfer area for a given heat duty because of higher heat transfer coefficients. Second, the heat transfer capacity for the given HE can be increased without changing physical size of the exchanger. Third, the use of enhancement can reduce pumping requirement in some cases, as enhanced HE can achieve higher overall heat transfer coefficients with lower velocities, which may lead to lower friction losses. Using enhancement techniques has practical advantages in Heat Exchanger Network (HEN) retrofit, as it can avoid modification of the network structure. The implementation of enhancement is a relatively simple task that can be easily achieved within a normal maintenance period, allowing production losses to be kept to a minimum level and no civil engineering requirement. This chapter provides an introduction to the enhancement methods of commercial shell-and-tube heat exchangers and their engineering application. The key aspects of enhancing shell-and-tube heat exchangers in HEN retrofit are presented and illustrated with examples involving both energy saving and fouling considerations.

N-N axially chiral skeletons are significant structural motifs in natural products, pharmaceuticals, and functional materials. Herein we disclose a method for the asymmetric synthesis of N-N axially chiral compounds by phase-transfer catalysis. A wide range of N-N axially chiral quinazolinone derivatives were prepared in high yields with excellent stereoselectivities. Furthermore, the synthetic utility of the protocol was proved by large-scale reaction and transformation of the product. Density functional theory calculations provide insight into the mechanism.

Pedestrian detection and tracking are critical functions in the application of computer vision for autonomous driving in terms of accident avoidance and safety. Extending the application to drones expands the monitoring space from 2D to 3D but complicates the task. Images captured from various angles pose a great challenge for pedestrian detection, because image features from different angles tremendously vary and the detection performance of deep neural networks deteriorates. In this paper, this multiple-angle issue is treated as a multiple-domain problem, and a novel multidomain joint learning (MDJL) method is proposed to train a deep neural network using drone data from multiple domains. Domain-guided dropout, a critical mechanism in MDJL, is developed to self-organize domain-specific features according to neuron impact scores. After training and fine-tuning the network, the accuracy of the obtained model improved in all the domains. In addition, we also combined the MDJL with Markov decision-process trackers to create a multiobject tracking system for flying drones. Experiments are conducted on many benchmarks, and the proposed method is compared with several state-of-the-art methods. Experimental results show that the MDJL effectively tackles many scenarios and significantly improves tracking performance.

Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation.We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19).The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p .0001) and having cystic fibrosis (CF) (OP = 10.1, p .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES.Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.

BACKGROUND Dialysis unit blood pressure (BP) pattern showed superiority in prognostic evaluation and interdialytic BP burden assessment. However previous studies mainly focused on the recurrent BP pattern within a session (intradialytic BP change or intradialytic BP slope), the clinical value of the weekly pattern of dialysis unit BP is unknown. METHODS We performed a prospective cohort study in adult end stage renal disease (ESRD) patients on thrice weekly hemodialysis (HD). The slope and the change of the postdialysis systolic BP (SBP) in the course of a week (post-SBP slope and post-SBP change) were used to characterize the weekly pattern of dialysis unit BP. Outcomes included all-cause mortality, cardiovascular mortality, and first cardiovascular event. We also measured the home BP in our cohort. RESULTS One hundred and twenty-nine subjects were followed over a median of 31 months. Higher post-SBP slope (≥0.185) was independently associated with increased risk of all-cause mortality, cardiovascular mortality, and first cardiovascular event. Results were similar for increased post-SBP change. HD patients with a higher post-SBP slope or an increased post-SBP change also had significant increased interdialytic BP burden measured by home SBP on both dialysis days and non-dialysis days. CONCLUSIONS Post-SBP slope and post-SBP change might be promising dialysis unit BP markers for prognostic evaluation and interdialytic BP burden assessment.

INTRODUCTION Targeted therapy with microRNAs (miRNAs) has been a significant challenge in recent years. Studying the role and mechanism through which miRNAs regulate various cancer processes is very critical in cancer treatment, including acute lymphoblastic leukemia (ALL). AREAS COVERED This review summarizes the diverse roles of miRNAs in ALL and provides new perspectives in miRNA-based therapeutic strategies. EXPERT OPINION MiRNAs belong to a kind of endogenous non-coding small RNA with the length of 19 ~ 25 nucleotides. They inhibit the expression of target genes and participate in almost all essential physiological processes such as cell proliferation, apoptosis, differentiation, and inflammatory responses. Many miRNAs are abnormally expressed in tumor cells, suggesting that they might be related to the occurrence and development of tumor. ALL is a common hematological malignancy in children. Its clinical manifestation, morphology, immunophenotype, and genetic characteristics are highly heterogeneous. A number of miRNAs have been found to be abnormally expressed in ALL and related to the biological characteristics, clinical features, diagnosis, and treatment in ALL patients. The understanding of miRNAs could help reveal ALL pathogenesis and identify accurate molecular markers for ALL diagnosis, prognosis, and therapeutic targets.

Compared with the well-developed C–C and C–N axial chirality, the asymmetric synthesis of N–N axial chirality remains elusive and challenging. Herein we report the first atroposelective N-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives. This reaction features mild conditions and a broad substrate scope and produces N–N axially chiral compounds with high yields and very good enantioselectivities. Besides, the synthetic utility of the protocol was proved by a large scale reaction, transformation of the product and the utilization of the product as an acylation kinetic resolution reagent. Moreover, DFT calculations provide convincing evidence for the interpretation of stereoselection., A highly efficient atroposelective N-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives was developed.

We present a graphics processing unit (GPU)-based real time distributed dynamic strain sensing in optical frequency domain reflectometry (OFDR). GPU can accelerate the data processing rate distributed sensing in OFDR because it contains many parallel processing steps. We analyze parameters and performance of tunable laser source (TLS), data acquisition card (DAQ) and GPU. We present a choice method of the thread number in a block based on the GPU streaming multiprocessor utilization efficiency. We construct several kernel functions based on process steps of strain sensing and discuss the selection of blocks number for each kernel function. In the experiment, we find that total process time by the parallel computing in GPU is enhanced about 81 times compared with the serial computing in CPU. The measurement rate of this system is up to 60 Hz for real time distributed dynamic strain sensing. We achieve a dynamic strain sensing with a peak-to-peak variation of $2.5~\mu \varepsilon $ , a vibration frequency of 20 Hz and a sensing spatial resolution of 20 cm at a sensing range of 200 m. More importantly, two strain areas simultaneously loaded with a distance interval of 20 cm can be distinguished clearly.