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To compare the outcomes of patients with hematological malignancies who received ATG-Fresenius (ATG-F) 20 mg/kg versus those who received ATG-Genzyme (ATG-G) 10 mg/kg in an unrelated donor hematopoietic stem cell transplantation (HSCT) procedure, a total of 186 patients who underwent their first allogeneic HSCT with an unrelated donor were retrospectively analyzed. One hundred and seven patients received ATG-F, and seventy-nine patients received ATG-G. Multivariate analysis showed that the type of ATG preparation had no effect on neutrophil engraftment (P = 0.61), cumulative incidence of relapse (P = 0.092), nonrelapse mortality (P = 0.44), grade II-IV acute graft-versus-host disease (GVHD) (P = 0.47), chronic GVHD (P = 0.29), overall survival (P = 0.795), recurrence-free survival (P = 0.945) or GVHD-free relapse-free survival (P = 0.082). ATG-G was associated with a lower risk of extensive chronic GVHD and a higher risk of cytomegaloviremia (P = 0.01 and HR = 0.41, P

Purpose Language networks are reorganized during glioma growth, leading to varying language performance in patients with gliomas located in language-eloquent areas. Therefore, pre-treated language performance reflects the neuroplasticity potential. Different domains of language processing, such as speech expression, repetition, and comprehension, involving different neural networks. We analyzed the effects of patient factors and tumor characteristics on the pre-treated performance to investigate neuroplastic potential of different language domains. Methods Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. The correlation with abnormal language performance was verified using univariate and multivariate logistic regression. Results In total, 104 patients were enrolled in this study. 44% of patients had repetitive abnormalities, 34.9% had comprehension abnormalities, and 32.1% had expression abnormalities. The proportion of language pathway involvement and normal language performance was 60% in grade 2 and 3 gliomas and 16% in grade 4 gliomas. Tumor grade (p = 0.006) and T2 volume (p = 0.008) were associated with abnormal performance in the expressive domain, education level (p = 0.004) and T1 C + volume (p = 0.049) in the repetitive domain, and education level (p = 0.013), T2 volume (p = 0.011), and tumor grade (p = 0.089) in the comprehensive domain. Conclusion Different clinical and radiological factors affected the abnormal performance of the three language domains, indicating their functional connectivity and neuroplastic potential are inherently varied. The dynamic interactions between patient factors, tumor characteristics, and language processing should be considered when resecting left hemispheric gliomas.

Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. Mechanistically, glutamine usage reinforces FAO-induced pro-inflammatory and anti-tumorigenic activation by fine-tuning the NAD+/NADH ratio via glutamine-to-lactate conversion. Genetic ablation of important metabolic enzymes involved in CD40-mediated metabolic reprogramming abolishes agonistic anti-CD40-induced antitumor responses and reeducation of tumor-associated macrophages. Together these data show that metabolic reprogramming, which includes FAO and glutamine metabolism, controls the activation of pro-inflammatory and anti-tumorigenic polarization, and highlight a therapeutic potential of metabolic preconditioning of tumor-associated macrophages before agonistic anti-CD40 treatments. ispartof: NATURE IMMUNOLOGY vol:24 issue:3 pages:452-+ ispartof: location:United States status: published

Innovations can overcome constraints posed by resources depletion, increasing environmental and ecological protection concerns. There is considerable amount of innovation that occurs in the construction industry. Accordingly, construction innovation is receiving increasing attention in China. However, the provincial development level of construction innovation remains unclear. To address this gap, the present study employs data-driven measurement for the level of construction innovation. A total of 25 alternative indexes were selected based on the innovation ecosystem theory. Then, text preprocessing, statistical methods, and search statistics were employed to acquire index data. The indexes weights were determined through expert scoring and a cloud model. The quantitative measurement of the level of construction innovation was finally performed. Additionally, the exploratory results were revealed with the analyses of the overall, regional and cluster. The results revealed that overall level of construction innovation in China is not high and regional distribution is uneven. Simultaneously, the level of construction innovation is consistent with local economic strength and it is most sensitive to innovation output in regional level. Moreover, the spatial distribution of the level of construction innovation in China was showed, which similarity with the characteristics of geographical location is. The measurement system this study represents breakthroughs over traditional methods that rely on statistics, cases or questionnaires, which can be applied to other research fields.

Hydroacoustic surveys at the accretionary wedge southwest of Taiwan reveal a confined active hydrocarbon seepage area of ~ 49,000 m2 in ~ 1350 m water depth on the northern crest of the Four-Way Closure Ridge, which we call Yam Seep. In this study, multibeam and side-scan sonar data acquired during surveys with an autonomous underwater vehicle during an expedition with R/V Ocean Researcher I in 2017 showed that the area is characterized by rough topography and high seafloor backscatter. Seafloor observations with a video sled and sediment sampling with gravity corers and the MeBo seafloor drill rig during an expedition with R/V SONNE in 2018 revealed that the area is almost entirely covered by intensely fractured methane-derived carbonates, which indicate that seepage has been ongoing for thousands of years. Hydroacoustic anomalies (‘flares’) in the water column indicated the presence of several gas bubble emission sites mostly at the center and eastern flank of the area in 2019. Drilling through massive carbonates in the northwestern part of Yam Seep induced free gas escape from a depth of ~ 5.1 m. This suggests the presence of gas hydrates in the subsurface as the seep area is located well within the gas hydrate stability zone. The inter-disciplinary investigations of the Yam Seep demonstrate that upward migration of light hydrocarbons and seafloor discharge has a considerable influence on the seabed properties.

To investigate the consequences and mechanisms of myocardium remodeling of aging left atrium, we analyzed the main cardiac electrophysiological parameters such as rest membrane potential, action potential amplitude, maximum rate of action potential increase (max dV/dt), action potential plateau, and 30, 50, and 90% action potential duration (APD

Background: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. Methods: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosome-specific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. Results: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. Conclusion: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.

The sources of P and N in water-carrying lakes include exogenous input and endogenous release. However, the influence of pollution from different sources on the dynamic distribution of N and P at the sediment-water interface in water-carrying lakes remains unclear. The objectives of this study were to investigate the differences in dynamic distribution characteristics of P compounds and N elements in Lake Jiaogang, a major water-carrying lake in eastern China. Four functional regions with different types of pollutant sources and different kinds of aquatic plants were selected to study the distribution of total P (TP), inorganic P, organic P, ammonium (NH

Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.

Purpose Large Rathke’s cleft cysts (LRCCs) and cystic craniopharyngiomas (CCPs) arise from the same embryological origin and may have similar MR presentations. However, the two tumors have different management strategies and outcomes. This study was designed to evaluate the clinical and imaging findings of LRCCs and CCPs, aiming to evaluate their pretreatment diagnosis and outcomes. Methods We retrospectively enrolled 20 patients with LRCCs and 25 patients with CCPs. Both tumors had a maximal diameter of more than 20 mm. We evaluated the patients’ clinical and MR imaging findings, including symptoms, management strategies, outcomes, anatomic growth patterns and signal changes. Results The age of onset for LRCCs versus CCPs was 49.0 ± 16.8 versus 34.2 ± 22.2 years (p = .022); the following outcomes were observed for LRCCs versus CCPs: 1) postoperative diabetes insipidus: 6/20 (30%) versus 17/25 (68%) (p = .006); and 2) posttreatment recurrence: 2/20 (10%) versus 10/25 (40%) (p = .025). The following MR findings were observed for LRCCs versus CCPs: 1) solid component: 7/20 (35%) versus 21/25 (84%) (p = .001); 2) thick cyst wall: 2/20 (10%) versus 12/25 (48%) (p = .009); 3) intracystic septation: 1/20 (5%) versus 8/25 (32%) (p = .030); 4) snowman shape: 18/20 (90%) versus 1/25 (4%) (p p = .001); and 6) oblique angle of the sagittal long axis of the tumor: 89.9° versus 107.1° (p = .001). Conclusions LRCCs can be differentiated from CCPs based on their clinical and imaging findings, especially their specific anatomical growth patterns. We suggest using the pretreatment diagnosis to select the appropriate surgical approach and thus improve the clinical outcome.

Background: The hypertrophy and conversion of postnatal muscle fibers largely determine the yield and quality of pork, and the growth and development of muscle fibers involve complex molecular regulation. miRNA is a kind of endogenous noncoding RNA fragments and widely involved in the proliferation and differentiation of livestock and poultry myoblasts.Results: In this paper, the longissimus dorsi muscle tissues of Lantang pigs at 1 and 90 days of age (LT1D and LT90D) were collected and profiled by miRNA-seq. The longissimus dorsi muscle of LT1D and LT90D expressed 1871 and 1729 miRNA candidates respectively, and 794 miRNAs were shared. We identified 16 differentially expressed miRNAs between LT1D and LT90D and explored the function of miR-493-5p in muscle development. The miR-493-5p inhibited the proliferation and promoted the differentiation of myoblast cells. GO and KEGG pathway analysis of 164 target genes of miR-493-5p, we found ATP2A2, PPP3CA, KLF15, MED28 and ANKRD17 genes related to muscle development. RT-qPCR detection showed that the expression level of ANKRD17 was highly expressed in LT1D libraries, and the double luciferase report test preliminarily proved that miR-493-5p and ANKRD17 have a directly targeting relationship. Conclusions: In this study, we revealed the roles of miR-493-5p in development of muscle fibers and identified the relationship network of miR-493-5p and ANKRD17, providing data support for pig breeding.

The ambiguous results of multiple CD34+ cell-based therapeutic trials for patients with heart disease have halted the large-scale application of stem/progenitor cell treatment. This study aimed to delineate the biological functions of heterogenous CD34+ cell populations and investigate the net effect of CD34+ cell intervention on cardiac remodeling. We confirmed, by combining single-cell RNA sequencing on human and mouse ischemic hearts and an inducible Cd34 lineage-tracing mouse model, that Cd34+ cells mainly contributed to the commitment of mesenchymal cells, endothelial cells (ECs), and monocytes/macrophages during heart remodeling with distinct pathological functions. The Cd34+-lineage-activated mesenchymal cells were responsible for cardiac fibrosis, while CD34+Sca-1high was an active precursor and intercellular player that facilitated Cd34+-lineage angiogenic EC-induced postinjury vessel development. We found through bone marrow transplantation that bone marrow-derived CD34+ cells only accounted for inflammatory response. We confirmed using a Cd34-CreERT2; R26-DTA mouse model that the depletion of Cd34+ cells could alleviate the severity of ventricular fibrosis after ischemia/reperfusion (I/R) injury with improved cardiac function. This study provided a transcriptional and cellular landscape of CD34+ cells in normal and ischemic hearts and illustrated that the heterogeneous population of Cd34+ cell-derived cells served as crucial contributors to cardiac remodeling and function after the I/R injury, with their capacity to generate diverse cellular lineages.

Dispersion results from the variation of index of refraction as well as electric field confinement in sub-wavelength structures. It usually results in efficiency decrease in metasurface components leading to troublesome scattering into unwanted directions. In this letter, by dispersion engineering, we report a set of eight nanostructures whose dispersion properties are nearly identical to each other while being capable of providing 0 to 2π full-phase coverage. Our nanostructure set enables broadband and polarization-insensitive metasurface components reaching 90% relative diffraction efficiency (normalized to the power of transmitted light) from 450 nm to 700 nm in wavelength. Relative diffraction efficiency is important at a system level – in addition to diffraction efficiency (normalized to the power of incident light) – as it considers only the transmitted optical power that can affect the signal to noise ratio. We first illustrate our design principle by a chromatic dispersion-engineered metasurface grating, then show that other metasurface components such as chromatic metalenses can also be implemented by the same set of nanostructures with significantly improved relative diffraction efficiency.

Chronic cluster headache (CH) substantially affects patients' quality of life, and treatment remains challenging. The current article reviewed controlled studies for new treatment options targeting calcitonin gene-related peptide (CGRP) or its receptors in CH and discussed the current gaps and future directions for the treatment of chronic CH.Two anti-CGRP monoclonal antibodies (i.e., galcanezumab and fremanezumab) completed randomized-control trials for efficacy for the preventive treatment of episodic and chronic CH. Galcanezumab was effective for preventing episodic CH but not chronic CH. Fremanezumab was ineffective in preventing episodic and chronic CH. Studies for other anti-CGRP monoclonal antibodies and CGRP antagonists are still pending for results. There are no randomized controlled trials for CGRP-targeted therapies that showed efficacy for chronic CH prevention. The different responses to galcanezumab between episodic and chronic CH may be due to the study design, i.e., the allowance of concomitant preventive therapies in the chronic CH study but not in the episodic CH study. Another reason for the discrepancies is the different roles and sensitivity of CGRP in chronic CH.

Urolithiasis is a common disease of the urinary system. Its recurrence rate is high and may increase medical expenses. Urine stones are composed of urine crystals and other impurities. We discovered the existence of autofluorescence in some of the urine crystals, especially in urolithiasis patients. The fluorescent molecule existed in urine crystals was verified and identified. We have applied micro-Raman and fluorescence microscopy to classify the urine crystals, used confocal laser scanning microscopy (CLSM) to examine the 3D images and spectra of autofluorescence in crystals, used Fourier transform infrared spectroscopy (FTIR) and mass spectrometry (MS) to identify the type of fluorophore in the autofluorescent urine crystals in urine. Riboflavin was identified as one of the major fluorophores in these autofluorescent urine crystals. The prevalence rates of the autofluorescent crystals in urolithiasis patients and subjects without the history of urolithiasis were to gather statistics. We observed that 80% of urolithiasis patients had autofluorescent crystals. Contrastingly, such crystals existed in only 7% of subjects without the history of urolithiasis. The presence of autofluorescent urine crystals may be linked to a sign of urolithiasis.

One of the classical and difficult problems in the theory of planar differential systems is to classify their centers. Here we classify the global phase portraits in the Poincaré disk of the class continuous piecewise differential systems separated by one straight line and formed by two cubic Hamiltonian systems with nilpotent bi-center at (± 1, 0). The main tools for proving our results are the Poincaré compactification, the index theory, and the theory of sign lists for determining the exact number of real roots or negative real roots of a real polynomial in one variable.

Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib.We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR.In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib.Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.