IL-2 regulates tumor-reactive CD8+ T cell exhaustion by activating the aryl hydrocarbon receptor.

CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+ T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+ T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.

Cell softness regulates tumorigenicity and stemness of cancer cells.

Identifying and sorting highly tumorigenic and metastatic tumor cells from a heterogeneous cell population is a daunting challenge. Here, we show that microfluidic devices can be used to sort marker-based heterogeneous cancer stem cells (CSC) into mechanically stiff and soft subpopulations. The isolated soft tumor cells (< 400 Pa) but not the stiff ones (> 700 Pa) can form a tumor in immunocompetent mice with 100 cells per inoculation. Notably, only the soft, but not the stiff cells, isolated from CD133+ , ALDH+ , or side population CSCs, are able to form a tumor with only 100 cells in NOD-SCID or immunocompetent mice. The Wnt signaling protein BCL9L is upregulated in soft tumor cells and regulates their stemness and tumorigenicity. Clinically, BCL9L expression is correlated with a worse prognosis. Our findings suggest that the intrinsic softness is a unique marker of highly tumorigenic and metastatic tumor cells.

Ethanol Embolization of Chest Wall Arteriovenous Malformations: Four-Year Findings.

OBJECTIVES: To summarize the clinical characteristics and investigate the efficacy of ethanol embolotherapy in the treatment of chest well arteriovenous malformation (AVM). Treatment-associated complications were also explored. MATERIALS AND METHODS: Between March 2017 and August 2021, 32 consecutive patients (mean age, 23.7 years; age range, 5-54 years) who underwent ethanol embolotherapy for chest well AVMs under general anesthesia were included in this study. Embolization was performed through a direct puncture, transarterial catheterization, or a combination of the 2 procedures. The mean follow-up duration after the last treatment was 18.0 months (range, 3-42 months). The degree of devascularization on follow-up (assessed using angiography or computed tomography), and the clinical signs and symptoms of AVMs were evaluated as the therapeutic outcomes. The major and minor complications associated with the procedures were recorded. RESULTS: A total of 103 embolization procedures (mean, 3.2; range, 2-7) comprising 101 ethanol embolization and 2 coil embolizations were performed on 32 patients with chest wall AVMs. The AVM nidus was accessed through the transarterial approach alone in 4 patients, by direct puncture in 11, and a combined procedure in 17 patients. Overall, more than 80% of the procedures were performed using the combined approach. Complete AVM devascularization was achieved in 12 (37.5%) patients. Moreover, 76% to 99% AVM was achieved in 18 patients (56.3%), and 50% to 75% in 2 patients (6.3%). Bleeding, pain, heart failure, and cosmetic deformities were the indications for treatment. For 3 patients (3/32, 9.4%) who had bleeding, the treatment stopped the hemorrhage. Complete pain relief was reported in 8 patients (8/32, 25.0%), whereas complete relief from congestive heart failure post-embolization was observed in 5 of the 6 patients with congestive heart failure (5/6, 83.3%). Complete correction of cosmesis deformities after embolization was achieved in 10 patients (10/32, 31.3%). Two patients who underwent surgery to correct persistent deformity after embolization only showed insignificant improvement. In addition, 6 (18.8%) patients developed 13 complications including blister, necrosis, hemothorax, transient hemoglobinuria, and transient pulmonary artery hypertension. CONCLUSIONS: Ethanol embolotherapy is a safe and effective procedure for chest well AVMs. Surgery is required for some patients with residual cosmesis deformity. CLINICAL IMPACT: Currently, there is no standard treatment for chest well AVMs due to their rarity and high heterogeneity. The present study shows that thanol embolotherapy is a safe and clinically effective treatment procedure for the chest well AVMs. Transarterial embolization in combination with direct puncture embolization can reach the AVM nidus. Ethanol embolotherapy can achieve complete obliteration of the AVM nidus in the majority of patients. Surgery may still be needed to correct cosmetic deformity after embolization. The present study provides valuable evidence to inform clinical decision-making.

Comprehensive analysis of exosomal circRNA, lncRNA, and mRNA profiles to identify the potential RNAs involved in the pathogenesis of venous malformation.

BACKGROUND: Venous malformation (VM) is a kind of congenital vascular anomaly with a high incidence of recurrence, detailed pathogenesis and standard treatment of VM still lack now. Increasing evidence showed exosomal RNA plays a pivotal role in various diseases. However, the underlying mechanism of VM based on the potential differentially exosomal RNAs remains unclear. METHODS: Comparative high-throughput sequencing with serum exosomes from three VM patients and three healthy donors was used to explore differentially expressed (DE) circRNAs, DE lncRNAs, and DE mRNAs involving the formation of VM. We identified and verified DE circRNAs, DE lncRNAs, and DE mRNAs via qRT-PCR assay. We explored the potential functions of these exosomal DE non-coding RNAs via performing further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Besides, circRNA/lncRNA-miRNA-mRNA linkages were also constructed to find their potential relationships in VM. RESULTS: A total of 121 circRNAs, 53 lncRNAs, and 42 mRNAs (|log2 FC| ≥ 2.0, FDR <0.05, n = 3) were determined to be differentially expressed. QRT-PCR validated that these top-changed DE circRNAs, lncRNAs, and mRNAs had significant expression changes. Functional studies demonstrated that DE circRNAs play a pivotal role in thyroid hormone signaling pathway, DE lncRNAs function as a key regulator in MAPK signaling pathway and DE miRNAs participate in the process of hepatocellular carcinoma mostly. CONCLUSION: Our study comprehensively depicted exosomal DE non-coding RNAs networks related to the pathogenesis of VM which can provide new insight into, a novel target for treating VM.

Efficacy and safety of apatinib combined with liposomal doxorubicin or paclitaxel versus liposomal doxorubicin or paclitaxel monotherapy in patients with recurrent platinum-resistant ovarian cancer.

AIM: Apatinib is an effective treatment for patients with gynecological cancers. This study aimed to further explore the efficacy and safety of apatinib plus chemotherapy in patients with recurrent platinum-resistant ovarian cancer (PROC). METHODS: Totally, 105 patients with recurrent PROC receiving apatinib plus chemotherapy (N = 51) and chemotherapy alone (N = 54) were retrospectively enrolled in this cohort study. RESULTS: Objective response rate (37.3% vs. 14.8%) (p = 0.009) and disease control rate (80.4% vs. 61.1%) (p = 0.030) were increased in the apatinib plus chemotherapy group versus the chemotherapy group. The median (95% confidence interval [CI]) progression-free survival (PFS) and overall survival (OS) were 5.5 (3.4-7.6) and 21.4 (16.2-26.6) months in the apatinib plus chemotherapy group, and they were 3.8 (3.0-4.6) and 14.8 (11.9-17.7) months in the chemotherapy group. Meanwhile, the Kaplan-Meier curves revealed that PFS (p = 0.008) and OS (p = 0.012) were prolonged in the apatinib plus chemotherapy group versus the chemotherapy group. This finding was confirmed by multivariate Cox's proportional regression analyses: enter method (hazard ratio [HR] = 0.515, p = 0.007 for PFS; HR = 0.222, p < 0.001 for OS) and step-forward method (HR = 0.608, p = 0.019 for PFS; HR = 0.346, p = 0.001 for OS). Additionally, the incidence of hypertension was increased in the apatinib plus chemotherapy group versus the chemotherapy group (p = 0.038), while others were not different between the two groups (all p > 0.05). Grades 3 and 4 adverse events were neutropenia, hypertension, leukopenia, hand-foot syndrome, nausea and vomiting, fatigue, thrombocytopenia, and anemia in the apatinib plus chemotherapy group. CONCLUSION: Apatinib combined with chemotherapy is a superior choice over chemotherapy alone for recurrent PROC management.

Serum differentially expressed angiogenic cytokines in head and neck vascular malformations.

BACKGROUNDS: Head and neck vascular malformation (HNVM) is a highly complex congenital condition that is difficult to diagnose, monitor and treat. Therefore, it is critical to explore serum cytokines that may be related to its pathology and prognosis. METHODS: An antibody-based microarray was used to examine the expression of 31 angiogenic cytokines in 11 HNVM patients relative to 11 healthy subjects. ELISA was used to verify the results. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially expressed cytokines (DECs). Additionally, we explored the function of DECs in human umbilical vein endothelial cells (HUVECs) in vitro via CCK-8, wound healing, transwell and tube formation assays. RESULTS: Expression of interleukin (IL)-10, matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor receptor 2 (VEGF-R2) in HNVM patients was significantly higher, whereas levels of IL-12p40 and angiostatin were significantly lower in HNVM patients relative to healthy controls (p < 0.05). However, ELISA only verified that IL-10, MMP-9, VEGF-R2 and IL-12p40 had significant expression changes. Functional enrichment analysis revealed DECs mainly participated in the RAS signalling pathway. Functional studies demonstrated that IL-10, MMP-9 and VEGF-R2 promote cell proliferation, migration, invasion and tube formation, while IL-12p40 inhibited these processes in HUVECs. CONCLUSIONS: The present study not only indicates that IL-10, MMP-9, VEGF-R2 and IL-12p40 may participate in the development of HNVMs but also provides a theoretical basis for the discovery of new targeted molecules in the treatment of HNVMs.

Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum-resistant recurrent ovarian cancer treatment: A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: Apatinib, an oral antiangiogenic drug, exerts potential anti-tumour effects on platinum-resistant recurrent ovarian cancer (PROC). This study intended to evaluate the efficacy and safety of apatinib plus paclitaxel compared to paclitaxel monotherapy in PROC patients. METHODS: This retrospective cohort study reviewed 70 PROC patients who received apatinib plus paclitaxel (apatinib plus paclitaxel group) (N = 32) or paclitaxel monotherapy (paclitaxel monotherapy group) (N = 38). The recommended regimens were as follows: paclitaxel (60 mg/m2 ) administrated once a week with a maximum of 18 weeks; apatinib (250-375 mg/day) administrated until disease progression or patient intolerance. RESULTS AND DISCUSSION: Disease control rate was elevated (84.4% vs. 60.5%, P = 0.028), whereas objective response rate only disclosed an increasing trend (lacked statistical significance) (37.5% vs. 18.4%, P = 0.074) in apatinib plus paclitaxel group compared with paclitaxel monotherapy group. Progression-free survival (median [95% confidence interval (CI)]: 5.0 [2.5-7.5] months vs. 3.8 [2.4-5.2] months, P = 0.033) and overall survival (median [95% CI]: 21.1 [13.2-29.0] months vs. 14.8 [11.4-18.2] months, P = 0.032) were both prolonged in apatinib plus paclitaxel group compared to paclitaxel monotherapy group, which were further verified in the multivariate Cox's proportional hazard regression analyses (both P < 0.050). Additionally, the incidence of each adverse event was not different between the two groups (all P > 0.050). WHAT IS NEW AND CONCLUSION: Apatinib plus paclitaxel exhibits better efficacy and acceptable toxicity compared with paclitaxel monotherapy in PROC patients.

Cell-free DNA from plasma as a promising alternative for detection of gene mutations in patients with Maffucci syndrome.

Maffucci syndrome (MS, OMIM 166000) is an extremely unusual, nonhereditary, multisystemic disorder that is characterized with multiple enchondromas and vascular lesions, most of which are spindle cell hemangiomas. Complications of MS, such as bone deformities and dysfunction caused by enchondromas, usually increase during childhood and adolescence. Malignant transformation of enchondromas and other malignancies are the most severe complications. MS is caused by somatic mosaic IDH1/2 mutations, 65% of which are the IDH1 p.Arg132Cys variant. Due to its rarity, there is no international consensus for the most appropriate treatment option of MS.Here, we report a case of a female patient presenting with multiple enchondromas and spindle cell hemangiomas (SCHs) on bilateral hand and feet diagnosed as MS. A detailed clinical, pathological and genetic diagnosis of MS was rendered. Integrative Genomics Viewer (IGV) visualization of next-generation sequencing (NGS) data revealed the consistent detection of the low-frequency somatic IDH1 p.Arg132Cys mutation between SCH tissue and cystic blood-derived cfDNA. This is the first successful molecular diagnosis of MS complicated with SCH utilizing minimally invasive cfDNA techniques. We suggest that cfDNA sequencing could potentially be used as an alternative, reliable and sensitive method to identify molecular information for genetic diagnosis and for future targeted therapies of MS.

Complex vascular anomalies and tissue overgrowth of limbs associated with increased skin temperature and peripheral venous dilatation: parks weber syndrome or PROS?

PIK3CA-related overgrowth spectrum (PROS) is a series of congenital, sporadic disorders that are associated with segmental overgrowth phenotypes and postzygotic, somatic gene mutations in the PIK3CA-ATK-mTOR pathway. The variability and overlapping phenotypes between PROS and other complex vascular malformations make the differential diagnosis confusing and challenging. PROS should be considered for the differential diagnosis with other complex vascular malformations and syndromes with a tissue overgrowth phenotype, such as Parkes-Weber syndrome (PWS).Herein, we diagnosed one unique clinically challenging case manifested as capillary malformation (CM), limb overgrowth, as well as increased skin temperature and peripheral venous dilatation of lower limb that indicated a potential fast-flow lesion. The patient was initially diagnosed with PWS. Contrary to the previous diagnosis, based on further MR imaging and digital subtraction angiography (DSA), which ruled out the existence of AVMs and AVFs, and molecular analysis with targeted next-generation sequencing (NGS) revealing a somatic PIK3CA mutation, we ultimately diagnosed that the patient had a unique form of PROS simulating PWS phenotypes. We suggest that it is important to propose the differential diagnosis of PWS and PROS, two diseases that share a common overgrowth phenotype. We recommended radiological diagnosis such as MRI, CT and DSA as well as further molecular diagnosis to provide more information for the assessment of vascular lesions and to further guide clinical treatment strategies.

Embolization for Arteriovenous Malformations in the Maxilla With Coils and Ethanol.

PURPOSE: Maxillary arteriovenous malformations (AVMs) are uncommon, limiting comprehensive research into standard treatment protocols. This study evaluated the management, outcomes, and clinical safety of embolization techniques for maxillary AVMs, using coils and ethanol. METHODS: In this retrospective case series, we enrolled a sample of patients with maxillary AVMs treated with embolization using coils with or without ethanol between June 2017 and July 2019. Coils were super-selectively placed into the nidus and dominant outflow vein to decrease the flow of the arteriovenous fistulas. Absolute ethanol was then injected to obliterate the nidus. Clinical follow-up was performed for all the patients, and therapeutic outcomes were measured by evaluating the degree of devascularization and symptoms. RESULTS: Ten patients were included in the present study, including 4 men (40%) and 6 women (60%), with a mean age of 18.1 years (range, 10 to 36 years). Transvenous release of coils (9 detachable coils and 143 pushable coils), either with or without absolute ethanol embolization, was used in all the patients. The amount of ethanol injected ranged from 0 to 12 mL (mean: 6.5 mL; 95% confidence interval: 3.489 to 9.511) in a single session. Seven (70%) of the 10 patients were cured, while 3 patients (30%) had partial remission. Follow-up times ranged from 26 to 42 months (median: 29.7 months). Tooth loosening and coil exposure occurred in 7 patients (70%) and healed after surgery. No major complications were noted. CONCLUSIONS: Coils and ethanol embolization have the potential to cure AVMs in the maxilla with an acceptable risk of minor complications.

Magnetic amino-functionalized metal-organic frameworks as a novel solid support in ionic liquids-based effervescent tablets for efficient extraction of polycyclic aromatic hydrocarbons in milks.

Herein, a kind of novel multi-layer core-shell nanocomposites (NSPN) was prepared by employing SiO2 and polyvinylpyrrolidone (PVP) polymers as modifiers and amino-functionalized metal-organic frameworks (NH2-MIL101(Fe)) as coating. It was referred to as the NSPN and ILs-based effervescence-assisted dispersive solid-phase microextraction, hereafter abbreviated as NIE-DSM. In terms of extraction efficiency, SiO2 and PVP as modifiers and NH2-MIL(Fe) as coating onto the surface of NiFe2O4 cores played a synergistically enhancing effect on adsorption/extraction. Effervescent tablets were prepared by integrating the NSPN magnetic nanoparticles as adsorbents with imidazolium-based ionic liquids (ILs) as extractants as well as acidic and alkaline sources. Under vigorous dispersion of CO2 bubbles, the NIE-DSM method realized the goal of rapidly diffusing and separating the adsorbent/extractant (~3 min) without needing conventional vortexing or centrifugation step. Consequently, the NIE-DSM approach combined dispersion and adsorption/extractant in a synchronous way. Under optimized conditions, the NIE-DSM/HPLC-FLD method gave low limits of detection (0.008-0.034 µg kg-1) and satisfactory extraction recoveries (74.1-101.6%) for five polycyclic aromatic hydrocarbons (PAHs; fluorene, anthracene, pyrene, chrysene and benzo(a)pyrene) in milk samples. The intra-day and inter-day precision, expressed as relative standard deviations, was < 5.9% and 6.5%, respectively, demonstrating a high precision. Owing to no requirement for electrical power, this method shows great potential for outdoor monitoring of trace-level PAHs in food matrices.

A support vector regression model to predict nitrate-nitrogen isotopic composition using hydro-chemical variables.

Nitrate is a prominent pollutant in surface and groundwater bodies worldwide. Isotopes in nitrate provide a powerful approach for tracing nitrate sources and transformations in waters. Given that analytical techniques for determining isotopic compositions are generally time-consuming, laborious and expensive, alternative methods are warranted to supplement and enhance existing approaches. Hence, we developed a support vector regression (SVR) model and explored its feasibility to predict nitrogen isotopic composition of nitrate (δ15N-NO3-) in a rural-urban river system in Southeastern China. A total of 16 easily obtained hydro-chemical variables were measured in the wet season (September 2019) and dry season (January 2020) and used to develop the SVR prediction model. The grading method utilized ~75% (35) of the samples for model building while the remaining 11 samples assessed model performance. Principal component analysis (PCA) extracted 7 principal components for SVR model inputs as PCA reduces superfluous variables. We optimized tuning parameters in the SVR model using a grid search technique coupled with V-fold cross-validation. The optimized SVR model provided accurate δ15N-NO3- predictions with a determination coefficient (R2) of 0.88, Nash-Sutcliffe (NS) of 0.87, and mean square error (MSE) of 0.53‰ in the testing step, and performed much better than the corresponding multivariate linear regression model (R2 = 0.60, NS = 0.58 and MSE = 1.76‰) and general regression neural network model (R2 = 0.66, NS = 0.65 and MSE = 1.45‰). Overall, the SVR model provides a potential indirect method to predict environmental isotope values for water quality management that will complement and enhance the interpretation of direct measurements of δ15N-NO3-.

Ethanol embolization of lingual arteriovenous malformations: Positive experience in 52 patients during 11 years.

OBJECTIVE: Lingual arteriovenous malformations (AVMs) are extremely rare in clinical practice, which has limited comprehensive research to find standard treatment protocols. This study summarizes the clinical features of lingual AVMs and assesses the safety and efficacy of ethanol embolotherapy in the management of these lesions. METHODS: Our study group was composed of 52 patients with lingual AVMs treated by ethanol embolization, all of whom received general anesthesia. The optimal access to the nidus of the AVM was by direct puncture, transarterial catheterization, transvenous catheterization, and a combination of these routes. Pure ethanol was manually injected into the nidus of the AVMs. The observed major or minor complications related to ethanol embolization were analyzed, and periodic follow-up of the patients was performed. The devascularization of the lingual AVMs between baseline and final angiography and the clinical outcomes of symptoms and signs after ethanol embolization were evaluated. RESULTS: There were 171 embolization procedures (mean, 3.3; range, 1-20) including 166 ethanol embolizations performed; the average volume of ethanol injected in a single ethanol embolization session was 29.8 mL (range, 1-65 mL). Therapeutic outcomes were complete response in 17 patients (33%), partial response in 33 patients (63%), and no response in 2 patients (4%). The effective therapeutic outcomes were gained in 96% of the patients with lingual AVMs treated with ethanol embolization; 25 (48%) of the patients had 83 complications, which were necrosis, infection, hemorrhage of the puncture point, transient hemoglobinuria, postoperative irritability, airway constriction, and coil migration, occurring in 78 procedures (46%). Regular follow-up of all the patients was performed, with the average follow-up period of 37.9 months (range, 1-125 months) after the last treatment. CONCLUSIONS: Ethanol embolization of lingual AVMs is safe and efficacious and is recommended to be the potential preferred method in the treatment of these complicated lesions.

Detachable Acoustophoretic System for Fluorescence-Activated Sorting at the Single-Droplet Level.

Droplet-based single-cell sequencing has emerged as a very powerful tool to study the cellular heterogeneity in diseased tissues for a variety of biological problems. However, the current droplet generation with a single particle and cell encapsulation is a random process and suffers from a low yield that is unable to fulfill the high-throughput analysis requirement. In this work, we present a new fluorescence-activated droplet sorting (FADS) system that can isolate single-cell droplets at high accuracy and high yield using a highly focused surface acoustic wave (HFSAW) with a beam width around 50 µm. The acoustic wave is locally coupled into the microfluidic channel for droplet sorting through a micropillar waveguide structure between the channel and the interdigitated transducer (IDT). This detachable acoustic sorting system allows the disposal of the microfluidic channel after a single use to avoid cross-contamination and keeps the expensive IDT device reusable. We have achieved rapid and accurate isolation of single-cell droplets with purity higher than 90% at ∼1 kHz sorting rate with three different encapsulation contents. In addition, with the uniformly produced droplet size at ∼40 µm, the present acoustic FADS system enables effective sorting of small particles down to submicrometer size, which is challenging for existing fluorescence-activated cell sorting systems.

Adjusting Aggregation Modes and Photophysical and Photovoltaic Properties of Diketopyrrolopyrrole-Based Small Molecules by Introducing B←N Bonds.

The packing mode of small-molecular semiconductors in thin films is an important factor that controls the performance of their optoelectronic devices. Designing and changing the packing mode by molecular engineering is challenging. Three structurally related diketopyrrolopyrrole (DPP)-based compounds were synthesized to study the effect of replacing C-C bonds by isoelectronic dipolar B←N bonds. By replacing one of the bridging C-C bonds on the peripheral fluorene units of the DPP molecules by a coordinative B←N bond and changing the B←N bond orientation, the optical absorption, fluorescence, and excited-state lifetime of the compounds can be tuned. The substitution alters the preferential aggregation of the molecules in the solid state from H-type (for C-C) to J-type (for B←N). Introducing B←N bonds thus provides a subtle way of controlling the packing mode. The photovoltaic properties of the compounds were evaluated in bulk heterojunctions with a fullerene acceptor and showed moderate performance as a consequence of suboptimal morphologies, bimolecular recombination, and triplet-state formation.

Embolotherapy for High-Flow Arteriovenous Malformations in the Hands Using Absolute Ethanol with Coil-Assisted Dominant Outflow Vein Occlusion.

PURPOSE: The purpose of this study was to evaluate the management, outcomes, and technical and clinical safety of coil-assisted dominant outflow vein (DOV) occlusion for the ethanol embolization of high-flow arteriovenous malformations (AVMs) in the hands. MATERIALS AND METHODS: Between March 2013 and October 2016, 12 consecutive patients with AVMs with DOVs underwent ethanol embolization combined with detachable and pushable coil-assisted DOV occlusion. All patients completed the course of clinical follow-up (range: 14-57 months; mean: 36.7 months), and imaging follow-up (range: 8-25 months; mean: 16.6 months) results from the final treatment session were available for 8 patients. The therapeutic effects, degree of devascularization, and complications at the time of follow-up arteriography were evaluated as the clinical outcomes. RESULTS: The patients underwent 23 ethanol embolization procedures (range: 1-3; mean, 1.9) with 24 detachable coils and 223 pushable coils. The average stretched length of the total coils per patient was 320.17 cm. Seven of 12 patients (58.3%) exhibited complete responses, and 5 patients (41.7%) exhibited partial responses. Minor complications, including blistering and focal swelling, occurred in all 12 patients (100%) but showed spontaneous and complete recovery. No major complications occurred. CONCLUSIONS: Ethanol embolization has the potential to control high-flow hand AVMs by using coil-assisted DOV occlusion with an acceptable risk of minor and major complications.

A Wide-Bandgap Conjugated Polymer Based on Quinoxalino[6,5-f ]quinoxaline for Fullerene and Non-Fullerene Polymer Solar Cells.

A wide-bandgap conjugated polymer, PNQx-2F2T, based on a ring-fused unit of quinoxalino[6,5-f ]quinoxaline (NQx), is synthesized for use as electron donor in polymer solar cells (PSCs). The polymer shows intense light absorption in the range from 300 to 740 nm and favorable energy levels of frontier molecular orbitals. The polymer has afforded decent device performance when blended with either fullerene-based acceptor [6,6]-phenyl-C71 -butylric acid methyl ester ([70]PCBM) or non-fullerene acceptor 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone-methyl))-5,5,11,11-tetrakis(4-n-hexylphenyl)-dithieno[2,3-d: 2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IT-M). The highest PCEs of 7.9% and 7.5% have been achieved for [70]PCBM or IT-M based PSCs, respectively. Moreover, the influence of molecular weight of PNQx-2F2T on solar cell performance has been investigated. It is found that fullerene-based devices prefer higher polymer molecular weight, while non-fullerene devices are not susceptible to the molecular weight of PNQx-2F2T. The device results are extensively explained by electrical and morphological characterizations. This work not only evidences the potential of NQx for constructing high-performance photovoltaic polymers but also demonstrates a useful structure-performance relationship for efficiency enhancement of non-fullerene PSCs via the development of new conjugated polymers.

Mitochondrial DNA variants modulate genetic susceptibility to Parkinson's disease in Han Chinese.

It is well recognized that mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). The mtDNA displacement loop (D-loop) region is known to accumulate structural alterations and mutations. To understand how mtDNA variants contribute to the susceptibility to sporadic PD in Chinese, a total of 500 PD patients and 505 controls were recruited from East China, and their D-loop regions were sequenced. A total of 389 variants were detected out of the 1005 subjects. There were 91 variants with frequencies >1%, which included 88 single nucleotide polymorphisms (SNPs), 2 deletions and 1 insertion. Amongst, 6 SNPs were significantly associated with sporadic PD. Specifically, the SNPs 151T/C, 189G/A, 16086C/T and 16271C/T contributed to increased susceptibility, while 318C/T and 16134T/C were associated with reduced risk for PD. Further analyses of mtDNA haplogroups and their risk for PD occurrence showed that subjects carrying haplogroup A5 were susceptible while haplogroup B5 carriers were more resistant to the disease. In summary, our study for the first time systematically analyzed mtDNA variants by sequencing the D-loop region in a Chinese population to understand their associations with PD. These results demonstrate that mtDNA variants modulate risk for sporadic PD.

Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation.

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1ß secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1ß secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1ß secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.

Absolute Ethanol Embolization Combined with Surgical Resection of Scalp Arteriovenous Malformations: Interim Results.

PURPOSE: To assess treatment methods, interim results, and complications of absolute ethanol embolization combined with surgical resection of scalp arteriovenous malformations (AVMs). MATERIALS AND METHODS: From September 2012 to January 2015, 15 consecutive patients (8 male and 7 female) with scalp AVMs underwent staged ethanol embolizations. Ethanol embolization was performed using transcatheter and/or direct puncture techniques. Ten patients with scalp AVMs with a dominant outflow vein (DOV) also underwent coil deployment before ethanol embolization. Two patients underwent surgical resection after ethanol embolization was achieved. Follow-up evaluations included clinical outcome of symptoms and signs and imaging at 1.5 months, 6 months, and annually thereafter. RESULTS: In 15 patients, 33 ethanol embolizations were performed; 16 coil deployments were performed in 10 patients who had scalp AVMs with a DOV. Of 15 patients, 8 (53.3%) were cured, 2 of whom underwent surgical resection. All 8 patients showed no recurrence in the follow-up period (range, 12-48 months; mean, 25 months). Seven patients (46.7%) had partial remission and will need further treatment sessions for residual AVMs (range, 1-12 months; mean, 7 months). In 3 of 15 patients (20%), 7 minor complications (skin blisters and necrosis) occurred. All minor complications healed with wound dressing and observation. There were no major complications. CONCLUSIONS: Ethanol embolization has the potential for cure in management of scalp AVMs, with an acceptable risk of minor and major complications. Once AVMs are devascularized, surgical resection can be performed to improve cosmetic results.