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Internet gaming addiction (IGD) is a common disease in teenagers which usually reflects the abnormalities in brain function or structure. Several computational models have been applied to investigate the characteristic of IGD brain networks, for instance, the conception of brain controllability. The primary objective of this study was to explore the relationship between brain controllability and IGD related clinical behaviour. A sample of 101 subjects, including 49 IGD patients and 52 normal controls, were recruited to undergo MR T1 and DTI scanning. Specifically, the MR images were used to generate the white matter connectivity matrix and the morphometry similarity network. The morphometry similarity network was then divided into several communities using modular decomposition. After, average controllability, modal controllability and synchronizability were calculated through measuring the adjacency matrix. The results indicated that the IGD group had greater synchronizability and modal controllability compared to that of the control group, and different morphological-based brain communities had different controllability properties. Furthermore, the addiction demonstrated the mediating effects between nodal or modular brain controllability as well as anxiety. In conclusion, brain controllability could be a potential biomarker of IGD.

Objective To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Methods Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. Results A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). Conclusion A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

SUMMARY Lipotransfer has become a powerful regenerative tool, largely because of its cellular components, the stromal vascular fraction (SVF). However, the clinical separation of cells with collagenase is strictly legislated. In 2017, Yao et al. postulated a novel fat-derived product mechanically concentrating SVF cells and an extracellular matrix (ECM) and named it stromal vascular fraction gel (SVF-gel). This review discussed the protocol of SVF-gel and its component as well as its inner structure. The histologic examination and the retention rate after the transplantation of SVF-gel were also rendered. Moreover, we summed up the rejuvenating and regenerative use of SVF-gel and introduced its possible mechanism.

By introducing copper(I) into Ln(NO3)3-PbI2-KI ternary system, three isostructural heterometallic iodoplumbates [Ln(DMSO)8][Pb2Cu2I9] (Ln = Pr (1), Sm (2), Gd (3)) (DMSO = dimethyl sulphoxide) have been prepared and structurally characterized. Compounds 1–3 contain 1D heterometallic Cu Pb iodometallate [Pb2Cu2I9]3− chains constructed by PbI6 and CuI4 units via edge and face-sharing. All Ln3+ ions are surrounded by eight DMSO molecules to form [Ln(DMSO)8]3+ complex cations acting as counterions to the iodometallate anions. Each [Pb2Cu2I9]n3n- anionic chain is surrounded by four arrays of the [Ln(DMSO)8]3+ complex cations. Their optical and thermal properties were investigated.

A field study on fog chemistry and aqueous-phase processing of aerosol particles was conducted in Fresno, California's San Joaquin Valley (SJV) during wintertime. Fog droplets were collected while interstitial submicron aerosol was characterized in real time using a High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-AMS). The fog samples were later analyzed using HR-AMS, ion chromatography (IC), and total organic carbon analyzer (TOC). Compared to interstitial aerosol, dissolved solutes in fog waters were composed of higher fractions of ammonium, nitrate, sulfate, methanesulfonic acid, and oxygenated organic compounds, likely due to aqueous formation of secondary species as well as enhanced gas-to-particle partitioning of water-soluble gases under humid conditions. The low-volatility dissolved organic matter in fog water (F-OA) was moderately oxidized with an average oxygen-to-carbon (O/C) ratio of 0.42. The chemical composition of F-OA appeared to be overall similar to that of oxygenated organic component in interstitial aerosol (OOA) and the HR-AMS mass spectra of F-OA and OOA are highly similar (r2 > 0.95). However, there are also significant chemical differences as F-OA appeared to contain a larger fraction of carboxylic functional groups than OOA, indicating enhanced organic acid formation through aqueous-phase reactions. In addition, F-OA was composed of substantially more nitrogen-containing compounds, with an average N/C ratio ∼4 times that of OOA. Most strikingly was that the F-OA spectra showed substantial enhancements of the CxHyN2+ (x ≥ 0; y ≥ 0) ions, which were likely contributed by imidazole- and/or pyrazine-based compounds formed from the aqueous reactions of aldehydes with amino compounds. The results of this study demonstrated that aqueous reactions in atmospheric droplets can significantly modify aerosol composition and contribute to the formation of oxygenated and nitrogen-containing organic compounds in atmospheric aerosol particles. This finding is important for understanding aerosol's effects on human health, air quality, and climate.

New Mn(II)-thioantimonate compounds [Mn(NH3)6]2[{Mn(NH3)3}2(μ3-SbS4)2]Cl2 (1), [Mn(NH3)6][{Mn(NH3)4}2(μ-SbS4)2]·2H2O (2), [Mn(NH3)6][{Mn2(μ-SbS4)2}(μ-N2H4)2] (3), and [{Mn(N2H4)}2{Mn(μ-SbS3)2(μ-N2H4)2}(μ-N2H4)2]n (4) were prepared in different hydrazine solution under solvothermal conditions. In 1, the tetrahedral SbS4 unit acts as a tridentate bridging ligand to connect the [Mn(NH3)3]2+ units into a 2-D lamellar anion [Mn(NH3)3(μ3-SbS4)2−]n containing 12-membered Mn3Sb3S6 heterorings. Two SbS4 ligands join two [Mn(NH3)4]2+ units with monodentate μ-1κ1S1: 2κ1S1 bridging mode, forming a binuclear [{Mn(NH3)4}2(μ-SbS4)2]2− anion in 2. In 3, the SbS4 ligand links [Mn2(μ-N2H4)2] units with tridentate bridging mode, to form a 1-D [{Mn2(μ-SbS4)2}(μ-N2H4)22−]n chain-like anion. Octahedral [Mn(NH3)6]2+ complex cation acts as the counter ion in compounds 1–3. In 4, the Mn(N2H4) units are interconnected into a neutral infinite [{Mn(N2H4)}2{Mn(μ-SbS3)2(μ-N2H4)2}(μ-N2H4)2]n chain by μ-SbS3 and μ-N2H4 bridging ligands. The trigonal pyramidal SbS3 unit adopts a tridentate bridging coordination mode μ-1κ2S1, S2:2κ2S1, S3. Compounds 1–4 exhibit tunable semiconducting band gaps varying in the range of 2.38–2.55 eV. Compounds 1 and 2 display higher photocatalytic activity in the degradation of crystal violet than in the degradation of methyl orange under visible light irradiation.

Organic-inorganic hybrid iodoplumbates [H2tmdp][PbI3]2∙DMF (1), [H2tmdp]2Pb7I18 (2), and [(H2tmdp)4(Hpyd)2(Me2NH2)][Pb6I22](I3)·2H2O (3) (tmdp = 4,4′-trimethylenedipiperidine, pyd = pyridine) were prepared using diammonium [H2tmdp]2+ as a structure directing agent under different conditions. The 1D [PbI3−]n polymeric anion in 1 is constructed by PbI6 octahedral units via face-sharing, while the 2D [Pb7I184−]n polymeric anion in 2 is composed of PbI6 units via both corner- and edge-sharing. The interconnection of PbI6 units via corner- and face-sharing generates a new iodoplumbate anion [Pb6I2210−]n in 3, featuring a waved layer structure. Compounds 1–3 exhibit steep band gaps at 2.32, 2.23, and 2.14 eV, respectively. Compounds 2 and 3 show photocatalytic activity in the degradation of methylene blue (MB) and rhodamine B (RhB) under visible light irradiation at room temperature. Compounds 1–3 are more effective in the photocatalytic degradation of MB than in the degradation of RhB.

Solvothermal reaction in tren/tatda mixed polyamines produced a transition metal (TM) thiostannate [Mn(tren)(H2O)][Mn(baen)]3Mn4Sn6S20∙9H2O (1) containing a novel T3 supertetrahedral nanocluster [Mn4Sn6S20]8−. The T3 cluster was constructed by SnS4 and MnS4 tetrahedra via corner-sharing with the SnS4 tetrahedra occupying four corners of the T3 cluster. It has different TM/Sn ratio from the traditional T3 cluster [TM5Sn5S20]10− (TM = Zn, Co) prepared by extraction method using alkali cations as the counter ions. Compound 1 is the first T3 cluster of the TM-Sn-Q phase prepared by solvothermal method and stabilized by TM-amino complex counter ions. The same solvothermal reaction with Se instead of S afforded a selenidostannate [Mn(baen)]2Sn2Se6 (2) containing a dimeric [Sn2Se6]4− anion. Compound 1 exhibits selective photocatalysis in photodegradation of organic dyes. It has higher photocatalytic effect in the photodegradation of crystal violet (CV) than rhodamine B (RhB) under visible light irradiation at room temperature.

This work aims to study the roles and mechanisms of metformin in glioma cells stemness and epithelial-mesenchymal transition. Here, we found that metformin suppressed glioma cells spheroid formation and size, inhibited the expression of glioma stemness-related marker, CD133. Additionally, Metformin attenuated TGF-β-induced epithelial-mesenchymal transition in glioma cells. Mechanistically, metformin inhibited the nuclear abundance of YAP, a key effector of Hippo pathway, subsequently leading to its cytoplasmic retention, and thus reduced YAP transcriptional modulating activity. Importantly, overexpression of a mutant form of YAP (YAP-5SA) attenuated the inhibition of metformin on glioma cells stemness and epithelial-mesenchymal transition. Thus, metformin inhibits glioma cells stemness and epithelial-mesenchymal transition via regulating YAP activity.

Water-soluble organic aerosol (WSOA) in fine particles (PM2.5) collected during wintertime in a polluted city (Handan) in Northern China was characterized using a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (AMS). Through comparing with real-time measurements from a collocated Aerosol Chemical Speciation Monitor (ACSM), we determined that WSOA on average accounts for 29% of total organic aerosol (OA) mass and correlates tightly with secondary organic aerosol (SOA; Pearson's r = 0.95). The mass spectra of WSOA closely resemble those of ambient SOA, but also show obvious influences from coal combustion and biomass burning. Positive matrix factorization (PMF) analysis of the WSOA mass spectra resolved a water-soluble coal combustion OA (WS-CCOA; O/C = 0.17), a water-soluble biomass burning OA (WS-BBOA; O/C = 0.32), and a water-soluble oxygenated OA (WS-OOA; O/C = 0.89), which account for 10.3%, 29.3% and 60.4% of the total WSOA mass, respectively. The water-solubility of the OA factors was estimated by comparing the offline AMS analysis results with the ambient ACSM measurements. OOA has the highest water-solubility of 49%, consistent with increased hygroscopicity of oxidized organics induced by atmospheric aging processes. In contrast, CCOA is the leastwater soluble, containing 17% WS-CCOA. The distinct characteristics of WSOA from different sources extend our knowledge of the complex aerosol chemistry in the polluted atmosphere of Northern China and the water-solubility analysis may help us to understand better aerosol hygroscopicity and its effects on radiative forcing in this region. (C) 2020 Published by Elsevier B.V.

PVA hydrogel has excellent adhesion ability and biocompatibility, and is considered as a promising material in the field of wound dressings. However, the traditional PVA hydrogel has poor mechanical properties, which greatly limits its application. In this article, we obtained a PVA/PAAm interpenetrating networks (IPN) hydrogel by a one-pot free radical polymerization method, which improved the mechanical strength and retained the original properties of the PVA. The IPN hydrogel was proved to possess excellent adhesion strength and rheological properties with certain conductivity, which can be used as a human motion monitor. To achieve the application of wound dressing, a polymer antibacterial agent of polyhexamethylene guanidine (PHMG) was introduced into the hydrogel. The results showed the antibacterial properties of the PVA/PAAm IPN hydrogel were enhanced obviously on both Gram-positive and Gram-negative bacteria. The prepared PVA/PAAm IPN hydrogel may provide the possibility for the application in the field of body sensors and wound dressing.

Dynamic covalent bonds (DCBs) have received widespread attention due to their unique reversibility and stimulus responsiveness. The introduction of DCBs often endows materials with good controllability and self-healing properties, which greatly improves the limitations of some current researches. This review summarizes the characteristics and reaction mechanisms of different types of DCBs, and provides a variety of typical dynamic covalent reactions and their reaction conditions. Finally, we summarize the latest developments in the application of DCBs, including tissue adhesives, tissue regeneration, drug delivery, sensors, 3D printing, fluorescent probes and coatings, and propose existing challenges and future development directions in this field.

Alcohol consumption is a commonly studied risk factor for many poor health outcomes. Various instruments exist to measure alcohol consumption, including the AUDIT-C, Single Alcohol Screening Questionnaire (SASQ) and Timeline Followback. The information gathered by these instruments is often simplified and analyzed as a dichotomous measure, risking the loss of information of potentially prognostic value. We discuss generalized additive models (GAM) as a useful tool to understand the association between alcohol consumption and a health outcome. We demonstrate how this analytic strategy can guide the development of a regression model that retains maximal information about alcohol consumption. We illustrate these approaches using data from the Russia ARCH (Alcohol Research Collaboration on HIV/AIDS) study to analyze the association between alcohol consumption and biomarker of systemic inflammation, interleukin-6 (IL-6). We provide SAS and R code to implement these methods. GAMs have the potential to increase statistical power and allow for better elucidation of more nuanced and non-linear associations between alcohol consumption and important health outcomes.

Purpose: To evaluate the margin negative (R0) resection rate of neoadjuvant FOLFIRINOX and losartan followed by chemoradiotherapy for locally-advanced pancreatic cancer (LAPC). Methods: LAPC patients (per NCCN), ECOG PS 0-1 were enrolled in a single-institution NCI-sponsored phase II study. Patients received 8 cycles of FOLFIRINOX/losartan. If the tumor was radiographically resectable after chemotherapy, patients received short-course chemoradiotherapy (CRT) in 5 fractions (protons 25 GyE, capecitabine 825 mg/m2 bid). If the tumor had persistent vascular involvement, patients received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. The primary endpoint was R0 resection rate. Secondary endpoints were tolerability, PFS, OS, and circulating biomarkers. Results: Fifty patients were enrolled from 8/2013 to 7/2017, with 49 patients evaluable (1 patient withdrew consent). Median age was 63y (42-78), median tumor size was 41mm (18-68), and was located in the pancreatic head in 63% of patients. Thirty-nine patients completed 8 cycles of FOLFIRINOX/losartan, while 10 had fewer than 8 cycles due to progression (5), losartan intolerance (3) and toxicity (2). Grade 3 or greater toxicity occurred in 25 (51%) patients. Forty-five (92%) patients received CRT: 7 patients (15%) had short -course, while 38 (85%) had long-course. Forty-two (86%) patients underwent attempted surgery, with 34 (69%) patients resected. R0 resection was achieved in 30 patients (61% of evaluable patients, 88% of resected patients). Median follow-up was 17.1 months. Overall mPFS was 17.5 months and mOS 31.4 months. Among resected patients, mPFS was 21.3 months and mOS was 33.0 months. Conclusions: Neoadjuvant FOLFIRINOX/losartan provides downstaging of LAPC allowing for R0 resection in 61% of patients. These findings are being validated in an ongoing multicenter randomized trial. Clinical Trial Number: ClinicalTrials.gov Identifier: NCT01821729 Funding Statement: This study was funded by NIH Proton Beam NCI/Federal Share Program grant C06 CA059267, and in part by the Cancer Clinical Investigator Team Leadership Award awarded by the National Cancer Institute though a supplement to P30CA006516 (TSH); P01CA080124, U01CA224173, R01CA208205 (RKJ, DGD, YB). DGD is also supported through The Samuel Singer Brown Fund for Pancreatic Ductal Adenocarcinoma Research. Declaration of Interests: Dr. Hong reports Novartis, Astra-Zeneca, Clinical Genomics, Taiho (clinical trial funding), EMD Serono (Advisory board). Dr. Ryan reports MPM Capital (consulting). Dr Faris reports Novartis (active employment), N-of-One and Merrimack Pharmaceuticals (consulting), and Exelixis, Takeda, and Roche (clinical trial funding). Dr. Kwak reports Novartis (active employment). Dr. Jain reports honorarium from Amgen; consultant fees from Merck, Ophthotech, Pfizer, SPARC, SynDevRx, XTuit; owns equity in Enlight, Ophthotech, SynDevRx, XTuit; served on the Board of Directors of XTuit and serves on the Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund, Tekla World Healthcare Fund. Neither reagents nor funding from these organizations were used in this study. No other authors reported conflicts of interest. Ethics Approval Statement: Patients with LAPC were prospectively enrolled in this NCI-sponsored clinical trial approved by the institutional review board (NCT01821729).

Lanthanide selenidostannates (H3O)n[Ce(tepa)(μ-1κ2:2κ2-Sn2Se6)]n (1), [{Yb(tepa)(μ-OH)}2(μ-1κ:2κ-Sn2Se6)]n·nH2O (2), [Htrien]2[{Ln(trien)(tren)}2(μ-1κ:2κ-Sn2Se6)][Sn2Se6] (Ln=Ce(3), Nd(4)) and [{Yb(dien)2}2(μ-OH)2]Sn2Se6 (5) were solvothermally prepared in different ethylene polyamines. The Sn2Se6 unit connects [Ce(tepa)]3+ and [{Yb(tepa)(μ-OH)}2]4+ fragments with tetradentate μ-1κ2Se1,Se2:2κ2Se5,Se6 and bidentate μ-1κSe1:2κSe5 bridging coordination modes in tepa, to form polymers 1 and 2, respectively. It joins two [Ln(trien)(tren)]3+ fragments as a μ-1κSe1:2κSe5 ligand to form binuclear complexes 3 and 4 in trien. Unlike the Sn2Se6 units in 1–4 that bind with Ln(III) centers as Se-donor ligands, the Sn2Se6 unit in 5 exists as a discrete ion. The syntheses of 1–5 show that the ethylene polyamines play an important role in the complexation of Sn2Se6 ligand with Ln(III) centers. Compounds 1–5 exhibit optical band gaps in the range of 2.09–2.42 eV, which are influenced by the complexation of Sn2Se6 with Ln(III) centers.

Protein acetylation has emerged as a major mechanism in regulating cellular metabolism. Whereas most glycolytic steps are reversible, the reaction catalyzed by pyruvate kinase is irreversible, and the reverse reaction requires phosphoenolpyruvate carboxykinase (PEPCK1) to commit for gluconeogenesis. Here, we show that acetylation regulates the stability of the gluconeogenic rate-limiting enzyme PEPCK1, thereby modulating cellular response to glucose. High glucose destabilizes PEPCK1 by stimulating its acetylation. PEPCK1 is acetylated by the P300 acetyltransferase, and this acetylation stimulates the interaction between PEPCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore promoting PEPCK1 ubiquitinylation and degradation. Conversely, SIRT2 deacetylates and stabilizes PEPCK1. These observations represent an example that acetylation targets a metabolic enzyme to a specific E3 ligase in response to metabolic condition changes. Given that increased levels of PEPCK are linked with type II diabetes, this study also identifies potential therapeutic targets for diabetes.

Two types of lanthanide selenidoantimonates [Ln(en){sub 4}(SbSe{sub 4})] (Ln=Ce(1a), Pr(1b)) and [Ln(en){sub 4}]SbSe{sub 4}.0.5en (Ln=Eu(2a), Gd(2b), Er(2c), Tm(2d), Yb(2e); en=ethylenediamine) were solvothermally synthesized by reactions of LnCl{sub 3}, Sb and Se with the stoichiometric ratio in en solvent at 140 deg. C. The four-en coordinated lanthanide complex cation [Ln(en){sub 4}]{sup 3+} formed in situ balances the charge of SbSe{sub 4}{sup 3-} anion. In compounds 1a and 1b, the SbSe{sub 4}{sup 3-} anion act as a monodentate ligand to coordinate complex [Ln(en){sub 4}]{sup 3+} and the neutral compound [Ln(en){sub 4}(SbSe{sub 4})] is formed. The Ln{sup 3+} ion has a nine-coordinated environment involving eight N atoms and one Se atom forming a distorted monocapped square antiprism. In 2a-2e the lanthanide(III) ion exists as isolated complex [Ln(en){sub 4}]{sup 3+}, in which the Ln{sup 3+} ion is in a bicapped trigonal prism geometry. A systematic investigation of the crystal structures reveals that two types of structural features of these lanthanide selenidoantimonates are related with lanthanides contraction across the lanthanide series. TG curves show that compounds 1a-1b and 2a-2e remove their organic components in one and two steps, respectively. - Graphical abstract: Two types of lanthanide selenidoantimonates [Ln(en){sub 4}(SbSe{sub 4})] (Ln=Ce, Pr) and [Ln(en){sub 4}]SbSe{submore » 4}.0.5en (Ln=Eu, Gd, Er, Tm, Yb; en=ethylenediamine) have been synthesized under the mild solvothermal conditions, and a systematic investigation of the crystal structures reveals that two types of structural features of these lanthanide selenidoantimonates are related with lanthanides contraction across the lanthanide series.« less