DSFedCon: Dynamic Sparse Federated Contrastive Learning for Data-Driven Intelligent Systems.

Federated learning (FL) makes it possible for multiple clients to collaboratively train a machine-learning model through communicating models instead of data, reducing privacy risk. Thus, FL is more suitable for processing data security and privacy for intelligent systems and applications. Unfortunately, there are several challenges in FL, such as the low training accuracy for nonindependent and identically distributed (non-IID) data and the high cost of computation and communication. Considering these, we propose a novel FL framework named dynamic sparse federated contrastive learning (DSFedCon). DSFedCon combines FL with dynamic sparse (DSR) training of network pruning and contrastive learning to improve model performance and reduce computation costs and communication costs. We analyze DSFedCon from the perspective of accuracy, communication, and security, demonstrating it is communication-efficient and safe. To give a practical evaluation for non-IID data training, we perform experiments and comparisons on the MNIST, CIFAR-10, and CIFAR-100 datasets with different parameters of Dirichlet distribution. Results indicate that DSFedCon can get higher accuracy and better communication cost than other state-of-the-art methods in these two datasets. More precisely, we show that DSFedCon has a 4.67-time speedup of communication rounds in MNIST, a 7.5-time speedup of communication rounds in CIFAR-10, and an 18.33-time speedup of communication rounds in CIFAR-100 dataset while achieving the same training accuracy.

Smart glypican-3-targeting peptide-chlorin e6 conjugates for targeted photodynamic therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive and lethal malignancy with poor prognosis, necessitating the urgent development of effective treatments. Targeted photodynamic therapy (PDT) offers a promising way to selectively eradicate tumor cells without affecting normal cells. Inspired by promising features of peptide-drug conjugates (PDCs) in targeted cancer therapy, herein a novel glypican-3 (GPC3)-targeting PDC-PDT strategy was developed for the precise PDT treatment of HCC. The GPC3-targeting photosensitizer conjugates were developed by attaching GPC3-targeting peptides to chlorin e6. Conjugate 8b demonstrated the ability to penetrate HCC cells via GPC3-mediated entry process, exhibiting remarkable tumor-targeting capacity, superior antitumor efficacy, and minimal toxicity towards normal cells. Notably, conjugate 8b achieved complete tumor elimination upon light illumination in a HepG2 xenograft model without harm to normal tissues. Overall, this innovative GPC3-targeting conjugation strategy demonstrates considerable promise for clinical applications for the treatment of HCC.

Enhanced Tumor Targeting and Penetration of Proteolysis-Targeting Chimeras through iRGD Peptide Conjugation: A Strategy for Precise Protein Degradation in Breast Cancer.

Proteolysis-targeting chimeras (PROTACs) have recently emerged as a promising technology for drug development. However, poor water solubility, limited tissue selectivity, and inadequate tumor penetration pose significant challenges for PROTAC-based therapies in cancer treatment. Herein, we developed an iRGD-PROTAC conjugation strategy utilizing tumor-penetrating cyclic peptide iRGD (CRGDK/RGPD/EC) to deliver PROTACs deep into breast cancer tissues. As a conceptual validation study, iRGD peptides were conjugated with a bromodomain-containing protein 4 (BRD4) PROTAC through a GSH-responsive linker. The resulting iRGD-PROTAC conjugate iPR showed enhanced water solubility, tumor-targeting capability, and penetration within tumor tissues, resulting in increased antibreast cancer efficacy in animal models and patient-derived organoids. This study demonstrates the advantages of combining iRGD and PROTACs in improving drug delivery and highlights the importance of tissue selectivity and penetration ability in PROTAC-based therapeutics.

Discovery of potent NAMPT-Targeting PROTACs using FK866 as the warhead.

Nicotinamide phosphoribosyltransferase (NAMPT) has emerged as a promising target for cancer therapy due to its strong correlation with nicotinamide adenine dinucleotide (NAD+) metabolism and tumorigenesis. Proteolysis targeting chimeras (PROTACs) provided an attractive strategy for developing NAMPT-targeting NAD+-depleting cancer drugs. Herein, a series of von Hippel-Lindau (VHL)-recruiting NAMPT-targeting PROTACs were designed using NAMPT inhibitor FK866 as the warhead. Among them, compound C5 degraded NAMPT (DC50 = 31.7 nM) in a VHL- and proteasome-dependent manner. Moreover, compound C5 effectively inhibited the proliferation of A2780 cells (IC50 = 30.6 nM) and significantly reduced the general cytotoxicity of FK866 to normal cells.

Occurrence and modeling of disinfection byproducts in distributed water of a megacity in China: Implications for human health.

Disinfection byproducts (DBPs) are initially formed in the process of chlorination in the drinking water treatment plants (DWTPs), then further formed in the distribution system due to the presence of residual chlorine and reactive organic matters. However, in China, DBPs are monitored in the effluent from the DWTPs, but less is known about concentrations of DBPs in tap water since they are usually monitored once per half a year. The smart water service system is establishing real-time monitoring of water indices, although DBPs are an urgent need, they are difficult to monitor in real-time due to their diversity and complicated detection methods. If the correlation between DBP concentration and routinely real-time monitored water quality parameters (e.g., pH value, residual chlorine, ammonia) can be evaluated, the concentration of DBPs can be predicted, which will strengthen the control of tap water safety. This article comprehensively assessed the physicochemical parameters and the occurrence of DBP formation in the tap water with an 18-month investigation in Z city (China). DBP formation in tap water of different seasons and different water sources were compared. Based on the relationship between DBPs and physicochemical parameters, linear prediction and nonlinear prediction models of trihalomethanes (THMs), haloacetonitriles (HANs) and haloacetic acids (HAAs) were established, and the accuracy of these models was verified by measured data. Finally, the toxicity and carcinogenic and non-carcinogenic health risk assessment of DBPs in tap water were analyzed.

Polysaccharides from Chrysanthemun indicum L. enhance the accumulation of polysaccharide and atractylenolide in Atractylodes macrocephala Koidz.

Atractylodes macrocephala Koidz. (AM), an herb of traditional Chinese medicine, is well-known for anti-oxidant, anti-tumor and immune regulation potential. However, it is low bioactive compound content that restricts the application of this species. Elicitation is considered as an effective method to enhance biomass and bioactive compound in plants. Our precious study found that polysaccharide of Chrysanthemun indicum L. could promote plant growth by triggering plant defense. In the present study, polysaccharide of Chrysanthemun indicum L. is used to stimulate the accumulation of biomass and bioactive compound with different concentration in Atractylodes macrocephala Koidz. during pot, plot and field experiments. The results suggested that polysaccharide of Chrysanthemun indicum L. could significantly enhance the accumulation of biomass, atractylenolides and polysacchrides. Moreover, 2 mg/mL is determined and verified to be the appropriate concentration during field experiments. In addition, RT-qPCR revealed that CIP-induced terpenoid synthesis in AM mainly depended on mevalonate (MVA) pathway. This is the first report on the discovery of polysaccharide of Chrysanthemun indicum L. for the enhanced accumulation of biaomass and bioactive compound and the use of its for agricultural production.

Waterborne zinc bioaccumulation influences glucose metabolism in orange-spotted grouper embryos.

Fish embryos, as an endogenous system, strictly regulate an energy metabolism that is particularly sensitive to environmental pressure. This study used orange-spotted grouper embryos and stable isotope 67Zn to test the hypothesis that waterborne Zn exposure had a significant effect on energy metabolism in embryos. The fish embryos were exposed to a gradient level of waterborne 67Zn, and then sampled to quantify 67Zn bioaccumulation and mRNA expressions of key genes involved glucose metabolism. The results indicated that the bioaccumulated 67Zn generally increased with increasing waterborne 67Zn concentrations, while it tended to be saturated at waterborne 67Zn > 0.7 mg L-1. As we hypothesized, the expression of PK and PFK gene involved glycolysis pathway was significantly up-regulated under waterborne 67Zn exposure >4 mg L-1. Waterborne 67Zn exposure >2 mg L-1 significantly suppressed PCK and G6PC gene expression involved gluconeogenesis pathway, and also inhibited the AKT2, GSK-3beta and GLUT4 genes involved Akt signaling pathway. Our findings first characterized developmental stage-dependent Zn uptake and genotoxicity in fish embryos. We suggest fish embryos, as a small-scale modeling biosystem, have a large potential and wide applicability for determining cytotoxicity/genotoxicity of waterborne metal in aquatic ecosystem.

Isolation, physical, structural characterization and in vitro prebiotic activity of a galactomannan extracted from endosperm splits of Chinese Sesbania cannabina seeds.

The purpose of this study was to identify and determine the physical and structural characterization of the water-soluble galactomannan extracted from endosperm splits of Chinese S. cannabina seeds. The Sesbania galactomannan (SP) was extracted and purified using a novel method with a high yield (40.3 ± 7.2%). The molecular structure of SP was determined by monosaccharide composition, FTIR and NMR spectroscopy. The structural data showed that SP was galactomannan which composed by a ß-(1/4)-linked mannose backbone with galactopyranosyl residues attached through α-(1/6) linkages. The constant mannose/galactose (M/G) ratio and average molecular weight (Mw) of SP was 1.6:1 and 2.16 × 105 g/mol, respectively. The physical results revealed that SP had many branches on the backbone and existed as a random coil state in aqueous solution. SP was a good biopolymer which had smooth and clearer surface with homogeneous composition, and had some degree of crystallinity and prebiotic activity. As a consequence, SP could be a potential prebiotic and was expected to be suitable for applications in food, pharmaceutical, biomedical or cosmetic industries as a promising new biomaterial.

Carbohydrate polymers exhibit great potential as effective elicitors in organic agriculture: A review.

Some carbohydrate polymers, usually oligosaccharides or polysaccharides, have great potential as an elicitor of plant defense. However, due to the complexity and diversity of poly- and oligosaccharide structure, the molecular mechanisms and structure-activity relationships of carbohydrate elicitors are still not well understood, which hinders the application of carbohydrate elicitors in agriculture. This review introduces the mechanisms of carbohydrate elicitor perception and signaling in plants. The structure and activity relationships of main poly- and oligosaccharides studied for the control of plant diseases are discussed and summarized. Additionally, the effects of carbohydrate elicitors on the secondary metabolite production are also summarized.

CIP elicitors on the defense response of A. macrocephala and its related gene expression analysis.

Plant-derived elicitor is a new type of plant vaccine developed in the contemporary era, and it has safe and broad application prospects in organic agriculture. Research on defense mechanisms triggered by elicitor has become a hot topic in recent years. The Chrysanthemum indicum polysaccharide (CIP) obtained by separation and purification from Chrysanthemum indicum was used as an elicitor in this work. This elicitor has been shown to be effective in Atractylodes macrocephala Koidz (A. macrocephala) against Sclerotium rolfsii sacc (S. rolfsii) infection and soil-borne diseases. However, the mechanism of induced disease resistance has not been elucidated. In this research, we study the CIP-induced A. macrocephala defense response from the level of signal molecules and the defensive enzyme gene expression. Several defense responses to CIP treatment have been found in A. macrocephala, including early hydrogen peroxide (H2O2) production, accumulation of salicylic acid (SA) and increased phytoalexin (PA) content. In addition, CIP significantly increased the activity of related defense enzymes in A. macrocephala. RT-qPCR analysis showed that defense-related genes such as polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL) were up-regulated after CIP treatment. To obtain the sequence of the defense enzyme gene, we are the first to provide a public and comprehensive A. macrocephala database by transcriptome sequencing. These results together demonstrate that CIP triggers defense responses in A. macrocephala. Our research not only provides further research on immune mechanism between plant and elicitor, but also sheds new light on strategy for biocontrol in the future.

Thirty-Day Outcomes of the Enterprise Stent in Treating Hypoperfusion of Symptomatic Intracranial Stenosis.

OBJECTIVE: To evaluate the 30-day outcomes of using the Enterprise stent to treat patients with hypoperfusion of symptomatic severe intracranial stenosis. METHODS: Patients with symptomatic severe intracranial stenosis (70%-99%) who underwent Enterprise stent intervention between August 2014 and November 2018 were retrospectively analyzed. The 30-day primary outcomes included the success rate of stenting and the incidence of complications, including ischemic stroke, cerebral hemorrhage, and death. The 30-day complication rates of patients with different lesion locations and classifications of Mori morphology were compared. RESULTS: Sixty-eight patients were treated using 70 Enterprise stents. The success rate was 100%. The 30-day complication rate was 4.4%. The rates of ischemic stroke, cerebral hemorrhage, and death were 1.5%, 2.9%, and 0%, respectively. No significant difference was found in the 30-day complication rate between patients with different lesion locations and classifications of Mori morphology (P > 0.05). CONCLUSION: Enterprise stents were relatively safe in treating patients with hypoperfusion of symptomatic severe intracranial stenosis.

Detection and identification of the oxidizing species generated from the physiologically important Fenton-like reaction of iron(II)-citrate with hydrogen peroxide.

The Fenton-like reaction of iron(II)-citrate with hydrogen peroxide is physiologically important because it is associated with the oxidative stress and pathological processes induced by the redox-active iron pool in vivo. However, the oxidizing species generated from this reaction at neutral pH has not been convincingly identified because two extremely unstable and hard-to-differentiate species, the hydroxyl radical (•OH) and iron(IV) (ferryl) species, can be produced. Identifying this species is essential for understanding the reaction mechanism. Although there were few data that reported the detection of •OH from this reaction by using the EPR and fluorescence techniques, most of these data were obtained without the necessary assessment with a •OH scavenger. Furthermore, these two techniques may not be able to differentiate the •OH and iron(IV) species. Thus, these reported data cannot lead to a convincing conclusion that the •OH, not the iron(IV) species, was generated. Therefore, in the study reported herein, we carried out systematic investigations first by using the EPR and fluorescence techniques combined with a •OH scavenger to detect the oxidizing species generated from this Fenton-like reaction. Then we utilized NMR spectroscopy and for the first time obtained convincing evidence to demonstrate that this oxidizing species is the •OH rather than iron(IV) species. We also determined the second-order rate constant of the reaction, 3.6 × 103 M-1s-1 (pH7.0, 25 °C), by using the stopped-flow spectrophotometry. On the basis of these findings, a scheme is proposed for the mechanism of this physiologically important Fenton-like reaction.

Silica in situ enhanced PVA/chitosan biodegradable films for food packages.

Non-degradable plastic food packages threaten the security of environment. The cost-effective and biodegradable polymer films with good mechanical properties and low permeability are very important for food packages. Among of biodegradable polymers, PVA/chitosan (CS) biodegradable films have attracted considerable attention because of feasible film forming ability. However, PVA/CS biodegradable films suffered from poor mechanical properties. To improve mechanical properties of PVA/CS biodegradable films, we developed SiO2in situ to enhance PVA/CS biodegradable films via hydrolysis of sodium metasilicate in presence of PVA and chitosan solution. The tensile strength of PVA/CS biodegradable films was improved 45% when 0.6 wt.% SiO2 was incorporated into the films. Weight loss of PVA/CS biodegradable films was 60% after 30 days in the soil. The permeability of oxygen and moisture of PVA/CS biodegradable films was reduced by 25.6% and 10.2%, respectively. SiO2in situ enhanced PVA/CS biodegradable films possessed not only excellent mechanical properties, but also barrier of oxygen and water for food packages to extend the perseveration time.

The nitroxide Tempo inhibits hydroxyl radical production from the Fenton-like reaction of iron(II)-citrate with hydrogen peroxide.

In vivo physiological ligand citrate can bind iron(II) ions to form the iron(II)-citrate complex. Inhibition of hydroxyl radical (OH) production from the Fenton-like reaction of iron(II)-citrate with H2O2 is biologically important, as this reaction may account for one of the mechanisms of the labile iron pool in vivo to induce oxidative stress and pathological conditions. Nitroxides have promising potentials as therapeutic antioxidants. However, there are controversial findings indicating that they not only act as antioxidants but also as pro-oxidants when engaged in Fenton reactions. Although the underlying mechanisms are proposed to be the inhibition or enhancement of the OH production by nitroxides, the proposed elucidations are only based on assessing biological damages and not demonstrated directly by measuring the OH production in the presence of nitroxides. In this study, therefore, we employed EPR and fluorescence spectroscopies to show direct evidence that nitroxide 2,2,6,6-tetramethyl-piperidine-1-oxyl (Tempo) inhibited OH production from the Fenton-like reaction of iron(II)-citrate with H2O2 by up to 90%. We also demonstrated spectrophotometrically, for the first time, that this inhibition was due to oxidation of the iron(II)-citrate by Tempo with a stoichiometry of Tempo:Iron(III)-citrate = 1.1:1.0. A scheme was proposed to illustrate the roles of nitroxides engaged in Fenton/Fenton-like reactions.

Prognostic and predictive value of Ki-67 in triple-negative breast cancer.

This study was to investigate the prognostic role of Ki-67 in further classification of triple negative breast cancer (TNBC), and to test whether high expression level of Ki67 can predict benefit from carboplatin. From January 2004 to December 2012, 363 patients operated for TNBC were identified through the institutional clinical database. After a median follow-up time of 34 months (5.2-120.0 months), 62 patients (17.1%) had relapses and 33 patients (9.1%) died of breast cancer. In univariate analysis, high Ki-67 index as well as larger tumor size and lymph node involvement was associated with shorter disease-free survival (DFS) and overall survival (OS). In multivariate analysis, high Ki-67 is an independent risk factor for DFS (Risk Ratio, RR: 2.835, 95% confidence interval, 95% CI: 1.586-5.068, P < 0.001) and OS (RR: 3.180, 95% CI: 1.488-6.793, P = 0.003). When analyzing the 3-year DFS by Ki-67 distribution, Subpopulation Treatment Effect Pattern Plot analysis showed a beneficial effect of carboplatin in patients with high Ki-67 index. In conclusion, TNBC is probably a heterogeneous disease with different characteristics and prognosis, and may be further subdivided according to the Ki-67 expression levels. Patients in the high Ki- 67 group seem to benefit more from treatment with carboplatin, but this needs to be further verified.

Spatiotemporal Features of the Three-Dimensional Architectural Landscape in Qingdao, China.

The evolution and development of the three-dimensional (3D) architectural landscape is the basis of proper urban planning, eco-environment construction and the improvement of environmental quality. This paper presents the spatiotemporal characteristics of the 3D architectural landscape of the Shinan and Shibei districts in Qingdao, China, based on buildings' 3D information extracted from Quickbird images from 2003 to 2012, supported by Barista, landscape metrics and GIS. The results demonstrated that: (1) Shinan and Shibei districts expanded vertically and urban land use intensity increased noticeably from year to year. (2) Significant differences in the 3D architectural landscape existed among the western, central and eastern regions, and among the 26 sub-districts over the study period. The differentiation was consistent with the diverse development history, function and planning of the two districts. Finally, we found that population correlates positively with the variation in the 3D architectural landscape. This research provides an important reference for related studies, urban planning and eco-city construction.

Cerebellar cavernous malformations with and without associated developmental venous anomalies.

BACKGROUND: The clinical profiles of cerebellar cavernous malformations (CCMs) with and without associated developmental venous anomalies (DVAs) are not well known. The aims of this study were to analyze the clinical and radiological characteristics of CCMs and to assess the various therapeutic strategies. METHODS: A consecutive series of 41 patients with identified CCMs were retrospectively reviewed. Of these, 11 patients (26.8%) were found to have associated DVAs. We compared the clinical profile of the two groups of patients (CCMs with and without DVAs). The CCMs with DVAs cases underwent radical resection of the CCMs, and the distal radicles of the DVAs that directly drain from the CCMs were coagulated and dissected at the length of the CCMs. RESULTS: There were no statistically significant differences between the two groups with regard to age, sex, location and size of lesions, multiplicity, and surgical prognosis. The patients with CCMs with DVAs did not experience any brain swelling or hemorrhagic tendency intraoperatively. The postoperative course was uneventful for all of the 36 surgical patients with the exception of two of the patients with CCMs with associated DVAs, who suffered from serious cerebellar edema, and one of these two patients underwent an emergency suboccipital decompression craniotomy. With the exception of three patients who were lost to follow-up (mean, 22.3 months), all of the CCMs patients exhibited good long-term prognosis (modified Rankin scale values of 0-2) and no reoccurrence. CONCLUSIONS: It is not rare that associated DVAs occur in CCMs. The total removal of the CCM combined with the coagulation and dissection of the distal radicles of DVA at the length of the associated CCM may result in good long-term prognosis in patients.

[Variation pattern and its affecting factors of three-dimensional landscape in urban residential community of Shenyang].

Based on the 1:10000 aerial photo in 1997 and the three QuickBird images in 2002, 2005, and 2008, and by using Barista software and GIS and RS techniques, the three-dimensional information of the residential community in Tiexi District of Shenyang was extracted, and the variation pattern of the three-dimensional landscape in the district during its reconstruction in 1997-2008 and related affecting factors were analyzed with the indices, ie. road density, greening rate, average building height, building height standard deviation, building coverage rate, floor area rate, building shape coefficient, population density, and per capita GDP. The results showed that in 1997-2008, the building area for industry decreased, that for commerce and other public affairs increased, and the area for residents, education, and medical cares basically remained stable. The building number, building coverage rate, and building shape coefficient decreased, while the floor area rate, average building height, height standard deviation, road density, and greening rate increased. Within the limited space of residential community, the containing capacity of population and economic activity increased, and the environment quality also improved to some extent. The variation degree of average building height increased, but the building energy consumption decreased. Population growth and economic development had positive correlations with floor area rate, road density, and greening rate, but negative correlation with building coverage rate.

[Extraction of buildings three-dimensional information from high-resolution satellite imagery based on Barista software].

The demand for accurate and up-to-date spatial information of urban buildings is becoming more and more important for urban planning, environmental protection, and other vocations. Today's commercial high-resolution satellite imagery offers the potential to extract the three-dimensional information of urban buildings. This paper extracted the three-dimensional information of urban buildings from QuickBird imagery, and validated the precision of the extraction based on Barista software. It was shown that the extraction of three-dimensional information of the buildings from high-resolution satellite imagery based on Barista software had the advantages of low professional level demand, powerful universality, simple operation, and high precision. One pixel level of point positioning and height determination accuracy could be achieved if the digital elevation model (DEM) and sensor orientation model had higher precision and the off-Nadir View Angle was relatively perfect.

[Dynamic changes of urban architecture landscape based on Barista: a case study in Tiexi District of Shenyang City].

In this paper, three-dimensional building information was extracted from high resolution satellite image based on Barista software. Combined with ArcGIS software, the dynamic changes of the building landscape in Tiexi District of Shenyang City during urban renewal process were analyzed from the conversion contribution rate, building density, average building height, and built-up area rate. It was found that during this urban renewal process, four dominant landscape types (vacant lot, residential building, industrial building, and road) were the main parts of the landscape changes. The areas of vacant lot, residential building, commercial building, and road increased, while that of industrial building decreased. The building density decreased, while the average building height increased. There was an obvious regional variation in building landscape. The building density in industrial district was higher than that in residential district, while the average building height was in adverse. The further from the city center, the lower the building density and building average height.