Influence of O-O formation pathways and charge transfer mediator on lipid bilayer membrane-like photoanodes for water oxidation

Inspired by the function of crucial components in photosystemⅡ(PSⅡ),electrochemical and dyesensitized photoelectrochemical(DSPEC)water oxidation devices were constructed by the selfassembly of well-designed amphipathic Ru(bda)-based catalysts(bda=2,2'-bipyrdine-6,6'-dicarbonoxyl acid)and aliphatic chain decorated electrode surfaces,forming lipid bilayer membrane(LBM)-like structures.The Ru(bda)catalysts on electrode-supported LBM films demonstrated remarkable water oxidation performance with different O-O formation mechanisms.However,compared to the slow charge transfer process,the O-O formation pathways did not determine the PEC water oxidation efficiency of the dyesensitized photoanodes,and the different reaction rates for similar catalysts with different catalytic paths did not determine the PEC performance of the DSPECs.Instead,charge transfer plays a decisive role in the PEC water oxidation rate.When an indolo[3,2-b]carbazole derivative was introduced between the Ru(bda)catalysts and aliphatic chain-modified photosensitizer in LBM films,serving as a charge transfer mediator for the tyrosine-histidine pair in PSⅡ,the PEC water oxidation performance of the corresponding photoanodes was dramatically enhanced.

An allelic variation in the promoter of the LRR-RLK gene,qSS6.1,is associated with melon seed size

Seed size is an important agronomic trait in melons that directly affects seed germination and subsequent seedling growth.However,the genetic mechanism underlying seed size in melon remains unclear.In the present study,we employed Bulked-Segregant Analysis sequencing(BSA-seq)to identify a candidate region(~1.35 Mb)on chromosome 6 that corresponds to seed size.This interval was confirmed by QTL mapping of three seed size-related traits from an F2 population across three environments.This mapping region represented nine QTLs that shared an overlapping region on chromosome 6,collectively referred to as qSS6.1.New InDel markers were developed in the qSS6.1 region,narrowing it down to a 68.35 kb interval that contains eight annotated genes.Sequence variation analysis of the eight genes identified a SNP with a C to T transition mutation in the promoter region of MELO3C014002,a leucine-rich repeat receptor-like kinase(LRR-RLK)gene.This mutation affected the promoter activity of the MELO3C014002 gene and was successfully used to differentiate the large-seeded accessions(C-allele)from the small-seeded accessions(T-allele).qRT-PCR revealed differential expression of MELO3C014002 between the two parental lines.Its predicted protein has typical LRR-RLK family domains,and phylogenetic analyses reveled its similarity with the homologs in several plant species.Altogether,these findings suggest MELO3C014002 as the most likely candidate gene involved in melon seed size regulation.Our results will be helpful for better understanding the genetic mechanism regulating seed size in melons and for genetically improving this important trait through molecular breeding pathways.

Harnessing male germline epigenomics for the genetic improvement in cattle

Sperm is essential for successful artificial insemination in dairy cattle,and its quality can be influenced by both epi-genetic modification and epigenetic inheritance.The bovine germline differentiation is characterized by epigenetic reprogramming,while intergenerational and transgenerational epigenetic inheritance can influence the offspring’s development through the transmission of epigenetic features to the offspring via the germline.Therefore,the selec-tion of bulls with superior sperm quality for the production and fertility traits requires a better understanding of the epigenetic mechanism and more accurate identifications of epigenetic biomarkers.We have comprehensively reviewed the current progress in the studies of bovine sperm epigenome in terms of both resources and biological discovery in order to provide perspectives on how to harness this valuable information for genetic improvement in the cattle breeding industry.

Granulation process analysis technologies and potential applications in traditional Chinese medicine

Pharmaceutical production is changing from batch production to continuous production,during which granulation is one of the most important unit operations.The quality of mass-produced products is traditionally guaranteed by conducting off-line testing,which cannot meet the demand of continuous production for real-time monitoring of critical process parameters and critical quality attributes(CQAs)of the pharmaceutical granulation technology.Since the U.S.Food and Drug Administration proposed process analytical technology(PAT)in 2004,many PAT tools have been developed to monitor the granulation process and provide information regarding the granulation operation conditions and endpoint determination.In this article,we review the recent research and application of two PAT modes in the granulation process,namely,single CQA and multi-CQA PAT,with the aim to provide references for comprehensively improving the technological level of the pharmaceutical granulation process.Furthermore,the potential applications in traditional Chinese Medicine are discussed.

Ameliorative effects of monascin from red mold rice on alcoholic liver injury and intestinal microbiota dysbiosis in mice

Monascus-fermented red mold rice(RMR)has excellent physiological efficacy on lipid metabolism and liver function.This study investigated the ameliorative effects of monascin(MS)from RMR on alcoholic liver injury(ALI)in mice,and further illustrated its mechanism of action.Results indicated that dietary MS intervention obviously ameliorated lipid metabolism and liver function in mice with over-drinking.In addition,MS intervention alleviated alcohol-induced oxidative stress in the liver by reducing the hepatic activities of lactate dehydrogenase(LDH)and hepatic levels of malondialdehyde(MDA),increasing the hepatic activities of catalase(CAT),superoxide dismutase(SOD),alcohol dehydrogenase(ADH)and hepatic levels of glutathione(GSH).16S rRNA amplicon sequencing showed that excessive drinking had a significant effect on the composition of the gut microbiota in mice.MS intervention was beneficial to ameliorate intestinal microbiota dysbiosis by elevating the proportion of Lactobacillus,Lachnospiraceae_UCG-006,Coriobacteriales,etc.,but decreasing the proportion of Staphylococcus,Muribaculaceae,Desulfovibrionaceae,etc.Additionally,correlation analysis indicated that the key intestinal bacterial taxa intervened by MS were closely related to some biochemical indicators of lipid metabolism,liver function and oxidative stress.Moreover,liver metabolomics analysis revealed that dietary MS supplementation significantly regulated the levels of liver metabolites involved in taurine and hypotaurine metabolism,riboflavin metabolism,and purine metabolism,etc.Furthermore,MS intervention regulated gene transcription and protein expression associated with lipid metabolism and oxidative stress in the liver.In short,these findings suggest that MS mitigates alcohol-induced hepatic oxidative damage through modulating the intestinal microbiome and liver metabolic pathway,and thus can be served as a functional component to prevent alcoholic liver disease.

Spectral purification improves monitoring accuracy of the comprehensive growth evaluation index for film-mulched winter wheat

In order to further improve the utility of unmanned aerial vehicle(UAV)remote-sensing for quickly and accurately monitoring the growth of winter wheat under film mulching, this study examined the treatments of ridge mulching,ridge–furrow full mulching, and flat cropping full mulching in winter wheat.Based on the fuzzy comprehensive evaluation (FCE) method, four agronomic parameters (leaf area index, above-ground biomass, plant height, and leaf chlorophyll content) were used to calculate the comprehensive growth evaluation index (CGEI) of the winter wheat, and 14 visible and near-infrared spectral indices were calculated using spectral purification technology to process the remote-sensing image data of winter wheat obtained by multispectral UAV.Four machine learning algorithms, partial least squares, support vector machines, random forests, and artificial neural network networks(ANN), were used to build the winter wheat growth monitoring model under film mulching, and accuracy evaluation and mapping of the spatial and temporal distribution of winter wheat growth status were carried out.The results showed that the CGEI of winter wheat under film mulching constructed using the FCE method could objectively and comprehensively evaluate the crop growth status.The accuracy of remote-sensing inversion of the CGEI based on the ANN model was higher than for the individual agronomic parameters, with a coefficient of determination of 0.75,a root mean square error of 8.40, and a mean absolute value error of 6.53.Spectral purification could eliminate the interference of background effects caused by mulching and soil, effectively improving the accuracy of the remotesensing inversion of winter wheat under film mulching, with the best inversion effect achieved on the ridge–furrow full mulching area after spectral purification.The results of this study provide a theoretical reference for the use of UAV remote-sensing to monitor the growth status of winter wheat with film mulching.

Disturbances rejection optimization based on improved two-degree-of-freedom LADRC for permanent magnet synchronous motor systems

Permanent magnet synchronous motor(PMSM)speed control systems with conventional linear active disturbance rejection control(CLADRC)strategy encounter issues regarding the coupling between dynamic response and disturbance suppression and have poor performance in suppressing complex nonlinear disturbances.In order to address these issues,this paper proposes an improved two-degree-of-freedom LADRC(TDOF-LADRC)strategy,which can enhance the disturbance rejection performance of the system while decoupling entirely the system's dynamic and anti-disturbance performance to boost the system robustness and simplify controller parameter tuning.PMSM models that consider total disturbances are developed to design the TDOF-LADRC speed controller accurately.Moreover,to evaluate the control performance of the TDOF-LADRC strategy,its stability is proven,and the influence of each controller parameter on the system control performance is analyzed.Based on it,a comparison is made between the disturbance observation ability and anti-disturbance performance of TDOF-LADRC and CLADRC to prove the superiority of TDOF-LADRC in rejecting disturbances.Finally,experiments are performed on a 750 W PMSM experimental platform,and the results demonstrate that the proposed TDOF-LADRC exhibits the properties of two degrees of freedom and improves the disturbance rejection performance of the PMSM system.

Microbiomics and metabolomics insights into the microbial regulation on the formation of flavor components in the traditional fermentation process of Chinese Hongqu aged vinegar

This study aimed to investigate microbial succession and metabolic dynamics during the traditional fermentation of Hongqu aged vinegar,and explore the core functional microbes closely related to the formation of flavor components.Microbiome analysis demonstrated that Lactobacillus,Acetobacter,Bacillus,Enterobacter,Lactococcus,Leuconostoc and Weissella were the predominant bacterial genera,while Aspergillus piperis,Aspergillus oryzae,Monascus purpureus,Candida athensensis,C.xylopsoci,Penicillium ochrosalmoneum and Simplicillium aogashimaense were the predominant fungal species.Correlation analysis revealed that Acetobacter was positively correlated with the production of tetramethylpyrazine,acetoin and acetic acid,Lactococcus showed positive correlation with the production of 2-nonanone,2-heptanone,ethyl caprylate,ethyl caprate,1-hexanol,1-octanol and 1-octen-3-ol,C.xylopsoci and C.rugosa were positively associated with the production of diethyl malonate,2,3-butanediyl diacetate,acetoin,benzaldehyde and tetramethylpyrazine.Correspondingly,non-volatile metabolites were also detected through ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.A variety of amino acids and functional dipeptides were identified during the traditional brewing of Hongqu aged vinegar.Correlation analysis revealed that Lactobacillus was significantly associated with DL-lactate,indolelactic acid,D-(+)-3-phenyllactic acid,pimelic acid,pregabalin and 3-aminobutanoic acid.This study is useful for understanding flavor formation mechanism and developing effective strategies for the suitable strains selection to improve the flavor quality of Hongqu aged vinegar.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases

The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

Programmable robotized‘transfer-and-jet’printing for large,3D curved electronics on complex surfaces

Large,3D curved electronics are a trend of the microelectronic industry due to their unique ability to conformally coexist with complex surfaces while retaining the electronic functions of 2D planar integrated circuit technologies.However,these curved electronics present great challenges to the fabrication processes.Here,we propose a reconfigurable,mask-free,conformal fabrication strategy with a robot-like system,called robotized‘transfer-and-jet’printing,to assemble diverse electronic devices on complex surfaces.This novel method is a ground-breaking advance with the unique capability to integrate rigid chips,flexible electronics,and conformal circuits on complex surfaces.Critically,each process,including transfer printing,inkjet printing,and plasma treating,are mask-free,digitalized,and programmable.The robotization techniques,including measurement,surface reconstruction and localization,and path programming,break through the fundamental constraints of 2D planar microfabrication in the context of geometric shape and size.The transfer printing begins with the laser lift-off of rigid chips or flexible electronics from donor substrates,which are then transferred onto a curved surface via a dexterous robotic palm.Then the robotic electrohydrodynamic printing directly writes submicrometer structures on the curved surface.Their permutation and combination allow versatile conformal microfabrication.Finally,robotized hybrid printing is utilized to successfully fabricate a conformal heater and antenna on a spherical surface and a flexible smart sensing skin on a winged model,where the curved circuit,flexible capacitive and piezoelectric sensor arrays,and rigid digital–analog conversion chips are assembled.Robotized hybrid printing is an innovative printing technology,enabling additive,noncontact and digital microfabrication for 3D curved electronics.

Interfacial electron rearrangement: Ni activated Ni(OH)_(2) for efficient hydrogen evolution

The rational modulation of electronic structure is highly desirable to develop an efficient alkaline hydrogen evolution reaction(HER)catalyst for renewable energy applications.Metal hydroxide such as Ni(OH)_(2) has been proven useful for promoting alkaline HER,but the performance remains unsatisfactory.Herein,the electronic structure of Ni(OH)_(2) is modulated by the interfacial electron rearrangement between Ni-Ni(OH)_(2) heterojunction.Combined experiments with DFT simulations,the electrons of Ni species accumulate to the interfacial Ni-Ni(OH)_(2) sites,which modifies the d band center for promoting conversion of hydrogen intermediates and narrows the energy gap for boosting charge transfer in the HER process.Thus,the integrated electrode exhibits an efficient HER performance to drive10 mA cm^(-2) at the overpotential of 72 mV with a low Tafel slope of 43 mV dec^(-1).Our work renders a valuable insight for understanding and rationally designing efficient catalysts in alkaline HER.

Understanding the changing mechanism of arc characteristics in ultrasound-magnetic field coaxial hybrid gas tungsten arc welding

Ultrasound-magnetic field coaxial hybrid Gas Tungsten Arc Welding(U-M-GTAW)is proposed as a means to control arc characteristics.The arc characteristics and the mechanism to change them,in an ultrasound-magnetic field coaxial hybrid GTAW,were studied by both experimental and theoretical analyses.The results showed that a periodic rotation and compression of the arc shape were obtained in U-M-GTAW and the arc energy was also enhanced.The most obvious compression of the arc shape in U-M-GTAW was obtained,compared with GTAW,M-GTAW and U-GTAW.At the same time,a periodic rotation of the arc was observed in U-M-GTAW.The geometric parameters of the arc shape in U-M-GTAW are reduced more than double compared with traditional GTAW.The arc voltage in the hybrid GTAW was increased,especially in the U-M-GTAW.The electromagnetic force and acoustic radiation force were the main factors for the change of arc characteristics in the U-M-GTAW.

Wavelet-based classification and influence matrix analysis method for the fast discrimination of Chinese herbal medicines according to the geographical origins with near infrared spectroscopy

A discriminant analysis technique using wavelet transformation(WT)and influence matrixanalysis(CAIMAN)method is proposed for the near infrared(NIR)spectroscopy classifi-cation.In the proposed methodology,NIR spectra are decomposed by WT for data com-pression and a forward feature selection is further employed to extract the relevant informationfrom the wavelet coefficients,reducing both classification errors and model complexity.Adiscriminant-CAIMAN(D-CAIMAN)method is utilized to build the classification model inwavelet domain on the basis of reduced wavelet coefficients of spectral variables.NIR spectradata set of 265 salviae miltiorrhizae radia samples from 9 different geographical origins is usedas an example to test the classification performance of the algorithm.For a comparison,k-nearest neighbor(KNN),linear discriminant analysis(LDA)and quadratic discriminant analysis(QDA)methods are also employed.D-CAIMAN with wavelet-based feature selection(WD-CAIMAN)method shows the best performance,achieving the total classification rate of ioo%in both cross-validation set and prediction set.It is worth noting that the WD-CAIMANclassifier also shows improved sensitivity,selectivity and model interpretability in thecla.ssifications.

Polybrominated Diphenyl Ethers in Surface Sediment from Songhua River Basin,Northeast of China

Sixty sediment samples were collected from the main Songhua River in three years. Twelve polybrominated diphenyl ether( PBDE) congeners( BDE17,28,47,66,99,100,153,154,138,183,and BDE-209) were detected to state the pollution situation. The results showed that the total concentration of total PBDEs ranges from 0. 424 to 23. 0 ng / g dry weight,with the mean of 3. 02 ng / g,and the total PBDEs concentration is at relative low level compared with those worldwide. The congener profile showed that BDE-209 is the dominant congener that accounts for more than 80. 1% of total PBDEs in sediments,followed by BDE-47 and BDE-99. These profiles are consistent with a high consumption of Deca-BDEs for the brominated flame retardant market in China. The results of spatial and seasonal observations indicated that local sources,temperature variation, and hydrologic conditions are significant factors on PBDEs concentrations. Hazard quotients suggested that PBDEs pose no potential risk to benthic organisms in detected area at present.

Alternative Fourier Series Expansions with Accelerated Convergence

The key objective of this paper is to improve the approximation of a sufficiently smooth nonperiodic function defined on a compact interval by proposing alternative forms of Fourier series expansions. Unlike in classical Fourier series, the expansion coefficients herein are explicitly dependent not only on the function itself, but also on its derivatives at the ends of the interval. Each of these series expansions can be made to converge faster at a desired polynomial rate. These results have useful implications to Fourier or harmonic analysis, solutions to differential equations and boundary value problems, data compression, and so on.

Chemical constituents,pharmacological activities and quality evaluation methods of genus Hippocampus:A comprehensive review

The genus Hippocampus is a multi-origin animal species with high medicinal and healthcare values.About 57 species of Hippocampus spread worldwide,of which about 14 species can be used as medicine,showing anti-oxidation,anti-inflammation,anti-depressant,anti-hypertension,anti-prostatic hyperplasia,antivirus,anti-apoptotic,antifatigue,and so on.And those pharmacological effects are mainly related to their active ingredients,including amino acids,abundant proteins(peptides and oligopeptides),fatty acids,nucleosides,steroids,and other small molecular compounds.The main means of authentication of Hippocampus species are morphological identification,microscopic identification,thin layer chromatography method,fingerprint method and genomics method.This review will provide useful insight for exploration,further study and precise medication of Hippocampus in the future.

A hybrid nickel/iron-pyromellitic acid electrocatalyst for oxygen evolution reaction

The migration of protons during the oxygen evolution reaction(OER)is a key factor that affects the performance of OER catalysts.To enhance proton transportation,we designed a catalyst based on nickel/iron-pyromellitic acid(NiFe-PMA)prepared by the electrochemical deposition method.This catalyst exhibited a low overpotential of 188 mV at a current density of 10 mA·cm^(-2),a Tafel slope of 28.2 mV·dec^(-1),and long-term stability for 30 days with a current of 50 mA·cm^(-2).We characterized the NiFe-PMA catalyst using various techniques,including Fourier transform infrared(FTIR)spectroscopy,Raman spectroscopy,X-ray photoelectron spectroscopy(XPS),X-ray absorption spectroscopy(XAS),transmission electron microscopy(TEM),scanning electron microscopy(SEM),and inductively coupled plasma-optical emission spectrometry(ICP-OES).Our results showed that NiFe-PMA contains nickel,iron atoms,and both coordinated and uncoordinated carboxylate groups.Additionally,XPS data confirmed that carboxylate ligands could adjust the outer electronic structure of metal ions,resulting in the high valence state of Ni in NiFe-PMA.The result of XAS indicated that the nickel atoms present in the catalyst might be easier to maintain a higher chemical state.Further investigations using kinetic isotope effects(KIEs)and proton inventory revealed that the uncoordinated carboxylic protons played a crucial role in receiving protons during the OER,which promoted the proton transfer of the rate-determining step of the OER.Our novel electrocatalysts provide a new strategy for designing more active and cost-effective catalysts for the OER.

Characterization of herbal powder blends homogeneity using near-infrared spectroscopy

Homogeneity of powder blend is essential to obtain uniform contents for the tablets and capsules.Near-infrared(NIR)spectroscopy with fiber-optic probe was used as an on-line technique for monitoring the homogeneity of pharmaceutical blend during the blending process instead of the traditional techniques,such as high performance liquid chromatograph(HPLC)method.In this paper NIRS with a SabIR difuse reflectance fiber optic probe was used to monitor the blending process of coptis powder and lactose(excipient)with different contents,and further qualitative methods,like similarity,moving block of standard deviation and mean square were used for calculation purposes with the ollected spectra after the pretreatment of multiplicative signal correction(MSC)and second derivative.Correlation spectrum was used for the wavelength selection.Four different coptis were blended with lactose separately to validate the proposed method,and the blending process of "liu wei di huang"pill was also simulated in bottles to verify this method on multiple herbal blends.The overall results suggest that NIRS is a simple,efective and noninvasive technique can be sucssfuly applied to the determination of homogeneity in the herbal blend.

A TMA-Seq2seq Network for Multi-Factor Time Series Sea Surface Temperature Prediction

Sea surface temperature (SST) is closely related to global climatechange, ocean ecosystem, and ocean disaster. Accurate prediction of SST isan urgent and challenging task. With a vast amount of ocean monitoring dataare continually collected, data-driven methods for SST time-series predictionshow promising results. However, they are limited by neglecting complexinteractions between SST and other ocean environmental factors, such as airtemperature and wind speed. This paper uses multi-factor time series SSTdata to propose a sequence-to-sequence network with two-module attention(TMA-Seq2seq) for long-term time series SST prediction. Specifically, TMASeq2seq is an LSTM-based encoder-decoder architecture facilitated by factorand temporal-attention modules and the input of multi-factor time series. Ittakes six-factor time series as the input, namely air temperature, air pressure,wind speed, wind direction, SST, and SST anomaly (SSTA). A factor attentionmodule is first designed to adaptively learn the effect of different factors onSST, followed by an encoder to extract factor-attention weighted features asfeature representations. And then, a temporal attention module is designedto adaptively select the hidden states of the encoder across all time steps tolearn more robust temporal relationships. The decoder follows the temporalattention module to decode the feature vector concatenated from the weightedfeatures and original input feature. Finally, we use a fully-connect layer tomap the feature into prediction results. With the two attention modules, ourmodel effectively improves the prediction accuracy of SST since it can notonly extract relevant factor features but also boost the long-term dependency.Extensive experiments on the datasets of China Coastal Sites (CCS) demonstrate that our proposed model outperforms other methods, reaching 98.29%in prediction accuracy (PACC) and 0.34 in root mean square error (RMSE).Moreover, SST prediction experiments in China’s East, South, and Yellow Seasite data show that the proposed model has strong robustness and multi-siteapplicability.

Exploring the association between gastrointestinal heat retention syndrome and adult chronic eczema: A caseecontrol study

Objective:To investigate the association between gastrointestinal heat retention syndrome(GHRS)and adult chronic eczema.Methods:This caseecontrol study compared GHRS/GHRS accompanied by damp-heat syndrome(GHRSDHS)and other patient characteristics between subjects with(cases)and without chronic eczema(controls)to identify potential factors associated with this condition.Semi-structured questionnaires were used to collect data via face-to-face interviews.Participants were recruited from Dongzhimen Hospital affiliated with Beijing University of Chinese Medicine.A logistic regression analysis was performed on the collected data,and odds ratios(ORs)were calculated.Results:A total of 168 cases and 172 controls were recruited.Among the cases of adult chronic eczema,there were 79 subjects with GHRS and 68 with GHRS-DHS.Sex(P=.02,OR=0.54,95%confidence interval[CI]:0.32-0.91),GHRS(P=.04,OR=1.90,95%CI:1.02-3.51),GHRS-DHS(P<.001,OR=4.89,95%CI:2.36-10.15),high sweet food consumption(P=.04,OR=2.03,95%CI:1.03-3.97),and mental stress(P=.01,OR=2.37,95%CI:1.26-4.47)were each found to be associated with chronic eczema.Furthermore,GHRS had a weak positive correlation with eczema EASI severity as measured by the eczema area and severity index(EASI)(P=003).Conclusion:GHRS/GHRS-DHS may be associated with adult chronic eczema.In the future,prospective cohort studies with larger samples should be conducted to investigate the cause and effect association between GHRS and adult chronic eczema.