Insights into the hydrogen evolution reaction in vanadium redox flow batteries:A synchrotron radiation based X-ray imaging study

The parasitic hydrogen evolution reaction(HER)in the negative half-cell of vanadium redox flow batteries(VRFBs)causes severe efficiency losses.Thus,a deeper understanding of this process and the accompanying bubble formation is crucial.This benchmarking study locally analyzes the bubble distribution in thick,porous electrodes for the first time using deep learning-based image segmentation of synchrotron X-ray micro-tomograms.Each large three-dimensional data set was processed precisely in less than one minute while minimizing human errors and pointing out areas of increased HER activity in VRFBs.The study systematically varies the electrode potential and material,concluding that more negative electrode potentials of-200 m V vs.reversible hydrogen electrode(RHE)and lower cause more substantial bubble formation,resulting in bubble fractions of around 15%–20%in carbon felt electrodes.Contrarily,the bubble fractions stay only around 2%in an electrode combining carbon felt and carbon paper.The detected areas with high HER activity,such as the border subregion with more than 30%bubble fraction in carbon felt electrodes,the cutting edges,and preferential spots in the electrode bulk,are potential-independent and suggest that larger electrodes with a higher bulk-to-border ratio might reduce HER-related performance losses.The described combination of electrochemical measurements,local X-ray microtomography,AI-based segmentation,and 3D morphometric analysis is a powerful and novel approach for local bubble analysis in three-dimensional porous electrodes,providing an essential toolkit for a broad community working on bubble-generating electrochemical systems.

Therapeutic potential of lysosomal cathepsins for neurodegenerative diseases

Lysosomes are ubiquitous and dynamic organelles with a central role in degradation and recycling of damaged cell components and misfolded proteins,otherwise known as autophagy.Autophagy plays a fundamental role in the process of correcting cell homeostasis and cellular survival.Unsurprisingly,this process is essential in the central nervous system,as neurons are not able to easily eliminate altered proteins given their post-mitotic state.

Role of the adipocyte immune brain axis in Parkinson's disease:friend or foe?

The classical role of adipocytokines is a negative feedback mechanism,providing information about bodily energy reserves to the brain,and thus controlling satiety and food intake (Campfield et al.,1995).Adipose tissue forms the largest endocrine organ of the body.After the initial description of leptin and its receptor,LEPR/OBR,with its main active isoform OBRb,there was an initial hope for a drugable pathway to counteract the increasing burden of overweight/adiposity,metabolic syndrome,and related disorders (Figure1).

A review on glass welding by ultra-short laser pulses

Glass welding by ultra-short pulsed(USP)lasers is a piece of technology that offers high strength joints with hermetic sealing.The joints are typically formed in glass that is transparent to the laser by exploiting nonlinear absorption effects that occur under extreme conditions.Though the temperature reached during the process is on the order of a few 1000°C,the heat affected zone(HAZ)is confined to only tens of micrometers.It is this controlled confinement of the HAZ during the joining process that makes this technology so appealing to a multitude of applications because it allows the foregoing of a subsequent tempering step that is typically essential in other glass joining techniques,thus making it possible to effectively join highly heat sensitive components.In this work,we give an overview on the process,development and applications of glass welding by USP lasers.

Coordination of Schwann cell myelination and node formation at the transcriptional level

Formation of the node of Ranvier as a highly coordinated event:Saltatory conduction ensures that information in the vertebrate nervous system is rapidly transmitted over large distances and efficiently processed in complex networks.It requires the insulation of axonal segments by myelin and the formation of highly structured nodes of Ranvier that are interspersed at regular intervals between successive myelin sheaths and regenerate the action potential as it propagates along the nerve(Rasband and Peles,2021).

The role of lysosomes in alpha-synucleinopathies: a focus on glial cells

Lysosomes are the major degradative compartments within eukaryotic cells.Besides their role in the degradation and recycling of intra-and extracellular molecules,they further mediate important biological processes,such as immune signaling and perpetuation of nutrientand energy homeostasis.

Sox9 in the developing central nervous system:a jack of all trades?

Sox9–gliogenesis and beyond:Neurons and glial cells are the major neuroectodermal cell types of the vertebrate central nervous system(CNS).Their generation from common progenitor cells takes place mostly during embryonic and early postnatal development.After closure of the neural tube,neural epithelial progenitor cells(NEPs)establish the ventricular zone(VZ).By asymmetrical cell division,NEPs first give rise to neuronal precursor cells(NPs)that then differentiate into various types of neurons.Later,NEPs predominantly produce glial precursor cells that become either astroglia or oligodendroglia.

Deciphering the Origins of P1-Induced Power Losses in Cu(In_(x),Ga_(1–x))Se2(CIGS)Modules Through Hyperspectral Luminescence

In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.

3D particle tracking velocimetry for the determination of temporally resolved particle trajectories within laser powder bed fusion of metals

Within this work,we present a system for the measurement of the three-dimensional(3D)trajectories of spatters and entrained particles during laser powder bed fusion(L-PBF)of metals.It is comprised of two ultrahigh-speed cameras and a reconstruction task specific processing reconstruction algorithm.The system enables an automated determination of 3D measures from the trajectories of a large number of tracked particles.Ambiguity evolving from an underdetermined geometrical situation induced by a two-camera setup is resolved within the tracking using a priori knowledge of L-PBF of metals.All processing steps were optimized to run on a graphics processing unit to allow the processing of large amounts of data within an appropriate time frame.The overall approach was validated by a comparison of the measurement results to synthetic images with a known 3D ground truth.

B-cell and antibody responses to SARS-CoV-2:infection,vaccination,and hybrid immunity

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

Linking leaf elemental traits to biomass across forest biomes in the Himalayas

Plants require a number of essential elements in different proportions for ensuring their growth and development.The elemental concentrations in leaves reflect the functions and adaptations of plants under specific environmental conditions.However,less is known about how the spectrum of leaf elements associated with resource acquisition,photosynthesis and growth regulates forest biomass along broad elevational gradients.We examined the influence of leaf element distribution and diversity on forest biomass by analyzing ten elements(C,N,P,K,Ca,Mg,Zn,Fe,Cu,and Mn)in tree communities situated every 100 meters along an extensive elevation gradient,ranging from the tropical forest(80 meters above sea level)to the alpine treeline(4200 meters above sea level)in the Kangchenjunga Landscape in eastern Nepal Himalayas.We calculated communityweighted averages(reflecting dominant traits governing biomass,i.e.,mass-ratio effect)and functional divergence(reflecting increased trait variety,i.e.,complementarity effect)for leaf elements in a total of 1,859 trees representing 116 species.An increasing mass-ratio effect and decreasing complementarity in leaf elements enhance forest biomass accumulation.A combination of elements together with elevation explains biomass(52.2%of the variance)better than individual elemental trait diversity(0.05%to 21%of the variance).Elevation modulates trait diversity among plant species in biomass accumulation.Complementarity promotes biomass at lower elevations,but reduces biomass at higher elevations,demonstrating an interaction between elevation and complementarity.The interaction between elevation and mass-ratio effect produces heterogeneous effects on biomass along the elevation gradient.Our research indicates that biomass accumulation can be disproportionately affected by elevation due to interactions among trait diversities across vegetation zones.While higher trait variation enhances the adaptation of species to environmental changes,it reduces biomass accumulation,especially at higher elevations.

碳纳米管/氮化硼混杂填料对尼龙6导热性能的影响及其机理

利用熔融共混工艺,首先制备了尼龙6/氮化硼(PA6/BN)复合材料。根据复合材料的热导率确定BN添加量后,在PA6/BN体系中添加碳纳米管(CNTs)并引入相容剂以改善填料与基体的界面相容性,通过测定材料的热导率,并借助差示扫描量热分析、动态力学热分析、扫描电镜等手段,探讨CNTs/BN混杂填料对于PA6材料性能的影响,在此基础上建立了相应的三维导热模型来解释体系的导热机理。结果表明,2%CNTs和20.83%BN混杂可显著改善复合材料的导热性能,热导率达0.76 W/(m·K),为纯PA6的2.45倍,同时保持较好的绝缘性;复合材料的动态力学分析结果与扫描电镜图及所搭建导热模型吻合较好。该PA6基导热材料有望应用于LED等电子电气的外壳材料。

The organization and function of the Golgi apparatus in dendrite development and neurological disorders

Dendrites are specialized neuronal compartments that sense, integrate and transfer information in the neural network. Their development is tightly controlled and abnormal dendrite morphogenesis is strongly linked to neurological disorders. While dendritic morphology ranges from relatively simple to extremely complex for a specified neuron, either requires a functional secretory pathway to continually replenish proteins and lipids to meet dendritic growth demands. The Golgi apparatus occupies the center of the secretory pathway and is regulating posttranslational modifications, sorting, transport, and signal transduction, as well as acting as a non-centrosomal microtubule organization center. The neuronal Golgi apparatus shares common features with Golgi in other eukaryotic cell types but also forms distinct structures known as Golgi outposts that specifically localize in dendrites. However, the organization and function of Golgi in dendrite development and its impact on neurological disorders is just emerging and so far lacks a systematic summary. We describe the organization of the Golgi apparatus in neurons, review the current understanding of Golgi function in dendritic morphogenesis, and discuss the current challenges and future directions.

Tumor microenvironment-dependent epigenetic imprinting in the vasculature predicts colon cancer outcome

Dear Editor,Tumor microenvironment(TME)-dependent stromal cell plasticity governs tumor development and therapy response.Tumor endothelial cells(TECs)are a major cellular component in this context[1].In colorectal carcinoma(CRC),the stromal cell-dependent impact of the TME is illustrated by an improved survival depending on an interferon(IFN)-γ-dominated Th1-like TME associated with high T-cell density[2]and suppressed angiogenesis[3,4].Cellular transcriptional memory is reported in cell lines after repeated exposure to IFN-γin vitro[5],suggesting that a Th1-like TME may also exert stable imprinting effects in vivo.Here,we investigated whether TME-dependent transcriptional imprinting in TECs from CRC patients can be exploited to retrieve clinically relevant signatures predicting outcomes.

Dissolution of WO_(3) modified with IrO_(x) overlayers during photoelectrochemical water splitting

WO_(3),an abundant transition metal semiconductor,is one of the most discussed materials to be used as a photoanode in photoelectrochemical water-splitting devices.The photoelectrochemical properties,such as photoactivity and selectivity of WO_(3) in different electrolytes,are already well understood.However,the understanding of stability,one of the most important properties for utilization in a commercial device,is still in the early stages.In this work,a photoelectrochemical scanning flow cell coupled to an inductively coupled plasma mass spectrometer is applied to determine the influence of co-catalyst overlayers on photoanode stability.Spray-coatedWO_(3) photoanodes are used as a model system.Iridium is applied to the electrodes by atomic layer deposition in controlled layer thickness,as determined by ellipsometry and x-ray photoelectron spectroscopy.Photoactivity of the iridium-modified WO_(3) photoanodes decreases with increasing iridium layer thickness.Partial blocking of the WO_(3) surface by iridium is proposed as the main cause of the decreased photoelectrochemical performance.On the other hand,the stability of WO_(3) is notably increased even in the presence of the thinnest investigated iridium overlayer.Based on our findings,we provide a set of strategies to synthesize nanocomposite photoelectrodes simultaneously possessing high photoelectrochemical activity and photostability.

Single-pulse real-time billion-frames-per-second planar imaging of ultrafast nanoparticle-laser dynamics and temperature in flames

Unburnt hydrocarbon flames produce soot,which is the second biggest contributor to global warming and harmful to human health.The state-of-the-art high-speed imaging techniques,developed to study non-repeatable turbulent flames,are limited to million-frames-per-second imaging rates,falling short in capturing the dynamics of critical species.Unfortunately,these techniques do not provide a complete picture of flame-laser interactions,important for understanding soot formation.Furthermore,thermal effects induced by multiple consecutive pulses modify the optical properties of soot nanoparticles,thus making single-pulse imaging essential.Here,we report single-shot laser-sheet compressed ultrafast photography(LS-CUP)for billion-frames-per-second planar imaging of flame-laser dynamics.We observed laser-induced incandescence,elastic light scattering,and fluorescence of soot precursors-polycyclic aromatic hydrocarbons(PAHs)in real-time using a single nanosecond laser pulse.The spatiotemporal maps of the PAHs emission,soot temperature,primary nanoparticle size,soot aggregate size,and the number of monomers,present strong experimental evidence in support of the theory and modeling of soot inception and growth mechanism in flames.LS-CUP represents a generic and indispensable tool that combines a portfolio of ultrafast combustion diagnostic techniques,covering the entire lifecycle of soot nanoparticles,for probing extremely short-lived(picoseconds to nanoseconds)species in the spatiotemporal domain in non-repeatable turbulent environments.Finally,LS-CUP’s unparalleled capability of ultrafast wide-field temperature imaging in real-time is envisioned to unravel mysteries in modern physics such as hot plasma, sonoluminescence, and nuclear fusion.

Retinal microvascular signs and recurrent vascular events in patients with TIA or minor stroke

Background and purpose Retinal pathologies are an independent risk factor for ischaemic stroke,but research on the predictive value of retinal abnormalities for recurrent vascular events in patients with prior stroke is inconclusive.We investigated the association of retinal pathologies with subsequent vascular events.Methods In a substudy of the Intensified secondary prevention intending a reduction of recurrent events in TIA and minor stroke patients(INSPiRE-TMS)trial,we enrolled patients with recent transient ischaemic attack(TIA)or minor stroke with at least one modifiable risk factor.Primary outcome was the composite of subsequent vascular events.Retinal photographs were taken at baseline and categorised into three different fundus groups by a telemedically linked ophthalmologist.Results 722 patients participated in the current study and 109 major vascular events occurred.After multivariable adjustments,we did not find a significant association between fundus categories and risk for subsequent vascular events(HRs for moderate vascular retinopathy and vascular retinopathy with vessel rarefaction in comparison to no vascular retinopathy 1.03(95%CI 0.64 to 1.67),p=0.905 and 1.17(95%CI 0.62 to 2.20),p=0.626).In a selective post hoc analysis in patients with diabetes mellitus and hypertension,patients with vascular retinopathy with vessel rarefaction had a higher risk for recurrent stroke(HR 24.14(95%CI 2.74 to 212.50),p=0.004).Conclusions Retinal changes did not predict major subsequent vascular events in patients with recent TIA or minor stroke.Further studies are needed to examine the utility of fundus photography in assessing the risk of stroke recurrence in patients with diabetes mellitus and hypertension.

Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases

Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models,indicating that NETs are potential therapeutic targets.Here,we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody(tACPA)has broad therapeutic potential.Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology,including inflammatory arthritis(IA),pulmonary fibrosis,inflammatory bowel disease and sepsis.We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention,whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects.Because citrullinated histones are generated during NET release,we investigated the ability of tACPA to inhibit NET formation.tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli.Moreover,tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo,which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA.To our knowledge,we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases,as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.

Artificial intelligence in cancer target identification and drug discovery

Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between components of cell systems underlying human diseases such as cancer.Here,we review and discuss how to employ artificial intelligence approaches to identify novel anticancer targets and discover drugs.First,we describe the scope of artificial intelligence biology analysis for novel anticancer target investigations.Second,we review and discuss the basic principles and theory of commonly used network-based and machine learning-based artificial intelligence algorithms.Finally,we showcase the applications of artificial intelligence approaches in cancer target identification and drug discovery.Taken together,the artificial intelligence models have provided us with a quantitative framework to study the relationship between network characteristics and cancer,thereby leading to the identification of potential anticancer targets and the discovery of novel drug candidates.