Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency

Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.

Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases

Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.

4天香烟烟雾暴露联合poly(I:C)刺激对小鼠肺部免疫应答及干扰素表达的影响

目的:探讨短期香烟烟雾暴露联合poly(I:C)刺激对小鼠肺部免疫应答及干扰素表达的影响。方法:BALB/c小鼠随机分为4组:对照组、熏烟组、poly(I:C)组和熏烟联合poly(I:C)组。检测支气管肺泡灌洗液(BALF)中总细胞数及细胞分类计数;普通光镜下观察各组细胞形态;荧光定量PCR检测肺组织细胞因子、趋化因子和干扰素及干扰素刺激基因表达。结果:与对照组相比,熏烟联合poly(I:C)组总细胞数计数、巨噬细胞与中性粒细胞计数明显升高(P<0.05),且熏烟联合poly(I:C)组巨噬细胞计数高于poly(I:C)组;与poly(I:C)组比较,熏烟联合poly(I:C)组小鼠气道灌洗液巨噬细胞体积较大,呈圆形或不规则形,细胞质较多空泡;与对照组相比,熏烟联合poly(I:C)组小鼠肺组织中性粒细胞趋化因子CXCL1(P<0.05)、CXCL2(P<0.01)和淋巴细胞趋化因子CCL2(P<0.01)mRNA表达升高,肺组织IL-1β、IL-6、TNF-αmRNA表达明显升高(P<0.01),肺组织IFN-β(P<0.01)、IFN-γ(P<0.05)、MX2(P<0.01)和IP-10(P<0.01)表达显著升高,且与poly(I:C)组小鼠相比,熏烟联合poly(I:C)组小鼠肺组织CXCL2(P<0.05)、TNF-α(P<0.01)和IFN-β(P<0.05)mRNA表达明显升高。结论:熏烟联合poly(I:C)诱导了小鼠肺部炎症反应和干扰素及干扰素刺激基因表达。同时,香烟暴露加剧了poly(I:C)诱导的小鼠肺部急性炎症反应和Ⅰ型干扰素表达。

Stable Cycling of All-Solid-State Lithium Metal Batteries Enabled by Salt Engineering of PEO-Based Polymer Electrolytes

Poly(ethylene oxide)(PEO)-based polymer electrolytes show the prospect in all-solid-state lithium metal batteries;however,they present limitations of low room-temperature ionic conductivity,and interfacial incompatibility with high voltage cathodes.Therefore,a salt engineering of 1,1,2,2,3,3-hexafluoropropane-1,3-disulfonimide lithium salt(LiHFDF)/LiTFSI system was developed in PEO-based electrolyte,demonstrating to effectively regulate Li ion transport and improve the interfacial stability under high voltage.We show,by manipulating the interaction between PEO matrix and TFSI^(-)-HFDF^(-),the optimized solid-state polymer electrolyte achieves maximum Li+conduction of 1.24×10^(-4)S cm^(-1)at 40℃,which is almost 3 times of the baseline.Also,the optimized polymer electrolyte demonstrates outstanding stable cycling in the LiFePO_(4)/Li and LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2)/Li(3.0-4.4 V,200 cycles)based all-solid-state lithium batteries at 40℃.

Flexible and Robust Functionalized Boron Nitride/Poly(p‑Phenylene Benzobisoxazole)Nanocomposite Paper with High Thermal Conductivity and Outstanding Electrical Insulation

With the rapid development of 5G information technology,thermal conductivity/dissipation problems of highly integrated electronic devices and electrical equipment are becoming prominent.In this work,“high-temperature solid-phase&diazonium salt decomposition”method is carried out to prepare benzidine-functionalized boron nitride(m-BN).Subsequently,m-BN/poly(pphenylene benzobisoxazole)nanofiber(PNF)nanocomposite paper with nacremimetic layered structures is prepared via sol–gel film transformation approach.The obtained m-BN/PNF nanocomposite paper with 50 wt%m-BN presents excellent thermal conductivity,incredible electrical insulation,outstanding mechanical properties and thermal stability,due to the construction of extensive hydrogen bonds andπ–πinteractions between m-BN and PNF,and stable nacre-mimetic layered structures.Itsλ∥andλ_(⊥)are 9.68 and 0.84 W m^(-1)K^(-1),and the volume resistivity and breakdown strength are as high as 2.3×10^(15)Ωcm and 324.2 kV mm^(-1),respectively.Besides,it also presents extremely high tensile strength of 193.6 MPa and thermal decomposition temperature of 640°C,showing a broad application prospect in high-end thermal management fields such as electronic devices and electrical equipment.

Research progress of sphingosine 1-phosphate and its signal transduction in central nervous system diseases

Sphingosine 1-phosphate(S1P),as a sphingolipid metabolite,has become a key substance in regulating various physiological processes,involved in differentiation,proliferation,migration,morphogenesis,cytoskeleton formation,adhesion,apoptosis,etc.process.Sphingosine 1-phosphate can not only activate the S1P-S1PR signaling pathway by binding to the corresponding receptors on the cell membrane,but also play a role in the cell.In recent years,studies have found that there is a certain relationship between its level changes and the occurrence and development of central nervous system diseases.This article reviews the latest knowledge of sphingosine-1-phosphate in the occurrence and treatment of nervous system diseases,and further clarifies its molecular mechanism in the treatment and development of central nervous system diseases.

Innovative approach to boosting the chemical stability of AZ31 magnesium alloy using polymer-modified hybrid metal oxides

Meeting the demands of complex and advanced applications requires the development of high-performance hybrid materials with unique properties.However,the integration of polymeric frameworks with MgO/WO_(3) composite layers faces challenges due to the lack of understanding of the formation mechanism and the challenge of determining the impact of self-assembled architecture on anticorrosive properties.In this study,we aimed to enhance the corrosion resistance of the MgO layer produced by plasma electrolysis(PE)of AZ31 Mg alloy by incorporating WO_(3) with partially phosphorated poly(vinyl alcohol)(PPVA).Two types of porous MgO layers were produced using the PE process with an alkaline-phosphate electrolyte,one with and one without WO_(3) nanoparticles,which were subsequently immersed in an aqueous solution of PPVA.Incorporating PPVA into the WO_(3)-MgO layer resulted in hybrids being deposited in a fragmented manner,creating a“laminar reef-like structure”that sealed most of the structural defects in the layer.The PPVA-sealed WO_(3)-based coating exhibited superior corrosion resistance compared to the other samples.Computational analyses were employed to explore the mechanism underlying the formation of PPVA/WO_(3) hybrids on the MgO layer.These findings suggest that PPVA-WO_(3)-MgO hybrid coatings can potentially improve corrosion resistance in various fields.

Tuning the cross-linked structure of basic poly(ionic liquid)to develop an efficient catalyst for the conversion of vinyl carbonate to dimethyl carbonate

Dimethyl carbonate(DMC)is a crucial chemical raw material widely used in organic synthesis,lithiumion battery electrolytes,and various other fields.The current primary industrial process employs a conventional sodium methoxide basic catalyst to produce DMC through the transesterification reaction between vinyl carbonate and methanol.However,the utilization of this catalyst presents several challenges during the process,including equipment corrosion,the generation of solid waste,susceptibility to deactivation,and complexities in separation and recovery.To address these limitations,a series of alkaline poly(ionic liquid)s,i.e.[DVBPIL][PHO],[DVCPIL][PHO],and[TBVPIL][PHO],with different crosslinking degrees and structures,were synthesized through the construction of cross-linked polymeric monomers and functionalization.These poly(ionic liquid)s exhibit cross-linked structures and controllable cationic and anionic characteristics.Research was conducted to investigate the effect of the cross-linking degree and structure on the catalytic performance of transesterification in synthesizing DMC.It was discovered that the appropriate cross-linking degree and structure of the[DVCPIL][PHO]catalyst resulted in a DMC yield of up to 80.6%.Furthermore,this catalyst material exhibited good stability,maintaining its catalytic activity after repeated use five times without significant changes.The results of this study demonstrate the potential for using alkaline poly(ionic liquid)s as a highly efficient and sustainable alternative to traditional catalysts for the transesterification synthesis of DMC.

Dual-salt poly(tetrahydrofuran) electrolyte enables quasi-solid-state lithium metal batteries to operate at -30 ℃

The stable operation of solid-state lithium metal batteries at low temperatures is plagued by severe restrictions from inferior electrolyte-electrode interface compatibility and increased energy barrier for Li^(+)migration.Herein,we prepare a dual-salt poly(tetrahydrofuran)-based electrolyte consisting of lithium hexafluorophosphate and lithium difluoro(oxalato)borate(LiDFOB).The Li-salt anions(DFOB−)not only accelerate the ring-opening polymerization of tetrahydrofuran,but also promote the formation of highly ion-conductive and sustainable interphases on Li metal anodes without sacrificing the Li^(+)conductivity of electrolytes,which is favorable for Li^(+)transport kinetics at low temperatures.Applications of this polymer electrolyte in Li||LiFePO_(4)cells show 82.3%capacity retention over 1000 cycles at 30℃and endow stable discharge capacity at−30℃.Remarkably,the Li||LiFePO4 cells retain 52%of their room-temperature capacity at−20℃and 0.1 C.This rational design of dual-salt polymer-based electrolytes may provide a new perspective for the stable operation of quasi-solid-state batteries at low temperatures.

Efficient and selective upcycling of waste polylactic acid into acetate using nickel selenide

The conversion of waste polylactic acid(PLA)plastics into high-value-added chemicals through electrochemical methods is a promising and sustainable approach.However,developing efficient and highly selective catalysts for lactic acid oxidation reaction(LAOR)and understanding the reaction process are challenging.Here,we report the electrooxidation of waste PLA to acetate at a high current density of 100 mA cm-2 with high Faraday efficiency(~95%)and excellent stability(>100 h)over a nickel selenide nanosheet catalyst.In addition,a total Faraday efficiency of up to 190%was achieved for carboxylic acids,including acetic acid and formic acid,by coupling with the cathodic CO_(2) reduction reaction.In situ experimental results and theoretical simulations revealed that the catalytic activity center of LAOR was dynamically formed NiOOH species,and the surface-adsorbed SeO_(x) species accelerated the formation of Ni~(3+)species,thus promoting catalytic activity.The mechanism of lactic acid electrooxidation was further elucidated.Lactic acid was dehydrogenated to produce pyruvate first and then formed CH_3CO due to preferential C-C bond cleavage,resulting in the presence of acetate.This work demonstrated a sustainable method for recycling waste PLA and CO_(2) into high-value-added products.

TOPCon太阳电池背面叠层poly工艺的优化及其对电性能的影响

通过增加TOPCon太阳电池poly层中的磷掺杂浓度可以增强poly层与硅基底之间的钝化效果并提高poly层与金属电极间的接触能力,但过高的掺杂浓度会导致磷原子扩散到硅基底,破坏氧化层与硅基底之间的界面钝化效果。为了解决这一问题,提出在poly层中间增加一层薄的氧化层作为阻挡层(即叠层poly工艺,下文简称为“叠层工艺”)的方案,将原本单一的poly-Si磷掺杂进行双层分布,底层poly-Si轻掺杂,表层poly-Si重掺杂;对常规工艺和叠层工艺制备TOPCon的太阳电池进行对比试验后,进一步优化叠层工艺,调整中间氧化层厚度,并研究不同中间氧化层厚度的叠层工艺对TOPCon太阳电池电性能的影响。实验结果表明:1)叠层工艺可以提高TOPCon太阳电池的电性能;2)当中间氧化层厚度提升至1.5 nm时,太阳电池的光电转换效率达到最高值(25.66%)。但中间氧化层的厚度是一个需要精确控制的工艺参数,需找到最佳的厚度平衡点,以提高太阳电池性能。

Anion competition for Li^(+)solvated coordination environments in poly(1,3 dioxolane)electrolyte to enable high-voltage lithium metal solid-state batteries

Gel-based polymer electrolytes are limited by the polarity of the residual solvent,which restricts the coupling-breaking behaviour during Li^(+)conduction,resulting in the Li^(+)transport kinetics being greatly affected.Here,we designed anion competitive gel polymer electrolyte(ACPE)by introducing lithium difluoro(oxalato)borate(LiDFOB)anion into the 1,3-dioxolane(DOL)in situ polymerisation system.ACPE enhances the ionic dipole interaction between Li^(+)and the solvent molecules and synergizes with Li^(+)across the solvation site of the polymer ethylene oxide(EO)unit,combination that greatly improves the Li^(+)transport efficiency.As a result,ACPE exhibits 1.12 mS cm^(−1)ionic conductivity and 0.75 Li^(+)transfer number at room temperature.Additionally,this intra-polymer solvation sheath allows preferential desolvation of DFOB−,which contributes to the formation of kinetically stable anion-derived interphase and effectively mitigates side reactions.Our results demonstrate that the assembled Li||NCM622 solid-state battery exhibits lifespan of over 300 cycles with average Coulombic efficiency of 98.8%and capacity retention of 80.3%.This study introduces a novel approach for ion migration and interface design,paving the way for high-safety and high-energy-density batteries.

Poly(p-coumaric acid)nanoparticles alleviate temporomandibular joint osteoarthritis by inhibiting chondrocyte ferroptosis

Oxidative stress and inflammation are key drivers of osteoarthritis(OA)pathogenesis and disease progression.Herein we report the synthesis of poly(p-coumaric)nanoparticles(PCA NPs)from p-courmaic acid(p-CA),a naturally occurring phytophenolic acid,to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis(TMJOA).Compared to hyaluronic acid(HA)that is clinically given as viscosupplementation,PCA NPs exhibited long-term efficacy,superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA.Notably,TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis,while reducing inflammation,oxidative stress,matrix degradation,and chondrocyte ferroptosis.Overall,our study demonstrates a multifunctional nanoparticle,synthesized from natural p-coumaric acid,that is stable and possess potent antioxidant,anti-inflammatory properties and ferroptosis inhibition,beneficial for treatment of TMJOA.

Stable Cycling of All-Solid-State Lithium Batteries Enabled by Cyano-Molecular Diamond Improved Polymer Electrolytes

The interfacial instability of the poly(ethylene oxide)(PEO)-based electrolytes impedes the long-term cycling and further application of all-solid-state lithium metal batter-ies.In this work,we have shown an effective additive 1-adaman-tanecarbonitrile,which con-tributes to the excellent per-formance of the poly(ethylene oxide)-based electrolytes.Owing to the strong interaction of the 1-Adamantanecarboni-trile to the polymer matrix and anions,the coordination of the Li^(+)-EO is weakened,and the binding effect of anions is strengthened,thereby improving the Li^(+)conductivity and the electrochemical stability.The diamond building block on the surface of the lithium anode can sup-press the growth of lithium dendrites.Importantly,the 1-Adamantanecarbonitrile also regulates the formation of LiF in the solid electrolyte interface and cathode electrolyte interface,which contributes to the interfacial stability(especially at high voltages)and protects the electrodes,enabling all-solid-state batteries to cycle at high voltages for long periods of time.Therefore,the Li/Li symmetric cell undergoes long-term lithium plating/stripping for more than 2000 h.1-Adamantanecarbonitrile-poly(ethylene oxide)-based LFP/Li and 4.3 V Ni_(0.8)Mn_(0.1)Co_(0.1)O_(2)/Li all-solid-state batteries achieved stable cycles for 1000 times,with capacity retention rates reaching 85%and 80%,respectively.

Poly (ADP-ribose): A double-edged sword governing cancer cell survival and death

Poly(ADP-ribose)(PAR),a polymer of ADP-ribose,is synthesized by PAR po-lymerase and is crucial for the survival of cancer cells due to its vital functions in DNA repair and post-translational modifications.Beyond its supportive role,PAR also triggers cancer cell death by excessive accumulation of PAR leading to an energy crisis and parthanatos.This phenomenon underscores the potential of targeting PAR regulation as a novel anticancer strategy,and the rationale would present an engaging topic in the field of anticancer research.Therefore,this editorial provides an overview of the mechanisms determining cancer cell fate,emphasizing the central role of PAR.It further introduces promising methods for modulating PAR concentrations that may pave the way for innovative anticancer therapies.

Synergistic coupling among Mg_(2)B_(2)O_(5),polycarbonate and N,Ndimethylformamide enhances the electrochemical performance of PVDF-HFP-based solid electrolyte

Polymer solid electrolytes(SPEs)based on the[solvate-Li+]complex structure have promising prospects in lithium metal batteries(LMBs)due to their unique ion transport mechanism.However,the solvation structure may compromise the mechanical performance and safety,hindering practical application of SPEs.In this work,a composite solid electrolyte(CSE)is designed through the organic-inorganic syner-gistic interaction among N,N-dimethylformamide(DMF),polycarbonate(PC),and Mg_(2)B_(2)O_(5) in poly(vinylidene fluoride-co-hexafluoropropylene)(PVDF-HFP).Flame-retardant Mg_(2)B_(2)O_(5) nanowires provide non-flammability to the prepared CSEs,and the addition of PC improves the dispersion of Mg_(2)B_(2)O_(5) nanowires.Simultaneously,the organic-inorganic synergistic action of PC plasticizer and Mg_(2)B_(2)O_(5) nanowires pro-motes the dissociation degree of LiTFSI and reduces the crystallinity of PVDF-HFP,enabling rapid Li ion transport.Additionally,Raman spectroscopy and DFT calculations confirm the coordination between Mg atoms in Mg_(2)B_(2)O_(5) and N atoms in DMF,which exhibits Lewis base-like behavior attacking adjacent C-F and C-H bonds in PVDF-HFP while inducing dehydrofluorination of PVDF-HFP.Based on the syner-gistic coupling of Mg_(2)B_(2)O_(5),PC,and DMF in the PVDF-HFP matrix,the prepared CSE exhibits superior ion conductivity(9.78×10^(-4) s cm^(-1)).The assembled Li symmetric cells cycle stably for 3900 h at a current density of 0.1 mA cm^(-2) without short circuit.The LFP||Li cells assembled with PDL-Mg_(2)B_(2)O_(5)/PC CSEs show excellent rate capability and cycling performance,with a capacity retention of 83.3%after 1000 cycles at 0.5 C.This work provides a novel approach for the practical application of organic-inorganic Synergistic CSEs in LMBs.

A comparative study for petroleum removal capacities of the bacterial consortia entrapped in sodium alginate,sodium alginate/poly(vinyl alcohol),and bushnell haas agar

The purpose of this study was to identify and compare the degradation efficiencies of free and entrapped bacterial consortia(Staphylococcus capitis CP053957.1 and Achromobacter marplatensis MT078618.1)to different polymers such as Sodium Alginate(SA),Sodium Alginate/Poly(Vinyl Alcohol)(SA/PVA),and Bushnell Haas Agar(BHA).In addition to SA and SA/PVA,which are cost-effective,non-toxic and have different functional groups,BHA,which is frequently encountered in laboratory-scale studies but has not been used as an entrapment material until now.Based on these,the polymers with different surface morphologies and chemical compositions were analyzed by SEM and FT-IR.While the petroleum removal efficiency was higher with the entrapped bacterial consortia than with the free one,BHA-entrapped bacterial consortium enhanced the petroleum removal more than SA and SA/PVA.Accordingly,the degradation rate of bacterial consortia entrapped with BHA was 2.039 day^(-1),SA/PVA was 1.560,SA was 0.993,the half-life period of BHA-entrapped bacterial consortia is quite low(t_(1/2)=0.339)compared with SA(t_(1/2)=0.444)and SA/PVA(t_(1/2)=0.697).The effects of the four main factors such as:amount of BHA(0.5,1,1.5,2,2.5,3 g),disc size(4,5,6,7,8 mm),inoculum concentration(1,2.5,5,7.5,10 mL),and incubation period on petroleum removal were also investigated.The maximum petroleum removal(94.5%)was obtained at≥2.5 mL of bacterial consortium entrapped in 2 g BHA with a 7 mm disc size at 168 h and the results were also confirmed by statistical analysis.Although a decrease was observed during the reuse of bacterial consortium entrapped in BHA,the petroleum removal was still above 50%at 10th cycle.Based on GC-MS analysis,the removal capacity of BHA-entrapped consortium was over 90%for short-chain n-alkanes and 80%for medium-chain n-alkanes.Overall,the obtained data are expected to provide a potential guideline in cleaning up the large-scale oil pollution in the future.Since there has been no similar study investigating petroleum removal with the bacterial consortia entrapped with BHA,this novel entrapment material can potentially be used in the treatment of petroleum pollution in advanced remediation studies.

High-performance and robust high-temperature polymer electrolyte membranes with moderate microphase separation by implementation of terphenyl-based polymers

Acid loss and plasticization of phosphoric acid(PA)-doped high-temperature polymer electrolyte membranes(HT-PEMs)are critical limitations to their practical application in fuel cells.To overcome these barriers,poly(terphenyl piperidinium)s constructed from the m-and p-isomers of terphenyl were synthesized to regulate the microstructure of the membrane.Highly rigid p-terphenyl units prompt the formation of moderate PA aggregates,where the ion-pair interaction between piperidinium and biphosphate is reinforced,leading to a reduction in the plasticizing effect.As a result,there are trade-offs between the proton conductivity,mechanical strength,and PA retention of the membranes with varied m/p-isomer ratios.The designed PA-doped PTP-20m membrane exhibits superior ionic conductivity,good mechanical strength,and excellent PA retention over a wide range of temperature(80–160°C)as well as satisfactory resistance to harsh accelerated aging tests.As a result,the membrane presents a desirable combination of performance(1.462 W cm^(-2) under the H_(2)/O_(2)condition,which is 1.5 times higher than that of PBI-based membrane)and durability(300 h at 160°C and 0.2 A cm^(-2))in the fuel cell.The results of this study provide new insights that will guide molecular design from the perspective of microstructure to improve the performance and robustness of HT-PEMs.

Antifouling Properties of Electrospun Polymeric Coatings Induced by Controlled Surface Morphology

Nosocomial infections affect implanted medical devices and greatly challenge their functional outcomes,becoming sometimes life threatening for the patients.Therefore,aggressive antibiotic therapies are administered,which often require the use of last-resort drugs,if the infection is caused by multi-drug-resistant bacteria.Reducing the risk of bacterial contamination of medical devices in the hospitals has thus become an emerging issue.Promising routes to control these infections are based on materials provided with intrinsic bactericidal properties(i.e.,chemical action)and on the design of surface coatings able to limit bacteria adhesion and fouling phenomena(i.e.,physical action),thus preventing bacterial biofilm formation.Here,we report the development and validation of coatings made of layer-by-layer deposition of electrospun poly(vinylidene fluoride-co-trifluoro ethylene)P(VDF-TrFE)fibers with controlled orientations,which ultimately gave rise to antifouling surfaces.The obtained 10-layer surface morphology with 90°orientation fibers was able to efficiently prevent the adhesion of bacteria,by establishing a superhydrophobic-like behavior compatible with the Cassie-Baxter regimen.Moreover,the results highlighted that surface wettability and bacteria adhesion could be controlled using fibers with diameter comparable to bacteria size(i.e.,achievable via electrospinning process),by tuning the intra-fiber spacing,with relevant implications in the future design of biomedical surface coatings.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.