Recent progress in ternary mixed matrix membranes for CO_(2) separation

Mixed matrix membranes(MMMs)could combine the advantages of both polymeric membranes and porousfillers,making them an effective alternative to conventional polymer membranes.However,interfacial incompatibility issues,such as the presence of interfacial voids,hardening of polymer chains,and blockage of micropores by polymers between common MMMsfillers and the polymer matrix,currently limit the gas sep-aration performance of MMMs.Ternary phase MMMs(consisting of afiller,an additive,and a matrix)made by adding a third compound,usually functionalized additives,can overcome the structural problems of binary phase MMMs and positively impact membrane separation performance.This review introduces the structure and fabrication processes for ternary MMMs,categorizes various nanofillers and the third component,and summarizes and analyzes in detail the CO_(2) separation performance of newly developed ternary MMMs based on both rubbery and glassy polymers.Based on this separation data,the challenges of ternary MMMs are also discussed.Finally,future directions for ternary MMMs are proposed.

Efficacy of transjugular intrahepatic portosystemic shunts in treating cirrhotic esophageal-gastric variceal bleeding

BACKGROUND Esophageal-gastric variceal bleeding(EGVB)represents a severe complication among patients with cirrhosis and often culminates in fatal outcomes.Interven-tional therapy,a rapidly developing treatment modality over the past few years,has found widespread application in clinical practice due to its minimally inva-sive characteristics.However,whether transjugular intrahepatic portosystemic shunt(TIPS)treatment has an impact on patient prognosis remains controversial.METHODS A retrospective study was conducted on ninety-two patients presenting with cirrhotic EGVB who were admitted to our hospital between September 2020 and September 2022.Based on the different modes of treatment,the patients were assigned to the study group(TIPS received,n=50)or the control group(per-cutaneous transhepatic varices embolization received,n=42).Comparative ana-lyses were performed between the two groups preoperatively and one month postoperatively for the following parameters:Varicosity status;hemodynamic parameters[portal vein flow velocity(PVV)and portal vein diameter(PVD);platelet count(PLT);red blood cell count;white blood cell count(WBC);and hepatic function[albumin(ALB),total bilirubin(TBIL),and aspartate transaminase(AST)].The Generic Quality of Life Inventory-74 was utilized to assess quality of life in the two groups,and the 1-year postoperative rebleeding and survival rates were compared.RESULTS Following surgical intervention,there was an improvement in the incidence of varicosity compared to the preoperative status in both cohorts.Notably,the study group exhibited more pronounced enhancements than did the control group(P<0.05).PVV increased,and PVD decreased compared to the preoperative values,with the study cohort achieving better outcomes(P<0.05).PLT and WBC counts were elevated postoperatively in the two groups,with the study cohort displaying higher PLT and WBC counts(P<0.05).No differences were detected between the two groups in terms of serum ALB,TBIL,or AST levels either preoperatively or postoperatively(P<0.05).Postoperative scores across all dimensions of life quality surpassed preoperative scores,with the study cohort achieving higher scores(P<0.05).At 22.00%,the one-year postoperative rebleeding rate in the study cohort was significantly lower than that in the control group(42.86%;P<0.05);conversely,no marked difference was obser-ved in the 1-year postoperative survival rate between the two cohorts(P>0.05).CONCLUSION TIPS,which has demonstrated robust efficacy in managing cirrhotic EGVB,remarkably alleviates varicosity and improves hemodynamics in patients.This intervention not only results in a safer profile but also contributes significantly to a more favorable prognosis.

Direct somatic embryogenesis and related gene expression networks in leaf explants of Hippeastrum ‘Bangkok Rose’

Hippeastrum, a highly diverse genus in the Amaryllidaceae family, is a valuable ornamental bulbous flowering plant. Somatic embryogenesis(SE) is an efficient method for mass production of Hippeastrum plantlets. Previous studies have been devoted to the in vitro propagation of Hippeastrum, but the SE and its regulatory networks are rarely reported. In this study, we established a direct SE method of Hippeastrum Bangkok Rose' using leaf bases as explants. MS supplemented with 1.00 mg·L^(-1)NAA +1.00 mg·L^(-1)KT + 0.25 mg·L^(-1)TDZ was the optimal medium for SE. Histological observations showed that the bipolar somatic embryo originated from the epidermal cell layer and underwent initiation,globular, scutellar and coleoptile stages. During SE, endogenous hormones of IAA, CTK, ABA, and SA were highly accumulated. Transcriptomic analysis revealed the genes encoding auxin biosynthesis/metabolic enzymes and efflux carriers were induced, while the auxin receptor of TIR1 and ARF transcriptional repressor of Aux/IAA were down-regulated and up-regulated, respectively, leading to suppression of auxin signaling. In contrast, cytokine signaling was promoted at the early stage of SE, as biosynthesis, transport, and signaling components were up-regulated.Various stress-related genes were up-regulated at the early or late stages of SE. Chromatin remodeling could also be dynamically regulated via distinct expression enzymes that control histone methylation and acetylation during SE. Moreover, key SE regulators, including WOXs and SERKs were highly expressed along with SE. Overall, the present study provides insights into the SE regulatory mechanisms of the Hippeastrum.

MSADCN:Multi-Scale Attentional Densely Connected Network for Automated Bone Age Assessment

Bone age assessment(BAA)helps doctors determine how a child’s bones grow and develop in clinical medicine.Traditional BAA methods rely on clinician expertise,leading to time-consuming predictions and inaccurate results.Most deep learning-based BAA methods feed the extracted critical points of images into the network by providing additional annotations.This operation is costly and subjective.To address these problems,we propose a multi-scale attentional densely connected network(MSADCN)in this paper.MSADCN constructs a multi-scale dense connectivity mechanism,which can avoid overfitting,obtain the local features effectively and prevent gradient vanishing even in limited training data.First,MSADCN designs multi-scale structures in the densely connected network to extract fine-grained features at different scales.Then,coordinate attention is embedded to focus on critical features and automatically locate the regions of interest(ROI)without additional annotation.In addition,to improve the model’s generalization,transfer learning is applied to train the proposed MSADCN on the public dataset IMDB-WIKI,and the obtained pre-trained weights are loaded onto the Radiological Society of North America(RSNA)dataset.Finally,label distribution learning(LDL)and expectation regression techniques are introduced into our model to exploit the correlation between hand bone images of different ages,which can obtain stable age estimates.Extensive experiments confirm that our model can converge more efficiently and obtain a mean absolute error(MAE)of 4.64 months,outperforming some state-of-the-art BAA methods.

Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer:A review

Hepatocyte growth factor(HGF)and its receptor,c-Met,play important roles in the occurrence,development,and treatment of gastric cancer(GC).This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms.As one of the most common malignant tumors worldwide,GC has a complex pathogenesis and limited therapeutic options.Therefore,a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods.The HGF/c-Met signaling pathway plays an important role in the proliferation,migration,and invasion of GC cells and has become a new therapeutic target.This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway,providing new ideas and directions for the treatment of GC.

Correlation between serum markers and transjugular intrahepatic portosystemic shunt prognosis in patients with cirrhotic ascites

BACKGROUND Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis.The transjugular intrahepatic portosystemic shunt(TIPS)is an efficacious intervention,but there is a lack of reliable tools for postoperative pro-gnosis assessment.Previously utilized clinical biochemical markers,such as the serum albumin concentration(Alb),sodium(Na+)concentration,and serum creatinine(Scr),have limited predictive value.Therefore,the quest for novel,specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance.A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021.These patients were followed up regularly for two years,and the death toll was meticulously documented.The patients were allocated into a survival group(n=45 patients)or a deceased group(n=30 patients)based on their prognosis status.The clinical data of the two groups were collected,and Child-Pugh scores and MELD scores were calculated for analysis.Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade,MELD score,and Cys C level.Additionally,a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites.The receiver operating characteristic curve(ROC)ascertained the predictive value of the Cys C concen-tration,Child-Pugh grade,and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients.RESULTS During a 2-year follow-up period,among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment,30 patients(40.00%)passed away.The deceased cohort exhibited heightened aspartate aminotrans-ferase,alanine aminotransferase,total bilirubin,Scr,prothrombin time,Cys C,international normalized ratio,Child-Pugh,and MELD scores compared to those of the survival cohort,while Alb and Na+levels were attenuated in the deceased group(P<0.05).Spearman analysis revealed moderate to high positive correlations between prognosis and Child-Pugh score,MELD score,and Cys C level(r=0.709,0.749,0.671,P<0.05).Multivariate analysis using the Cox proportional hazard model demonstrated that the independent risk factors for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites were Cys C(HR=3.802;95%CI:1.313-11.015),Child-Pugh(HR=3.030;95%CI:1.858-4.943),and MELD(HR=1.222;95%CI:1.073-1.393)scores.ROC analysis confirmed that,compared to those of the classic prognostic models for Child-Pugh and MELD scores,the predictive accuracy of Cys C for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites was slightly lower.This analysis yielded sensitivity and specificity values of 83.33%and 82.22%,respectively.The area under the curve value at this juncture was 0.883,with an optimal cutoff value set at 1.95 mg/L.CONCLUSION Monitoring the serum Cys C concentration is valuable for assessing the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites.Predictive models based on serum Cys C levels,as opposed to Scr levels,are more beneficial for evaluating the condition and prognosis of patients with ascites due to cirrhosis.

Analysis of the Characteristics of the Low-level Jets in the Middle Reaches of the Yangtze River during the Mei-yu Season

Here,we analyze the characteristics and the formation mechanisms of low-level jets(LLJs)in the middle reaches of the Yangtze River during the 2010 mei-yu season using Wuhan station radiosonde data and the fifth generation of the European Centre for Medium-Range Weather Forecasts(ERA5)reanalysis dataset.Our results show that the vertical structure of LLJs is characterized by a predominance of boundary layer jets(BLJs)concentrated at heights of 900-1200 m.The BLJs occur most frequently at 2300 LST(LST=UTC+8 hours)but are strongest at 0200 LST,with composite wind velocities>14 m s^(-1).Synoptic-system-related LLJs(SLLJs)occur most frequently at 0800 LST but are strongest at 1100LST,with composite wind velocities>12 m s^(-1).Both BLJs and SLLJs are characterized by a southwesterly wind direction,although the wind direction of SLLJs is more westerly,and northeasterly SLLJs occur more frequently than northeasterly BLJs.When Wuhan is south of the mei-yu front,the westward extension of the northwest Pacific subtropical high intensifies,and the low-pressure system in the eastern Tibetan Plateau strengthens,favoring the formation of LLJs,which are closely related to precipitation.The wind speeds on rainstorm days are greater than those on LLJ days.Our analysis of four typical heavy precipitation events shows the presence of LLJs at the center of the precipitation and on its southern side before the onset of heavy precipitation.BLJs were shown to develop earlier than SLLJs.

A-D-A covalent organic-inorganic heterojunctions with enhanced photocatalytic performance for robust anti-bacteria

Background:Organic semiconductors have attracted much attention due to their excellent biocompatibility,tunable electronic structure,low cost,and antimicrobial phototherapy.However,owing to the high exciton binding energies,organic semiconductor is constrained by their short exciton diffusion length,leading to inefficient transportation of photogenerated carriers and deficient antibacterial capability.Methods:To address this issue,a quad-channel synergistic antibacterial nano-platform of copper sulfide/organic semiconductor(CuS/IEICO-4F)heterojunctions with enhanced photocatalytic performance is designed and manufactured,which can produce localized heat and raise the levels of extracellular reactive oxygen species under near-infrared laser irradiation.Simultaneously,the released Cu2+can consume intrabacterial glutathione,destroying the defense system and ultimately leading to bacterial inactivation.Results:In vitro antibacterial experiments demonstrate that the organic-inorganic bio-heterojunctions possess the potent antibacterial capacity and effective bacterial eradication.Conclusion:This countermeasure shows great promise for application in infectious wound regeneration.

Synthesis, characterization and antibacterial properties of multifunctional hindered amine light stabilizers

A series of novel hindered amine light stabilizers containing an N-halamine moiety were designed and synthesized. Their structures were characterized by FT-IR, 1H NMR, and MS. The compounds were tested for antibacterial activity against Candida albicans, Staphylococcus aureus, and Escherichia coll. At a concentration of 0.5 mmol/L, these compounds all exhibited satisfactory antibacterial activity against all the three types of bacteria.

促进幼儿入学准备的园本活动体系

入学准备指学龄前儿童为了能够从即将开始的正规学校教育中受益所需要具备的各种关键特征或基础条件,主要涵盖身体素质适应、社会性适应和学习适应三个方面。构建促进幼儿入学准备的园本活动体系需要以促进幼儿身体素质发展为前提,以社会性适应为重点,帮助幼儿做好在早期读写和数概念学习等方面的准备。

Integrative Monsoon Frontal Rainfall Experiment(IMFRE-I):A Mid-Term Review

The mei-yu season,typically occurring from mid-June to mid-July,on average,contributes to 32%of the annual precipitation over the Yangtze-Huai River Valley(YHRV)and represents one of the three heavy-rainfall periods in China.Here,we briefly review the large-scale background,synoptic pattern,moisture transport,and cloud and precipitation characteristics of the mei-yu frontal systems in the context of the ongoing Integrative Monsoon Frontal Rainfall Experiment(IMFRE)field campaign.Phase one of the campaign,IMFRE-I,was conducted from 10 June to 10 July 2018 in the middle reaches of the YHRV.Led by the Wuhan Institute of Heavy Rain(IHR)with primary support from the National Natural Science Foundation of China,IMFRE-I maximizes the use of our observational capacity enabled by a suite of ground-based and remote sensing instruments,most notably the IHR Mesoscale Heavy Rainfall Observing System(MHROS),including different wavelengths of radars,microwave radiometers,and disdrometers.The KA350(Shanxi King-Air)aircraft participating in the campaign is equipped with Ka-band cloud radar and different probes.The comprehensive datasets from both the MHROS and aircraft instruments are combined with available satellite observations and model simulations to answer the three scientific questions of IMFRE-I.Some highlights from a previously published special issue are included in this review,and we also briefly introduce the IMFRE-II field campaign,conducted during June-July 2020,where the focus was on the spatiotemporal evolutions of the mei-yu frontal systems over the middle and lower reaches of the YHRV.

Developmental expression of three prmt genes in Xenopus

DEAR EDITOR Protein arginine methyltransferases (PRMTs)are involved in many cellular processes via the arginine methylation of histone or non-histone proteins.We examined the expression patterns of prmt4,prmt7,and prmt9 during embryogenesis in Xenopus using whole-mount in situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-PCR).Xenopus prmt4 and prmt7 were expressed in the neural crest,brain,and spinal cord,and also detected in the eye,branchial arches,and heart at the tailbud stage.Specific print9 signals were not detected in Xenopus embryos until the late tailbud stage when weak expression was observed in the branchial arches.Quantitative RT-PCR indicated that the expression of prmt4 and prmt7 was up-regulated during the neurula stage,whereas prmt9 maintained its low expression until the late tailbud stage,consistent with the whole-mount in situ hybridization results.Thus,the developmental expression patterns of these three print genes in Xenopus embryos provide a basis for further functional study of such genes.

COMONOMER SEQUENCE DISTRIBUTION IN METALLOCENE-BASED ETHYLENE/1-BUTENE (S-34) AND ETHYLENE/1-HEXENE (S-43) COPOLYMERS

Metallocene based polyethylenes were prepared by SMOPEC's 'metallocene adduct' technology in a gas phase fluidized bed model reactor. The C-13-NMR spectra of ethylene/1-butene (S-34) and ethylene/1-hexene(S-43) copolymers were studied in a manner analogous to that established by Hsieh and Cheng. The comonomer sequence distributions of copolymer samples were obtained. The results show that these metallocene based copolymers contain a small amount of butene and hexene, and the EE and EEE sequences are dominant.

Predictive value of serum NSE, umbilical cord blood albumin levels in hyperbilirubinemia full-term neonates with brain injury

Objective:To investigate the predictive value of of serum NSE,umbilical cord blood albumin levels in hyperbilirubinemia full-term neonates with brain injury.Methods:300 cases of hyperbilirubinemia full-term neonates in our hospital during January 2018 to November 2019 were chosen as hyperbilirubinemia group,200 cases of healthy full-term neonates who were delivered in our hospital during the same period and whose general information matched were chosen as normal control group.According to whether the hyperbilirubinemia group had brain injury,they were further divided into bilirubin encephalopathy group(n=34)and non-bilirubin encephalopathy group(n=266).NSE,umbilical cord blood albumin levels in hyperbilirubinemia group and normal control group were compared.Clinical data,NSE and umbilical cord blood albumin levels between bilirubin encephalopathy group,non-bilirubin encephalopathy group were compared.Risk factors associated with brain injury in full-term newborn with hyperbilirubinemia were analyzed by logistics regression,predictive value of NSE and umbilical cord blood albumin on brain injury in full-term newborn with hyperbilirubinemia were evaluated by ROC curve.Results:NSE level in hyperbilirubinemia group was higher than that in normal control group(P<0.05).There was no significant difference in umbilical cord blood albumin between two groups(P>0.05).Incidence of jaundice,anemia,indirect bilirubin peak,total bilirubin peak and NSE level in bilirubin encephalopathy group were higher than those in non-bilirubin encephalopathy group,level of umbilical cord blood albumin was lower than that in non-bilirubin encephalopathy group(P<0.05).Logistic regression analysis showed that jaundice,anemia,indirect bilirubin peak,total bilirubin peak,NSE and umbilical cord blood albumin within 24h after birth were risk factors for hyperbilirubinemia with brain injury(P<0.05).When NSE was 67.09 ng/mL,the yoden index was the highest,with sensitivity and specificity of 79.70%,55.88%respectively.When the umbilical cord blood albumin was 4.20mg/mL,the jorden index was the highest,sensitivity and specificity were 76.32%,82.35%respectively.Conclusion:Abnormal changes in serum NSE,umbilical cord blood albumin levels are observed in full-term neonates with hyperbilirubinemia,moreover they have value of early prediction for subsequent brain injury.

Residential relocation in response to light rail transit investment:case study of the Hudson–Bergen Light Rail system

It is widely acknowledged that the improved accessibility enabled by investment in public transport services can, under favorable market conditions, impact the local real estate market within the zone of influence of the service＇s stations. The motivation for this study is to establish the nature of two such impacts, specifically the spatial and socio-economic patterns of residential relocations that are driven by the new light rail transit （LRT） service. Using empirical data （n = 1,023） from the Hudson-Bergen Light Rail system in New Jersey （US）, we report findings regarding the impacts of the introduction of the new LRT service. We investigate two linked dimensions; the first is the distinctive socio-economic profile of LRT passengers who self-report having relocated to the new transit corridor due, at least in part, to the new transit service. The second is their proximity （following their resi- dential relocation） to the new LRT line＇ s stations. We present a novel analysis that accounts for endogeneity between these two dimensions of residential relocation. Of light rail passengers who engaged in a residential relocation in the 5 years prior to the survey, two-thirds （69 %） indicate that proximity to the light rail service was a ＇somewhat＇ or ＇very＇ important consideration. Via the multivariate analysis, we demonstrate that small household size, low income, youth （as opposed to older age）, and low car ownership are each positively linked, ceteris paribus, with having engaged in a residential reloca- tion motivated by the new transit service. Finally, higher household income is found to be associated with distance （after relocation） to the nearest transit station, which is consistent with bid-rent theory.

A Semiparametric Additive-multiplicative Rates Model for the Weighted Composite Endpoint of Recurrent and Terminal Events

Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In this paper,we consider to use a weighted composite endpoint of recurrent and terminal events,which is weighted by the severity of each event,to assess the overall effects of covariates on the two types of events.A flexible additive-multiplicative model incorporating both multiplicative and additive effects on the rate function is proposed to analyze such weighted composite event process,and more importantly,the dependence structure among the recurrent and terminal events is left unspecified.For the estimation,we construct the unbiased estimating equations by virtue of the inverse probability weighting technique,and the resulting estimators are shown to be consistent and asymptotically normal under some mild regularity conditions.We evaluate the finite-sample performance of the proposed method via simulation studies and apply the proposed method to a set of real data arising from a bladder cancer study.

Palmitoylation regulates myelination by modulating the ZDHHC3-Cadm4 axis in the central nervous system

The downregulation of Cadm4 (Cell adhesion molecular 4) is a prominent feature in demyelination diseases, yet, the underlying molecular mechanism remains elusive. Here, we reveal that Cadm4 undergoes specific palmitoylation at cysteine-347 (C347), which is crucial for its stable localization on the plasma membrane (PM). Mutation of C347 to alanine (C347A), blocking palmitoylation, causes Cadm4 internalization from the PM and subsequent degradation. In vivo experiments introducing the C347A mutation (Cadm4-KI) lead to severe myelin abnormalities in the central nervous system (CNS), characterized by loss, demyelination, and hypermyelination. We further identify ZDHHC3 (Zinc finger DHHC-type palmitoyltransferase 3) as the enzyme responsible for catalyzing Cadm4 palmitoylation. Depletion of ZDHHC3 reduces Cadm4 palmitoylation and diminishes its PM localization. Remarkably, genetic deletion of ZDHHC3 results in decreased Cadm4 palmitoylation and defects in CNS myelination, phenocopying the Cadm4-KI mouse model. Consequently, altered Cadm4 palmitoylation impairs neuronal transmission and cognitive behaviors in both Cadm4-KI and ZDHHC3 knockout mice. Importantly, attenuated ZDHHC3-Cadm4 signaling significantly influences neuroinflammation in diverse demyelination diseases. Mechanistically, we demonstrate the predominant expression of Cadm4 in the oligodendrocyte lineage and its potential role in modulating cell differentiation via the WNT-β-Catenin pathway. Together, our findings propose that dysregulated ZDHHC3-Cadm4 signaling contributes to myelin abnormalities, suggesting a common pathological mechanism underlying demyelination diseases associated with neuroinflammation.

基于呼吸系统健康效应的室内空气微生物研究现状与展望

室内空气微生物是人体呼吸系统疾病的重要诱因,明确室内空气微生物与呼吸系统健康效应关系对建立室内健康微生物环境标准具有积极意义.近十多年,环境和人类呼吸道健康相关的微生物学深入研究已使人们对微生物的看法从纯粹致病性、传染性的负面作用逐渐转变为潜在保护性、预防性的正面作用.然而,目前室内空气微生物与呼吸系统的量化作用机制尚未建立,现行的公共卫生政策和室内空气微生物控制标准仍倾向于使室内保持尽可能低的微生物浓度,以防止致病菌传播和人群感染.本文总结了室内空气微生物与呼吸系统健康效应的相关研究,指出了基于呼吸道健康效应的室内空气微生物定量表征的关键理论欠缺和技术瓶颈,并以此为依据,提出了基于采样工具、统计学工具以及实验工具优化的研究展望,为未来量化呼吸系统健康效应与室内空气微生物作用的关系、室内空气微生物的表征提供借鉴.

Sequential gastrodin release PU/n-HA composite scaffolds reprogram macrophages for improved osteogenesis and angiogenesis

Wound healing is a highly orchestrated process involving a variety of cells,including immune cells.Developing immunomodulatory biomaterials for regenerative engineering applications,such as bone regeneration,is an appealing strategy.Herein,inspired by the immunomodulatory effects of gastrodin(a bioactive component in traditional Chinese herbal medicine),a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane(gastrodin-PU)and nano-hydroxyapatite(n-HA)(gastrodin-PU/n-HA)composites were developed.RAW 264.7 macrophages,rat bone marrow mesenchymal stem cells(rBMSCs),and human umbilical vein endothelial cells(HUVECs)were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin(0.5%,1%,and 2%)to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro.Results demonstrated that,compared with PU/n-HA,gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype,as evidenced by the higher expression level of pro-regenerative cytokines(CD206,Arg-1)and the lower expression of pro-inflammatory cytokines(iNOS).The expression levels of osteogenesis-related factors(BMP-2 and ALP)in the rBMSCs and angiogenesis-related factors(VEGF and BFGF)in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium.The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory(M1)phenotype to an anti-inflammatory and pro-healing(M2)phenotype were validated in a rat subcutaneous implantation model.And the 2%gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis.Additionally,2%gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis.Thus,the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.

Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication.Despite the extensive clinical use of antibiotics to treat bacterial infections,the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health.To address this daunting concern,we devise and develop a photo-activated cascade bio-heterojunctions(C-bio-HJs)for rapid sterilization and diabetic cutaneous regeneration.In the designed C-bio-HJs,photo-generated electron-hole pairs of graphite-phase carbon nitride(g-C_(3)N_(4))are effectively separated with the marriage of molybdenum disulfide(MoS_(2)),which achieves the augmented photodynamic antibacterial effect.Moreover,glucose oxidase(GOx)tethered on the bio-HJs catalyzes glucose into hydrogen peroxide(H_(2)O_(2))in diabetic wounds for starvation therapy.Furthermore,Mo4+enables the catalysis of H_(2)O_(2)into a highly effective hydroxyl radical(⋅OH)for chemodynamic-photothermal combined antibacterial therapy.Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs,which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.