A new age in understanding adult hippocampal neurogenesis in Alzheimer’s disease

Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.

Broiler Tissue Enrichment with Docosahexaenoic Acid (DHA) through Dietary Supplementation with <i>Aurantiochytrium limacinum</i>Algae

The omega-3 fatty acid (n-3 FA) content of broiler tissues can be increased through dietary supplementation of hens with n-3 FA-rich microalgae. The aim of this study was to evaluate the effect of three different dietary inclusion levels of a docosahexaenoic acid (DHA)-rich microalgae (AURA) on broiler performance and the enrichment of tissues with n-3 FA. The randomized study was conducted using 352 birds, housed in 32 pens with 11 birds per pen. Pens were randomly assigned to one of four treatments, with each treatment replicated 8 times. The treatments included one unsupplemented control (0%) and three wheat-soya based experimental diets supplemented with AURA at a level of 0.5%, 1.5% and 2.5% for the starter, grower and finisher periods. Birds were weighed on days 0, 10, 24, 35 and 41, and feed intake was recorded per pen. On day 41, five birds per treatment were euthanized and individually weighed. Thigh muscle, breast muscle, liver, kidney and skin samples were taken post-mortem, freeze dried and DHA content quantified, following fat extraction and methylation, by GC-FID (AOAC 996.06 method). Performance and tissue data were analyzed by ANOVA with Dunnett’s (2-sided) post-hoc test to determine the differences between the mean values for each treatment. Dietary supplementation with AURA had no effect on body weight or feed intake during any period of the study. For thigh muscle, kidney and skin the DHA increased linearly (P < 0.05) with increasing level of dietary AURA, whilst there was a quadratic response in uptake of DHA in breast muscle and liver. The study demonstrated the potential of efficiently enriching broiler meat and organs with DHA by feeding AURA.

Phytochemical bioprospecting, antioxidant, antimicrobial and cytotoxicity activities of saline extract from Tithonia diversifolia(Hemsl) A.Gray leaves

Objective:To evaluate antimicrobial and antioxidant properties of saline extract from Tithonia diversifolia leaves by phytochemical bioprospecting,and investigate its safety against animal cells.Methods:The saline extract was prepared,with NaCl(0.15 M),by constant stirring of the dried and pulverized leaves,followed by volume reduction by lyophilization.The extract was phytochemical characterized using ultra-performance liquid chromatography,and total phenol and flavonoid analysis also was performed.The antioxidant capacity was determined through DPPH*radical,the antimicrobial property was evaluated against standard bacteria and fungi,and the viability assays were performed against mice splenocytes.Results:Fifteen compounds were identified belonging to two main classes terpenoids and phenolics.The extract showed 22.185 mg GAE/g of total phenolic compounds and 3.220 mg QE/g of flavonoid.Moreover,extract showed higher antioxidant ability similar to butylated hydroxytoluene a standard molecule[(3.042±0.019)mg AAE/g and(4.12±0.10)mg AAE/g to saline extract and butylated hydroxytoluene,respectively].The antimicrobial assays demonstrated that the extract had a significant antifungal potential against Candida species and could be used with safety against mice splenocytes,in concentrations lower than 50μg/mL,promoting higher proliferation in these cells.Conclusions:Saline extract from Tithonia diversifolia leaves presents potential antioxidant,antifungal properties and induces immunostimulation in mice splenocytes.

Conocarpus erectus L., a plant with a high content of structural sugars, ions and phenolic compounds, shows antioxidant and antimicrobial properties promoted by different organic fractions

Objective: To evaluate the structural and chemical composition of plant and the antioxidant and antimicrobial activities promoted by hexanic, ethanolic and ethyl acetate fractions obtained from leaves of Conocarpus erectus.Methods: Organic fractions were characterized through UPLC-MS and GC-MS.Antioxidant potential was performed through DPPH and molybdenum phosphate techniques.Antibacterial and antifungal assays were performed in accordance with Clinical and Laboratory Standards Institute protocols.Results: The obtained biomass of Conocarpus erectus leaves showed the high presence of glucose(0.45 g/L), cellulose(28.69%), Na(55.126 μg/L) and K(31.163 μg/L).We identified seven compounds in the hexanic and ethyl acetate fractions, and eight compounds in ethanolic fraction.Moreover, phenolic compounds are prevalent in all organic fractions with values of(10.04 ± 0.24),(221.26 ± 1.84),(340.53 ± 0.84) mg/g GAE to hexanic, ethyl acetate and ethanolic fraction, respectively.Antioxidant results showed a high potential in ethyl acetate fraction(71.82 ± 6.87)% and(10.89 ± 0.05)% in DPPH and molybdenum phosphate techniques, respectively.The ethanolic fraction showed moderate bacteriostatic and bactericidal activity against Staphylococcus aureus and presented a high fungistatic potential for all Candida species tested.Conclusions: Organic fractions obtained from leaves of Conocarpus erectus present antimicrobial and antioxidant properties, and these findings contribute to scientific information for the effectiveness on use of this plant in the development of a phytotherapic compound.

Roles of cell fusion, hybridization and polyploid cell formation in cancer metastasis

Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations.Factors that stimulate cell fusion are inflammation and hypoxia.Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes,e.g.,reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition.There is now considerable in vitro,in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis.Of the many changes in cancer cells after hybridizing with leucocytes,it is notable that hybrids acquire resistance to chemo-and radiation therapy.One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization.Regardless of the mechanism of polyploid cell formation,it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive.Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis.In addition,we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.

Ethnobotanical database based screening and identification of potential plant species with antiplasmodial activity against chloroquine-sensitive(3D7) strain of Plasmodium falciparum

Objective: To evaluate the antiplasmodial activity of aqueous-methanolic plant extracts of nine plant species selected, based on ethnobotanical data. Methods: Based on ethnobotanical database, the selected plants were tested for their antiplasmodial activity against chloroquinesensitive(3 D7) strain of Plasmodium falciparum. Qualitative tests and high performance thin layer chromatography analysis were carried out to explore the phytocomponents present in the plant extracts. 1,1-diphenyl-2-picrylhydrazyl antioxidant activity was also determined to check the antioxidant activity of the plant extracts. Results: Moringa oleifera(IC_(50): 3.906 μg/mL),Acalypha indica(IC_(50): 3.906 μg/mL), Hyptis suaveolens(IC_(50): 3.906 μg/mL), Mangifera indica(IC_(50): 4.150 μg/mL) and Averrhoa bilimbi(IC_(50): 4.881 μg/mL) showed very good antiplasmodial activity. Conclusions: Crude extracts of Mangifera indica and Hyptis suaveolens demonstrated the most efficacious antimalarial activity. A bioassay-guided fractionation of these extracts to identify the lead compound is proved to be useful. The results validate the traditional use of the selected plants as antimalarials.

Genetic Analysis of Selected Mutants of Cowpea (<i>Vigna unguiculata</i>[L.] Walp) Using Simple Sequence Repeat and <i>rcb</i>L Markers

Genetic diversity evaluation of mutant lines is essential to facilitate their conservation and utility in breeding programs. Characterization of plant genotypes using morphological markers has limitations which make the procedure inefficient. Application of molecular tools for characterization and diversity assessment has been found useful to complement phenotypic evaluation of plant population. Therefore genetic diversity of some cowpea mutant lines was studied using simple sequence repeats (SSR) markers. DNA barcoding marker, ribulose-1,5-bisphosphate carboxylase(rbcL) of the chloroplast DNA (cpDNA) was also used for characterization and identification of the mutants to species level. The mean polymorphic information content (0.51) obtained from the microsatellites showed high polymorphism in accessing wide genetic diversity among the mutants and their parents. Dendrogram generated revealed 8 groups with most mutants clustered separately from their parents. Sequence analysis revealed insertions/deletions (InDels) and base substitutions as the two main classes of mutations induced in the plastid DNA of the mutants studied. The nucleotide frequencies were 26.95% (A), 34.43% (T), 24.09% (C) and 14.53% (G). A total of 61.38% AT rich region was identified, while GC rich region was found to be 38.62%. Highest rate of mutations were observed in region 3 - 4 indicating that the region is less conserved in cowpea rbcL gene. The present study proved that SSR markers are useful for the genetic diversity assessment of cowpea mutants. It also proved the efficiency of rbcL markers in mutants’ identification. The results indicate that the mutants are valuable genetic resources that have been developed to widen cowpea genetic base.

Lipopeptides for the Fragment-Based Pharmaceutics Design

This paper describes the synthesis of peptide fragments for use in a new type of combinatorial discovery technology, in which the building blocks are brought together by non-covalent interactions, rather than direct chemical bonding. The building blocks of interest—in this case different amino acids—are converted to amphiphiles by attachment to lipid tails. The amphiphiles, when mixed together in aqueous phase, are designed so that they aggregate spontaneously to form micelles. The building blocks form the headgroups of each of the amphiphiles, and these headgroups cover the surface of the micelle in a dynamic close-packed fluid mosaic array. These building blocks come together so closely that two- or three-dimensional structures are created on the surface of the micelles, and these can be screened in biological assays to find out which combination of building blocks is able to elicit a biological response. Lipopeptides consisting of two residues of lipoamino acid and other amino acids moieties have been designed, synthesized, characterized and the ability of these constructs to form supra-molecular assemblies is demonstrated.

Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections

Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like reactions.Compared to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy barrier.Meanwhile,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues.The in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.

Nanoengineered Gallium Ion Incorporated Formulation for Safe and Efficient Reversal of PARP Inhibition and Platinum Resistance in Ovarian Cancer

Platinum-based chemotherapy remains the main systemic treatment of ovarian cancer(OC).However,the inevitable development of platinum and poly(adenosine diphosphate-ribose)polymerase inhibitor(PARPi)resistance is associated with poor outcomes,which becomes a major obstacle in the management of this disease.The present study developed“all-in-one”nanoparticles that contained the PARPi olaparib and gallium(Ga)(III)(olaparib-Ga)to effectively reverse PARPi resistance in platinum-resistant A2780-cis and SKOV3-cis OC cells and in SKOV3-cis tumor models.Notably,the olaparib-Ga suppressed SKOV3-cis tumor growth with negligible toxicity.Moreover,the suppression effect was more evident when combining olaparib-Ga with cisplatin or carboplatin,as evaluated in A2780-cis and SKOV3-cis cells.Mechanistically,the combined treatment induced DNA damage,which elicited the activation of ataxia telangiectasia mutated(ATM)/AMT-and Rad3-related(ATR)checkpoint kinase 1(Chk1)/Chk2 signal transduction pathways.This led to the arrest of cell cycle progression at S and G2/M phases,which eventually resulted in apoptosis and cell death due to unrepairable DNA damage.In addition,effective therapeutic responses to olaparib-Ga and cisplatin combination or olaparib-Ga and carboplatin combination were observed in SKOV3-cis tumor-bearing animal models.Altogether,the present findings demonstrate that olaparib-Ga has therapeutic implications in platinum-resistant OC cells,and the combination of olaparib-Ga with cisplatin or carboplatin may be promising for treating patients with OC who exhibit resistance to both PARPi and platinum.

Advanced surgical technologies for lung cancer treatment:Current status and perspectives

Lung cancer has become one of the key life-threatening factors and is the most common type of tumor.With the improvement of equipment and the improvement of lung cancer awareness,the surgical treatment of lung cancer is becoming more and more mature.Surgery can provide an important part of individualized treatment strategies for patients with different stages of lung cancer and different wishes.In addition,the concept of minimally invasive,precise,and intelligent has triggered a revolutionary change in the surgical treatment strategy for lung cancer.Therefore,this review focuses on the development of lung cancer surgery history,summarizing the era from traditional surgery to the era of minimally invasive thoracic surgery based on TV-assisted thoracic surgery.The operating methods and treatment effects of different surgical methods are comprehensively introduced,and the optimization and improvement of different surgical methods in the future are also discussed.Along with the concept of minimally invasive surgical techniques,there are more and more explorations of nanotechnology in the surgical treatment of lung cancer.The application of nanotechnology in lung cancer imaging,and the combination of surgery with nanomedicine is an effective solution for cancer treatment today.So,this review also summarizes the application prospects of nanotechnology before,during and after lung cancer surgery.

Silica Nanoparticles with Virus-Mimetic Spikes Enable Efficient siRNA Delivery In Vitro and In Vivo

Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades,but its broad applications are severely hampered by delivery vectors.Widely used viral vectors and lipid nanovectors are suffering from immune clearance after repeating usage or requiring refrigerated transportation and storage,respectively.In this work,amino-modified virus-mimetic spike silica nanoparticles(NH_(2)-SSNs)were fabricated using a 1-pot surfactant-free approach with controlled spike lengths,which were demonstrated with excellent delivery performance and biosafety in nearly all cell types and mice.It indicated that NH2-SSNs entered cells by spike-dependent cell membrane docking and dynamin-dependent endocytosis.The positively charged spikes with proper length on the surface can facilitate the efficient encapsulation of RNAs,protect the loaded RNAs from degradation,and trigger an early endosome escape during intracellular trafficking,similarly to the cellular internalization mechanism of virions.Regarding the fantastic properties of NH_(2)-SSNs in nucleic acid delivery,it revealed that nanoparticles with solid spikes on the surface would be excellent vehicles for gene therapy,presenting self-evident advantages in storage,transportation,modification,and quality control in large-scale production compared to lipid nanovectors.

Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics

Background:Excessive scarring and fibrosis are the most severe and common complications of burn injury.Prolonged exposure to high levels of glucocorticoids detrimentally impacts on skin,leading to skin thinning and impaired wound healing.Skin can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme(11β-HSD1).We hypothesised that burn injury would induce 11β-HSD1 expression and local glucocorticoid metabolism,which would have important impacts on wound healing,fibrosis and scarring.We additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn scarring.Methods:Skin 11β-HSD1 expression in burns patients and mice was examined.The impacts of 11β-HSD1 mediating glucocorticoid metabolism on burn wound healing,scar formation and scar elas-ticity and quality were additionally examined using a murine 11β-HSD1 genetic knockout model.Slow-release scaffolds containing therapeutic agents,including active and inactive glucocorticoids,were developed and pre-clinically tested in mice with burn injury.Results:We demonstrate that 11β-HSD1 expression levels increased substantially in both human and mouse skin after burn injury.11β-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition,tensile strength and stiffness,features characteristic of excessive scarring.Application of slow-release prednisone,an inactive glucocorticoid,slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation,myofibroblast generation,collagen production and scar stiffness.Conclusions:Skin 11β-HSD1 expression is a key regulator of wound healing and scarring after burn injury.Application of an inactive glucocorticoid capable of activation by local 11β-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics post burn injury.

Self-crosslinkable chitosan-hyaluronic acid dialdehyde nanoparticles for CD44-targeted siRNA delivery to treat bladder cancer

Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.

Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

Here, we evaluate the contribution of two major biological processes--DNA replication and transcription--to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expres- sion breadth, replication time in local regions and SNP density. SNP density of tissue-specific （TS） genes is sig- nificantly higher than that of housekeeping （HK） genes. TS genes tend to locate in late-replicating genomic re- gions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addi- tion, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

Delivery of therapeutic oligonucleotides in nanoscale

Therapeutic oligonucleotides(TOs)represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable.However,efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations.Emerging as a significant drug delivery vector,nanoparticles(NPs)can not only protect TOs from nuclease degradation and enhance their tumor accumulation,but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index.Furthermore,targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs.In the past decades,remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes.In this review,we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs,and then describe the obstacles that prevent the clinical translation of TOs,followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles,polymeric nanoparticles,gold nanoparticles,porous nanoparticles,DNA/RNA nanoassembly,extracellular vesicles,and imaging-guided drug delivery nanoparticles.

Construction of Dual-Biofunctionalized Chitosan/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration

Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration.However,most studies on novel biofunctionalized implants have emphasized the promotion of neuronal and axonal repair over vascularization,a process critical for long-term functional restoration.We constructed a dual-biofunctionalized chitosan/collagen composite scaffold with Ile-Lys-Val-Ala-Val(IKVAV)and vascular endothelial growth factor(VEGF)by combining solution blending,in situ lyophilization,and surface biomodification.Immobilization of VEGF and IKVAV on the scaffolds was confirmed both qualitatively by staining and quantitatively by ELISA.Various single-and dual-biofunctionalized scaffolds were compared for the promotion of endothelial cell(EC)and Schwann cell(SC)proliferation as well as the induction of angiogenic and neuroregeneration-associated genes by these cells in culture.The efficacy of these scaffolds for vascularization was evaluated by implantation in chicken embryos,while functional repair capacity in vivo was assessed in rats subjected to a 10mm sciatic nerve injury.Dual-biofunctionalized scaffolds supported robust EC and SC proliferation and upregulated the expression levels of multiple genes and proteins related to neuroregeneration and vascularization.Dual-biofunctionalized scaffolds demonstrated superior vascularization induction in embryos and greater promotion of vascularization,myelination,and functional recovery in rats.These findings support the clinical potential of VEGF/IKVAV dual-biofunctionalized chitosan/collagen composite scaffolds for facilitating peripheral nerve regeneration,making it an attractive candidate for repairing critical nerve defect.The study may provide a critical experimental and theoretical basis for the development and design of new artificial nerve implants with excellent biological performance.

Bionic Microbubble Neutrophil Composite for InflammationResponsive Atherosclerotic Vulnerable Plaque Pluripotent Intervention

Rupture or erosion of inflammatory atherosclerotic vulnerable plaque is essential to acute coronary events,while the target intervene of vulnerable plaque is very challenging,due to the relatively small volume,high hemodynamic shear stress,and multifactorial nature of the lesion foci.Herein,we utilize the biological functionality of neutrophil and the versatility of microbubble in the acoustic field,to form Neu-balloon through CD11b antibody binding.The Neu-balloon inherits the advantage of neutrophils on firming the endothelium adhesion even at shear stress up to 16 dyne/cm^(2)and also maintains the acoustic enhancement property from the microbubble,to accumulate at atherosclerotic lesions under acoustic in an atherosclerotic Apo E^(-/-) mice model.Interestingly,Neo-balloon also has high and broad drug loading capacity,which enables the delivery of indocyanine green and miR-126a-5p into vulnerable plagues in vivo.Overall,the bionic Neu-balloon holds great potential to boost on-demand drug transportation into plaques in vivo.

Sexual selection and incipient speciation in Hawaiian Drosophila

We conducted sexual selection experiments to produce strains with high and low mating discrimination in females of laboratory strains of Hawaiian Drosophila, D.silvestris, then examined secondary sexual traits of these two lines, and compared them with that of standard line. In order to do this, we screened out super-males which mated successfully with females and with high mating records;and poor males which usually could not mate successfully with females and had low mating records. In the meantime,choosy females were also screened out, which almost never responded to males' nuptial dance and were difficult to be mated; but indiscriminate females were on the contrary,which were very ready to accept male's nuptial dance and were very easy to be mated. As a result, by mating supermales with choosy females, we were able to produce the high-line strain; similarly, for the low line, we mated poor males with indiscriminate females and we had a strain that was significantly different from our standard strain within just two generations of selection, i.e., morphological trait differences were measured between the standard strain and the two selected lines, which indicated that mating discrimination has affected secondary sexual traits of the lowline strain significantly: Cilia number on the foretibia of low-line males is significantly different from that of the standard line, which perhaps was the indication of incipient speciation in Hawaiian Drosophila.

Helper T Cell(CD4^(+))Targeted Tacrolimus Delivery Mediates Precise Suppression of Allogeneic Humoral Immunity

Antibody-mediated rejection(ABMR)is a major cause of dysfunction and loss of transplanted kidney.The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells.However,the prognosis of patients following current treatment is poor.T follicular helper cells(Tfh)play an important role in allograft-specific antibodies secreting plasma cell(PC)development.Tfh cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders,such as transplant rejection and autoimmune diseases.Tacrolimus(Tac),the primary immunosuppressant,prevents rejection by reducing T cell activation.However,its administration should be closely monitored to avoid serious side effects.In this study,we investigated whether Tac delivery to helper T(CD4^(+))cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen exposure.Results showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development,PC,and donor-specific antibody(DSA)generation without causing severe side effects compared with delivery through the drug administration pathway.This study provides a promising therapeutic strategy for preventing humoral rejection in solid organ transplantation.The specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.