Organoid-derived human retinal progenitor cells promote early dedifferentiation of Müller glia in Royal College of Surgeons rats

AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferentiation,thus improving visual function and delaying retinal degenerative progression.METHODS:h ERO-RPCs were subretinally transplanted into Royal College of Surgeons(RCS)rats.Electroretinography(ERG)recording was performed at 4 and 8wk postoperation to assess retinal function.Using immunofluorescence,the changes in outer nuclear layer(ONL)thickness and retinal Müller glia were explored at 2,4,and 8wk postoperation.To verify the effect of h ERO-RPCs on Müller glia in vitro,we cocultured h ERO-RPCs with Müller glia with a Transwell system.After coculture,Ki67 staining and quantitative polymerase chain reaction(q PCR)were performed to measure the proliferation and m RNA levels of Müller glia respectively.Cell migration experiment was used to detect the effect of h ERO-RPCs on Müller glial migration.Comparisons between two groups were performed by the unpaired Student’s t-test,and comparisons among multiple groups were made with one-way ANOVA followed by Tukey’s multiple comparison test.RESULTS:The visual function and ONL thickness of RCS rats were significantly improved by transplantation of h ERO-RPCs at 4 and 8wk postoperation.In addition to inhibiting gliosis at 4 and 8wk postoperation,h ERO-RPCs significantly increased the expression of dedifferentiation-associated transcriptional factor in Müller glia and promoted the migration at 2,4 and 8wk postoperation,but not the transdifferentiation of these cells in RCS rats.In vitro,using the Transwell system,we found that h ERO-RPCs promoted the proliferation and migration of primary rat Müller glia and induced their dedifferentiation at the m RNA level.CONCLUSION:These results show that h ERO-RPCs might promote early dedifferentiation of Müller glia,which may provide novel insights into the mechanisms of stem cell therapy and Müller glial reprogramming,contributing to the development of novel therapies for retinal degeneration disorders.

Accurate time synchronization of power reference station based on BD3 system

A Beidou 3(BD3)system-based power reference station can provide high-precision time synchronization for power distribution systems by sending synchronization data packets to devices in a multi-hop routing fashion.However,optimizing route selection to reduce both time synchronization error and delay is a challenging problem.In this paper,we establish a software-defined network-enabled power reference station time synchronization framework based on BD3.Then,we formulate the joint problem to minimize cumulative synchronization error and delay through multi-hop route selection optimization.A back propagation(BP)neural network-improved intelligent time synchronization route selection algorithm named BP-RS is proposed to learn the optimal route selection,which uses a BP neural network to dynamically adjust the exploration factor to achieve rapid convergence.Simulation results show the superior performance of BP-RS in synchronization delay,synchronization error,and adaptability with changing routing topologies.

Characterization of the Novel Insecticidal Crystal Protein Cyt3Aa1 from <i>Bacillus thuringiensis</i>TD516

Bacillus thuringiensis (Bt) produces two families of insecticidal crystal proteins, i.e., crystalline (Cry) and cytolytic (Cyt) toxins. Cyt3Aa1, the newest Cyt family member, is produced by Bt TD516. Bioassay results have shown that Cyt3Aa1 has weak hemolytic activity against human red blood cells and is not toxic to A. aegypti larvae, but causing a teratogenic effect. The three-dimensional structure of Cyt3Aa1 has a typical cytolysin fold containing a β-sheet held by two surrounding α-helical layers, resembling the previously reported Cyt1Aa and Cyt2Aa structures, which indicated that Cyt3Aa1 might be a membrane-perforation toxin and could induce synergism with Cry protein. This study provides a new source of insecticidal crystal proteins, and presents a foundation for understanding the biological characterization of it, which will aid in the development of strategies to cope with the potential problem of insect resistance.

Clinical significance of changes in the Th17/Treg ratio in autoimmune liver disease

AIM To investigate the levels, ratios, and clinical significance of T helper 17(Th17) cells and regulatory T(Treg) cells in the peripheral blood of patients with autoimmune liver disease(AILD). METHODS F o r t y-t w o A I L D p a t i e n t s w e r e i n c l u d e d i n t h e experimental group(group E), and 11 healthy subjects were recruited as the control group(group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients. RESULTS The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C(P < 0.01), whereas the percentage of Tregs was lower in the group E patients(P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission(P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment(P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD.CONCLUSION A high Th17/Treg ratio appears to predict poor shortterm prognosis in patients with AILD in the active stage.

Less and shrunken pollen 1(LSP1) encodes a member of the ABC transporter family required for pollen wall development in rice(Oryza sativa L.)

Pollen fertility is an agronomic trait that strongly influences rice yield. Recent studies have revealed that the development of the pollen wall is required for pollen fertility and is regulated by several genes. However, the mechanisms underlying pollen and pollen wall development in rice remain largely unknown. In the present study, a point mutation in a gene on chromosome 1 was identified that resulted in the production of less and shrunken pollen(LSP) and led to defects in pollen wall formation. This gene was named LSP1 and was found to encode a member of the adenosine triphosphate-binding cassette(ABC)transporter G subfamily, OsABCG3. Two other loss-of-function mutants of LSP1/OsABCG3,generated using CRISPR/Cas9 technology, showed the same male sterile phenotype. The LSP1/OsABCG3 gene showed a spatio-temporal expression pattern in the developing anthers, and is an ortholog of the Arabidopsis genes At ABCG1 and At ABCG16, which play an important role in pollen wall development. Mutation of LSP1/OsABCG3 affected the expression of several genes involved in pollen and pollen wall formation. These results suggest that LSP1/OsABCG3 is critical for normal pollen fertility and shed light on the molecular mechanisms underlying rice pollen wall development.

Power-Minimizing Resource Allocation in Multiuser Cooperative Relay Communications

In this paper, we investigate the power-minimizing resource allocation problem in multiuser cooperative relay communication systems. A joint optimization problem involving subcarrier assignment, relay selection and power allocation is formulated. Since the problem cannot be solved directly, we decompose it into three subproblems. According to the equivalent channel gains and the target rates of users, the subcarrier assignment and relay selection are conducted. Motivated by the water-filling algorithm, we propose a power allocation algorithm with cooperative features. Simulations results indicate that the proposed algorithm performs better in terms of the total transmit power consumption than the existing algorithms.

The Pael-R gene does not mediate the changes in rotenone-induced Parkinson's disease model cells

In this study, we established cell models for Parkinson＇s disease using rotenone. An RNA interfer- ence vector targeting Parkin-associated endothelin receptor-like receptor （Pad-R） was transfected into the model cells. The results of reverse-transcription polymerase chain reaction and western blot analysis showed that Pael-R expression was decreased after RNA interference compared with the control group （no treatment） and the model group （rotenone treatment）, while the rate of apoptosis and survival of dopaminergic cells did not differ significantly between groups, as detected by flow cytometry and an MTT assay. These experimental findings indicate that the Pael-R gene has no role in the changes in rotenone-induced Parkinson＇s disease model cells.

Mechanical characteristics of composite honeycomb sandwichstructures under oblique impact

Carbon fiber reinforced polymer(CFRP)and CFRP-based composite honeycomb sandwich structures are particularly sensitive to impact.The mechanical characteristics of composite honeycomb sandwich structures under oblique impact are studied by numerical simulation and experiment.The oblique impact model is established,and the reliability of the model is verified by the oblique impact test.To further analyze the influence of structural parameters on energy absorption under oblique impact,the influence of impact angle,face sheet thickness and wall thickness of the honeycomb is numerically studied.The results show that the impact angle has an important effect on energy distribution.The structural parameters also have an effect on the peak contact force,contact time,and energy absorption,and the effect is different from normal impact due to the presence of frictional dissipation energy.Compared with normal impact,the debonding of oblique impact will be reduced,but the buckling range of the honeycomb core will be expanded.

Preparation and Electrorheological Response of PAL/TiO_(2)/PANI Nanorods

Using palygorskite(PAL)as template,the PAL/TiO_(2)/PANI nano-rods were synthesized by heterogeneous precipitation and in-situ polymerization.The synthesized PAL/TiO_(2)/PANI nanorods were used as a novel electrorheological(ER)fluid by mixing with silicone oil,which showed excellent ER effect.The yield stress of the PAL/TiO_(2)/PANI based ER fluid(15 vol%)reached 8.8 kPa under 4 kV mm^(−1) electric field.The dynamic shear stress of the PAL/TiO_(2)/PANI based ER fluid could maintain a stable level in the shear rate range of 0.1–100 s^(−1).Furthermore,the PAL/TiO_(2)/PANI ER fluid exhibited excellent suspension stability.

Development-related mitochondrial properties of retinal pigment epithelium cells derived from hEROs

AIM:To explore the temporal mitochondrial characteristics of retinal pigment epithelium(RPE)cells obtained from human embryonic stem cells(hESC)-derived retinal organoids(hEROs-RPE),to verify the optimal period for using hEROs-RPE as donor cells from the aspect of mitochondria and to optimize RPE cell-based therapeutic strategies for age-related macular degeneration(AMD).METHODS:RPE cells were obtained from hEROs and from spontaneous differentiation(SD-RPE).The mitochondrial characteristics were analyzed every 20 d from day 60 to 160.Mitochondrial quantity was measured by MitoTracker Green staining.Transmission electron microscopy(TEM)was adopted to assess the morphological features of the mitochondria,including their distribution,length,and cristae.Mitochondrial membrane potentials(MMPs)were determined by JC-1 staining and evaluated by flow cytometry,reactive oxygen species(ROS)levels were evaluated by flow cytometry,and adenosine triphosphate(ATP)levels were measured by a luminometer.Differences between two groups were analyzed by the independentsamples t-test,and comparisons among multiple groups were made using one-way ANOVA or Kruskal-Wallis H test when equal variance was not assumed.RESULTS:hEROs-RPE and SD-RPE cells from day 60 to 160 were successfully differentiated from hESCs and expressed RPE markers(Pax6,MITF,Bestrophin-1,RPE65,Cralbp).RPE features,including a cobblestonelike morphology with tight junctions(ZO-1),pigments and microvilli,were also observed in both hEROs-RPE and SDRPE cells.The mitochondrial quantities of hEROs-RPE and SD-RPE cells both peaked at day 80.However,the cristae of hEROs-RPE mitochondria were less mature and abundant than those of SD-RPE mitochondria at day 80,with hEROsRPE mitochondria becoming mature at day 100.Both hEROs-RPE and SD-RPE cells showed low ROS levels from day 100 to 140 and maintained a normal MMP during this period.However,hEROs-RPE mitochondria maintained a longer time to produce high levels of ATP(from day 120 to 140)than SD-RPE cells(only day 120).CONCLUSION:hEROs-RPE mitochondria develop more slowly and maintain a longer time to supply high-level energy than SD-RPE mitochondria.From the mitochondrial perspective,hEROs-RPE cells from day 100 to 140 are an optimal cell source for treating AMD.

Impulse Radio UWB Signal Detection Based on Compressed Sensing

The extremely high sampling rate is a challenge for ultra-wideband (UWB) communication. In this paper, we study the compressed sensing (CS) based impulse radio UWB (IR-UWB) signal detection and propose an IR-UWB signal detection algorithm based on compressive sampling matching pursuit (CoSaMP). The proposed algorithm relies on the fact that UWB received signal is sparse in the time domain. The new algorithm can significantly reduce the sampling rate required by the detection and provides a better performance in case of the low signal-to-noise ratio when comparing with the existing matching pursuit (MP) based detection algorithm. Simulation results demonstrate the effectiveness of the proposed algorithm.

Photoredox-neutral ring-opening pyridylation of cyclic oximes via phosphoranyl radical-mediated N-O/C-C bond cleavages and sequential radical-radical coupling

A novel photoredox-neutral ring-opening pyridylation of non-prefunctionalized cyclic oximes has been accomplished through phosphoranyl radical-mediated N-O/C-C bond cleavages followed by radicalradical coupling.This mild acid-,base-,and oxidant-free protocol provides highly site-selective and efficient access to distally pyridylated alkylnitriles,which could be scale-up synthesized and readily converted into skeletally diverse compounds.Notably,the oxidized ground-state photocatalyst generated via the SET oxidation of the highly reducing excited-state photocatalyst by cyanopyridines might initiate the following phosphoranyl radical-mediated deoxygenative process.

Ferroptosis:mechanisms and links with diseases

Ferroptosis is an iron-dependent cell death,which is different from apoptosis,necrosis,autophagy,and other forms of cell death.The process of feroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids,which can be prevented by iron chelators(e.g.deferiprone,deferoxamine)and small lipophilic antioxidants(e.g,ferrostatin,liproxstatin).This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association withseveral pathways,including iron,lipid,and cysteine metabolism.We have further discussed the contribution of ferroptosis to thepathogenesis of several diseases such as cancer,ischemia/reperfusion,and various neurodegenerative diseases(e.g.Alzheimersdisease and Parkinson's disease),and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.

Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion

Ischemic stroke represents a significant danger to human beings,especially the elderly.Interventions are only available to remove the clot,and the mechanism of neuronal death during ischemic stroke is still in debate.Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs.

GRAIN LENGTH AND AWN 1 negatively regulates grain size in rice

Grain size is an important factor determining yield in rice. Here, we identified a recessive mutant gene, grain length and awn 1 (gla1), which caused a significant increase in grain length and weight, and was associated with long awns. The gla1 mutation was mapped to a single-nucleotide polymorphism in a gene encoding a cytoplasmically-localized mitogen-activated protein kinase (MAPK) phosphatase. Overexpression of GLA1 caused a decrease in grain length, and the GLA1 protein interacted with OsMAPK6. These results suggest that GLA1 may serve as a negative regulator of the OsMAPKK4-OsMAPK6 cascade, controlling grain size via the dephosphorylation of OsMAPK6.

The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease

In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor(VDR)gene polymorphisms from PubMed,Web of Science,Cochrane Library,and Embase databases.We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity.Furthermore,higher vitamin D concentrations are linked to better cognitive function and mood in PD patients.Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent,but the Fokl(C/M)polymorphism is significantly linked with PD.The occurrence of Fokl(CT)gene polymorphism may influence the risk,severity,and cognitive ability of PD patients,while also possibly influencing the effect of Vitamin D3 supplementation in PD patients.In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission,interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.

DEAP1 encodes a fasciclin-like arabinogalactan protein required for male fertility in rice

Arabinogalactan proteins(AGPs)are widely distributed in plant cells.Fasciclin-like AGPs(FLAs)belong to a subclass of AGPs that play important roles in plant growth and development.However,little is known about the biological functions of rice FLA.Herein,we report the identification of a male-sterile mutant of DEFECTIVE EXINE AND APERTURE PATTERNING1(DEAP1)in rice.The deap1 mutant anthers produced aberrant pollen grains with defective exine formation and a flattened aperture annulus and exhibited slightly delayed tapetum degradation.DEAP1 encodes a plasma membrane-associated member of groupⅢplant FLAs and is specifically and temporally expressed in reproductive cells and the tapetum layer during male development.Gene expression studies revealed reduced transcript accumulation of genes related to exine formation,aperture patterning,and tapetum development in deap1 mutants.Moreover,DEAP1 may interact with two rice D6 PROTEIN KINASE-LIKE3 s(OsD6PKL3s),homologs of a known Arabidopsis aperture protein,to affect rice pollen aperture development.Our findings suggested that DEAP1 is involved in male reproductive development and may affect exine formation and aperture patterning,thereby providing new insights into the molecular functions of plant FLAs in male fertility.

Ultrathin,elastic,and self-adhesive nanofiber bio-tape:An intraoperative drug-loading module for ureteral stents with localized and controlled drug delivery properties for customized therapy

During the postoperative management of urinary diseases,oral or intravenous administration of drugs and implanting ureteral stents are usually required,making localized drug delivery by ureteral stent a precise and effective medication strategy.In the traditional drug loading method,the drug was premixed in the implants in production lines and the versatility of drugs was restricted.However,the complex situation in the urinary system fails the possibility of finding a“one fits all”medication plan,and the intraoperative drug-loading of implants is highly desired to support customized therapy.Here,we designed an ultrathin(8μm),elastic,and self-adhesive nanofiber bio-tape(NFBT)that can easily encapsulate drugs on the stent surface for controllable localized drug delivery.The NFBT exhibited high binding strength to a ureteral stent,a sustained release over 7 d in PBS for hydrophilic drug,and a zero-order release curve over 28 days for the hydrophobic drug nitrofurantoin(NFT).Further in vivo experiments using a porcine ureteral tract infection model demonstrated that NFBT loaded with NFT could significantly reduce the bacterial concentration in urine.The total amount of NFT delivered by the NFBT was about 2.68 wt%of the recommended dose for the systemic administration.

Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in nonsmall cell lung cancer

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma(NSCLC),we performed a two-cohort of genome-wide association studies(GWAS),including 34 for WES-based and 433 for microarray-based analyses,as well as two independent validation cohorts.After integrating the results of two studies,the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples,and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments.We found that a total of 68 variations were significant at P<1×10^(-3)in cohort 1 discovery stage,of which 3 SNPs were verified in 262 independent samples.A total of541 SNPs were significant at P<1×10^(-4)in cohort 2 discovery stage,of which 8 SNPs were verified in 347 independent samples.Comparing the validated SNPs in two GWAS,ADCY1 gene was verified in both independent studies.The results of fine-mapping showed that the G allele carriers of ADCY1rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy.In conclusion,our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.