Search

In many bilaterians, Hox genes are generally clustered along the chromosomes and expressed in spatial and temporal order. In vertebrates, the expression of Hox genes follows a whole-cluster spatio-temporal collinearity (WSTC) pattern, whereas in some invertebrates the expression of Hox genes exhibits a subcluster-level spatio-temporal collinearity pattern. In bilaterians, the diversity of collinearity patterns and the cause of collinearity differences in Hox gene expression remain poorly understood. Here, we investigate genomic organization and expression pattern of Hox genes in the echiuran worm Urechis unicinctus (Annelida, Echiura). Urechis unicinctus has a split cluster with four subclusters divided by non-Hox genes: first subcluster ( Hox1 and Hox2 ), second subcluster ( Hox3 ), third subcluster ( Hox4 , Hox5 , Lox5 , Antp and Lox4 ), fourth subcluster ( Lox2 and Post2 ). The expression of U. unicinctus Hox genes shows a subcluster-based whole-cluster spatio-temporal collinearity (S-WSTC) pattern: the anterior-most genes in each subcluster are activated in a spatially and temporally colinear manner (reminiscent of WSTC), with the subsequent genes in each subcluster then being very similar to their respective anterior-most subcluster gene. Combining genomic organization and expression profiles of Hox genes in different invertebrate lineages, we propose that the spatio-temporal collinearity of invertebrate Hox is subcluster-based.

The mechanism of short-term and high-magnitude sea-level oscillation has long been debated between glacio- and aquifer-eustasy (Miller et al., 2005; Haq, 2014), largely due to the sparse robust evidence for the aquifer-eustasy, and the little knowledge about hydrological dynamics behind it. Non-marine/ continental greenhouse archives (e.g. lake level) and their temporal correlation to marine successions (e.g. sea level) could give clue to aquifer-eustasy (Wagreich et al., 2014). The Songliao Basin (SLB), in Northeast China, is one of the largest Mesozoic terrestrial inland basins and has deposited the near whole Cretaceous successions (Wang et al., 2013). The greenhouse Late Santonian-Early Campanian Lower Nenjiang Formation (K2n1+2), recovered from three boreholes in SLB provides a unique opportunity for validating and decoding the aquifer-eustasy. Initially the cyclostratigraphy of logging gamma ray (GR) and Thorium (Th) series from three boreholes was implemented, which in junction with the radioactive ages renewed the chronology framework of SLB. Using the astronomically tuned GR and Th series, the lake level of SLB, which is recovered from sedimentary noise modeling (Li et al., 2019) and presents the water table of groundwater reservoir, shows a clear out-of-phase relationship with the coeval sea level, validating the aquifer-eustasy hypothesis. The lake level shows prominent ~1.2Myr cycles and a well-coupled relationship with sea level and obliquity modulation, indicating that the orbital obliquity drove the lake level and modulated the water exchange between ocean and continent during the Cretaceous greenhouse period. The strong precipitation indicated by the negative excursion of Ostracods δ18O (Chamberlain et al., 2013) well correlates to the high lake level, high obliquity, and low sea level, suggesting that during obliquity modulation maxima, more moisture was precipitated into the high-latitude continents, consequently recharging the aquifer and raising the lake level while drawing down the sea level and vice versa. The close correspondence between reported marine incursion layers (Hu et al., 2015) and lowstand of sea level casts a doubt on marine incursion hypothesis in the SLB, more work is needed to reconcile this paradox. Overall, this study gives robust geological evidence for aquifer-eustasy and firstly decodes its role on Cretaceous short-term eustasy.

Background Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes. Results In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log2(TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct = − 0.5405 log2(TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data. Conclusion Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus.

A new method of replacing soft soil with lightweight foam concrete (lightweight foam concrete replacement method, LFCRM) is carried out to treat deep soft foundation under the low-filled embankment. Two-dimensional models with different thicknesses of replacement are established by the finite element platform (MIDAS/GTS). Moreover, the deformation and stress distribution law of treated foundation is analyzed by numerical simulation with different models. The results are as follows: (1) LFCRM can offset part of dead load; (2) the transverse distribution of settlement presents an “arc” shape; (3) the replacement made of lightweight foam concrete can spread stress well; (4) increase of replacement thickness will cause the necking of the additional stress “bubble”; (5) initial excess pore water pressure is related to the additional stress, and its dissipation path is deduced; (6) preliminary analysis indicates the feasibility of LFCRM for treating deep soft foundation with the low-filled embankment.

Two phosphorylcarboxylic acids, 3-((bis(2-ethylhexyloxy))phosphoryl)propanoic acid (PPA) and 3-((bis(2-ethylhexyloxy))phosphoryl)-3-phenylpropanoic acid (PPPA), were synthesized for separating yttrium from other rare earths in the chloride feed of ion-adsorption type rare earth concentrate. The effect of the factors such as pH1/2, temperature, saponification degree and phase modifiers was investigated. The separation efficiencies of PPA and PPPA are obviously better than the typical extractants such as sec-octylphenoxy acetic acid (CA-12) and naphthenic acid (NA). The extraction process of rare earths by PPA and PPPA is a cation exchanging reaction, which is similar to those of CA-12 and NA. The loaded rare earths in both PPA and PPPA systems can be effectively back-extracted by 0.5 mol/L HCl or higher concentration. A cascade extraction process for separating yttrium from other rare earths was developed using PPPA as the extractant. The yttrium product with the purity of 97.20 wt% was obtained by 35 stages of extraction and 12 stages of scrubbing.

As an extensively used gasoline additive, methyl tertiary butyl ether (MTBE) can leak into the subsurface, and this not only damages the ecological environment but also affects the geotechnical characteristics of the soil. In this study, the geotechnical properties of MTBE-contaminated soil, such as the basic physical properties of strength, compressibility, hydraulic conductivity, leachability, electrical resistivity and microstructural characteristics, are comprehensively investigated. The results show that the Atterberg limits consistently decrease with increasing MTBE content in the soil. As the MTBE content increases from 0 to 10%, the specific surface area of the soil decreases by 28%, the sand content increases by 22%, and the clay and silt contents decrease by 3 and 18%, respectively. The soil compression index, hydraulic conductivity, leached MTBE concentration and electrical resistivity increase, while the unconfined compressive strength (UCS) decreases, with increasing MTBE content. Microstructural analysis shows that increasing the MTBE content results in mineralogical alterations that decrease the illite and kaolinite content of the soil. The aggregation and flocculated structures can be detected by an increase in the number and size of inter-aggregate pores. In addition, the electrical resistivity of the contaminated soil is used to assess the geotechnical properties of the MTBE-contaminated soil based on well-established empirical relations.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses. ispartof: INTERNATIONAL JOURNAL OF CANCER vol:151 issue:1 pages:128-137 ispartof: location:United States status: published

Iron (Fe) deficiency seriously affects crop growth and yield. This study investigated whether and how an endophytic isolate, strain Bacillus sp. WR12, alleviates Fe deficiency in wheat (Triticum aestivum L.). Bacillus sp. WR12 and wheat seedlings were hydroponically co-cultured for 2 weeks under Fe-deficient conditions. To evaluate the Fe deficiency alleviating potential, wheat growth parameters were compared. To elucidate possible mechanisms, the genome of WR12 was sequenced, and production of siderophores was detected. In addition, transcriptomes of wheat root were compared, and accumulation of phenolic compounds was measured. Bacillus sp. WR12 significantly increased root length and dry weight, leaf chlorophyll content and Fe content in Fe-deficient wheat seedlings. Genome analysis of WR12 and CAS agar diffusion test demonstrated that WR12 had a dhbACEBF operon and produced siderophores. Significant upregulation of this operon and more siderophore synthesis in WR12 were observed when Fe was insufficient. Transcriptomic data of roots indicated change of expression of a large number of genes in Fe-deficient wheat after WR12 inoculation. Particularly, PAL, CYP73A, COMT, F5H, HCT and CAD genes involved in phenylpropane biosynthesis were significantly up-regulated. Moreover, elevated phenol accumulation was detected in the root of wheat after inoculation with WR12 under Fe deficiency. Bacillus sp. WR12 alleviates Fe deficiency in wheat and this can be partially attributed to enhanced siderophore production and phenol accumulation.

Background The genus Aster on the Qinghai-Tibet Plateau is an important part of its ecosystem. In this study, 94 accessions of Astereae species (including 25 taxa from the Qinghai-Tibet Plateau) were included for the phylogenetic analyses using nrDNA ITS and cpDNA trnL-F sequences. Then, based on the phylogenetic analysis results of Bayesian method, the chart of network topology, the graph of divergence time, the map of biogeography and the figure of ancestral state reconstruction (including the number of ray florets, number of pappus and number of bracts.) were constructed. Results (1)Phylogenetic analysis of the ITS gene showed that Astereae species in Qinghai-Tibetan Plateau were divided into two branches, but the analysis result of the trnL-F gene showed that they were clustered in one branch. (2)Molecular dating estimated that the divergence time of Astereae species in Qinghai-Tibet Plateau could be dated back to 2.02 Ma. (3)The ancestral state of Astereae species was reconstructed, and the results showed that the trait evolution in the Qinghai-Tibet Plateau region was different from that in other regions. (4)Biogeography results showed that Aster species in the Qinghai-Tibet Plateau were mainly from Eurasia. Conclusion This study provides a scientific basis and reference for the genetic relationship of Aster species and related genera.

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

Aiming at the slow speed and low accuracy of traditional facial expression recognition, a new method combining the attention mechanism is proposed. Firstly, group convolution is used to reduce network parameters. The channels of traditional convolution are grouped to cut off redundant connections so that the number of parameters decreases significantly. Secondly, the ERFNet network model was improved by combining the asymmetric residual module and the weak bottleneck module to improve the running speed and reduce the loss of accuracy. Finally, the attention mechanism was added into the feature extraction network to improve the recognition precision. The experiment shows that compared with traditional face recognition methods, the proposed method can improve the recognition precision and recall significantly; in CK+, Jaffe, and Fer2013 datasets, the recognition precision can reach 88.81%, 82.16%, and 79.33%, respectively.

An innovative melt treatment method known as internal electromagnetic stirring is proposed and used in direct chill casting to refine the microstructure and homogenize the composition of a large-scale 7075 aluminum alloy billet. The effects of internal electromagnetic stirring on the billet are investigated. The results show that the internal electromagnetic stirring significantly refines the microstructure and decreases macrosegregation compared with conventional direction chill casting. The average grain size is decreased to 211–219 μm, and the largest relative positive and negative macrosegregation rates of Zn, Mg, and Cu are decreased to 2.44% and 2.11%, 1.56% and 1.32%, and 2.64% and 1.98%, respectively. The internal electromagnetic stirring refines the microstructure by increasing the number of nuclei, creating a relatively low and homogeneous temperature field, and decreasing the sump depth. Furthermore, the internal electromagnetic stirring decreases the macrosegregation by inhibiting the thermo-solutal convection, strengthening the equivalent shrinkage-induced flow, and decreasing the permeability.

It is a challenge to regulate charge flow synergistically at the atomic level to modulate gradient hydrogen migration (H migration) for boosting photocatalytic hydrogen evolution. Herein, a self-adapting S vacancy (Vs) induced with atomic Cu introduction into ZnIn2S4 nanosheets was fabricated elaborately, which can tune charge separation and construct a gradient channel for H migration. Detailed experimental results and theoretical simulations uncover the behavior mechanism of Vs generation with Cu introduction after substituting a Zn atom tendentiously. Cu-S bond shrinkage and Zn-S bond distortion are presented around Vs areas. Besides, Vs induced by Cu introduction lowers the internal electric field to restrain electron transmission between layers, which are enriched on the Vs area because of the lower surface electrostatic potential. Atomic Cu and Vs show a synergistic effect for regulating regional charge separation due to the Cu dopant being a hole trap and Vs being an electron trap. The channels for H migration with gradient ΔGH0 are constructed by different S atom sites, which are modulated by Vs. Gradient H migration driven by a photothermal effect occurs on an identical surface without striding across a heterogeneous interface, which is a valid pathway with lower resistance for boosting H2 release. Ultimately, 5 mol % Cu confined in ZnIn2S4 nanosheets achieves an optimum photocatalytic hydrogen evolution activity of 9.8647 mmol g-1 h-1, which is 14.8 times higher than 0.6640 mmol g-1 h-1 for ZnIn2S4, and apparent quantum efficiency reaches 37.11% at 420 nm. This work demonstrates the behavior mechanism of atomic substitution and provides cognition for hydrogen evolution mechanism deeply.

An efficient and widely tunable Si-prism-array coupled terahertz-wave parametric oscillator (TPO) with a very narrow linewidth is demonstrated by using a shallow surface cross-pump configuration. The shallow surface cross-pumping form was realized by totally reflect the pump beam at the THz-wave exit surface. Widely THz-wave tuning range of 0.6–3.9 THz is realized with a 1-mm diameter pump, and the high-frequency end even reached 5.5 THz with a 2-mm diameter pump to increase the nonlinear gain length. The measured Stokes linewidth was 0.07 nm, which is compressed by 70% for that of the conventional TPOs. The highest THz-wave output energy of 2.4 μJ was achieved at 2 THz under 15 mJ pumping, corresponding to an energy conversion efficiency of 1.6 × 10−4. The mechanism of the frequency-selection effect in cross-pumped stimulated polariton scatterings was discussed by calculating the single-pass parametric gain for different phase mismatches.

The geometric bone model of patients is an important basis for individualized biomechanical modeling and analysis, formulation of surgical planning, design of surgical guide plate, and customization of artificial joint. In this study, a rapid three-dimensional (3D) reconstruction method based on statistical shape model was proposed for femur. Combined with the patient plain X-ray film data, rapid 3D modeling of individualized patient femur geometry was realized. The average error of 3D reconstruction was 1.597-1.842 mm, and the root mean square error was 1.453-2.341 mm. The average errors of femoral head diameter, cervical shaft angle, offset distance and anteversion angle of the reconstructed model were 0.597 mm, 1.163°, 1.389 mm and 1.354°, respectively. Compared with traditional modeling methods, the new method could achieve rapid 3D reconstruction of femur more accurately in a shorter time. This paper provides a new technology for rapid 3D modeling of bone geometry, which is helpful to promote rapid biomechanical analysis for patients, and provides a new idea for the selection of orthopedic implants and the rapid research and development of customized implants.患者的骨几何模型是个体化生物力学建模与分析、手术规划方案制定、手术导板设计、人工关节定制的重要基础。本研究针对股骨提出一种基于统计形状模型的三维快速重建方法，结合患者X线平片数据，实现了个体化患者股骨几何的快速三维建模。模型三维重建的平均误差在1.597~1.842 mm之间，均方根误差在1.453~2.341 mm之间。重建模型的股骨头直径、颈干角、偏置距离和前倾角的平均误差分别为0.597 mm、1.163°、1.389 mm和1.354°。相比传统建模方法，新方法能够在更短时间内较为准确地实现股骨三维快速重建。本文为骨几何三维快速建模提供了新技术，有助于推动针对患者的快速生物力学分析，为骨科植入物的选择与定制植入物假体的快速研发提供新的思路。.

Optically pumped gas molecular terahertz (THz) lasers are promising for generating high-power and high-beam-quality coherent THz radiation. However, for pulsed gas THz lasers, the temporal behavior of the output THz pulse has rarely been investigated. In this study, the temporal behavior of a pulsed gas THz pumped by a fundamental-mode TEA CO

Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes.201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors.PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.

The root of

Cartilage defects caused by mechanical tear and wear are challenging clinical problems. Articular cartilage has unique load-bearing properties and limited self-repair ability. The current treatment methods, such as microfractures and autogenous cartilage transplantation to repair full-thickness cartilage defects, have apparent limitations. Tissue engineering technology has the potential to repair cartilage defects and directs current research development. To enhance the regenerative capacities of cartilage in weight-bearing areas, we attempted to develop a biomimetic scaffold loaded with a chondroprotective factor that can recreate structure, restore mechanical properties, and facilitate anabolic metabolism in larger joint defects. For enhanced spatial control over both bone and cartilage layers, it is envisioned that biomaterials that meet the needs of both tissue components are required for successful osteochondral repair. We used gelatin methacrylate (GELMA) and polyethylene glycol diacrylate (PEGDA) light-cured dual-network cross-linking modes that can significantly increase the mechanical properties of scaffolds and are capable of restoring function and prolonging the degradation time. Once the hydrogel complex was injected into the osteochondral defect,iin situ/iUV light curing was applied to seamlessly connect the defect repair tissue with the surrounding normal cartilage tissue. The small molecule active substance kartogenin (KGN) can promote cartilage repair. We encapsulated KGN in biomimetic scaffolds so that, as the scaffold degrades, scaffold-loaded KGN was slowly released to induce endogenous mesenchymal stem cells to home and differentiate into chondrocytes to repair defective cartilage tissue. Our experiments have proven that, compared with the control group, GELMA/PEGDA + KGN repaired cartilage defects and restored cartilage to hyaline cartilage. Our study suggests that implementing photosensitive, injectable, interpenetrating, and kartogenin-modified GELMA/PEDGA biomimetic scaffolds may be a novel approach to restore cartilage integrity in full-thickness osteochondral defects.

Posterior-stabilized total knee prostheses have been widely used in orthopedic clinical treatment of knee osteoarthritis, but the patients and surgeons are still troubled by the complications, for example severe wear and fracture of the post, as well as prosthetic loosening. Understanding the后稳定型全膝关节假体已经被广泛应用于骨科临床治疗膝骨关节炎，但是胫骨衬垫立柱的磨损、断裂以及假体松动等失效问题依然困扰着患者和医生。了解患者体内膝关节假体的生物力学特性有利于降低术后的假体翻修率和患者不满意度。本文针对6种不同后稳定型全膝关节假体分别建立了全膝关节置换的骨肌多体动力学模型，在模拟走路、右转和下蹲3种生理活动下，对比研究了6种后稳定型全膝关节假体的生物力学差异。结果表明，在走路、右转和下蹲活动中PFC Sigma和 Scorpio NGR两种假体的立柱所受接触力较大，增加了立柱断裂和磨损破坏以及假体早期松动的风险。Gemini SL的螺旋型立柱设计更有利于膝关节的内外旋转运动，同时避免了立柱边沿接触磨损。后稳定型全膝关节假体矢状面较低的关节面匹配度设计和较晚的立柱-凸轮相遇接触设计将导致较大的前后平移运动。本文为临床指导医生选择、改进假体设计和降低假体失效提供了理论支撑。.

Background: We and others have previously demonstrated that glycine is neuroprotective in cerebral ischemia-reperfusion injury. But glycine has low permeability to the blood–brain barrier (BBB). To deliver glycine into the ischemic brain to confer neuroprotection, we designed a novel glycine-containing and BBB-permeable tripeptide, the H-glycine-cysteine-phenylalanine-OH (GCF).Methods: For the synthesis of GCF, phenylalanine was included to increase the BBB permeability of the tripeptide. Cysteine was conjugated with glycine to enable the release of glycine from GCF. With the use of immunofluorescence labeling and HPLC assays, we measured the distribution and level of GCF. We used TTC labeling, LDH release, and MTT assays to evaluate the neuroprotective effect of GCF.Results: Following intravenous injection in a rat model of cerebral ischemia-reperfusion injury, GCF was intensively distributed in the ischemic neurons. Intravenous injection of GCF, but not the non-cleavable acetyl-GCF, resulted in the elevation of glycine in the ischemic brain. GCF but not acetyl-GC conferred neuroprotection in ischemic stroke animals.Conclusion: GCF protects against cerebral ischemia-reperfusion injury in the rat. In contrast to peptide drugs that exert therapeutic effect by interfering with signaling interaction, GCF acts as a BBB shuttle and prodrug to deliver glycine to confer neuroprotection, representing a novel therapeutic strategy for acute ischemic stroke.