Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Development of immature ovarian teratoma after mature teratoma in a girl with familial ovarian teratoma:A case report

BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.

Adult neurogenesis in the primate hippocampus

Adult hippocampal neurogenesis(AHN) is crucial for learning,memory,and emotion.Deficits of AHN may lead to reduced cognitive abilities and neurodegenerative disorders,such as Alzheimer’s disease.Extensive studies on rodent AHN have clarified the developmental and maturation processes of adult neural stem/progenitor cells.However,to what extent these findings apply to primates remains controversial.Recent advances in next-generation sequencing technologies have enabled in-depth investigation of the transcriptome of AHN-related populations at single-cell resolution.Here,we summarize studies of AHN in primates.Results suggest that neurogenesis is largely shared across species,but substantial differences also exist.Marker gene expression patterns in primates differ from those of rodents.Compared with rodents,the primate hippocampus has a higher proportion of immature dentate granule cells and a longer maturation period of newly generated granule cells.Future research on species divergence may deepen our understanding of the mechanisms underlying adult neurogenesis in primates.

Inhibition of VEGF-A expression in hypoxia-exposed fetal retinal microvascular endothelial cells by exosomes derived from human umbilical cord mesenchymal stem cells

Objective:This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell(hucMSC)-derived exosomes(hucMSC-Exos)in inhibiting hypoxia-induced cell hyper proliferation and overexpression of vascular endothelial growth factor A(VEGF-A)in immature human fetal retinal microvascular endothelial cells(hfRMECs).Methods:Exosomes were isolated from hucMSCs using cryogenic ultracentrifugation and characterized through various techniques,including transmission electron microscopy,nanoparticle tracking analysis,bicinchoninic acid assays,and western blotting.The hfRMECs were identified using von Willebrand factor(vWF)co-staining and divided into four groups:a control group cultured under normoxic condition,a hypoxic model group,a hypoxic group treated with low-concentration hucMSC-Exos(75μg/mL)and a hypoxic group treated with high-concentration hucMSC-Exos(100μg/mL).Cell viability and proliferation were assessed using Cell Counting Kit-8(CCK-8)assay and EdU(5-ethynyl-2′-deoxyuridine)assay respectively.Expression levels of VEGF-A were evaluated using RT-PCR,western blotting and immunofluorescence.Results:Hypoxia significantly increased hfRMECs’viability and proliferation by upregulating VEGF-A levels.The administration of hucMSC-Exos effectively reversed this response,with the high-concentration group exhibiting greater efficacy compared to the lowconcentration group.Conclusion:In conclusion,hucMSC-Exos can dose-dependently inhibit hypoxia-induced hyperproliferation and VEGF-A overexpression in immature fetal retinal microvascular endothelial cells.

Different endodontic treatments induced root development of two nonvital immature teeth in the same patient:A case report

BACKGROUND Pulp revascularization is a novel way to treat immature teeth with periapical disease,and the technique has become increasingly well established in recent years.By puncturing the periapical tissue,bleeding is induced,and a blood clot is formed in the root canal.The blood clot acts as a natural bioscaffold onto which mesenchymal stem cells from periapical tissue can be seeded and restore pulp vascularity,thus promoting root development as well as apical closure.Although the effect of pulp revascularization is ideal,there are certain requirements for the apical condition of the teeth.The apical barrier technique and apexification are still indispensable for teeth that cannot achieve ideal blood clot formation.In addition,a meta-analysis of several clinical studies concluded that pulp revascu-larization has no significant advantages over other treatments.CASE SUMMARY A 10-year-old girl complained of pain in the right upper and lower posterior teeth for 2 d.Clinical and radiological examinations revealed that both the right maxillary and mandibular second premolars were immature with periapical radiolucency.The right maxillary second premolar was treated by pulp revascu-larization,while the right mandibular second premolar was treated by conven-tional apical barrier surgery after revascularization failed.The purpose of this report is to compare the different root maturation processes induced by the pulp revascularization and apical barrier techniques in the same patient in homonymous teeth from different jaws.Twelve months of follow-up showed that the apical foramen of both teeth presented a clear tendency to close;however,the tooth treated with pulp revascularization showed a significant increase in root length as well as root canal wall thickness.CONCLUSION For the treatment of nonvital immature teeth,pulp revascularization showed a superior therapeutic effect in comparison with the apical barrier technique.

Determination of the ovine ovarian reserve during the prenatal and neonatal periods

Objective:To determine the ovine ovarian histomorphology and follicular staging at various age periods in Awassi breed.Methods:Ovaries were collected from prenatal fetuses[gestational age(95±5)days],neonatal(day 0),and prepubertal ewe lambs(two and four months of age);each age group included six animals.Ovaries(n=12,each group)were dissected and processed for hematoxylin and eosin staining.Stained sections(n=24,each group)were imaged and utilized for histomorphology assessment,follicle measurement,and classification.Results:Prenatal ovaries were mainly enriched with primordial follicles accompanied by a lower proportion of primary follicles.In addition to primordial and primary follicles,neonatal ovaries demonstrated a proportion of centrally located multilayered and antral follicles.In comparison with neonatal ovaries,the proportion of multilayered and antral follicles was significantly higher in the ovaries of two-month-old lambs;conversely,the proportion of peripherally situated primordial follicles dramatically declined compared to that of earlier age of lamb.Although there was no statistical variation in the sizes of primordial follicles across groups,the mean diameter of the primary follicle in the prenatal ovaries was substantially smaller than in postnatal ovaries.Compared to the neonatal ovaries,the size of the multilayered and antral follicles in the prepubertal ovaries was substantially larger.Conclusions:The earliest follicular developmental stages were established prenatally whereas the advanced growth stages started in the neonatal period and greatly increased in the prepubertal period.

Fractures around the shoulder in the skeletally immature:A scoping review

Fractures around the shoulder girdle in children are mainly caused by sports accidents.The clavicle and the proximal humerus are most commonly involved.Both the clavicle and the proximal humerus have a remarkable potential for remodeling,which is why most of these fractures in children can be treated conservatively.However,the key is to understand when a child benefits from surgical management.Clear indications for surgery of these fractures are lacking.This review focuses on the available evidence on the management of clavicle and proximal humerus fractures in children.The only strict indications for surgery for diaphyseal clavicle fractures in children are open fractures,tenting of the skin with necrosis,associated neurovascular injury,or a floating shoulder.There is no evidence to argue for surgery of displaced clavicle fractures to prevent malunion since most malunions are asymptomatic.In the rare case of a symptomatic malunion of the clavicle in children,corrective osteosynthesis is a viable treatment option.For proximal humerus fractures in children,treatment is dictated by the patient's age(and thus remodeling potential)and the amount of fracture displacement.Under ten years of age,even severely displaced fractures can be treated conservatively.From the age of 13 and onwards,surgery has better outcomes for severely displaced(Neer types III and IV)fractures.Between 10 and 13 years of age,the indications for surgical treatment are less clear,with varying cut-off values of angulation(30-60 degrees)or displacement(1/3–2/3 shaft width)in the current literature.

A Review of Main Factors Involved in the Maturation of Oil Palm (Elaeis guineensis Jacq.) Fruit Bunches

The oil palm (Elaeis guineensis Jacq.) is a diploid perennial plant of the Arecaceae family. It is the most important plant cultivated for oil production. To ensure this production, certain optimal conditions are required: temperature, sunshine, rainfall, etc. The oil palm ensures its survival through the fruits borne on bunches located at the axis of the 17th to 20th leaves from the central stem. From pollination to the maturity of a bunch it takes about 4.5 to 6 months. Several events occur during this period: seed enlargement, weight increase, colour change, etc., but also important physiological changes: synthesis of some pigments (anthocyanin), increase in oil content correlated with the decrease in water content, etc. All of these constitute factors that can provide a better understanding of the biology of the seed. The aim of this work was to review some of the important parameters involved in the development and maturation of oil palm fruit bunches. These factors are classified into physiological, biochemical as well as environmental. The physiological parameters are color, appearance of embryo, seed weight and fruit detachment from bunches;Biochemical parameters include water content, oil content, carbohydrate, protein, mineral contents and lipase activity while temperature is the main environmental factor that affects fruit maturation. Thorough research has not yet been done at the different stages of maturation and ripening, thus a deep look into this may open up new avenues for research on early germinated oil palm seed production prior to seed dormancy.

Research on the Educational Issues of the Emerging Tourism Industry in Developing Countries

This research explores emerging concepts of tourism education,training,and entrepreneurship development.Nowadays,the discourses on this theme have been growing in both developed and developing countries,especially to reduce unemployment rates through the education of young people.For this purpose,this study uses secondary data sources to analyze individual rationality and the creativity of educated young people for entrepreneurship development in the business sector.The analytical framework begins from the investigation of the tourism industry and the processes for empowering those people since tourism industry is considered as one of the agents of economic changes in developing countries,such as Nepal.However,skilled and trained manpower are required to operate well.The main theme of this study is that the aforesaid manpower can be developed with entrepreneurship skills by providing education and training in this business.This study entirely agrees that once the tourism industry is well run by removing the hurdles seen in this sector,there would be an increase in employment opportunities and a raise in the country’s revenue in addition to solving many other social problems.

Plasma 17-hydroxyprogesterone/cortisol ratio is not a predictor of systemic hypotension in extremely premature infants

Background/aims: To determine whether the 17-hydroxyprogesterone (17-OHP)/cortisol ratio as a marker of immature11-beta hydroxylase activity can predict severe systemic hypotension in preterm neonates. Methods: Serum cortisol and 17-OHP concentrations were measured in capillary blood deposited on blotter paper on day 3 post-natal age (Day 3) in infants less than 32 weeks postmenstrual age (PMA). The predictive value of 17-OHP/cortisol ratio for a first episode of systemic hypotension occurring after Day 3 (FESH) was evaluated. Results: Of 105 infants included, 14 patients (13%) presented a FESH. Neither the 17-OHP/cortisol ratio, nor the 17-OHP or cortisol concentrations were associated with the occurrence of a FESH when adjusted for potential confounding factors. 17-OHP and cortisol were inversely associated to PMA (r = ﹣0.36 and ﹣0.40, respectively). Cortisol, but not 17-OHP, was associated with the type of hospitalization unit, the respiratory support and the presence of a patent ductus arteriosus. The 17-OHP/cortisol ratio was associated with the type of hospitalization unit only. Conclusions: The 17-OHP/ cortisol ratio at Day 3 did not predict the occurrence of a first episode of systemic hypotension after Day3 inpreterm neonates.

The Junggar Immature Continental Crust Province and Its Mineralization

According to the study on the peripheral orogenic belts of the Junggar basin and combined with the interpretation of geophysical data, this paper points out that there is an Early Paleozoic basement of immature continental crust in the Junggar area, which is mainly composed of Neoproterozoic-Ordovician oceanic crust and weakly metamorphosed covering sedimentary rocks. The Late Paleozoic tectonism and mineralization were developed on the basement of the Early Paleozoic immature continental crust. The Junggar metallogenic province is dominated by Cr, Cu, Ni and Au mineralization. Those large and medium-scale deposits are mainly distributed along the deep faults and particularly near the ophiolitic melange zones, and formed in the Late Paleozoic with the peak of mineralization occurring in the Carboniferous-Permian post-collisional stage. The intrusions related to Cu, Ni and Au mineralization generally have low Is, and positive εNd(t) values. The δ34S values of the ore deposits are mostly near zero, and the lead isotopes are mostly of normal lead. All these indicate that the ore-forming material comes either directly from the mantle-derived magma (for chromite and Cu-Ni deposits) or from recirculation of the basement material of the Early Paleozoic immature crust (for most Cu and Au deposits).

Quantitative Assessment of Hydrocarbon Expulsion of Petroleum Systems in the Niuzhuang Sag, Bohai Bay Basin, East China

Based on a detailed survey of the distribution and organic geochemical characteristics of potential source rocks in the South Slope of the Niuzhuang Sag, Bohai Bay Basin, eastern China, a new approach to assess the amount of hydrocarbons generated and expelled has been developed. The approach is applicable to evaluate hydrocarbons with different genetic mechanisms. The results show that the models for hydrocarbon generation and expulsion vary with potential source rocks, depending on thermal maturity, types of organic matter and paleoenvironment. Hydrocarbons are mostly generated and expelled from source rocks within the normal oil window. It was calculated that the special interval (algal-rich shales of the ES4 member formed in brackish environments) in the South Slope of the Niuzhuang Sag has a much higher potential of immature oil generation than the other intervals in the area. This suggests that hydrocarbons can definitely be generated in early diagenesis, especially under certain special geological settings. The proportion of hydrocarbons generated and expelled from the ES4 shales in the early diagenetic stage is up to 26.75% and 17.36%, respectively. It was also observed that laminated shales have a much higher expulsion efficiency than massive mudstones. In contrast, the special interval of the ES4 shales proposed from previous studies is probably not the whole rock for oil in the South Slope of the Niuzhuang Sag because of the small proportion of the gross volume and corresponding low percentage of hydrocarbons generated and expelled. A much lower expulsion efficiency of the source rock during the early stage relative to that within the normal oil window has been calculated. Our results indicate that the ES4 mudstones rather than the shales deposited in the Niuzhuang and Guangli Sag are the main source rocks for the oil discovered.

Long-term follow-ups of revascularized immature necrotic teeth:three case reports

Revascularization of immature necrotic teeth is a reliable treatment alternative to conventional apexogenesis or apexification. In case 1, a 12-year-old boy had his necrotic, immature mandibular left second premolar treated with a revascularization technique. At a 24-month follow-up, periapical radiolucency had disappeared and thickening of the root wall was observed. In cases 2 and 3, a lO-year-old boy had his necrotic, immature, bilateral mandibular second premolars treated with the same modality. At 48-month （in case 2） and 42-month （in case 3） follow-ups, loss of periapical radiolucencies and increases in the root wall thickness were also observed.

Application of Biomarkers to Quantitative Source Assessment of Oil Pools

Recent detailed organic geochemical and geological investigation indicate that oils of the Bamianhe oilfield, Bohai Bay Basin, East China are the mixture of less mature oils and normal oils derived from the ES4 mudstones and shales with a wide range of thermal maturity from immature to middle-maturity, and most of the oils were proved to be sourced from the depocenter of the Niuzhuang Sag immediately adjacent to the Bamianhe oilfield. Two approaches to quantify the amount of immature oils mixed through quantitative biomarkers were established. One is a relatively simple way only through organic geochemical analysis while the other is to be combined with basin modeling. Selecting biomarkers as proxies is the crucial point in both of them. The results show that the less mature oils mixed in the Bamianhe oilfield is less than 10% and 18% respectively based on the two approaches, which coincide with the results of oil-source rock correlation.

Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin （DCX）＋ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX＋ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX＋ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.

Improvement of Plant Regeneration from Immature Embryos of Wheat Infected by Agrobacterium tumefaciens

Wheat, one of the most important food crops, has been extensively studied with respects to plant regeneration and transformation employing the immature embryos as recipient tissues. However, the transformed tissues often become severely necrotic after co-cultivation with Agrobacterium, which is one of the major obstacles in gene delivery. In this study, wheat varieties CB037, Kenong 199, Xinchun 9, Lunxuan 987, and Shi 4185 showed desirable culture potential or high infection ability in Agrobacterium-mediated transformation. Similarly, optimal regeneration conditions were determined by testing their ability to inhibit the cell necrosis and cell death phenotype. Two auxins of 2,4-dichlorophenoxyacetic acid （2,4-D） and 3,6-dichloro-o-anisic acid （dicamba） were evaluated for highly significant effect on both callus and plantlet production, although they were genotype-dependent in wheat. Substitution of 2,4-D by dicamba enhanced the growth and regeneration ability of callus from the immature embryos of most genotypes tested. The callus growth state couldn’t be modified by adding antioxidants such as ascorbic acid, cysteine, and silver nitrate or organic additives such as thiamine HCl and asparagine to the media. On the contrary, the best tissue statement and plant regeneration was achieved by employing the media containing the simplest MS （Murashige and Skoog） components and dicamba without organic components and vitamins. Thereby, our results are thought to inhibit wheat cell necrosis effectively and suggested to be used for more wheat genotypes.

Mechanism of immune tolerance induced by donor derived immature dendritic cells in rat high-risk corneal transplantation

·AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high -risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. ·METHODS: Seventy-five SD rats (recipient) and 39 Wistar rats (donor) were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC) group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high -risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1 ×10 6 respectively 1 week before corneal transplantation tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. ·RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all 【0.05). The expression level of Foxp3 on CD4 + CD25 + T cells of imDC group (2.24 ±0.18) was significantly higher than that in the control (1.68 ±0.09) and mDC groups (1.46±0.13) (all 【0.05).·CONCLUSION: Donor -derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells. ·

Effects of Environmental Temperature on the Regeneration Frequency of the Immature Embryos of Wheat(Triticum aestivum L.)

The immature embryos （IEs） of wheat are the most widely used tissues for in vitro culture and genetic transformation due to its high regeneration competency. However, this explant can only be maintained in 4℃ daily cooler for a short period time for its use in plant tissue culture or transformation experiments. This study aimed to investigate the effects of environmental temperature, cryopreservation storage temperature, and heat shock culture （HSC） temperature on the regeneration frequency of wheat IEs. Results indicated that environmental temperature significantly affected the induction of embryonic calli. The optimum total accumulated temperature （TAT） during the time of anthesis and sampling for regeneration of these tissues was around 280℃ for spring wheat type cv. CB037 and approximately 300℃ for winter wheat type cv. Kenong 199. Regeneration ability obviously declined when the highest environmental temperature was over 35℃ for 1 d or a high temperature between 30 and 33℃ lasted for 5 d during anthesis and sampling. This finding was verified by culturing the freshly isolated IEs under different temperatures from 29 to 37℃ in different controlled growth incubators for 5 d; the IEs almost completely lost regeneration ability when the temperature rose to 37℃. Cryopreservation of-20℃ caused the wheat samples lost ability of producing callus or embryonic callus in a few days, and cryopreservation of-10℃ more than 10 d made the regeneration potential of the tissues dramatically declined. Comparatively, the temperature that best maintained high regeneration ability was -5℃, at which the materials can be maintained for around 1 mon. In addition, the preservation of the immature samples at -5 or -10℃ inhibited the direct germination of the IEs, avoiding the embryo axis removing process. Our results are useful for ensuring that field collection and cryopreservation of the wheat IEs are done correctly to enable tissue culture and genetic transformation.

The Selection of Transgenic Recipients from New Elite Wheat Cultivars and Study on Its Plant Regeneration System

In the protocol of wheat transformation, to use elite wheat cultivars as exogenous gene recipients can speed up the process of commercial field applications of transgenic wheat. However, it is necessary to screen wheat cultivars with good tissue culture response （TCR） continuously from plenty of elite wheat cultivars released for wheat transformation, and it is also important to find a plant regeneration system that is suitable for these cultivars. So, the TCR of mature and immature embryos of six wheat cultivars Chuannong 11 （CN11）, Chuannong12 （CN12）, Chuannong17 （CN17）, Chuannong18 （CN18）, Chuannong19 （CN19）, and Chuannong21 （CN21）, which possess superior agronomic traits, were investigated by using a good TCR wheat cultivar Bobwhite as control. The results indicated that only the immature and mature embryos of CN12, CN17, and CN18 exhibited good TCR compared with Bobwhite. No significant differences were observed between embryos of Bobwhite and of the three cultivars in TCR. Mature embryo-derived calli of CN12 were used as explants for transformation by particle bombardment of SAMDC gene. Seven transformants were obtained and the efficiency was 2.3%. This research supplies three new elite recipient cultivars for wheat transformation. The wheat plant regeneration system used in this research is different from those successful ones reported previously and it could be a reference for other wheat genotypes. Furthermore, Bobwhite and the three wheat cultivars were proved to be 1RS/1BL translocation, by methods of A-PAGE, C- banding, and genomic in situ hybridization （GISH）. These results imply that probably there is some relationship between 1RS/1BL translocation and TCR of wheat embryos. So this research gives us a hint that we should pay more attention to the 1RS/1BL translocations when we screen the wheat cultivars with good TCR and also that the mechanism of the effect of 1RS/ 1BL translocation on TCR is worthy of being investigated.

maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model

AIM To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).METHODS In the present study, ALPPS, partial hepatecotmy(PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified. Afterwards, the detection of liver function followed by cluster analysis of functional gene expression were performed to evaluate the maturity.RESULTS Compared with PHx and sham groups, the proliferation of f LR was significantly higher in ALPPS group(P = 0.023 and 0.001 at second day, P = 0.034 and P < 0.001 at fifth day after stage I). Meanwhile, the increased expression of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1 verified the accelerated liver regeneration derived from ALPPS procedure. However, ALPPS-induced Sox9 positive hepatocytes significantly increased beyond the portal triad, which indicated the progenitor hepatic cell was potentially involved. And the characteristics of ALPPSinduced hepatocytes indicated the lower expression of hepatocyte nuclear factor 4 and anti-tryptase in early proliferative stage. Both suggested the immaturity of ALPPS-derived liver regeneration. Additionally, the detection of liver function and functional genes expression confirmed the immaturity of renascent hepatocytes derived in early stage of ALPPS-derived liver regeneration.CONCLUSION Our study revealed the immaturity of ALPPS-derived proliferation in early regenerative response, which indicated that the volumetric assessment overestimated the functional proliferation. This could be convincing evidence that the stage Ⅱ of ALPPS should be performed prudently in patients with marginally adequate f LR, as the ALPPS-derived proliferation in volume lags behind the functional regeneration.