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Methods: Herein, we obtained and characterized deltaN p63- and adenosine triphosphate-binding cassette subfamily G member 2-expressing limbal stem cells (LSCs). Chitosan and carboxymethyl chitosan (CTH) were cross-linked to be an in situ thermosensitive hydrogel (ACH), which was printed through fourdimensional (4D) printing to obtain a porous carrier with uniform pore diameter (4D-CTH). Rabbits were injected with alloxan to induce diabetes mellitus (DM). Following this, the LSC-carrying hydrogel was spread on the surface of the cornea of the diabetic rabbits to cure corneal epithelium injury. Results: Compared with the control group (LSCs only), rapid wound healing was observed in rabbits treated with LSC-carrying 4D-CTH. Furthermore, the test group also showed better corneal nerve repair ability. The results indicated the potential of LSC-carrying 4D-CTH in curing corneal epithelium injury. Conclusion: 4D-CTH holds potential as a useful tool for studying regenerative processes occurring during the treatment of various diabetic corneal epithelium pathologies with the use of stem cell-based technologies. [ABSTRACT FROM AUTHOR]

Probiotics are defined as living or dead bacteria and their byproducts that maintain the balance of the intestinal microbiome. They are non-toxic, non-pathogenic, and do not release any toxins either within or outside the body. Adequate consumption of probiotics can enhance metabolite production, increase immunity, maintain a balanced intestinal flora, and stimulate growth. Probiotics do not have negative antibiotic effects and help maintain the natural flora in animals in a balanced state or prevent dysbacteriosis. Heyndrickxia coagulans (H. coagulans) is a novel probiotic species that is gradually being used for the improvement of human health. Compared to commonly used probiotic lactic acid bacteria, H. coagulans can produce spores, which provide the species with high resistance to adverse conditions. Even though they are transient residents of the gut, beneficial bacteria can have a significant impact on the microbiota because they can outnumber harmful germs, and vice versa. This article discusses the probiotic mechanisms of H. coagulans and outlines the requirements for a substance to be classified as a probiotic. It also addresses how to assess strains that have recently been discovered to possess probiotic properties. [ABSTRACT FROM AUTHOR]

Background: Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) is a rare, mature T-cell non-Hodgkin lymphoma. The prognosis of patients with relapsed or refractory ALCL following first-line chemotherapy is extremely poor. NCCN guidelines recommend intensified chemotherapy with or without ASCT consolidation for r/r ALCL, however, this is not an effective treatment for all ALK+ALCL. Case report: Herein, we report a patient with relapsed/refractory ALK+ ALCL who received crizotinib and brentuximab vedotin as bridging therapy, followed by autologous stem cell transplantation and sequential anti-CD30 CAR T cell therapy. Conclusion: The patient achieved complete remission and long-term disease-free survival of months and continues to be followed up. The combination therapy model in this case may provide guidance for the management of relapsed/refractory ALK+ ALCL, and further prospective trials are needed to confirm its effectiveness. [ABSTRACT FROM AUTHOR]

Background: ALK-negative anaplastic large cell lymphoma (ALK-ALCL) is a rare heterogeneous malignancy of T-cell origin.ALK- ALCL has a poor prognosis, with more patients experiencing relapses and refractory to treatment, and its treatment remains challenging. We report a case with bone involvement as the main clinical manifestation of recurrent, and the patient achieved significant partial remission after brentuximab vedotin(BV) combined with a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome (PLM60) with the addition of chidamide maintenance therapy and received regular follow-up, with a disease-free survival of 16 months to date. A literature review of the clinical presentation and treatment of ALCL was also conducted to identify strategies for its diagnosis and management. Conclusions: ALK-ALCL with bone involvement as the main manifestation of recurrent is relatively rare. Here, BV combined a modified CHEP chemotherapy containing mitoxantrone hydrochloride liposome was applied for the first time in a patient with relapsed ALK-ALCL, inducing remission and extending survival. However, further prospective studies with many patients are needed to determine the biological characteristics of this rare type of ALK-ALCL and relevant treatment strategies. [ABSTRACT FROM AUTHOR]

Boron (B) and nitrogen (N) co-doped 3D hierarchical micro/meso porous carbon (BNPC) were successfully fabricated from cellulose nanofiber (CNF)/ boron nitride nanosheets (BNNS)/ zincmethylimidazolate framework-8 (ZIF-8) nanocomposites prepared by 2D BNNS, ZIF-8 nano-particles, and wheat straw based CNFs. Herein, CNF/ZIF-8 acts as versatile skeleton and imparts partial N dopant into porous carbon structure, while the introduced BNNS can help strengthen the hierarchical porous superstructure and endow abundant B/N co-dopants within BNPC matrix. The obtained BNPC electrode possesses a high specific surface area of 505.4 m²/g, high B/N co-doping content, and desirable hydrophilicity. Supercapacitors assembled with BNPC-2 (B/N co-doped porous carbon with a CNF/BNNS mass ratio of 1:2) electrodes exhibited exceptional electro-chemical performance, demonstrating high capacitance stability even after 5 000 charge-discharge cycles. The devices exhibited outstanding energy density and power density, as well as the highest specific capacitance of 433.4 F/g at 1.0 A/g, when compared with other similar reports. This study proposes a facile and sustainable strategy for efficiently fabrication of rich B/N co-doped hierarchical micro/meso porous carbon electrodes from agricultural waste biomass for advanced supercapacitor performance. [ABSTRACT FROM AUTHOR]

Background: Ampullary carcinoma (AC) is a rare cancer of the digestive system that occurs in the ampulla at the junction of the bile duct and pancreatic duct. However, there is a lack of predictive models for overall survival (OS) and disease -specific survival (DSS) in AC. This study aimed to develop a prognostic nomogram for patients with AC using data from the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: Data from 891 patients between 2004 and 2019 were downloaded and extracted from the SEER database. They were randomly divided into the development group (70%) and the verification group (30%), and then univariate and multivariate Cox proportional hazards regression, respectively, was used to explore the possible risk factors of AC. The factors significantly related to OS and DSS were used to establish the nomogram, which was assessed via the concordance index (C-index), and calibration curve. An internal validation was conducted to test the accuracy and effectiveness of the nomogram. Kaplan-Meier calculation was used to predict the further OS and DSS status of these patients. Results: On multivariate Cox proportional hazards regression, the independent prognostic risk factors associated with OS were age, surgery, chemotherapy, regional node positive (RNP), extension range and distant metastasis with a moderate C-index of 0.731 (95% confidence interval (CI): 0.719-0.744) and 0.766 (95% CI: 0.747-0.785) in the development and verification groups, respectively. While, marital status, surgery, chemotherapy, regional node positive (RNP), extension range and distant metastasis were significantly linked to AC patients' DSS, which have a better C-index of 0.756 (95% confidence interval (CI): 0.741-0.770) and 0.781 (95% CI: 0.757-0.805) in the development and verification groups. Both the survival calibration curves of 3- and 5-year OS and DSS brought out a high consistency. Conclusion: Our study yielded a satisfactory nomogram showing the survival of AC patients, which may help clinicians to assess the situation of AC patients and implement further treatment. [ABSTRACT FROM AUTHOR]

The pathogenesis of acute leukemia is still complex and vague. Most types of acute leukemia are related tosomaticgenemutations, andfamilial incidence is rare. Herewe report a case of familial leukemia. The proband presented to our hospitalwith vaginal bleeding and disseminated intravascular coagulation at the age of 42 and was diagnosed with acute promyelocytic leukemia with typical PML-RARα fusion gene caused by t(15;17)(q24;q21) translocation. By taking the history, we found that the patient's seconddaughterhad beendiagnosedwithB-cell acute leukemia with ETV6- RUNX1 fusion gene at age 6. Then we performed whole exome sequencing in peripheral blood mononuclear cells from these two patients at remission status and identified 8 shared germline genemutations. Using functional annotation and Sanger sequencing validation, we finally focused on a single nucleotide variant in RecQ like helicase (RECQL), rs146924988, which was negative in the proband's healthy eldest daughter. This gene variant potentially led to a relative lack of RECQL protein, disordered DNA repair and chromatin rearrangement, which may mediate the occurrence of fusion genes, as driving factors for leukemia. This study identified a novel possible leukemia-related germline gene variant and provided a new understanding for the screening and pathogenesis of hereditary predisposition syndromes. [ABSTRACT FROM AUTHOR]

Microglia are important resident immune cells in the central nervous system (CNS) and play an important role in its development, homeostasis, and disease treatments. Activated microglia perform diverse functions in mouse models of CNS neurodegenerative diseases or deficits. In humans, microglia have been linked to various neurodegenerative diseases. Following brain or spinal cord injury, microglia express pro- and anti-inflammatory phenotypes at different stages of recovery. With the development of pharmacological and genetic tools for microglial depletion, studies have demonstrated that microglial depletion exerts both positive and negative effects in the treatment of CNS diseases. Notably, microglial depletion provides an empty niche that stimulates production of new microglia. Microglial depletion and repopulation can not only treat diseases by eliminating dysfunctional microglia but can also provide an indication of the molecular mechanisms of diseases. Although this approach has shown impressive results, its use is still in its infancy. In this review, we summarize the current pharmacological and genetic tools for microglial depletion and highlight recent advances in microglial repopulation therapy for the treatment and functional recovery of neurological diseases and deficits. Finally, we briefly discuss the therapeutic challenges and prospective uses of microglial repopulation therapy. [ABSTRACT FROM AUTHOR]

Refill friction stir spot welding (RFSSW) was used to weld the 2060 aluminum alloy with 2 mm thickness. Joint formation, defect characteristics and mechanical properties were investigated. Results show that stir zone (SZ) is clarified into dynamic recrystallization zone (DRZ) and heat extruded zone (HEZ) due to different microstructural features. The size of void near the hook tip decreases with the increase of the plunge depth. Different hook morphologies are obtained under different plunge depths. The tensile-shear load of joint with the void defect initially decreases and then increases with increasing plunge depth. The mean loads of joints under different plunge depths are in the range of 5.1-5.8 kN. The void separates the hook from lap interface, so the cracks initiating from the hook propagate along the sleeve retreating path. The hook has a larger influence on the tensile-shear load of joint than void. All the tensile specimens present a shear-plug fracture mode. [ABSTRACT FROM AUTHOR]

Wet-storage is the most common way to maintain sugarcane bagasse in the pulping and paper-making industry, although there are few studies focused on the selectivity of delignification in pulping for bagasse treated by wet-storage. In this study, wet-storage of bagasse was carried out before alkali-oxygen pulping. The influence of wetstorage pretreatment on the chemical compositions, morphology of bagasse, and the consumption of NaOH in alkali impregnated bagasse meal were investigated. The wet-storage of bagasse resulted in significant improvement in delignification selectivity of alkali-oxygen pulping. After the bagasse was pretreated by wet-storage with bleaching water, the screened yield and crystallinity of the resulting alkali-oxygen pulp were increased. [ABSTRACT FROM AUTHOR]

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Environmental temperature has a significant impact on insect behavior. The present study aimed to determine the effects of temperature on the development, survival, and reproduction of Thrips hawaiiensis (Thysanoptera: Thripidae), an important flower-inhabiting thrips. These effects were evaluated at five constant temperatures (18, 21, 24, 27, and 30°C) on thrips reared in the laboratory on excised Gardenia jasminoides flowers. The developmental durations of egg, first instar, second instar, prepupa, pupa, and the entire immature stages were shortened in response to a temperature increase from 18 to 30°C. The highest generational survival rate was at 27°C (75.00%), whereas the lowest was at 18°C (46.00%). The minimum threshold and effective accumulated temperatures for completing a generation of T. hawaiiensis were 7.62°C and 171.26 degree-days, respectively. The highest fecundity (95.80) was at 27°C, but it was not significantly different than at 24°C (84.72) or 30°C (84.32). The highest oviposition rate of 5.57 eggs per female per day occurred at 27°C, which was significantly higher than at any other temperature. Both the highest intrinsic rate of increase, at 0.200, and net reproduction rate, at 44.97, for T. hawaiiensis were observed at 27°C, whereas the lowest values of 0.114 and 25.56, respectively, were observed at 18°C. These results suggest that T. hawaiiensis is well adapted to temperate conditions, with an optimal temperature range for development of 24 to 30°C, with the most suitable temperature for both development and reproduction being 27°C. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)-217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR-217 in AML have not yet been recognized. The expression of miR-217 was determined by quantitative polymerase chain reaction (qPCR). Following transfection with miR-217 mimics, an MTT assay, chemosensitivity assay, cell apoptosis assay and western blot analysis were performed in AML cell lines. Functional assays were also performed to explore the effects of endogenous Kirsten rat sarcoma viral oncogene homolog (KRAS) in AML. The results revealed that miR-217 was downregulated in patients with AML. Overexpression of miR-217 inhibited cellular proliferation and enhanced cell chemosensitivity to doxorubicin by the cell apoptosis pathway in AML cells. A dual-luciferase reporter assay demonstrated that KRAS was a direct target gene of miR-217 in vitro. qPCR and western blot analysis revealed that miR-217 negatively regulated KRAS protein expression, but had no impact on KRAS mRNA expression. Knockdown of KRAS expression markedly suppressed AML cellular proliferation, and enhanced cell chemosensitivity to doxorubicin via the cell apoptosis pathway. These findings indicate that miR-217 functions as a tumor suppressor in AML by directly targeting KRAS. Therefore, miR-217-based therapeutic strategies may provide a novel strategy for the enhancement of efficacy in the treatment of AML. [ABSTRACT FROM AUTHOR]

We report on the first experimental study of the layer-to-layer compression and enhanced optical properties of few-layer graphene nanosheet by applying ion irradiation. The deformation of graphene layers is investigated both theoretically and experimentally. It is observed that after the irradiation of energetic ion beams, the space between separate graphene layers is reduced due to layer-to-layer compression, resulting in tighter contact of the graphene sheet with the surface of the substrate. This processing enables enhanced interaction of the graphene with the evanescent-field wave near the surface, which induces reinforced polarization- dependent light absorption of the graphene. Utilizing the ion-bombarded graphene nanosheets as saturable absorbers, we have realized efficient Q-switched waveguide lasing with enhanced performance through the interaction of the graphene and evanescent field. [ABSTRACT FROM AUTHOR]

Background: Several observational studies have shown that statin use may modify the risk of haematological malignancies. To quantify the association between statin use and risk for haematological malignancies, we performed a detailed meta-analysis of published studies regarding this subject. Methods: We conducted a systematic search of multiple databases including PubMed, Embase, and Cochrane Library Central database up to July 2013. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed. Results: A total of 20 eligible studies (ten case-control studies, four cohort studies, and six RCTs) reporting 1,139,584 subjects and 15,297 haematological malignancies cases were included. Meta-analysis showed that statin use was associated with a statistically significant 19% reduction in haematological malignancies incidence (RR = 0.81, 95% CI [0.70, 0.92]). During subgroup analyses, statin use was associated with a significantly reduced risk of haematological malignancies among observational studies (RR = 0.79, 95% CI [0.67, 0.93]), but not among RCTs (RR = 0.92, 95% CI [0.77, 1.09]). Conclusions: Based on this comprehensive meta-analysis, statin use may have chemopreventive effects against haematological malignancies. More studies, especially definitive, randomized chemoprevention trials are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Aim:To establish an efficient culture system to support embryonic stem (ES) cell differentiation into hepatocytes that coexpress F-VIII and F-IX.Methods:Mouse E14 ES cells were cultured in differentiation medium containing sodium butyrate (SB), basic fibroblast growth factor (bFGF), and/or bone morphogenetic protein 4 (BMP4) to induce the differentiation of endoderm cells and hepatic progenitor cells. Hepatocyte growth factor, oncostatin M, and dexamethasone were then used to induce the maturation of ES cell-derived hepatocytes. The mRNA expression levels of endoderm-specific genes and hepatocyte-specific genes, including the levels of F-VIII and F-IX, were detected by RT-PCR and real-time PCR during various stages of differentiation. Protein expression was examined by immunofluorescence and Western blot. At the final stage of differentiation, flow cytometry was performed to determine the percentage of cells coexpressing F-VIII and F-IX, and ELISA was used to detect the levels of F-VIII and F-IX protein secreted into the culture medium.Results:The expression of endoderm-specific and hepatocyte-specific markers was upregulated to highest level in response to the combination of SB, bFGF, and BMP4. Treatment with the three inducers during hepatic progenitor differentiation significantly enhanced the mRNA and protein levels of F-VIII and F-IX in ES cell-derived hepatocytes. More importantly, F-VIII and F-IX were coexpressed with high efficiency at the final stage of differentiation, and they were also secreted into the culture medium.Conclusion:We have established a novel in vitro differentiation protocol for ES-derived hepatocytes that coexpress F-VIII and F-IX that may provide a foundation for stem cell replacement therapy for hemophilia. [ABSTRACT FROM AUTHOR]

AbstractAim:The feasibility of inducing endocrine pancreatic differentiation of embryonic stem (ES) cells has been well documented. However, whether ES cells possess the potential for exocrine pancreatic differentiation requires further exploration. Here, we investigated whether sodium butyrate and glucocorticoids were conducive to the exocrine pancreatic differentiation of ES cells.Methods:E14 mouse ES cells were cultured in suspension to form embryoid bodies (EBs). These EBs were cultured in differentiating medium containing varying concentrations of sodium butyrate. The effects of activinA and dexamethasone (Dex) on exocrine differentiation were also explored. Finally, the combination of sodium butyrate, activinA, and Dex was used to promote the differentiation of exocrine pancreatic cells. Specific exocrine pancreatic gene expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and amylase expression was examined by immunofluorescence staining. Flow cytometry analysis was also performed to determine the percentage of amylase-positive cells after the treatment with activinA, sodium butyrate, and Dex.Results:Exposure of ES cells to 1 mmol/L sodium butyrate for 5 days promoted exocrine pancreatic gene expression. Further combination with Dex and other pancreatic-inducing factors, such as activinA, significantly enhanced the mRNA and protein levels of exocrine pancreatic markers. Additionally, flow cytometry revealed that approximately 17% of the final differentiated cells were amylase-positive.Conclusion:These data indicate that the exocrine pancreatic differentiation of ES cells can be induced by activinA, sodium butyrate, and Dex, providing a potential tool for studying pancreatic differentiation and pancreas-related diseases. [ABSTRACT FROM AUTHOR]

Aim: There is increasing evidence indicating that embryonic stem (ES) cells are capable of differentiating into hepatocyte-like cells in vitro. However, it is necessary to improve the differentiation efficiency so as to promote the clinical application. Here, we report an efficient culture system to support hepatocyte differentiation from ES cells by utilizing cholestatic serum. Methods: One week after the induction of E14 mouse ES cells into hepatocytes with sodium butyrate, cholestatic serum was added into the culture system at various concentrations and hepatocyte-like cells were induced to proliferate. The morphological and phenotypic markers of hepatocytes were characterized using light microscopy, immunocytochemistry, and RT-PCR, respectively. The function of glycogen storage of the differentiated cells was detected by Periodic acid-Schiff (PAS) reaction, and the ratio of hepatic differentiation was determined by counting the albumin and PAS-positive cells. Results: In the presence of conditional selective medium containing cholestatic serum, numerous epithelial cells resembling hepatocytes were observed. The RT-PCR analysis showed that undifferentiated ES cells did not express any hepatic-specific markers; however, in the presence of sodium butyrate and conditional selective medium containing cholestatic serum, hepatic differentiation markers were detected. Immunofluorescence staining showed that those ES-derived hepatocytes were α-fetoprotein, albumin, and cytokeratin 18 positive, with the ability of storing glycogen. Further determination of the hepatic differentiation ratio showed that the application of cholestatic serum efficiently enriched ES-derived hepatocyte-like cells by inducing lineage differentiation and enhancing lineage proliferation. Conclusion: The conditional selective medium containing cholestatic serum is optimal to selectively enrich hepatocyte-like cells from mixed differentiated ES cells, which may provide a novel method to improve the hepatic differentiation ratio of ES cells. [ABSTRACT FROM AUTHOR]

The article examines the late ordovician to early silurian tectonic events in the Himalayan terrain. Topics discussed include separation of zircons from representative samples, identifying growth of zircon grains by cathodoluminescence and back-scattered electronic imaging techniques; and granitic rocks showing geochemistry consistent with syn-collisonal granites.

This work demonstrates the realization of a lasing in scattering media, which contains dispersive solution of ZnO nanoparticles (NPs) and laser dye 4-dicyanomethylene-2-methyle-6-(p-dimethylaminostyryl)-4H-pyran(DCM) in negative liquid crystals (LCs) that was injected into a cell. The lasing intensity of the dye-doped negative LC laser can be tuned from low to high if the NPs concentration is increased. The tunability of the laser is attributable to the clusters-sensitive feature in effective refractive index of the negative LCs. Such a tunable negative liquid crystal laser can be used in the fabrication of new optical sources, optical communication, and liquid crystal laser displays. [ABSTRACT FROM AUTHOR]