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Abstract Spinal cord injury (SCI) can cause a range of functional impairments, and patients with SCI have limited potential for functional recovery. Previous studies have demonstrated that autophagy plays a role in the pathological process of SCI, but the specific mechanism of autophagy in this context remains unclear. Therefore, we explored the role of autophagy in SCI by identifying key autophagy-related genes and pathways. This study utilized the GSE132242 expression profile dataset, which consists of four control samples and four SCI samples; autophagy-related genes were sourced from GeneCards. R software was used to screen differentially expressed genes (DEGs) in the GSE132242 dataset, which were then intersected with autophagy-related genes to identify autophagy-related DEGs in SCI. Subsequently, the expression levels of these genes were confirmed and analyzed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein–protein interaction (PPI) analysis was conducted to identify interaction genes, and the resulting network was visualized with Cytoscape. The MCODE plug-in was used to build gene cluster modules, and the cytoHubba plug-in was applied to screen for hub genes. Finally, the GSE5296 dataset was used to verify the reliability of the hub genes. We screened 129 autophagy-related DEGs, including 126 up-regulated and 3 down-regulated genes. GO and KEGG pathway enrichment analysis showed that these 129 genes were mainly involved in the process of cell apoptosis, angiogenesis, IL-1 production, and inflammatory reactions, the TNF signaling pathway and the p53 signaling pathway. PPI identified 10 hub genes, including CCL2, TGFB1, PTGS2, FN1, HGF, MYC, IGF1, CD44, CXCR4, and SERPINEL1. The GSE5296 dataset revealed that the control group exhibited lower expression levels than the SCI group, although only CD44 and TGFB1 showed significant differences. This study identified 129 autophagy-related genes that might play a role in SCI. CD44 and TGFB1 were identified as potentially important genes in the autophagy process after SCI. These findings provide new targets for future research and offer new perspectives on the pathogenesis of SCI.

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 four-dimensional (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.

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.

Background: The prognostic significance of the ratio of activated CD4 T cells to Tregs infiltrating tumor tissues in gastric cancer (GC) remains unknown. Materials and methods: For the quantification of infiltration of immune cells, the ssGSEA algorithm, which is a single sample gene set enrichment analysis, was utilized. Group A was defined as having activated CD4 T cells/Tregs >1, while group B was defined as having activated CD4 T cells/Tregs

BackgroundAnaplastic 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 reportHerein, 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.ConclusionThe 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.

Key Clinical Message Immune checkpoint inhibitors are a very popular method of treating malignant tumors. But its side effects cannot be ignored. This study revealed obstructive complications during immune consolidation therapy following sequential chimeric antigen receptor T cell therapy with autologous hematopoietic stem cell transplantation in two patients with diffuse large b cell lymphoma (DLBCL). Both our patients had the same symptoms of vomiting and inability to eat due to pyloric obstruction, it should be highlighted that this is a relatively rare and irreversible complication of upper gastrointestinal caused by immune consolidation therapy. Abstract Immune checkpoint inhibitors (ICIs) have become the standard therapy for many malignant tumors.However, ICIs are associated with unique immune‐related adverse events (irAEs) caused by dysregulated immune activation and associated complications have been observed in patients. Here, we report two cases of patients with pyloric obstruction and duodenal ulcers induced by the use of sintilimab, which provides some guidance for the widely used anti‐programmed death‐1 therapy. During the entire treatment progression for such patients, the correct differential diagnosis of adverse effects and the use of immunosuppressive agents such as glucocorticoids are essential to facilitate early prevention and intervention of irAEs.

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)/ zinc-methylimidazolate framework-8 (ZIF-8) nanocomposites prepared by 2D BNNS, ZIF-8 nanoparticles, 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 electrochemical 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.

BackgroundALK-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.ConclusionsALK-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.

Product development projects usually contain many interrelated activities with complex information dependences, which induce activity rework, project delay and cost overrun. To reduce negative impacts, scheduling interrelated activities in an appropriate sequence is an important issue for project managers. This study develops a double-decomposition based parallel branch-and-prune algorithm, to determine the optimal activity sequence that minimizes the total feedback length (FLMP). This algorithm decomposes FLMP from two perspectives, which enables the use of all available computing resources to solve subproblems concurrently. In addition, we propose a result-compression strategy and a hash-address strategy to enhance this algorithm. Experimental results indicate that our algorithm can find the optimal sequence for FLMP up to 27 activities within 1 h, and outperforms state of the art exact algorithms.

Both oxyhydrogen and butanol are renewable alternative fuels. Based on gasoline/butanol compound injection mode, although the introduction of oxyhydrogen can effectually enhance the optimal BDIr (butanol direct injection ratio), it also leads to an increase in NO emission. Therefore, this paper further studies the influence of lean-burn on the combustion and emission of ternary-fuel combined supply engine with oxyhydrogen/butanol/gasoline. In this paper, three variables are set, namely five BDIr (0–80%), five ONPIv (oxyhydrogen negative pressure inhalation volume) (0–16 L/min) and five λ (1.0–1.4). The results show that the larger the λ, the more significant the impact of oxyhydrogen on improving combustion and thermal transfer inside the cylinder. With the increase of ONPIv, CoVIMEP, CA 10–90 and CA 0-10 decrease, IMEP increases. Under all lean-burn conditions, ONPI can reduce CO and HC emissions. Under the condition of λ = 1.4, when ONPIv = 16 L/min, NO emission is 49.98% lower than the value of the original engine. Moreover, based on BDIr = 40%, 16 L/min ONPIv can elevate the λ limit from 1.41 to 1.83. In summary, “1.1 = λ ≤ 1.2+ONPIv = 16 L/min+60%≤BDIr≤80%” is the excellent control strategy of ONPI + BDI + GPI engine. The synergistic influence of lean-burn and larger BDIr can greatly reduce gasoline consumption and NOx emission caused by oxyhydrogen, but also worsen the mixture combustion atmosphere. ONPI can effectively improve this problem, and further increase energy efficiency. The coupling technology of ternary-fuel combined supply and lean-burn has a positive impact on improving thermal transfer efficiency, optimizing mixture combustion and decreasing gaseous emission.

The pathogenesis of acute leukemia is still complex and vague. Most types of acute leukemia are related to somatic gene mutations, and familial incidence is rare. Here we report a case of familial leukemia. The proband presented to our hospital with 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 second daughter had been diagnosed with B-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 gene mutations. 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.

Research into cavitation phenomena in various fields shows that the elastic modulus of a boundary has a potential impact on cavitation erosion. To obtain the direct relationship between the elastic modulus of the boundary and cavitiation erosion, single-layer samples with different chemical composition and moduli, and double-layer samples with different elastic moduli and the same surface layer material, were prepared with silicone rubber. The results of cavitation experiments on single-layer samples, show that the coating chemical composition and mechanical properties together affect the cavitation morphology of the coating, and dominant factors vary with erosion stage. Through the cavitation test of double-layer samples, it was found that there is a positive correlation between the elastic modulus of the coating and the degree of cavitation. This study helps us to understand the relationship between coating elastic modulus and cavitation more directly, and provides theoretical and technical guidance for the application of anti-cavitation for elastic coating in engineering.

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: Fluid-absent and fluid-fluxed melting of muscovite in metasedimentary sources are two types of crustal anatexis to produce the Himalaya Cenozoic leucogranites. Apatite grains separated from melts derived from the two types of parting melting have different geochemical compositions. The leucogranites derived from fluid-fluxed melting have relict apatite grains and magmatic crystallized apatite grains, by contrast, there are only crystallized apatite grains in the leucogranites derived from fluid-absent melting. Moreover, apatite grains crystallized from fluid-fluxed melting of muscovite contain higher Sr, but lower Th and LREE than those from fluid-absent melting of muscovite, which could be controlled by the distribution of partitioning coefficient (DAp/Melt) between apatite and leucogranite. DAp/Melt in granites derived from fluid-absent melting is higher than those from fluid-fluxed melting. So, not only SiO2 and A/CNK, but also types of crustal anatexis are sensitive to trace element partition coefficients for apatite. In addition, due to being not susceptible to alteration, apatite has a high potential to yield information about petrogenetic processes that are invisible at the whole-rock scale and thus is a useful tool as a petrogenetic indicator.©2021 China Geology Editorial Office.

BackgroundIntravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive, large B-cell non-Hodgkin’s lymphoma. The prognosis of IVLBCL in patients with central nervous system recurrence after first-line chemotherapy treatment is extremely poor. Among immunotherapies, chimeric antigen receptor (CAR) T-cell immunotherapy has been recently found to be a highly effective treatment for B-cell lymphoma, especially for relapsed or refractory diffuse large B-cell lymphoma. However, no guidelines are available that provide a clear consensus regarding the management of patients with relapsed/refractory IVLBCL. Here, we report, for the first time, the use of autologous hematopoietic stem cell transplantation (ASCT) and CAR T-cell therapy in a patient with relapsed/refractory IVLBCL.Case PresentationA 42‐year‐old woman was diagnosed with IVLBCL based on liver biopsy and developed central nervous system (CNS) progression. The patient received ASCT combined with murine monoclonal anti-CD19 and anti-CD22 CAR T-cell therapy. She achieved complete remission for 22 months so far with negative minimal residual disease and continues to be followed up.ConclusionASCT combined with CAR T-cell therapy was the best choice for treatment of relapsed/refractory IVLBCL, as it allowed the achievement of a lasting complete remission.

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.

Currently, neural network algorithms based on time-domain features are used for change-point detection problems, and they have proven to be effective. However, due to the instability of human biosignals, establishing a training dataset with labels is difficult. For supervised learning methods, wherein parameters are updated on a small sample set through a feed-forward mechanism, it is difficult to ascertain the degree to which the performance of the trained neural network corresponds to the overfitting of the dataset upon which the network was trained. To this end, this paper attempted to directly replace the parameters in the convolutional neural network that need to be updated by training. A method based on the combination of the Teager–Kaiser energy operator (TKEO) and the convolutional neural network is proposed. We tested the proposed method on simulated EMG data with different signal-to-noise ratios and real data with labels, respectively. Compared with multiple detection methods, the proposed method had significant advantages in terms of reliability, accuracy, and computational speed. Furthermore, the proposed method does not require any prior knowledge about the signal, lending itself to be flexible and adaptable to any application. It may be a promising alternative to solving change-point detection problems.

Disseminated visceral Kaposi sarcoma (KS) following allogeneic haematopoietic stem cell transplantation (HSCT) is a rare but life-threatening posttransplant complication. A suitable management strategy for disseminated KS involvement in transplant patients is unclear. Here, we reported a patient who developed disseminated visceral KS following HSCT, which was the first detailed report documenting the relationship among KS development, delayed immune reconstitution, and HHV-8 DNA levels by metagenomic next-generation sequencing (mNGS). The HHV-8 viral load peaked at 2071 sequence reads with an absolute lymphocyte count of 0.17×109/L on day +242. On day +536, the HHV-8 viral load became undetectable, with an absolute lymphocyte count of 1.06×109/L and the KS disappearance. HHV-8 load in blood detected by mNGS may be used as an early prediction marker for KS, a guide for early withdrawal of immunosuppression, and a tool to monitor KS treatment response in the setting of HSCT, especially in patients with CMV-seropositive or graft failure postengraftment. Through whole-exome sequencing, we explored the molecular mechanism underlying the patient’s longer latency of haematopoietic or immune reconstitution and recurrent infections. Germline mutations in the FANCI and RAD51 genes might impair the patient’s DNA repair ability, leading to a degree of immunodeficiency and tumour susceptibility. We strongly recommended evaluating the clinical history of the donor and investigating whether there were possible germline mutations suspected for immunodeficiency or familial neoplasms. Disseminated visceral KS patients could likely benefit from chemotherapy, especially if the disease appears to be aggressive.

The alkaline complex in the southwest region of Luxi Terrane of the North China Craton is spatially correlated with the newly discovered Longbaoshan REE deposit. Its petrogenesis, however, remains ambiguous. In this study, we present an integrated petrology, whole-rock geochemistry, sphene U-Pb and rare earth element data from the Longbaoshan alkaline complex to investigate the petrogenesis, magma source and tectonic evolution. The Longbaoshan alkaline complex consists of mafic to intermediate rocks of hornblende diorite and alkaline hornblende syenite porphyry, biotite monzonite porphyry and aegirine diorite porphyrite. The hornblende diorites show a composition of low SiO2, high MgO, Fe2O3 and moderate Na2O, CaO and are metaluminous and medium-to-high-K calc-alkaline. The hornblende syenite porphyries, biotite monzonites and argirine diorite porphyrites display a relatively higher content of SiO2, Na2O, K2O and Al2O3 and lower contents of MgO, Fe2O3 and CaO and are metaluminous, peralkaline, high-K calcic-alkaline and shoshonite. The sphene U-Pb data shows that the parent magma of the hornblende diorite was emplaced at ca. 120 Ma. All these samples show a common depletion in Th, Nb-Ta and Zr-Hf and enrichment in large ion lithophile elements (e.g., Pb, Ba, Sr) and Light Rare Earth Elements. The magma may have experienced fractionation of pyroxene, amphibole, sphene, apatite and zircon during its evolution. The variable La content, La/Sm, Rb/Sr and (Ta/Th) N ratios indicate that the parent magma may produce by partial melting of a mantle source that was interacted with sediment-derived melts in a subduction setting. Therefore, we propose that the parent magma of the Longbaoshan alkaline complex was derived from a lithospheric mantle which was metasomatized by sediment-derived melt in a prior subduction process. The enriched magma was emplaced through an extension process and experienced subsequent fractionation and assimilation with the continental crust during the rollback of the Paleo Pacific Ocean plate.

Evaluating the development level of urban logistics can significantly inform policies for the sustainable development of each city in an urban agglomeration. This study analyzed the logistics development of 11 cities in the Guanzhong Plain urban agglomeration (GPUA) of China. Compared to traditional urban logistics evaluation methods considering individual attributes, this study constructed a multi-layer complex logistics network of urban agglomerations (MCLNUA) based on complex network theory, which takes into account the multiple connections between cities. The development levels of logistics in these cities were evaluated from a multi-dimensional perspective of “point–line–surface”, (the “point” represents the node characteristic index of the city, the “line” represents the strength and direction of urban logistics connections between cities, and the “surface” represents the cohesive subgroup of cities). An urban spatial hierarchy and corresponding spatial development plan for urban logistics were also developed. The results show that there are significant differences in logistics levels between different cities. The spatial structure of the overall network connections shows the pattern of being strong in the south and weak in the north, and strong in the east and weak in the west. There are differences in the strength of connections between cohesive subgroups. The research provides a reference for the sustainable development of regional logistics in other urban agglomerations.

The Luxi Terrane (eastern China) exposes widespread Early Cretaceous alkaline rocks, whereas their petrogenesis remains controversial, including fractional crystallization, partial melting and crustal contamination regime. Here, we present petrology, geochemistry, sphene U-Pb geochronology and trace element data from the syenogranite, quartz syenite and quartz monzonite of the Guandimiao alkaline complex rocks to investigate their petrogenesis. Geochemical data suggest that these alkaline rocks show alkalic and peralkaline characters, and high Ga/Al ratios, SiO2, light rare-earth element (LREE), Zr and Nb, and low MgO, CaO, Eu contents, corresponding to A-type granites. Sphene trace elements in syenogranite and quartz monzonite show obvious fractionation between LREE and heavy rare-earth element (HREE) and high Th/U ratios, indicating a magmatic origin. They yield U-Pb lower intercept ages of 128 ± 2.3 Ma and 127 ± 1.3 Ma, representing the crystallization ages of these alkaline rocks. The negative correlations between CaO, Fe2O3 (Total), MgO, P2O5, TiO2, MnO and the pronounced depletion in Nb, Ta and Ti suggest that the alkaline rocks were formed by fractional crystallization. Additionally, the positive correlation between La/Hf and La, Th and Th/V, Ce/Yb and K2O, and Tb/Yb and Yb suggest that the alkaline melts are generated by partial melting. Such high Rb/Nb, (Th/Nb)N and Nb/Th ratios indicate crustal contamination during the magma emplacement. We, therefore, propose the magma source of the alkaline rocks in the Guandimiao complex originated by partial melting of lithospheric mantle, which experienced fractional crystallization and crustal contamination processes during its emplacement. Such complex alkaline rocks were probably formed in an extensional back-arc setting induced by the retreat of the subducting Izanagi plate.

The Weishan REE deposit is located in the southwest of the Luxi Terrane of the North China Craton (NCC), where a large number of lamprophyre dikes are spatially exposed with the deposit. Here, we report petrology, geochemistry and zircon U-Pb geochronology data for the lamprophyre of the Weishan REE deposit in order to develop constraints for the determination of the petrogenesis, magma source and evolution of the lamprophyre and the tectonic environment. LA-LCP-MS zircon U-Pb dating shows that the crystallization age of the lamprophyre is 125 ± 0.86 Ma. The geochemical data suggest that these lamprophyres have high levels of Al2O3, K2O, MgO and alkalis, moderate level of Na2O and low levels of SiO2, Fe2O3 and TiO2, and that they are enriched with LREEs (La, Ce) and LILEs (Rb, Ba) and depleted with regard to HREEs and HFSEs (Nb, Ta, Ti). They displayed negative εHf(t) values of −14.98 to −9.03, TDM1 ages of 1.1–1.4 Ga and TDM2 ages of 1.7–2.1 Ga, which suggest that the magma source originates from an enriched mantle. Low Rb/Sr and high Dy/Yb ratios suggest that the enriched mantle source was partially melted at the amphibole-bearing lherzolite garnet-facies. The high Ba/Th and Sr/Th ratios indicate that the enriched source was derived from subduction dehydration fluids of the oceanic crust. We propose that the mafic dike intrusions are consistent with an Early Cretaceous alkaline magma emplacement in an extensional setting, in which the magma was not contaminated by crustal material during its emplacement.

Background/Aims: Bortezomib (BTZ) is largely used as a chemotherapeutic agent for the treatment of multiple myeloma. However, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. The purpose of this study was to examine the underlying mechanisms leading to neuropathic pain induced by BTZ. Methods: ELISA and western blot analysis were used to examine the levels of tumor necrosis factor alpha (TNF-α) and its receptor, transient receptor potential ankyrin 1 (TRPA1) and intracellular p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical pain and cold sensitivity in a rat model. Results: Systemic injection of BTZ significantly increased mechanical pain and cold sensitivity as compared with control animals (P< 0.05 vs. control rats). Our data also showed that protein expression of TRPA1 was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical pain and cold sensitivity in control rats and BTZ rats (P< 0.05 vs. vehicle control). Notably, the inhibitory effect of blocking TRPA1 on mechanical pain and cold sensitivity was smaller in BTZ rats than that in control rats. In addition, a blockade of TNF-α attenuated intracellular p38-MAPK and JNK signal in the dorsal root ganglion. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. Conclusion: We revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ. The data also suggest that blocking TRPA1 and tumor necrosis factor alpha is beneficial to alleviate neuropathic pain during BTZ intervention.

Social life cycle assessment is an important method to assess products’ social impacts throughout their life cycles. There are already some indicators and software to assist conducting social life cycle assessment. However, it is hard for users to share or reuse assessment results because of different application data structures. To resolve this problem, a knowledge-based social life cycle assessment–aided design method is developed in this research. With this method, all elements in the social life cycle assessment process are analyzed and represented as classes, their relationships are described as object properties, and the data structure is represented as data properties to construct an ontology system for social life cycle assessment. Based on the ontology, a social life cycle assessment–aided product development web is developed. According to the data property structure, a bidirectional mapping between database and ontology is realized using JENA and ontology-based data access, which enables the result data to be automatically inputted into ontology individuals. Thus, the result data can be accumulated, shared, and reused among users. A case study with a floor product as well as a user test is carried out to prove the feasibility and usability of the web. The ontology-based social life cycle assessment–aided design method provides users with a new high-efficiency approach, setting the foundation for the intellectualization of life cycle assessment.

This study contributes to a method based on an aqueous solution of ammonia direct injection for NOx emissions control from internal combustion engines. Many previously published studies about deNOx technology are based on selective catalytic reduction (SCR), but only few deal with inner selective non-catalytic reduction (inner SNCR) technology, which is an intensive improvement of selective non-catalytic reduction (SNCR) applied in the in-cylinder purification procedure. Before numerical calculations were carried out, the computational fluid dynamic (CFD) simulation model was validated with steady-state experimental results. The main results revealed that with the increasing concentration of aqueous solution of ammonia, nitrogen oxides gradually decrease, and the largest decline of NOx is 65.1% with little loss of cylinder peak pressure. Unburned hydrocarbon (UHC) and carbon monoxide (CO) may increase using inner SNCR, and soot emissions show a decreased tendency. However, there is little change when ammonia content varies. Ulteriorly, refining the direct injection phase is of great help to inner SNCR technology to enhance the reduction of NOx and reduce NH3 oxidation and NH3 slipping.

BACKGROUND: We conducted a systematic review and meta-analysis to clarify the incidence and risk of cardiotoxicity associated with bortezomib in cancer patients. METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to July 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating bortezomib in cancer patients with adequate data on cardiotoxicity. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 5718 patients with a variety of malignancies from 25 clinical trials were included in our analysis. The incidence of all-grade and high-grade cardiotoxicity associated with bortezomib was 3.8% (95%CI: 2.6-5.6%) and 2.3% (1.6-3.5%), with a mortality of 3.0% (1.4-6.5%). Patients treated with bortezomib did not significantly increase the risk of all-grade (OR 1.15, 95%CI: 0.82-1.62, p=0.41) and high-grade (OR 1.13, 95%CI: 0.58-2.24, p=0.72) cardiotoxicity compared with patients treated with control medication. Sub-group analysis showed that the incidence of cardiotoxicity varied with tumor types, treatment regimens and phases of trials. No evidence of publication bias was observed. CONCLUSIONS: The use of bortezomib does not significantly increase the risk of cardiotoxicity compared to control patients. Further studies are recommended to investigate this association and risk differences among different tumor types, treatment regimens and phases of trials.

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]

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]

The chemical fraction of Heavy metals (Cu, Fe, Mn, Ni, Zn, Cd, Cr and Pb) in surface sediments from Yinchuan section of Yellow River in China were measured by a sequential extraction to evaluate the distribution and pollution level of heavy metals. The metals in sediments were found to be in the range of Fe, 21240.0-29143.3 mg/kg, Mn, 485.27-674.83 mg/kg; Cr, 5.66-15.86 mg/kg; Ni, 29.25-53.40 mg/kg; Pb, 0.32-4.55 mg/kg; Cd, 0.73- 1.11 mg/kg; Zn, 75.87-89.33 mg/kg, and Cu, 18.83- 28.89 mg/kg. The arrangement of metal contents from higher to lower was: Fe>Mn>Zn>Ni>Cu>Cr>Pb>Cd. Fe, Mn and Cu performed common origin according to their correlations. The quantity of immobile fraction (residual) was observed to be higher when compared with mobile fraction (acid soluble, reducible, and oxidizable) of Fe, Zn, Cd and Cr. The highly enrichment factors of Cd, Cr and Pb could create a high environmental risk. The order of contamination level for heavy metals in sediment was Cr>Pb> Cd>Cu>Fe>Ni>Mn>Zn on the basis of performance of enrichment factor, geo-accumulation index and pollution load index. [ABSTRACT FROM AUTHOR]

The concentrations of heavy metals in 21 samples collected from surface sediments from the Qinghai section of the Yellow were investigated in order to evaluate their distribution and pollution levels. The total concentrations showed wide variations with Cu 11.86~57.02 mg/kg, Fe 17236.67~41340.00 mg/kg, Mn 431.93~877.27 mg/kg, Ni 14.58~86.11 mg/kg, Zn 67.18~149.00 mg/kg, Cr 87.84~169.70 mg/kg, Pb 1.21~20.69 mg/kg, and Cd 0.27~1.43 mg/kg. The mean values of the heavy metal contents were arranged in the following decreasing order: Fe>Mn>Cr>Zn>Ni>Cu>Pb>Cd. The correlation between Cu, Fe, and Zn concentrations was significantly positive. These heavy metals had common sources, mutual dependence, and identical behavior during transport. However, there was no significant correlation among some of these metals, indicating different anthropogenic and natural sources. PCA extracted three components with eigenvalues explaining 76.259% of the total variance. Fe, Mn, and Zn had a common natural origin controlled by the first component. Cu, Ni, and Cd could originate anthropogenic sources controlled by the second component. The higher values of geo-accumulation index, enrichment factor, and pollution load index of Cr in the Qinghai section were attributed principally to anthropogenic activities such as industrial effluents, vehicular emissions, and terrigenous influx from the river. Zn appeared to pose no risk at all of the sites of the system. In total, the pollution class from the Qinghai section of the river is 0-1, belonging to the unpolluted to moderately polluted degree. [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]

Background & objectives: Cerebral hypoxia is known to be involved in many neurodegenerative diseases such as Alzheimer's and cerebrovascular dementia. The present study was designed to investigate the effects of flavonoids from aerial part of Scutellaria baicalensis Georgi (SSF) on potassium cyanide (KCN)-induced hypoxic cytotoxicity in rat pheochromocytoma cell line PC12, and to understand the probable mechanism. Methods: The rat pheochromocytoma cell fine PC12 was subjected to hypoxia by 200 )µM KCN for 30 min. The cytotoxicity of KCN was assessed by cell viability assay, morphological observation, lactate dehydrogenase (LDH) release, malondialdehyde (MDA) production, and the activities of superoxide dismutase (SOD) and Na+-K+-ATPase measurements. The effects of SSF on the changes induced by KCN in PC12 cells were detected. Results: Treatment of PC12 cells with 200 µM KCN for 30 min increased cell death when compared with control, as assayed by MTT reduction, morphological observation and lactate dehydrogenase release measurement. These cell lesions were accompanied by disorders in SOD and Na+-K+- ATPase activities as well as MDA production. In contrast, the PC12 cells pre-treated with SSF for 24 h prior to 200 µM KCN exposure have shown protection against hypoxic toxicity. The KCN -- induced decreased cell viability and activities of SOD and Na+-K+-ATPase, as well as increased MDA production were reversed by SSF pre-treatment. Interpretation & conclusions: SSF exerted neuroprotections against KCN -induced hypoxic cytotoxicity in PC12 cells and the probable mechanisms involved free radicals and energy metabolism. Our findings may have implications in future in the treatment of neurodegenerative 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]