Search

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.

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.

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.