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Abstract Background The origin recognition complex 1 (ORC1) is a large subunit of the origin recognition complex and acts as the master subunit of the precoding complex. Objective To explore potential function and clinical significance of ORC1 in cancers. Methods The expression level of ORC1 in different types of tumor tissues and matched normal tissues were detected by The Cancer Genome Atlas (TCGA) and validated by datasets from the gene expression omnibus (GEO) database. The association between ORC1 expression and infiltration levels of immune cell was analyzed. ORC1 and its co-expression genes were subjected to enrichment analysis to explore potential mechanisms in cancers, and the protein-protein interaction (PPI) network was constructed. Finally, the expression of ORC1 in tumor tissue and adjacent tissue was verified by immunohistochemistry (IHC). Results ORC1 was highly expressed in the majority of tumors, and the expression level of ORC1 was associated with the pathological stages of ACC, LUAD, OV and SKCM. ORC1 was closely related with poor prognosis in ACC, LIHC, PAAD, READ and THCA. ORC1 in ACC and KICH was positively correlated with the infiltration level of immune cells while it was negatively correlated with the infiltration level of immune cells in THYM. Co-expression network analysis showed that CDCA3, GSG2, KIF2C, NCAPH and PLK1 were positively correlated with ORC1 in cancer, and enrichment analysis showed a correlation with cytosol, ATP binding and cell division. The expression of ORC1 in UCEC and KICH was higher than that in the adjacent tissues. Conclusion ORC1 over-expressed in most tumors and could be severed as a novel biomarker for diagnosis. This study revealed that ORC1 might inhibit tumor immunity and might be a potential therapeutic target in cancers.

Voltage sags resulting from symmetrical or asymmetrical faults pose a significant threat to power quality. In response to this challenge, a voltage sag loss assessment method based on a two-stage Taguchi quality perspective approach is proposed to address the quantitative analysis of voltage sag economic losses. Initially, using the Taguchi quality perspective method, single-index quality loss functions are separately established for voltage sag magnitude and fault duration. Subsequently, by introducing a comprehensive load tolerance curve, sensitivity parameters within the quality loss function are accurately calculated. This yields a deterministic model for voltage sag assessment. Building upon this, the relative impact of the two indices on voltage sag loss is evaluated using the quality loss function. Consequently, a comprehensive loss model under the influence of multiple indices is formed by integrating two single-index evaluation models. The simulation results indicate that this method can effectively assess the economic losses of voltage sags under the combined influence of multiple factors. Compared to the original economic loss assessment method, it improves quantitative accuracy by approximately 3.72%. Moreover, the method reduces the computational complexity of loss assessment through the consolidation of intervals with similar sensitivity parameters.

Environmental pollution often occurs in the process of mining, beneficiation and smelting of metal mines.Arsenic pollution caused by acid mine drainage (AMD) is one of the most serious pollution problems of heavy metals. At present, the understanding of the evolution process of secondary minerals is insufficient. This paper summarizes the occurrence form of arsenic in metal sulfide.The specific chemical process of activation and migration in different minerals are discussed.Three rules of form transformation are concluded. ①Pyrite and arsenopyrite are the most common arsenic-bearing minerals in metal sulfide mines; ②Arsenic is activated by the oxidation and dissolution of primary minerals, existing mainly in the form of arsenate and arsenite in AMD of which arsenite is more migratory. ③Adsorptive precipitation of secondary minerals in AMD (such as ferro-vanadium, goethite, scallion, etc.) can slow the migration rate and reduce the migration amount of arsenic but cannot prevent the migration process. The migration mechanism of arsenic in the mine environment is reviewed, and new treatment schemes and research directions are proposed.

IntroductionChimeric antigen receptor T (CAR-T) cell therapy presents a promising treatment option for various cancers, including solid tumors. Carcinoembryonic antigen (CEA) is an attractive target due to its high expression in many tumors, particularly gastrointestinal cancers, while limited expression in normal adult tissues. In our previous clinical study, we reported a 70% disease control rate with no severe side effects using a humanized CEA-targeting CAR-T cell. However, the selection of the appropriate single-chain variable fragment (scFv) significantly affects the therapeutic efficacy of CAR-T cells by defining their specific behavior towards the target antigen. Therefore, this study aimed to identify the optimal scFv and investigate its biological functions to further optimize the therapeutic potential of CAR-T cells targeting CEA-positive carcinoma.MethodsWe screened four reported humanized or fully human anti-CEA antibodies (M5A, hMN-14, BW431/26, and C2-45), and inserted them into a 3rd-generation CAR structure. We purified the scFvs and measured the affinity. We monitored CAR-T cell phenotype and scFv binding stability to CEA antigen through flow cytometry. We performed repeated CEA antigen stimulation assays to compare the proliferation potential and response of the four CAR-T cells, then further evaluated the anti-tumor efficacy of CAR-T cells ex vivo and in vivo.ResultsM5A and hMN-14 CARs displayed higher affinity and more stable CEA binding ability than BW431/26 and C2-45 CARs. During CAR-T cell production culture, hMN-14 CAR-T cells exhibit a larger proportion of memory-like T cells, while M5A CAR-T cells showed a more differentiated phenotype, suggesting a greater tonic signal of M5A scFv. M5A, hMN-14, and BW431/26 CAR-T cells exhibited effective tumor cell lysis and IFN-γ release when cocultured with CEA-positive tumor cells in vitro, correlating with the abundance of CEA expression in target cells. While C2-45 resulted in almost no tumor lysis or IFN-γ release. In a repeat CEA antigen stimulation assay, M5A showed the best cell proliferation and cytokine secretion levels. In a mouse xenograft model, M5A CAR-T cells displayed better antitumor efficacy without preconditioning.DiscussionOur findings suggest that scFvs derived from different antibodies have distinctive characteristics, and stable expression and appropriate affinity are critical for robust antitumor efficacy. This study highlights the importance of selecting an optimal scFv in CAR-T cell design for effective CEA-targeted therapy. The identified optimal scFv, M5A, could be potentially applied in future clinical trials of CAR-T cell therapy targeting CEA-positive carcinoma.

This work uses rice husk to fabricate mesoporous silica nanoparticles (D-RMN) for breast cancer therapy. The biocompatible dual-responsive (DAN-RMN) was developed by polymerizing acrylic acid (AA) and n-isopropyl acrylamide (NIPAM) on the DV-RMN surface monomeric ratio to increase drug delivery efficiency after vinyl groups were added to the surface of nanoparticles (DAN-RMN). Various analytical and spectroscopical methods characterized the fabricated nanoparticles. Additionally, further encapsulation with SN-38 into the DAN-RMN enhances anticancer efficiency. The in-vitro controlled SN-38 release displayed remarkable temperature and pH response. The MTT assay established the biocompatibility and cytotoxicity of natural sources of silica and DAN-RMN. The fabricated SN-38@DAN-RMN nanoparticles effectively killed the MDA-MB-231 and 4T1 cancerous cells, confirmed by the MTT assay. The IC50 values of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 1.8 μg/mL and 1.7 μg/mL, respectively. In addition, acridine orange-ethidium bromide (AO-EB) dual staining methods were used to determine morphological changes of cell shrinkage and fragmentation. Nuclear staining methods confirmed the nuclear fragmentation and condensation of the cells. Further, the cell death was examined using dual staining Annexin V-FITC/PI in flow cytometric analyses to assess apoptosis in the MDA-MB-231 and 4T1 cell lines. The apoptotic cell ratio of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 27.8 and 32.8, respectively. Since there is no drug leakage in the blood while the carrier is in circulation, the DAN-RMN nanocarrier may be used for targeted and stimuli-responsive administration using ultrasound imaging.

In this paper, multiple autonomous underwater vehicle (multi-AUV) formation control with obstacle avoidance ability in 3D complex underwater environments based on an event-triggered model predictive control (EMPC) is proposed. Firstly, multi-AUV motion model systems are developed. The navigation reference trajectory of the follower AUVs can be obtained using a multi-AUV relative motion model. Secondly, in order to overcome the speed jump and obstacle avoidance problem in multi-AUV systems, compatibility constraints are presented in MPC that limit the uncertainty deviation of each AUV. The event-triggered mechanism (ET) is designed to decrease the computational load, which is based on the error between the optimal predicted and current state of the AUV. Finally, the effectiveness and superiority of the proposed algorithm are confirmed via simulation and compared with those of other algorithms.

An in-depth study on the fixed-time event-triggered obstacle avoidance consensus control in heterogeneous USV-AUV systems with input delay and uncertain disturbances are conducted in this paper. When initial state of the system fails to achieve consensus, the desired heterogeneous USV-AUV formation can be achieved by fixed-time consensus control, within a fixed predetermined time, regardless of the initial states. Besides, an event-triggered communication strategy among the agents is introduced in the system, significantly reducing communication energy consumption. By employing the proposed control strategy, the Zeno behavior also can be avoided. Additionally, an obstacle avoidance control algorithm for the heterogeneous USV-AUV system based on improved artificial potential fields (IAPF) is designed, which helps in avoiding both static and dynamic obstacles. Compared to existing research, this algorithm reduces control input jitter, resulting in smoother obstacle avoidance paths. Through extensive simulation experiments and comparisons with other methods, effectiveness and superiority of the proposed algorithm is validated.

Background: Lenvatinib combined with a PD-1 inhibitor has obtained a satisfactory antitumor effect in several solid tumors. However, the efficacy and tumor response of lenvatinib with a PD-1 inhibitor in advanced intrahepatic cholangiocarcinoma still need further exploration.Methods: This is a single-arm study for the assessment of the efficacy and tolerability of lenvatinib with a PD-1 inhibitor in intrahepatic cholangiocarcinoma patients who had chemotherapy failure. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1).Results: A total of 40 patients with advanced intrahepatic cholangiocarcinoma were enrolled after the chemorefractory effect. The median progression-free survival was 5.83 ± 0.76 months. The 3-month and 6-month progression-free survival rates were 80.0% and 32.5%, respectively. The median overall survival was 14.30 ± 1.30 months. The 12-month and 18-month overall survival rates were 61.4% and 34.7%. The 3-month RECIST 1.1 evaluation was that seven patients (17.5%) showed partial response, 23 patients (57.5%) had stable disease, and 10 patients (25.0%) had progressive disease. The objective response rate was 17.5%, and the disease control rate was 75.0%. All the recorded any-grade adverse events inducing treatment termination were controllable, and there were no AE-related deaths.Conclusion: Our study showed that a combination of lenvatinib with the PD-1 inhibitor could be an effective treatment for advanced intrahepatic cholangiocarcinoma after the chemorefractory effect.

Resumo Fundamento A aterosclerose é a principal causa da maioria das doenças cardiovasculares, e novos biomarcadores para essa condição são sempre necessários. O domínio da peptidase M20 contendo 1 (PM20D1) está associado ao metabolismo lipídico e à obesidade. No entanto, nenhum estudo se concentra no papel do PM20D1 na aterosclerose carotídea. Objetivo O objetivo deste estudo foi investigar o papel do PM20D1 em pacientes com aterosclerose carotídea. Métodos Estudo observacional prospectivo conduzido com um total de 231 pacientes com aterosclerose carotídea que estiveram em nosso departamento entre julho de 2018 e dezembro de 2019. Amostras de sangue e dados médicas foram obtidos de outros 231 indivíduos saudáveis com o mesmo índice de massa corporal (IMC) dos pacientes com aterosclerose carotídea. O PM20D1 sérico foi determinado por ensaio imunossorvente ligado a enzima (ELISA). As características clínicas e demográficas de todos os pacientes foram listadas, incluindo idade, sexo biológico, IMC e histórico médico. Os níveis de proteína C reativa (PCR), fator de necrose tumoral, homocisteína, colesterol total, triglicerídeos, leptina-colesterol de alta densidade e leptina-colesterol de baixa densidade foram registrados. Realizou-se análise estatística no software SPSS, com p

BackgroundPosaconazole is confirmed to be more effective for preventing invasive fungal infections (IFIs) than first-generation triazoles (fluconazole and itraconazole), but its economic value has not been comprehensively evaluated in China. This study compared the cost-effectiveness of these two antifungal prophylaxis regimens in hematological-malignancy patients at high risk for IFIs from the Chinese healthcare perspective.MethodsA hybrid decision tree and Markov model were built using published data to estimate the total costs and quality-adjusted life-years (QALYs) of antifungal prophylaxis with posaconazole oral suspension and first-generation triazoles. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the threshold of willingness to pay (WTP) were considered cost-effective. One-way and probabilistic sensitivity analyses were performed to assess model robustness. The regional imbalance of economic development and the tablet formulation of posaconazole were considered in the scenario analyses.ResultsIn the base-case analysis, posaconazole oral suspension provided an additional 0.109 QALYs at an incremental cost of $954.7, yielding an ICER of $8,784.4/QALY, below the national WTP threshold of $31,315/QALY. One-way and probabilistic sensitivity analyses showed that the results were robust. Scenario analyses showed that the base-case ICER was consistently below the WTP thresholds of all 31 Chinese provinces, with the likelihood of posaconazole being cost-effectiveness ranging from 78.1 to 99.0%. When the posaconazole oral suspension was replaced by the tablet formulation, the ICER increased to $29,214.1/QALY, still below the national WTP threshold and WTP thresholds of 12 provinces.ConclusionsPosaconazole oral suspension is a highly cost-effective regimen for preventing IFI in high-risk hematological-malignancy patients from the Chinese healthcare perspective. Posaconazole tablets may also be considered in some high-income regions of China.

Shale gas extraction via horizontal drilling and hydraulic fracturing (HF) has enhanced gas production worldwide, which has altered global energy markets and reduced the prices of natural gas and oil. Water management has become the most challenging issue of HF, as it demands vast amounts of freshwater and generates high volumes of complex liquid wastes contaminated by diverse potentially toxic elements at variable rates. This critical review focuses on characterizing HF wastewater and establishing strategies to mitigate environmental impacts. High prioritization was given to the constituents with mean concentrations over 10 times greater than the maximum contamination level (MCL) guidelines for drinking water. A number of potentially harmful organic compounds in HF wastewaters were identified via the risk quotient approach to predict the associated toxicity for freshwater organisms in recipient surface waters. Currently, two options for HF wastewater treatment are preferred, i.e., disposal by deep well injection or on-site re-use as a fracturing fluid. Supplementary treatment will be enforced by increasingly rigorous regulations. Partial treatment and reuse remain the preferred method for managing HF wastewater where feasible. Otherwise, advanced technologies such as membrane separation/distillation, forward osmosis, mechanical vapor compression, electrocoagulation, advanced oxidation, and adsorption-biological treatment will be required to satisfy the sustainable requirements for reuse or surface discharge. Keywords: Unconventional energy, Hydraulic fracturing, Environmental pollution, Metals/metalloids, Wastewater treatment, Sustainable remediation

Ibrutinib is a small molecule drug that targets Bruton's tyrosine kinase in B‐cell malignancies and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia. However, the anti‐cancer activity of ibrutinib against solid tumors, such as non‐small cell lung cancer (NSCLC), remains low. To improve the cytotoxicity of ibrutinib towards lung cancer, we synthesized a series of ibrutinib derivatives, of which Ibr‐7 exhibited superior anti‐cancer activity to ibrutinib, especially against epithelial growth factor receptor (EGFR) wild‐type NSCLC cell lines. Ibr‐7 was observed to dramatically suppress the mammalian target of Rapamycin complex 1 (mTORC1)/S6 signaling pathway, which is only slightly affected by ibrutinib, thus accounting for the superior anti‐cancer activity of Ibr‐7 towards NSCLC. Ibr‐7 was shown to overcome the elevation of Mcl‐1 caused by ABT‐199 mono‐treatment, and thus exhibited a significant synergistic effect when combined with ABT‐199. In conclusion, we used a molecular substitution method to generate a novel ibrutinib derivative, termed Ibr‐7, which exhibits enhanced anti‐cancer activity against NSCLC cells as compared with the parental compound.

This paper evaluates a novel sorbent for the removal of potentially toxic elements, inherent cations, and hetero-chloride from hydraulic fracturing wastewater (FWW). A series of iron-biochar (Fe-BC) composites with different Fe/BC impregnation mass ratios (0.5:1, 1:1, and 2:1) were prepared by mixing forestry wood waste-derived BC powder with an aqueous FeCl3 solution and subsequently pyrolyzing them at 1000 °C in a N2-purged tubular furnace. The porosity, surface morphology, crystalline structure, and interfacial chemical behavior of the Fe-BC composites were characterized, revealing that Fe chelated with CO bonds as COFe moieties on the BC surface, which were subsequently reduced to a CC bond and nanoscale zerovalent Fe (nZVI) during pyrolysis. The performance of the Fe-BC composites was evaluated for simultaneous removal of potentially toxic elements (Cu(II), Cr(VI), Zn(II), and As(V)), inherent cations (K, Na, Ca, Mg, Ba, and Sr), hetero-chloride (1,1,2-trichlorethane (1,1,2-TCA)), and total organic carbon (TOC) from high-salinity (233 g L−1 total dissolved solids (TDS)) model FWW. By elucidating the removal mechanisms of different contaminants, we demonstrated that Fe-BC (1:1) had an optimal reducing/charge-transfer reactivity owing to the homogenous distribution of nZVI with the highest Fe0/Fe2+ ratio. A lower Fe content in Fe-BC (0.5:1) resulted in a rapid exhaustion of Fe0, while a higher Fe content in Fe-BC (2:1) caused severe aggregation and oxidization of Fe0, contributing to its complexation/(co-)precipitation with Fe2+/Fe3+. All of the synthesized Fe-BC composites exhibited a high removal capacity for inherent cations (3.2–7.2 g g−1) in FWW through bridging with the CO bonds and cation-π interactions. Overall, this study illustrated the potential efficacy and mechanistic roles of Fe-BC composites for (pre-)treatment of high-salinity and complex FWW. Keywords: Engineered biochar, Mineral-carbon composites, Metals/metalloids, Fracturing wastewater treatment, Sustainable remediation

In water scenes, where hazy images are subject to multiple scattering and where ideal data sets are difficult to collect, many dehazing methods are not as effective as they could be. Therefore, an unsupervised water scene dehazing network using atmospheric multiple scattering model is proposed. Unlike previous image dehazing methods, our method uses the unsupervised neural network and the atmospheric multiple scattering model and solves the problem of difficult acquisition of ideal datasets and the effect of multiple scattering on the image. In our method, in order to embed the atmospheric multiple scattering model into the unsupervised dehazing network, the unsupervised dehazing network uses four branches to estimate the scene radiation layer, transmission map layer, blur kernel layer and atmospheric light layer, the hazy image is then synthesized from the four output layers, minimizing the input hazy image and the output hazy image, where the output scene radiation layer is the final dehazing image. In addition, we constructed unsupervised loss functions which applicable to image dehazing by prior knowledge, i.e., color attenuation energy loss and dark channel loss. The method has a wide range of applications, with haze being thick and variable in marine, river and lake scenes, the method can be used to assist ship vision for target detection or forward road recognition in hazy conditions. Through extensive experiments on synthetic and real-world images, the proposed method is able to recover the details, structure and texture of the water image better than five advanced dehazing methods.

An end-to-end sea fog removal network using multiple scattering model was proposed. In this network, the atmospheric multiple scattering model was re-formulated and used for sea fog removal. Compared with the atmospheric single scattering model, the atmospheric multiple scattering model could more comprehensively consider the effect of multiple scattering, which was important to the dense fog scenes, such as in ocean scene. Therefore, we used the atmospheric multiple scattering model to avoid image blurring. The model can directly generate the dehazing results, and unify the three parameters of the transmission map, the atmospheric light and the blur kernel into one formula. The latest smooth dilation and sub-pixel techniques were used in the network model. The latest techniques can avoid the gridding artifacts and the halo artifacts, the multi-scale sub-network was used to consider the features of multi-scale. In addition, multiple loss functions were used in end-to-end network. In the experimental results, the model was superior to the state-of-the-art models in terms of quantitatively and qualitatively.

Arsenic-alkali residue (AAR) from antimony smelting is highly hazardous due to its ready leachability of As, seeking for proper disposal such as stabilization treatment. However, As stabilization in AAR would be challenging due to the high content of coexisting soluble carbonate. This study conducted the stabilization treatments of AAR by ferrous sulfate and lime, respectively, and revealed the significant influence of coexisting carbonate. It was found that ferrous sulfate was more efficient than lime, which required only one-tenth of dosages of lime to reduce the As leaching concentration from 915 mg/L to a level below 2.5 mg/L to meet the Chinese regulatory limit. The combining qualitative and quantitative analyses based on XRD, SEM–EDS, and thermodynamic modeling suggested that the formation of insoluble arsenate minerals, ferrous arsenate or calcium arsenate, was the predominant mechanism for As stabilization in the two treatment systems, and their efficiency difference was primarily attributed to the coexisting carbonate, which had a slight effect on ferrous arsenate but severely obstructed calcium arsenate formation. Moreover, the examination of As leaching concentrations in 1-year-cured samples indicated that the long-term stability of ferrous sulfate treatment was far superior to that of lime treatment. This study provides ferrous salts as a promising and green scheme for stabilization treatment of AAR as well as other similar As-bearing solid wastes with coexisting soluble carbonate. Keywords: Arsenic-alkali residue, Arsenic stabilization, Ferrous sulfate, Lime, Arsenate minerals, Coexisting soluble carbonate

Abstract Background Microsporidia are a group of eukaryotic intracellular parasites that infect almost all vertebrates and invertebrates. However, there is little information available of how microsporidia obtain nutrients and energy from host cells. The purpose of this study was to investigate the energy and material requirements of Nosema bombycis for the invasion procedure through analyzing the global variation of the gene expression, protein abundance, fatty acids level and ATP flux induced by the microsporidia N. bombycis infection in the midgut of the silkworm Bombyx mori. Methods A suppression subtractive hybridization (SSH) and quantitative real-time PCR (qPCR) analysis were performed to identify the genes upregulated in the midgut of B. mori 48 h following N. bombycis infection. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to annotate and summarize the differentially expressed genes, according to the categories ‘molecular function’, ‘cellular component’ and ‘biological process’. To evaluate the nutrition material and energy costs in B.mori infected by N. bombycis, biochemical analysis was performed to determine the variation of protein abundance, fatty acid levels and ATP flux with or without the microsporidia N. bombycis infection in the midgut of the silkworm B. mori. Results A total of 744 clones were obtained, 288 clones were randomly selected for sequencing, and 110 unigenes were generated. Amongst these, 49.21%, 30.16% and 14.29% genes were involved in 19 molecular functions, 19 biological processes and nine cellular components, respectively. A total of 11 oxidative phosphorylation- and eight proton-coupled ATP synthesis-related genes were upregulated. Seven protein degradation-, three fat degradation-related genes were upregulated, and no genes related to the de novo synthesis of amino acids and fatty acids were significantly upregulated. The data from the biochemical analysis showed the contents of total protein and ATP of B. mori midgut tissues decreased significantly, whereas the fatty acid content did not significantly change after four days of N. bombycis infection. Microsporidia N. bombycis infection upregulated the expression level of genes involved in host ATP synthesis, protein and fat degradation, which eventually causes the obvious decline of protein content and ATP synthesis in the host midgut, whereas the fatty acids content did not change significantly. Conclusions This study suggested to some extent that N. bombycis invasion can activate the host protein degradation and accelerate the production of host ATP. Microsporidia of N. bombycis show preference for proteins rather than fatty acids from the host to ensure the material preparation required by their parasitic life-cycle. Requirements of N. bombycis for energy were also mainly dependent on the host ATP production. This study provides a new data that may help our understanding of the molecular mechanisms of obtaining energy and nutrients from the host by the microsporidium N. bombycis.

The Halictidae, where the Seladonia aeraria belongs, was an important model organism for studying the evolution of insect social behavior. We first sequenced the complete mitochondrial genome (mitogenome) of Seladonia aeraria. The mitogenome was 15, 410 bp in length, including 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a hypothetical control region. In order to reveal the phylogenetic position of Seladonia aeraria form mitogenomic level, we performed phylogenetic analysis of 13 PCGs from 15 species. The results revealed that the genus-level relationship of Halictidae was Seladonia + Lasioglossum and Seladonia aeraria was more closely related to Seladonia tumulorum than Lasioglossum sp. SJW_2017. The complete mitogenome of S. aeraria will provide a basis for further study evolution and phylogenetic analysis of Halictidae.

Chinese sacbrood disease (CSD), which is caused by Chinese sacbrood virus (CSBV), is a major viral disease in Apis cerana cerana larvae. Analysis of lipid composition is critical to the study of CSBV replication. The host lipidome profiling during CSBV infection has not been conducted. This paper identified the lipidome of the CSBV–larvae interaction through high-resolution mass spectrometry. A total of 2164 lipids were detected and divided into 20 categories. Comparison of lipidome between healthy and CSBV infected-larvae showed that 266 lipid species were altered by CSBV infection. Furthermore, qRT-PCR showed that various sphingolipid enzymes and the contents of sphingolipids in the larvae were increased, indicating that sphingolipids may be important for CSBV infection. Importantly, Cer (d14:1 + hO/21:0 + O), DG (41:0e), PE (18:0e/18:3), SM (d20:0/19:1), SM (d37:1), TG (16:0/18:1/18:3), TG (18:1/20:4/21:0) and TG (43:7) were significantly altered in both CSBV_24 h vs. CK_24 h and CSBV_48 h vs. CK_48 h. Moreover, TG (39:6), which was increased by more than 10-fold, could be used as a biomarker for the early detection of CSD. This study provides evidence that global lipidome homeostasis in A. c. cerana larvae is remodeled after CSBV infection. Detailed studies in the future may improve the understanding of the relationship between the sphingolipid pathway and CSBV replication.

The towing operation of multi-tug-assisted ship navigation mainly relies on the experience of the captain, and there is no set of effective operation methods. Therefore, it is difficult to achieve accurate assisted navigation when multiple tugboats work in coordination. The calculation method of maneuverability of the towing system with multi-tug-assisted navigation is proposed in this paper. In view of the complexity of multi-tug-assisted large ship maneuvering, this article focuses on solving the problems of force analysis and maneuvering modeling between the multi-tug and ship systems. Firstly, a maneuvering mathematic model for towing ships is established, and the hydrodynamic force of the hull, rope force of the tugs, and force of wind interference are analyzed. The thrust and moment of the ducted azimuthal propeller are calculated, and the mathematical model of the tug’s cable tension is discussed. Then, the fourth-order Runge–Kutta method is used to solve the differential equations of the maneuvering motion of the ships and each tug. Based on the ship-towing process by multiple tugs, a multi-tug-assisted ship towing simulation platform was built by using the Visual Studio development tool. Finally, on the simulation platform, multi-tug longitudinal-towing-simulation experiments at different speeds were carried out, and the simulation of turning towing maneuvers under the influence of wind was done. The simulation results showed that as the towing speed increases, the initial towing speed fluctuates greatly. There is a significant drift effect on the ships by the wind force. And the wind will cause a fluctuation in the tug’s rope force. The simulation of the multi-tugs towing a ship entering the port was carried out in the port environment. The results showed that the multi-tug towing system and simulation platform may be used for the safety training of the tug’s crew.

Rare earth-β-diketone ligand complex luminescent material has stable chemical properties and excellent luminous property. Using europium oxide and (γ-NTA) as raw materials, novel rare earth-β-dione complexes are synthesized by solid state coordination chemistry. The synthesis temperature and milling time are discussed for optimization. Experimental results show that the suitable reaction situation is at 50 ℃ and 20 h for solid-phase synthesis. The compositions and structures of the complexes are characterized by means of elemental analysis, UV-Vis and FTIR methods, and the phase stability of the complex is determined by using TG-DTA technique. It is proved that preparation of waterless binary rare earth complexes by the solid phase reaction method results in a higher product yield. The fluorescence spectra show that between Eu (Ⅲ) and γ-NTA, there exists efficient energy transfer, and the rare earth complexes synthesis is an excellent red bright light-emitting material with excellent UV excited luminescence properties.

Microsporidia have attracted considerable attention because they infect a wide range of hosts, from invertebrates to vertebrates, and cause serious human diseases and major economic losses in the livestock industry. There are no prospective drugs to counteract this pathogen. Eukaryotic protein kinases (ePKs) play a central role in regulating many essential cellular processes and are therefore potential drug targets. In this study, a comprehensive summary and comparative analysis of the protein kinases in four microsporidia—Enterocytozoon bieneusi, Encephalitozoon cuniculi, Nosema bombycis and Nosema ceranae—was performed. The results show that there are 34 ePKs and 4 atypical protein kinases (aPKs) in E. bieneusi, 29 ePKs and 6 aPKs in E. cuniculi, 41 ePKs and 5 aPKs in N. bombycis, and 27 ePKs and 4 aPKs in N. ceranae. These data support the previous conclusion that the microsporidian kinome is the smallest eukaryotic kinome. Microsporidian kinomes contain only serine-threonine kinases and do not contain receptor-like and tyrosine kinases. Many of the kinases related to nutrient and energy signaling and the stress response have been lost in microsporidian kinomes. However, cell cycle-, development- and growth-related kinases, which are important to parasites, are well conserved. This reduction of the microsporidian kinome is in good agreement with genome compaction, but kinome density is negatively correlated with proteome size. Furthermore, the protein kinases in each microsporidian genome are under strong purifying selection pressure. No remarkable differences in kinase family classification, domain features, gain and/or loss, and selective pressure were observed in these four species. Although microsporidia adapt to different host types, the coevolution of microsporidia and their hosts was not clearly reflected in the protein kinases. Overall, this study enriches and updates the microsporidian protein kinase database and may provide valuable information and candidate targets for the design of treatments for pathogenic diseases.

CD19-targeted chimeric antigen receptor T lymphocytes (CAR-T) has demonstrated a high proportion of complete remission in the treatment of relapsed refractory acute B cell lymphoblastic leukemia (r/r B-ALL). It is of great clinical significance to explore which factors will impact long-term disease-free survival of patients with r/r B-ALL after CAR-T therapy without bridging bone marrow transplantation. Our study found that, in patients with r/r B-ALL without bridging transplantation, the patients' age; infusion dosage; whether they had undergone allo-stem cell transplantation before CAR-T therapy, using CD-19-targeted or CD19/CD22-dual-targeted CAR-T; whether there is fusion gene; tumor burden before therapy; and comorbidity had no significant relationship with their long-term disease-free survival. We found only that CAR-T persistence was highly correlated with patients' long-term disease-free survival. So, we further profiled CAR-T cells using single-cell sequencing and found that there is a specific T cell subset that may be associated with the long-term persistence of CAR-T. Finally, according to the single-cell sequencing results, we established cell production process named PrimeCAR, which shared common signaling pathways with the T cell subset identified. In the preliminary clinical study, prime CAR-Ts yield good persistence in peripheral blood of patients with B-ALL and lymphoma, without observing grade 2 or higher cytokine release syndrome., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)