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A large number of waste brewer’s spent grains (BSGs) have been produced every year in brewing industry of China, which have the advantages of high volatile matter content and low sulfur content, especially suitable for being utilized as gasification raw materials. Fluidized-bed gasifiers are famous for their excellent gas-solid mixing and temperature uniformity. Therefore, it is of great significance to realize the resource use and energy utilization of BSGs by fluidized-bed gasification. In order to investigate the effects of particle sizes on gas-solid flow behavior and gas production in the fluidized-bed gasification of BSGs, the numerical simulations of the gasification of BSGs in a bubbling fluidized-bed gasifier with air and water vapor as gasification agents were performed, based on computational particle fluid dynamics (CPFD) method. The effects of bed-materials particle sizes and BSGs particle sizes were both studied. The distribution of particle volume fraction, the particle distributions of BSGs and bed materials, and the mole fractions of main gas components were obtained by the CPFD numerical simulation. An experimental apparatus for bubbling fluidized-bed gasification was used to study the effects of bed-materials particle sizes and BSGs particle sizes on the volume fractions of main gas components in the product gas, which validated the numerical simulation results. The results showed that the increases of bed-materials particle sizes were not conductive to adequate fluidization and particle mixing, which made the temperature distribution uneven along the height. The increases of bed-materials particle sizes were also not conductive to the intensive mixing of carbon particles and water vapor, and the uniform heat absorption or heat release of gas-solid reaction and gas-phase reaction, resulting in a significant reduction of H2 mole fraction. The appropriate increases of BSGs particle sizes helped to prolong their residence time in the gasifier, thus improving the reaction conversion rate between solid carbon and water vapor or carbon dioxide, and generating more H2 and CO. However, excessive large BSGs particle sizes caused the poor mixing of BSGs and bed materials, which reduced the specific surface areas of BSGs, and were not conducive to the pyrolysis and gasification reaction, leading to the reduction of the molar fractions of combustible components such as H2, CO, CH4 and NH3.

Air pollution significantly impacts lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic mutation analysis revealed XWLC as a distinct subtype of LUAD separate from cases associated with smoking or endogenous factors. Mutational signature analysis suggested that Benzo[a]pyrene (BaP) is the major risk factor in XWLC. The BaP-induced mutation hotspot, EGFR-G719X, was present in 20% of XWLC which endowed XWLC with elevated MAPK pathway activations and worse outcomes compared to common EGFR mutations. Multi-omics clustering of XWLC identified four clinically relevant subtypes. These subgroups exhibited distinct features in biological processes, genetic alterations, metabolism demands, immune landscape, and radiomic features. Finally, MAD1 and TPRN were identified as novel potential therapeutic targets in XWLC. Our study provides a valuable resource for researchers and clinicians to explore prevention and treatment strategies for air-pollution-associated lung cancers.

The production of huge amounts of biogas slurry during livestock breeding has resulted in pressing environmental issues. Although paddy fields can be potential sinks for the disposal of biogas slurry, the impacts of biogas slurry on rice production, grain quality, and relevant environmental risks in the Yangtze Delta region remain unclear. Herein, we conducted a field trial from 2021 to 2023 which involved different gradients of biogas slurry utilization, including CK (no fertilizer), CN (100% chemical nitrogen (N) of 240 kg ha−1), NBS (biogas slurry replacing 50% chemical N), BS1 (replacing 100% chemical N), BS1.5 (replacing 150% chemical N), and BS2 (replacing 200% chemical N). The results showed that there were no significant differences in average rice yields between CN, NBS, BS1.5, and BS2 over the three-year study period, with an average yield of 8283 kg ha−1, and the average yields of BS1 and CK were 7815 kg ha−1 and 6236 kg ha−1, respectively. However, heavy utilization of biogas slurry (BS1.5 and BS2) not only significantly reduced the rice seed-setting rate, the 1000-grain weight, and the processing quality, but also significantly increased the protein, amylose, Cu, and Zn content in rice grains; additionally, higher N losses occurred via surface water and increased NH3 volatilization was observed, finally resulting in lower nitrogen-use efficiency. Meanwhile, moderate utilization of biogas slurry (NBS and BS1) led to better rice quality and nitrogen-use efficiency, lower potential food safety risk, and N loss. Further, compared to BS1, NBS showed higher yield, harvest index, processing quality, gel consistency, palatability scores, and nitrogen-use efficiency, but lower N losses were present. Overall, the NBS treatment balanced the agronomic benefits and environmental risks in the Yangtze River Delta region. In the future, more attention should be paid to food safety and environmental risks when using biogas slurry.

To overcome the problem of easily falling into local extreme values of the whale swarm algorithm to solve the material emergency dispatching problem with changing road conditions, an improved whale swarm algorithm is proposed. First, an improved scan and Clarke-Wright algorithm is used to obtain the optimal vehicle path at the initial time. Then, the group movement strategy is designed to generate offspring individuals with an improved quality for refining the updating ability of individuals in the population. Finally, in order to maintain population diversity, a different weights strategy is used to expand individual search spaces, which can prevent individuals from prematurely gathering in a certain area. The experimental results show that the performance of the improved whale swarm algorithm is better than that of the ant colony system and the adaptive chaotic genetic algorithm, which can minimize the cost of material distribution and effectively eliminate the adverse effects caused by the change of road conditions.

Despite significant improvements in prognosis, a subset of patients with primary central nervous system lymphoma (PCNSL) remains at high risk for relapse. The treatment of relapsed and refractory (R/R) PCNSL remains a major clinical challenge. Herein, we present a 24-year-old patient with PCNSL who relapsed 4 years after initial diagnosis and subsequently became refractory to high-dose methotrexate (HD-MTX), temozolomide, whole brain radiation therapy (WBRT), ibrutinib, and lenalidomide. She received thiotepa with anti-programmed cell death protein 1 (PD-1) antibody and achieved partial remission and then underwent autologous stem cell transplantation (ASCT) with thiotepa-based conditioning. Post-transplant maintenance with thiotepa and anti-PD-1 at 3-month intervals resulted in a durable complete response (CR) in this case of R/R PCNSL. Our report highlights the important role of thiotepa in the treatment of patients with R/R PCNSL.

For patients with primary refractory AML, allogeneic hematopoietic cell transplantation (allo-HCT) is considered the only curative approach. However, the therapeutic efficacy of salvage transplantation in the non-remission (NR) state remains controversial. We present a patient with primary refractory AML and concomitant central nervous system (CNS) leukemia, who received salvage allo-HCT, localized radiotherapy and venetoclax maintenance. Although he experienced systemic chronic graft-versus-host disease (cGVHD), he remained disease-free for 2 years. We propose that salvage transplantation is a feasible for primary refractory AML and discuss strategies to prevent relapse after allo-HCT, including maintenance therapy and donor lymphocyte infusion (DLI). Finally, we highlight the importance of radiotherapy, which can exert immunomodulatory effects to enhance immune responses against leukemia.

Abstract Induction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3–4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.

Radiation-induced cerebral necrosis, also known as radiation encephalopathy, is a debilitating condition that significantly impacts the quality of life for affected patients. Secondary central nervous system lymphoma (SCNSL) typically arises from highly aggressive mature B-cell lymphoma, but rarely from extranodal natural killer T-cell lymphoma (ENKTL). Treatment will be guided by differentiation between lymphoma progression from brain necrosis, and is particularly important for critically ill patients in an acute setting. However, differential diagnosis remains challenging because they share similar clinical manifestations and have no specific imaging features. We present the case of a 52-year-old man with ENKTL who suffered an emergency brain herniation secondary to massive radiation necrosis. The diagnosis established by brain biopsy ultimately led to appropriate treatment. The importance of the diagnostic biopsy is highlighted in this case for distinguishing between radiation necrosis and SCNSL.

Abstract Background Leber’s congenital amaurosis (LCA) is a severe hereditary retinopathy disease that is characterized by early and severe reduction of vision, nystagmus, and sluggish or absent pupillary responses. To date, the pathogenesis of LCA remains unclear, and the majority of cases are caused by autosomal recessive inheritance. In this study, we explored the variant in the Crumbs homologue 1 (CRB1) gene in a Chinese family with LCA. Methods We conducted comprehensive ocular examinations and collected 5 ml of blood samples from members of a Chinese family with LCA. A pathogenic variant was identified by capturing (the panel in NGS) and Sanger sequencing validation. Results A nonsense variant (c.1499C>G) in the 6th exon of CRB1 gene in a Chinese family with LCA was identified, which predicted a change in the protein p. S500*, may lead to loss of gene function. We summarized the 76 variants reported thus far in CRB1 that caused LCA8. Conclusions This study reported a novel variant c.1499C>G (p. S500*) of the CRB1 gene occurred in a Chinese family with LCA, thus expanding the spectrum of CRB1 variants causing LCA.

In order to solve the problem that the scheduling scheme cannot be updated in real time due to the dynamic change of node demand in material emergency dispatching, this article proposes a dynamic attention model based on improved gated recurrent unit. The dynamic codec framework is used to track the change of node demand to update the node information. The improved gated recurrent unit is embedded between codecs to improve the representation ability of the model. By weighted combination of the node information of the previous time, the current time and the initial time, a more representative node embedding is obtained. The results show that compared with the elitism-based immigrants ant colony optimization algorithm, the solution quality of the proposed model was improved by 27.89, 27.94, 28.09 and 28.12% when the problem scale is 10, 20, 50 and 100, respectively, which can effectively deal with the instability caused by the change of node demand, so as to minimize the cost of material distribution.

The phase summation effect in sum-frequency mixing process is utilized to avoid a nonlinearity obstacle in the power scaling of single-frequency visible or ultraviolet lasers. Two single-frequency fundamental lasers are spectrally broadened by phase modulation to suppress stimulated Brillouin scattering in fiber amplifier and achieve higher power. After sum-frequency mixing in a nonlinear optical crystal, the upconverted laser returns to single frequency due to phase summation, when the phase modulations on two fundamental lasers have a similar amplitude but opposite sign. The method was experimentally proved in a Raman fiber amplifier-based laser system, which generated a power-scalable sideband-free single-frequency 590 nm laser. The proposal manifests the importance of phase operation in wave-mixing processes for precision laser technology.

Chimeric antigen receptor (CAR)-T cell therapy is a novel cell therapeutic approach that is increasingly being used to treat patients with relapsed refractory B-cell lymphoma. Despite the efficacy of CAR T cell therapy, it has various adverse effects that can affect any organ in the body. The application of immune checkpoint inhibitors such as programmed death 1 (PD-1), programmed death ligand 1 (PDL-1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies has previously been reported to be associated with immune-related adverse events such as thyroid dysfunction and thyroiditis. Reports of immune-related adverse reactions after CAR T therapy are currently extremely rare, with only one case of a cytokine storm (CRS) combined with severe arthritis in a patient with ALL after treatment. Here, we describe two cases of Hashimoto’s thyroiditis secondary to CAR T therapy. Two patients with relapsed refractory diffuse large B-cell lymphoma developed elevated peroxidase and globulin antibodies secondary to CAR-T cell therapy and developed Hashimoto’s thyroiditis. Complete remission was achieved in two patients at 1 and 3 months after CAR-T cell therapy. The inflammation of the thyroid tissue may be directly or indirectly related to CAR T cell therapy, and the mechanisms needs to be further investigated.

Roads extracted from high-resolution remote sensing images are widely used in many fields, such as autonomous driving, road planning, disaster relief, etc. However, road extraction from high-resolution remote sensing images has certain deficiencies in connectivity and completeness due to obstruction by surrounding ground objects, the influence of similar targets, and the slender structure of roads themselves. To address this issue, we propose a novel dual-path convolutional neural network with a strip dilated attention module, named DPSDA-Net, which adopts a U-shaped encoder–decoder structure, combining the powerful advantages of attention mechanism, dilated convolution, and strip convolution. The encoder utilizes ResNet50 as its basic architecture. A strip position attention mechanism is added between each residual block to strengthen the coherent semantic information of a road. A long-distance shortcut connection operation is introduced to preserve the spatial information characteristics of the original image during the downsampling process. At the same time, a pyramid dilated module with a strip convolution and attention mechanism is constructed between the encoder and decoder to enhance the network feature extraction ability and multi-scale extraction of road feature information, expand the model’s receptive field, and pay more attention to the global spatial semantic and connectivity information. To verify the reliability of the proposed model, road extraction was carried out on the Massachusetts dataset and the LRSNY dataset. The experimental results show that, compared with other typical road extraction methods, the proposed model achieved a higher F1 score and IOU. The DPSDA-Net model can comprehensively characterize the structural features of roads, extract roads more accurately, retain road details, and improve the connectivity and integrity of road extraction in remote sensing images.

Objective(s): Previously we reported functional leukocyte immunoglobulin-like receptor A3 (LILRA3) leads to susceptibility and sub-phenotypes of several autoimmune diseases. LILRA3 levels in blood serum and CD14+ monocytes enhanced in systemic lupus erythematosus and resulted in disease severity. However, the mechanism of LILRA3 in the pathogenesis of autoimmunity remains elusive. This study aims to explore the potential impact of LILRA3 on the differentiation, maturation, and function of monocyte-derived DCs (MoDCs).Materials and Methods: The human monocytic cell line (THP-1) was cultured to derive MoDCs in vitro. We performed plasmid transfection to examine the impact of LILRA3 on monocyte differentiation. Surface markers on MoDCs were measured using FACS. To assess the function of mature MoDCs, IL-12p70, IFN-γ and IL-4 levels were detected after the mixed leucocyte response by enzyme-linked immunosorbent assay. Western blot assay was employed in this study to determine the signaling pathways in MoDCs activation.Results: LILRA3 promotes MoDCs maturation, our results showed significant up-regulation of CD40, CD80, CD86, CD209, and HLA-DR and increased production of pro-inflammatory cytokine IL-12. LILRA3-treated MoDCs exhibited a robust proliferation of allogeneic CD4+ T cells and induced naïve CD4+ T cell polarization into the Th1 phenotype. Furthermore, the preceding activation of MoDCs maturation and LILRA3 function might be attributed to p38 MAPK and STAT1 signaling pathway’s aberrant activation. Conclusion: This is the first study to report that LILRA3 played a critical role in promoting MoDCs maturation and directing MoDCs to modulate Th1 cell differentiation, which may have a role in the pathogenesis of autoimmune diseases.

High-power continuous-wave single-frequency Er-doped fiber amplifiers at 1560 nm by in-band and core pumping of a 1480 nm Raman fiber laser are investigated in detail. Both co- and counter-pumping configurations are studied experimentally. Up to 59.1 W output and 90% efficiency were obtained in the fundamental mode and linear polarization in the co-pumped case, while less power and efficiency were achieved in the counter-pumped setup for additional loss. The amplifier performs indistinguishably in terms of laser linewidth and relative intensity noise in the frequency range up to 10 MHz for both configurations. However, the spectral pedestal is raised in co-pumping, caused by cross-phase modulation between the pump and signal laser, which is observed and analyzed for the first time. Nevertheless, the spectral pedestal is 34.9 dB below the peak, which has a negligible effect for most applications.

A 7.8-GHz linewidth ytterbium-doped fiber (YDF) laser with an output power of 75 W at 1,018 nm is demonstrated based on narrow-bandwidth fiber Bragg gratings. Effective suppression of spectral broadening and amplified spontaneous emission is achieved by optimizing the resonator structure and active fiber parameters. An 1,178-nm diamond Raman output pumped by this narrow-linewidth 1,018 nm source is addressed in this study, which shows a promising application of generating the sodium guide star laser at 589 nm. A single-longitudinal-mode Stokes with an output power of 0.6 W is obtained using this multimode 1,018 nm laser at the pump power of 13 W. The impact of pump spectral linewidth on the effective Raman gain coefficient is analyzed, and the laser threshold of the diamond Stokes resonator increases with the broadening of the pump linewidth.

ObjectiveThe multisystem involvement and high heterogeneity of systemic lupus erythematosus (SLE) lead to great challenges in its diagnosis and treatment. The purpose of this study was to find new lncRNAs in peripheral blood mononuclear cells of SLE patients by transcriptome sequencing and explore their potential as biomarkers and their correlation with clinical features.Materials and MethodsTranscriptome sequencing was used to screen differentially expressed lncRNAs (DELs) and mRNAs (DEMs). The expression of these selected lncRNAs and mRNAs in SLE patients and healthy controls was verified by qPCR. DAVID and WebGestalt were used to perform enrichment analysis. Cytoscape was used to construct a protein–protein network, a coexpression network, and a competitive endogenous RNA network to reveal the regulatory mechanisms of lncRNAs at the transcriptome level.ResultsA total of 1737 DELs and 4078 DEMs were identified between SLE patients and healthy controls. Ten lncRNAs and eight genes were verified by qPCR in a larger sample set. The lncRNA NONHSAT101022.2 was significantly downregulated in SLE patients and was also significantly related to the activity and severity of disease. The upregulated genes were enriched in defense and the immune response, while the downregulated genes were mainly enriched in SLE-related pathways. Topology network analysis revealed that the lncRNAs were involved in regulation at the transcriptome level, including acting directly on mRNA or indirectly affecting gene expression by acting on miRNA.ConclusionIn this work, we identified many mRNAs and novel lncRNAs by transcriptome sequencing. The functions and regulatory mechanisms of these lncRNAs were analyzed by bioinformatic methods. The novel lncRNA NONHSAT101022.2 is significantly downregulated in SLE patients and is significantly related to the activity and severity of disease. Additionally, we propose that NONHSAT101022.2 may enhance the signal transduction of β2-AR by cis regulating LMBRD2, inducing NK cells to produce high levels of IFN-γ and thereby exacerbating SLE.

Microgrids (MGs) are composed of multiple distributed generators (DGs) interfaced to micronetwork through paralleled connected power inverters (PIs). Load sharing among multiple DG units is an important task for autonomous operation of microgrids. In order to realize satisfactory power sharing and voltage regulation between DG units, different voltage droop control strategies have been reported in the literature. In the medium voltage (MV) microgrids, power sharing, and voltage regulation often deteriorate due to dependence on nontrivial feeder impedances. The conventional control strategies are subject to steady-state active and reactive power-sharing errors along with system voltage and frequency deviations. Furthermore, complex microgrid configurations either in looped or meshed networks often make power balancing and voltage regulations more challenging. This paper presents an improved control strategy that can be extended for radial networks in order to enhance the accuracy of power sharing and voltage regulation. The proposed control strategy considers load voltage magnitude regulation as opposed the voltage regulation at inverters terminals. At the same time, a supervisory control loop is added to observe and correct system frequency deviations. This proposed method is aimed at replacing paralleled inverter control methods hitherto used. Simulation studies of the proposed scheme in comparison with the conventional control strategy in MATLAB/Simulink validate the effectiveness of the proposed strategy.