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Abstract Background Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery and provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) that regulate lipid homeostasis after SCI and elucidating their potential mechanisms in promoting LDs clearance in microglia have become focal points of SCI research. Methods We established a subacute C5 hemicontusion SCI model in mice and performed transcriptomic sequencing on the injury epicenter to identify differentially expressed genes and associated pathways. Confocal imaging was employed to observe LDs accumulation. Multi-omics analyses were conducted to identify differentially expressed mRNA and miRNA post-SCI. Pathway enrichment analysis and protein-protein interaction network construction were performed using bioinformatics methods, revealing miR-223-Abca1 as a crucial miRNA-mRNA pair in lipid metabolism regulation. BV2 microglia cell lines overexpressing miR-223 were engineered, and immunofluorescence staining, western blot, and other techniques were employed to assess LDs accumulation, relevant targets, and inflammatory factor expression, confirming its role in regulating lipid homeostasis in microglia. Results Histopathological results of our hemicontusion SCI model confirmed LDs aggregation at the injury epicenter, predominantly within microglia. Our transcriptomic analysis during the subacute phase of SCI in mice implicated ATP-binding cassette transporter A1 (Abca1) as a pivotal gene in lipid homeostasis, cholesterol efflux and microglial activation. Integrative mRNA-miRNA multi-omics analysis highlighted the crucial role of miR-223 in the neuroinflammation process following SCI, potentially through the regulation of lipid metabolism via Abca1. In vitro experiments using BV2 cells overexpressing miR-223 demonstrated that elevated levels of miR-223 enhance ABCA1 expression in myelin debris and LPS-induced BV2 cells. This promotes myelin debris degradation and LDs clearance, and induces a shift toward an anti-inflammatory M2 phenotype. Conclusions In summary, our study unveils the critical regulatory role of miR-223 in lipid homeostasis following SCI. The mechanism by which this occurs involves the upregulation of ABCA1 expression, which facilitates LDs clearance and myelin debris degradation, consequently alleviating the lipid burden, and inhibiting inflammatory polarization of microglia. These findings suggest that strategies to enhance miR-223 expression and target ABCA1, thereby augmenting LDs clearance, may emerge as appealing new clinical targets for SCI treatment.

Abstract Heat shock protein 90 (HSP90) is overexpressed in numerous cancers, promotes the maturation of numerous oncoproteins and facilitates cancer cell growth. Certain HSP90 inhibitors have entered clinical trials. Although less than satisfactory clinical effects or insurmountable toxicity have compelled these trials to be terminated or postponed, these results of preclinical and clinical studies demonstrated that the prospects of targeting therapeutic strategies involving HSP90 inhibitors deserve enough attention. Nanoparticulate-based drug delivery systems have been generally supposed as one of the most promising formulations especially for targeting strategies. However, so far, no active targeting nano-formulations have succeeded in clinical translation, mainly due to complicated preparation, complex formulations leading to difficult industrialization, incomplete biocompatibility or nontoxicity. In this study, HSP90 and CD44-targeted A6 peptide functionalized biomimetic nanoparticles (A6-NP) was designed and various degrees of A6-modification on nanoparticles were fabricated to evaluate targeting ability and anticancer efficiency. With no excipients, the hydrophobic HSP90 inhibitor G2111 and A6-conjugated human serum albumin could self-assemble into nanoparticles with a uniform particle size of approximately 200 nm, easy fabrication, well biocompatibility and avoidance of hepatotoxicity. Besides, G2111 encapsulated in A6-NP was only released less than 5% in 12 h, which may avoid off-target cell toxicity before entering into cancer cells. A6 peptide modification could significantly enhance uptake within a short time. Moreover, A6-NP continues to exert the broad anticancer spectrum of Hsp90 inhibitors and displays remarkable targeting ability and anticancer efficacy both in hematological malignancies and solid tumors (with colon tumors as the model cancer) both in vitro and in vivo. Overall, A6-NP, as a simple, biomimetic and active dual-targeting (CD44 and HSP90) nanomedicine, displays high potential for clinical translation.

Objective Nowadays, more than 90% of people over 50 years suffer from intervertebral disc degeneration (IDD), but there are exist no ideal drugs. The aim of this study is to identify a new drug for IDD. Methods An approved small molecular drug library including 2040 small molecular compounds was used here. We found that taurocholic acid sodium hydrate (NAT) could induce chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs). Then, an in vivo mouse model of IDD was established and the coccygeal discs transcriptome analysis and surface plasmon resonance analysis (SPR) integrated with liquid chromatography–tandem mass spectrometry assay (LC‐MS) were performed in this study to study the therapy effect and target proteins of NAT for IDD. Micro‐CT was used to evaluate the cancellous bone. The expression of osteogenic (OCN, RNX2), chondrogenic (COL2A1, SOX9), and the target related (ERK1/2, p‐ERK1/2) proteins were detected. The alkaline phosphatase staining was performed to estimate osteogenic differentiation. Blood routine and blood biochemistry indexes were analyzed for the safety of NAT. Results The results showed that NAT could induce chondrogenesis and osteogenesis in MSCs. Further experiments confirmed NAT could ameliorate the secondary osteoporosis and delay the development of IDD in mice. Transcriptome analysis identified 128 common genes and eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for NAT. SPR‐LC–MS assay detected 57 target proteins for NAT, including MAPK3 (mitogen‐activated protein kinase 3), also known as ERK1 (extracellular regulated protein kinase 1). Further verification experiment confirmed that NAT significantly reduced the expression of ERK1/2 phosphorylation. Conclusion NAT would induce chondrogenesis and osteogenesis of MSCs, ameliorate the secondary osteoporosis and delay the progression of IDD in mice by targeting MAPK3.Furthermore, MAPK3, especially the phosphorylation of MAPK3, would be a potential therapeutic target for IDD treatment.

Objective Although it is an effective fixation technique for an unstable odontoid, anterior fixation remains challenging in pediatric populations. Our study measures the anatomical parameters of the odontoid to identify the feasibility of anterior fixation with a single screw for children. Methods We retrospectively collected data from 112 normal male and female children (aged between 2 and 18) in our institute from January 1, 2022 to December 31, 2022. Subjects were divided into a youth group (2–6 years old), a juvenile group (7–12 years old), and an adolescent group (13–18 years old). Sagittal and coronal computed tomography images of the upper cervical spine were used to measure the screw length, angle, and inner and outer diameters of the odontoid. One‐way analysis of variance with the Tukey test was used to analyze the parameters among the groups, while the t‐test was used to analyze gender differences. Correlations between parameters and age were assessed using Pearson's test. Results There were significant differences between male and female subjects in screw length and inner and outer diameters (of both sagittal and coronal views) but not in screw angle. The narrowest diameter of the odontoid was 4.0 ± 1.5 mm in the youth group, 5.5 ± 1.5 mm in the juvenile group, and 5.6 ± 1.1 mm in the adolescent group, respectively. There were significant differences among the three groups in screw length (p 4 mm. Screw length and inner and outer diameters in lateral view were positively correlated with age, and screw angle was negatively correlated with age. Conclusion It is feasible to insert a standard single screw (Φ 3.5 mm) into the odontoid of children aged 7–18 years old but not those aged 2–6 years old. How the anatomical parameters of the odontoid change with age, especially the narrowest diameters, is worthy of attention.

Objective To evaluate the biomechanical stability of anterior transarticular crossing screw (ATCS) and compare it with anterior transarticular screw (ATS) which may provide basic evidence for clinical application. Methods Eight human fresh cadaveric specimens (occiput-C4) were tested with 5 conditions including the intact status, the injury status (type II odontoid fracture), the injury+ATS fixation status (traditional bilateral ATS fixation); the injury+unilateral ATCS fixation status; and the injury+bilateral ATCS fixation status. Specimens were applied to a pure moment of 1.5 Nm in flexion-extension, lateral bending, and axial rotation, respectively. The range of motions (ROMs) and the neutral zones (NZs) of C1 to C2 segment were calculated and compared between 5 status. Results ATS and ATCS fixations significantly reduced the motions in all directions when compared with the intact and injury statues (p < 0.05). In flexion-extension, the ROMs of ATS, unilateral ATCS, and bilateral ATCS were 4.7° ±2.5°, 4.1° ±1.9°, and 3.2° ±1.2°, respectively. Bilateral ATCS resulted in a significant decrease in ROM in flexion-extension when compared with ATS and unilateral ATCS (p = 0.035 and p = 0.023). In lateral bending and axial rotation, there was no significant difference in ROM between the 3 fixations (p > 0.05). Three fixations resulted in similar NZs in all directions (p > 0.05). Conclusion ATCS is a biomechanically effective alternative or supplemental method for atlantoaxial instability.

Objective There is lack of an internal fixation following resection of a dumbbell tumor by hemi‐laminectomy and facetectomy that achieves adequate stability with less trauma. Unilateral fixation and reconstruction (unilateral pedicle screw and contralateral lamina screw fixation combined with lateral mass reconstruction, UPS + CLS + LM) may be an ideal technique to address this problem. A biomechanical comparison and a case report were designed to evaluate its spinal stability and clinical effect. Methods Seven fresh‐frozen human subcervical specimens were used for the biomechanical testing. The conditions tested were: (1) intact; (2) injured (single‐level hemi‐laminectomy and facetectomy); (3) unilateral pedicle screw (UPS) fixation; (4) UPS fixation combined with lateral mass (LM) reconstruction (UPS + LM); (5) UPS fixation and contralateral lamina screw fixation (UPS + CLS); (6) UPS + CLS + LM; (7) UPS fixation and contralateral transarticular screw fixation (UPS + CTAS); (8) bilateral pedicle screw (BPS) fixation. Range of motion (ROM) and neutral zone (NZ) were obtained at C5‐C7 segment under eight conditions. In addition, we report the case of a patient with a C7‐T1 dumbbell tumor that was treated by UPS + CLS + LM technique. Results Except left/right lateral bending and right axial rotation (all, p 0.05). There was no significant difference between UPS + CLS + LM and the UPS + CTAS condition in other directions of ROM (all, p > 0.05), except in left/right axial rotation (both, p 0.05). There was no significant difference between UPS + CLS + LM and UPS + CTAS condition in NZ in all directions (all, p > 0.05). Axial rotation NZ of UPS + CLS + LM condition was significantly reduced compared to UPS + CLS condition (p

ABSTRACTThe impact region of the dactyl club of mantis shrimp features a rare sinusoidally helicoidal architecture, contributing to its efficient impact-resistant characteristics. This study aims to attain bioinspired sinusoidally architected composites from a practical engineering way. Morphological features of plain-woven fabric were characterized, which demonstrated that the interweaving warp and weft yarns exhibited a sinusoidal architecture. Interconnected woven composites were thus employed and helicoidally stacked to achieve the desired structure. Quasi-static three-point bending and low-velocity impact tests were subsequently performed to evaluate their mechanical performance. Under three-point bending condition, the dominant failure mode gradually changed from fiber breakage to delamination with the increase in the pitch angle. Failure displacement and energy absorption of the helicoidal woven composites were, respectively, 43.89% and 141.90% greater than the unidirectional ones. Under low-velocity impact condition, the damage area of the helicoidal woven composites decreased by 49.66% while the residual strength increased by 10.10% compared with those of the unidirectional ones, exhibiting better damage resistance and tolerance. Also, effects of fiber architecture on mechanical properties were examined. This work will shed light on future design of the next-generation impact-resistant architected composites.

Drought stress is the key factor limiting soybean yield potential. Soybean seed formation involves a coordinated “subtending leaf-podshell-seed” process, but little is known about the assimilation and transport of photoassimilates in subtending leaves, podshells and seeds or their relationships with soybean seed formation under drought stress. To address these research gaps, two-year experiments with two soybean cultivars, Wandou 37 (drought tolerant) and Zhonghuang 13 (drought sensitive), were conducted under three soil water content (SWC) conditions in 2020 and 2021 based on the responses of their yield to drought. We analyzed the photosynthetic assimilation and translocation of photoassimilates in subtending leaves, podshells and seeds by stable isotope labeling. Compared with those under 75% SWC, 60% SWC and 45% SWC significantly decreased the Wandou 37 seed weight by 19.4% and 37.5%, respectively, and that of Zhonghuang 13 by 26.9% and 48.6%, respectively. Compared with those under 75% SWC, drought stress decreased the net photosynthetic rate and the activities of sucrose phosphate synthase (SPS) and sucrose synthase (SuSy), which in turn decreased the photosynthetic capacity of the subtending leaves. The podshells ensure the input of photoassimilates by increasing the SuSy activity, but the weakened source–sink relationship between podshells and seeds under drought stress leads to a decrease in the translocation of assimilates from podshells to seeds. The lack of assimilates under drought stress is an important factor restricting the development of soybean seeds. We conclude that the decrease in seed weight was caused by the decrease in the photosynthetic capacity of the subtending leaves and the decrease in the overall availability of photoassimilates; moreover, by a decrease in the translocation of assimilates from podshells to seeds.

Abstract This paper studies the blind recognition method of the sparse parity‐check matrices of low‐density parity‐check codes in noncooperative communication, which is critical to the reverse analysis of communication protocols using LDPC codes. In this paper, two improvements are made to the algorithm of Liu Qian et al. (2021) for this problem. Firstly, a Gaussian elimination method based on random column exchange and soft information is proposed to enhance the fault tolerance of the elimination process. Secondly, according to the sparse property of the parity‐check matrices of LDPC codes, a random extraction method is proposed to further improve the fault tolerance of the algorithm, and it is verified theoretically. Finally, simulations verify the superior performance of the algorithm proposed in this paper.

Under irrigation with saline wastewater, SO42−, Cl−, and Ca2+ aggregated in the topsoil, and Mg2+ was significantly higher in the deeper soil than in the topsoil and 40 cm soil layers. The abundance of Zoopagomycota, Ascomycota, Mortierellomycota, Basidiomycota, Chytridiomycota, Rozellomycota, Blastocladiomycota, Monoblepharomycota, Mucoromycota and Olpidiomycota in the surface soil was influenced by Mg2+, whereas Ca2+ affected the abundance of Zoopagomycota and Chytridiomycota. In the 40 cm soil layer, Mg2+ and Cl− promoted Actinobacteria, Proteobacteria, Nitrospirae, Firmicutes, Entotheonellaeota, Myxococcota, Gemmatimonadota and Methylomirabilota, whereas they inhibited Planctomycetota, Acidobacteria, Chloroflexi, Patescibacteria and Bacteroidota. In the 80 cm soil layer, SO42− and Cl− promoted Rozellomycota, Mortierellomycota, Chytridiomycota, Ascomycota, and Mucoromycota, but had a negative effect on Glomeromycota, Blastocladiomycota, Olpidiomycota and Monoblepharomycota. The increase in salinity significantly reduced the abundance of the Actinomycetes phylum and the Amoebozoa phylum. Both saprophytic and symbiotic fungi decreased with increasing salinity.

Resumo Fundamento Muitos estudos clínicos confirmaram que a legumain está intimamente relacionada à aterosclerose. Infelizmente, chegaram-se a conclusões diferentes e ainda faltam análises e estudos sobre as características da placa aterosclerótica em pacientes com níveis plasmáticos aumentados de legumain. Objetivos Este estudo teve como objetivo investigar a correlação entre as características da legumain e da placa aterosclerótica coronariana. Métodos Um total de 81 pacientes com doença cardíaca aterosclerótica coronariana (DCAC), incluindo 43 pacientes com angina instável (AI) e 38 pacientes com angina estável (AE), foram examinados por angiografia coronária. Foi realizado ultrassom intravascular (IVUS) para avaliar as características das placas ateroscleróticas coronarianas, e os níveis plasmáticos de legumain também foram medidos. Valores de p < 0,05 foram considerados significativos. Resultados A concentração de legumain foi significativamente maior nos dois subgrupos de doença coronariana do que no grupo controle (todos p

Abstract Background There are many reports on the treatment of sacroiliac joint dysfunction by manipulation of oblique pulling (MOP). However, the specific mechanism of MOP on the sacroiliac joint remains unclear. This study aimed to investigate the effect of MOP on the biomechanics of the sacroiliac joint and the effect of the anterior sacroiliac ligament on the stability of the sacroiliac joint. Methods First, MOP-F1 (F: force) and MOP-F2 were applied to nine cadaveric pelvises. Then, segmental resection of the anterior sacroiliac ligament was performed. The range of motion of the sacroiliac joint was observed in all procedures. Results Under MOP-F1 and F2, the average total angles were 0.84° ± 0.59° and 1.52° ± 0.83°, and the displacements were 0.61 ± 0.21 mm and 0.98 ± 0.39 mm, respectively. Compared with MOP-F1, MOP-F2 caused greater rotation angles and displacements of the sacroiliac joint (p = 0.00 and p = 0.01, respectively). In addition, the rotation angles and displacements of the sacroiliac joint significantly increased after complete resection of the anterior sacroiliac ligament (p = 0.01 and p = 0.02, respectively). The increase was mainly due to the transection of the upper part of the anterior sacroiliac ligament. Conclusions MOP-F2 caused greater rotation angles and displacements of the sacroiliac joint and was a more effective manipulation. The anterior sacroiliac ligament played an important role in maintaining the stability of the sacroiliac joint; the upper part of the anterior sacroiliac ligament contributed more to the stability of the joint than the lower part.

Abstract As one of the key technologies of modern communication, a linear scrambler is a technique to randomize the data to be transmitted at the bit layer to improve the timing recovery and confidentiality of the transmitted data. Therefore, the reconstruction of scramblers under non‐cooperative communication conditions has attracted extensive research interest. Existing efficient reconstruction methods are implemented by traversing the primitive polynomial of all orders, leading to extremely high computational complexity. Here, a fast reconstruction method for feedback polynomials of synchronous scramblers is proposed. The order of the feedback polynomial is first estimated by a hypothesis testing method, and then the primitive polynomial of the corresponding order is traversed to reduce the traversal range of the primitive polynomial, which greatly reduces the computational complexity of the reconstruction method. The simulation results verify the performance of the scheme.

IntroductionBariatric surgery is one of the most effective methods for treating obesity. It can effectively reduce body weight and reduce the incidence of obesity-related breast cancer. However, there are different conclusions about how bariatric surgery changes breast density. The purpose of this study was to clarify the changes in breast density from before to after bariatric surgery.MethodsThe relevant literature was searched through PubMed and Embase to screen for studies. Meta-analysis was used to clarify the changes in breast density from before to after bariatric surgery.ResultsA total of seven studies were included in this systematic review and meta-analysis, including a total of 535 people. The average body mass index decreased from 45.3 kg/m2 before surgery to 34.4 kg/m2 after surgery. By the Breast Imaging Reporting and Data System score, the proportion of grade A breast density from before to after bariatric surgery decreased by 3.83% (183 vs. 176), grade B (248 vs. 263) increased by 6.05%, grade C (94 vs. 89) decreased by 5.32%, and grade D (1 vs. 4) increased by 300%. There was no significant change in breast density from before to after bariatric surgery (OR=1.27, 95% confidence interval (CI) [0.74, 2.20], P=0.38). By the Volpara density grade score, postoperative volumetric breast density increased (standardized mean difference = -0.68, 95% CI [-1.08, -0.27], P = 0.001).DiscussionsBreast density increased significantly after bariatric surgery, but this depended on the method of detecting breast density. Further randomized controlled studies are needed to validate our conclusions.

Shear thickening fluid (STF) is a nano-smart material that exhibits an instantaneous increase in viscosity when subjected to specific external loads. Notably, its viscosity response does not necessitate external energy input, making it widely applicable in vibration control, energy absorption, and vibration reduction. This paper first presents an introduction and analogy to the evolution of the thickening mechanism of STF. It then discusses factors that influence the rheological properties of STF, including the dispersed phase, dispersion medium, additives, and external environment. Furthermore, it explores various calculation models of STF in engineering applications, considering their advantages, disadvantages, and applicability. The paper later reviews the progress of STF utilization in vibration reduction and energy consumption, specifically focusing on improving mechanical properties in STF sandwich panels. Finally, it delves into the feasibility of STF application in vibration control by detailing the dynamic mechanical properties and applicability of vibration reduction equipment and calculation models based on STF.

In this study, a 3D model of a proton exchange membrane fuel cell (PEMFC) with crossed channels and an ultra-thin membrane is developed to investigate the feasibility of self-humidification; experiments utilizing a PEMFC stack with identical configurations are conducted to validate the simulation results and further investigate the effects of various operating conditions (OCs) on self-humidification. The results indicate that the crossed flow channel leads to enhanced uniformity of water distribution, resulting in improved cell performance under low/no humidification conditions. External humidifiers for the anode can be removed since the performance difference is negligible (≤3%) between RHa = 0% and 100%. Self-humidification can be achieved in the stack at 90 °C or below with an appropriate back pressure among 100–200 kPa. As the current density increases, there is a gradual convergence and crossing of the voltage at low RH with that at high RH, and the crossover points are observed at 60–80 °C with suitable pressure when successful self-humidification is achieved. Below the current density of the point, the stack’s performance is inferior at lower RH due to membrane unsaturation, and conversely, the performance is inferior at higher RH due to flooding; this current density decreases with higher pressure and lower temperature.

Abstract Background The nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been reported to be involved in the pathological process of osteoarthritis (OA) inflammation. Here, we investigated the ketogenic diet (KD), which has been previously demonstrated to inhibit NLRP3 inflammasome activation, to elucidate its protective mechanism against OA in rats. Methods Anterior cruciate ligament transaction (ACLT) together with partial medial meniscectomy was used to create a rat knee joint OA model. After treatment with KD or standard diet (SD) for 8 weeks, the knee specimens were obtained for testing. Results The KD significantly increased the content of β-hydroxybutyrate (βOHB) in rats. Compared to the SD group, the KD significantly reduced the damage caused by OA in the articular cartilage and subchondral bone. The NLRP3 inflammasome and inflammatory cytokines interleukin-1 β (IL-1β) and IL-18 were significantly increased in the SD group compared with the sham group, while their expression was significantly decreased in rats treated with the KD. In addition, MMP13 was significantly decreased in the KD group compared to that in the SD group, while COL2 was significantly increased. Conclusions KD can protect the articular cartilage and subchondral bone in a rat OA model by inhibiting NLRP3 inflammasome activation and reducing the OA inflammatory response.

IntroductionHeterosis is a critical phenomenon in crop improvement. Cytoplasmic male sterility (CMS) and Restorer gene (Rf) systems are essential components for heterosis-based breeding. However, the molecular mechanism underlying CMS remains largely unclear in soybean.MethodsWe integrated a morphological investigation with comparative analyses of transcriptomic and proteomic changes in pollen from the CMS line W931A and its maintainer line, W931B, at the uninucleate microspore (UM) and binucleate pollen (BP) stages.ResultsCompared to W931B, which had healthy, oval pollen grains, W931A showed shrunken or degraded pollen grains with an irregularly thickened endothelium and decreased starch accumulation. Transcriptomic comparisons revealed a total of 865 differentially expressed genes (DEGs) in W931A over the two stages. These genes were primarily associated with pentose and glucuronate interconversions, sphingolipid metabolism, and glycerolipid metabolism. Proteomic analysis revealed 343 differentially expressed proteins (DEPs), which were mainly involved in carbon metabolism, glycolysis/gluconeogenesis, and nitrogen metabolism. Consistently, Gene Ontology (GO) biological process terms related to pollen development were enriched among DEGs at the UM and BP stages. Notably, four genes with demonstrated roles in pollen development were differentially expressed, including AGAMOUS-LIKE 104, PROTEIN-TYROSINE-PHOSPHATASE 1, and PHOSPHOLIPASE A2. A total of 53 genes and the corresponding proteins were differentially expressed in W931A at both the UM and BP stages, and many of these were pectinesterases, polygalacturonases, peroxidases, and ATPases.DiscussionThe results of this study suggest that pollen development in W931A is likely regulated through suppression of the identified DEGs and DEPs. These findings increase our understanding of the molecular mechanism underlying CMS in soybean, aiding future research into soybean fertility and promoting the efficient use of heterosis for soybean improvement.

Abstract The recent concept of contextual information in error correcting code (ECC) can significantly improve the capacity of the blind recognition of codes with deep learning (DL) approaches. However, the fundamental challenges of existing DL‐based methods are inflexible structure and limited kernel size which bring great difficulties to exploit the characteristics of contextual information in ECC. To handle this problem, in this paper, a state‐of‐the‐art framework for natural language processing (NLP), bidirectional encoder representation from transformers (BERT), is utilized in ECC classification scenarios. To strengthen the effectiveness of contextual information, the BERT model is improved by weighted relative positional encoding and error bit embedding. The proposed approach achieves higher classification accuracy than the methods based on Gauss‐Jordan elimination and traditional deep learning schemes. Further simulation results show that the classification accuracy is affected by block length and the employment of weighted relative positional encoding and error bit embedding to a large extent.

Abstract Background B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy has obtained promising results in relapsed or refractory multiple myeloma (R/R MM), while some patients do not response, or relapse in short term after treatment. Combining with anti-CD38 might solve the problem of targeting BCMA alone. We aimed to assess the efficacy and safety of BCMA and CD38 (BCMA-CD38) bispecific CAR-T cells in R/R MM patients. Methods We did a single-center, single-arm clinical study at the Second Affiliated Hospital of Yangtze University in China. Patients meeting with the inclusion criteria were administered with fludarabine and cyclophosphamide before CAR-T cells infusion. Response and adverse events were assessed after infusion. This study was registered with the Chinese Clinical Trial Registration Center (ChiCTR1900026286). Results First, we found BCMA-CD38 CAR-T cells exhibited enhanced killing effect on BCMA+CD38+ cells in vitro, compared to BCMA CAR-T and CD38 CAR-T cells. We further demonstrated its anti-tumor activity in vivo. Then, we enrolled 16 R/R MM patients for safety and efficacy analyses. Of the 16 evaluable patients, 14 (87.5%) respond to the treatment, including 13 stringent complete response (sCR) and one partial response (PR), while two patients did not respond. At a median follow-up of 11.5 months, of the 13 patients who achieved sCR, 76.9% (10/13) did not relapse or progress during follow-up. Relapse occurred in 3 patients (Patient 2, 3 and 4) after achieving sCR. In sum, four patients died, of which one died of hemophagocytic lymphohistiocytosis syndrome secondary to severe cytokine release syndrome (CRS) and three died of disease progression or relapse. The 1-year progression-free survival rates was 68.8%. The 1-year overall survival rate was 75.0%. Extramedullary lesions were eliminated in 62.5% (5/8) patients. The most common symptoms after CAR-T infusion were cytopenia (16, 100%), fever (10, 62.5%), fatigue (8, 50.0%) and myalgias (8, 50.0%). Twelve patients (75.0%) were observed with various grades of CRS, of which five patients (31.3%) got serious CRS (Grade ≥ 3). The CAR+ cell expansion levels were associated with the severity of CRS. Transient clonal isotype switch was observed after CAR-T infusion. Conclusion Our results confirm that BCMA-CD38 CAR-T cells therapy is feasible in treating R/R MM patients, with high response rate, low recurrence rate and manageable CRS, which will be a promising treatment option for R/R MM. Trial registration ChiCTR1900026286, registered on September 29, 2019, retrospectively registered, URL: https://www.chictr.org.cn/showproj.aspx?proj=43805

Objective: Imatinib mesylate (IM), a tyrosine kinase inhibitor, exhibits clinically prominent effects against chronic myeloid leukemia (CML); however, a few patients have shown resistance to IM treatment, resulting in disease progression. Smad4 is a tumor inhibitor that transduces TGF-β signaling and modulates genomic stability. Previous studies have indicated that decreased Smad4 expression played a bidirectional role in chemosensitivity in many types of cancers. Therefore, this study aims to evaluate the association between IM sensitivity and decreased Smad4 expression in human CML K562 cells. Methods: Bone marrow (BM) samples were acquired from the patients prior to treatment. qRT-PCR, Western Blotting (WB), colony formation assay (CFA), and apoptosis assay were used to detect relevant indices. Results: Smad4 expression was downregulated in the bone marrow and plasma of patients with multidrug-resistant CML as well as IM-resistant K562 (K562R) cells compared with samples collected from CML patients and K562 cells. Smad4 overexpression inhibited IM-treated K562R cell proliferation and augmented apoptosis, whereas Smad4 silencing promoted viability and inhibited apoptosis in IM-treated K562 cells. In addition, Smad4 expression was inversely correlated with laminin subunit gamma 1 (LAMC1) expression. The upregulation or downregulation of LAMC1 expression partially abolished the effect of Smad4 overexpression or silencing on the IM resistance of CML cells. Conclusion: The downregulation of Smad4 expression might induce drug resistance in CML cells and displayed a possible mechanism through which Smad4 modulates CML cell survival and apoptosis upon IM treatment.

Abstract Background BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. Methods We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. Results BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1–2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10–4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. Conclusion Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. Trial registration: Chictr.org.cn ChiCTR1800018143.

This article presents a method to calibrate a 16-channel 40 GS/s time-interleaved analog-to-digital converter (TI-ADC) based on channel equalization and Monte Carlo method. First, the channel mismatch is estimated by the Monte Carlo method, and equalize each channel to meet the calibration requirement. This method does not require additional hardware circuits, every channel can be compensated. The calibration structure is simple and the convergence speed is fast, besides, the ADC is worked in background mode, which does not affect the conversion. The prototype, implemented in 28 nm CMOS, reaches a 41 dB SFDR with an input signal of 1.2 GHz and 5 dBm after the proposed background offset and gain mismatch calibration. Compared with previous works, the spurious-free dynamic range (SFDR) and the effective number of bits (ENOB) are better, the estimation accuracy is higher, the error is smaller and the faster speed of convergence improves the efficiency of signal processing.

BackgroundTo curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients.ObjectiveTo investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown.MethodsWe conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic.ResultsA total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications.ConclusionThe medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown; the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

YG8 is a common cemented carbide material with excellent mechanical properties and mechanical properties, so it is widely used in the actual industry. However, due to the active chemical properties and strong affinity of tungsten alloy steel, it is easy to produce bonding and peeling in application, resulting in an unstable process and short service life. In order to control and reduce the surface wear of YG8 cemented carbide, groove-textured surface (GS) and flocking surface (FS) were prepared on smooth surface (SS). The friction characteristics of the samples were studied under different applied load conditions. The results show that the average friction coefficient of SS, GS and FS is inversely proportional to the load in dry/oil environment. Compared with SS, FS exhibits the lowest friction coefficient, which is reduced by 30.78% (dry friction) and 13.13% (oil lubrication). FS effectively improves the tooth jump phenomenon of the sample and the amplitude of the friction coefficient, friction force and load, and has the best anti-friction characteristics. At the same time, the FS with the fastest contact angle drop at any time also showed excellent wetting ability, and the wear rate decreased by an order of magnitude. The implantation of fibers in the groove inhibits the spalling and furrow of wear track, which is attributed to the effect of fibers on damage repair. In the friction process, FS increases the content of the O element and induces the formation of oxides. The friction mechanism is mainly chemical wear. The excellent tribological properties of FS have a good guiding significance and theoretical support for improving the tribological properties of high hardness material surfaces.

In this study, a nonlinear prediction model of antislide pile top displacement is proposed. Based on the quantitative analysis of the rock mass structure characteristics of the soft and hard interbedded sliding bed in the Jurassic strata, the post-thrust force and geometric characteristics of the top of antislide pile displacement, and bending moment, the main controlling factors affecting the displacement of the top of antislide pile were determined by maximal information coefficient (MIC). Through orthogonal experiment design and 3DEC numerical experiment, a database of main controlling factors (sliding bedrock inclination, thrust size, embedded depth, and pile section size) of pile top displacement was established and a nonlinear prediction model of the displacement of the top of antislide pile based on the main controlling factors was proposed. Finally, two engineering examples were used to validate the performance of this model, with the comparisons of four prediction methods (SVR, MIC-SVR, LSTM, and ELMAN). The results show that the MIC-SVR model has a practical reference value for the prediction of the displacement of the top of an antislide pile in the Jurassic landslide in the Three Gorges Reservoir Area.

Objective: To investigate the neuroprotective effects of trihydroxyethyl rutin in rats with cervical spinal cord hemi-contusion.Methods: Adult male Sprague–Dawley rats were subjected to hemi-contusion at a stroke depth of 1.2 mm, and then intraperitoneally injected with 50 or 100 mg/kg trihydroxyethyl rutin per day for 12 weeks (T50 and T100 groups, respectively). Changes in somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and behavior were continuously monitored. At 12 weeks post-injury, immunohistochemical staining was performed to assess changes in cervical spinal cord microvascular morphology. Magnetic resonance imaging (MRI) scans were performed to examine end-stage injury in the cervical spinal cord, and Eriochrome cyanine-stained slices of spinal cord tissue were evaluated for injury.Results: There were no significant differences in biomechanical parameters among the spinal cord injury, T50 and T100 rat groups. At 3 days-post-injury, there was a significant decrease in grip strength. At 12 weeks post-injury, grip strength recovery was significantly better in the T50 and T100 groups than in the injury group. Compared with the injury group, the total limb placement frequency was significantly higher in the T50 group at 2, 4, 6, 10, and 12 weeks post-injury and in the T100 group at 2, 6, 8, and 10 weeks post-injury. Ipsilateral SEPs and MEPs were dynamic, increasing in latency and decreasing in amplitude in the injury compared with sham group. MRI scanning demonstrated that the coronal, sagittal, and transversal lesion areas were smaller in the T50 and T100 groups than in the injury group. Microvascular density showed a greater reduction in the injury group compared with the T50 and T100 groups. Eriochrome cyanine staining showed that the ipsilateral side, residual parenchyma, and gray matter areas were larger in the T50 and T100 groups than in the injury group.Conclusion: Trihydroxyethyl rutin exhibits robust neuroprotective effects, improving limb motor function and nerve electrophysiological parameters after spinal cord injury, maintaining microvascular density, and reducing the area of injury and degree of demyelination.

In this paper, we propose an Extended Kalman Filtering with phase noise reconstruction (EKF-PC) scheme to enhance the carrier recovery capability for probabilistic shaping of coherent optical communication systems with various shaping factors. We first investigate the weights of the shaping factor and the noise rejection window length of EKF-PC for PS-64QAM at a fixed signal-to-noise ratio (SNR). After that, we jointly optimize the shaping factor and the noise rejection window length to obtain the maximum achievable information rate at a variety of SNRs. Then, we numerically analyze the carrier recovery performance of the EKF-PC for different linewidths and SF conditions. Finally, we conduct simulation experiments to compare EKF-PC, PCPE, and other currently available Kalman CPE algorithms with the SFs of 0.02, 0.025, 0.03, and 0.035 under back-to-back (B2B) scenarios. The experimental results show that EKF-PC obtains an average SNR improvement of 0.13–0.5 dB compared to PCPE and an average performance improvement of 0.5–1 dB compared to other Kalman algorithms.

Affine mortality models are well suited for theoretical and practical application in pricing and risk management of mortality risk. They produce consistent, closed-form stochastic survival curves allowing for the efficient valuation of mortality-linked claims. We model USA age-cohort mortality data using five multi-factor affine mortality models. We focus on three-factor models and compare four Gaussian models along with a model based on the Cox–Ingersoll–Ross (CIR) process, allowing for Gamma-distributed mortality rates. We compare and assess the Gaussian Arbitrage-Free Nelson–Siegel (AFNS) mortality model, which incorporates level, slope and curvature factors, and the canonical Gaussian factor model, both with and without correlations in the factor dynamics. We show that for USA mortality data, the probability of negative mortality rates in the Gaussian models is small. Models are estimated using discrete time versions of the models with age-cohort data capturing variability in cohort mortality curves. Poisson variation in mortality data is included in the model estimation using the Kalman filter through the measurement equation. We consider models incorporating factor dependence to capture the effects of age-dependence in the mortality curves. The analysis demonstrates that the Gaussian independent-factor AFNS model performs well compared to the other affine models in explaining and forecasting USA age-cohort mortality data.

The improvement of rural living standards in developing countries and the continuous upgrading of the rural industrial economy have prompted the diversification of rural areas and residential forms. Thus, an integrated rural sewage treatment process has gradually become the mainstream technology for rural sewage treatment. Numerous studies have reported the effects of ecological wastewater treatment. Meanwhile, the relevant process technologies, evaluations, and operating models of the integrated rural sewage treatment process have yet to be thoroughly summarized. This review aims to fill these gaps. First, the applicability of artificial wetland, soil infiltration, stabilization pond, and integrated rural sewage treatment process technology in rural sewage treatment are outlined and compared. Second, the process flow, technical characteristics, and economic indicators of typical integrated sewage treatment processes (i.e., Anoxic/Oxic (A/O) process, Membrane Bio-Reactor (MBR) process, biological contact oxidation process, Sequencing Batch Reactor Activated Sludge (SBR) process) are introduced. The engineering application effects of the integrated rural sewage treatment process in different countries are also described. Third, the practical and effective evaluation methods of the integrated rural sewage treatment process are introduced. Bearing in mind the current operation and maintenance management modes of the integrated rural sewage treatment process in developed and developing countries, combined with the national conditions of developing countries, the prospect section provides development proposals for further optimization and improvement of the integrated rural sewage treatment process in developing countries.

This paper proposes a novel and efficient low-complexity chromatic dispersion equalizer (CDE) based on finite impulse response (FIR) filter architecture for polarization-multiplexed coherent optical communication systems. The FIR filter coefficients are optimized by weights to reduce the energy leakage caused by the truncation effect, and then quantization is used uniformly to reduce the number of real number additions and real number multiplications by utilizing the diversity of the quantized coefficients. Using Optisystem 15 to build a coherent optical communication system for simulation and experimental demonstration, the results show that after the filter coefficients are optimized by weights. Compared with the time-domain chromatic dispersion equalizer (TD-CDE), the proposed design has a lower bit error rate (BER) and better equalization effect. When the transmission distance is 4000 km and the system quantization stages M = 16, the multiplication operation and addition operations reduce computing resources by 99% and 43%, and the BER only increases by 5%. Compared with frequency-domain chromatic dispersion equalizer (FD-CDE), widely used in long-distance communication, the multiplication operation reduces computing resources by 30%. The proposed method provides a new idea for high-performance CDE in long-distance coherent optical communication systems.

Chromatic dispersion equalization (CDE) in coherent optical communication systems is extremely critical for subsequent digital signal processing (such as frequency offset estimation and carrier phase recovery). Various methods mentioned in the published literature are not satisfactory when the signal bandwidth is limited. This paper proposes a way of using singular value decomposition least square (SVDLS) to obtain the optimal tap weight of the CDE filter and a method to introduce the adaptive mutation particle swarm optimizer (AMPSO) algorithm into the CDE. We show that the two proposed approaches are based on the best approximation of the frequency domain response of the designed and ideal CDE filter. Compared with the traditional CDE method, which needs to be implemented in the full frequency band, the two methods can be implemented in the narrow frequency band. The simulation shows that the effective bandwidth of the baseband signal is limited by squared-root-raised-cosine (SRRC) pulse shaping with a roll-off factor of 0.25 in different modulation formats (DP-QPSK, DP-16 QAM, DP-64 QAM) when the number of taps of the filter is 131, which is 37.5% less than the full frequency band. The designed filter is superior to the existing filter in terms of filtering effect and implementation complexity.

Objective • This study aimed to assess the efficacy of combining four-dimensional (4D) color ultrasound with maternal serological index testing in prenatal screening for fetal anomalies. Methods • A retrospective analysis was conducted on data from 864 pregnant women who underwent prenatal checkups at the hospital between January 2020 and January 2021. During the mid-pregnancy period, serological tests were performed to determine levels of alpha-fetoprotein (AFP), free β-subunit of human chorionic gonadotropin (Free-HCG β), pregnancyassociated plasma protein A (PAPP-A), and vitamin B12 (VitB12). Additionally, 4D color ultrasound examinations were conducted. The gold standard for evaluation was the results of delivery or labor induction. AFP, Free-HCG β, PAPP-A, and VitB12 levels were compared between the anomaly group and the normal group. The diagnostic efficacy of single and combined detection of serological indexes and 4D color ultrasound was analyzed, with the calculation of the areas under the curve (AUC) for different detection methods. Results • Among the 864 pregnant women, 44 cases (5.09%) exhibited fetal anomalies, while 820 cases (94.91%) did not. The anomaly group showed significantly higher multiples of the median (MOM) values for AFP and Free-HCG β (P < .001) and significantly lower PAPP-A MOM and VitB12 levels (P < .001) compared to the normal group. The sensitivity of single detections for AFP MOM, Free-HCG β MOM, PAPP-A MOM, VitB12, 4D color ultrasound, and combined detection were 63.64%, 68.18%, 65.91%, 54.55%, 77.27%, and 97.93%, respectively. The corresponding AUC values were 0.805, 0.829, 0.818, 0.761, 0.885, and 0.974. Conclusions • The combination of 4D color ultrasound with maternal serological index testing demonstrated high sensitivity in prenatal screening for fetal anomalies. [ABSTRACT FROM AUTHOR]