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Simple Summary: Chimeric antigen receptor T cell (CAR-T) therapy has demonstrated significant success in B-cell lymphoma. The combination with autologous stem cell transplantation (ASCT) further enhances the efficacy of CAR-T cell therapy, although its impact on adverse reactions remains inconclusive. This study examined 147 patients who received CAR-T alone and 145 patients who underwent ASCT combined with CAR-T for B-cell lymphoma. The combined group had a higher incidence of overall and grade 1–2 CRS, but the risk of grade 3–4 CRS and CRES was not elevated. A univariate logistic regression analysis revealed that females had a lower incidence of grade 3–4 CRS but a higher incidence of severe CRES. The involvement of the central nervous system also correlated with increased CRES occurrence. The findings suggest that combining ASCT with CAR-T does not heighten the risk of severe adverse effects post-infusion. However, further validation through multicenter, prospective clinical studies is necessary to establish CAR-T combined with ASCT as a superior treatment paradigm. (1) Background: The combination of CAR-T with ASCT has been observed to enhance the efficacy of CAR-T cell therapy. However, the impact of this combination on adverse reactions is still uncertain. (2) Methods: Between January 2019 and February 2023, 292 patients diagnosed with r/r B-cell lymphoma received either CAR-T therapy alone or in combination with ASCT at our institution. We evaluated the incidence of CRS and CRES and utilized a logistic regression model to identify factors contributing to severe CRS (grade 3–4) and CRES (grade 3–4). (3) Results: The overall incidence of CRS and CRES was 78.9% and 8.2% in 147 patients receiving CAR-T alone, and 95.9% and 15.2% in 145 patients receiving CAR-T combined with ASCT, respectively. The incidence of overall CRS (p < 0.0001) and mild CRS (grade 1–2) (p = 0.021) was elevated in the ASCT combined with CAR-T group. No significant difference was observed in severe CRS and CRES between the groups. Among the 26 cases of lymphoma involving the central nervous system (CNS), 96.2% (25/26) developed CRS (15.4% grade 3–4), and 34.6% (9/26) manifested CRES (7.7% grade 3–4). Female patients had a lower incidence of severe CRS but a higher incidence of severe CRES. Lymphomas with CNS involvement demonstrated a higher risk of CRES compared to those without central involvement. (4) Conclusions: The combination of ASCT with CAR-T demonstrated a preferable option in r/r B-cell lymphoma without an increased incidence of severe CRS and CRES. [ABSTRACT FROM AUTHOR]

Polymeric dielectrics exhibit remarkable dielectric characteristics and wide applicability, rendering them extensively employed within the domain of electrical insulation. Nevertheless, the electrical strength has always been a bottleneck, preventing its further utilization. Nanocomposite materials can effectively improve insulation strength, but uniform doping of nanofillers in engineering applications is a challenge. Consequently, a nanocomposite interfacial coating was meticulously designed to interpose between the electrode and the polymer, which can significantly improve DC breakdown performance. Subsequently, the effects of filler concentration and coating duration on DC breakdown performance, high field conductivity, and trap distribution characteristics were analyzed. The results indicate that the composite coating introduces deep traps between the electrode-polymer interface, which enhances the carrier confinement, resulting in reduced conductivity and enhanced DC breakdown strength. The incorporation of a composite coating at the interface between the electrode and polymer presents novel avenues for enhancing the dielectric insulation of polymers. [ABSTRACT FROM AUTHOR]

Lactobacillus rhamnosus (LBS) is a well-documented probiotic strain in oncology and has a pivotal role in clinical applications. Here, we have investigated the protective effect of Lactobacillus rhamnosus on intestinal mucositis induced by cisplatin (CP) and explored the underlying mechanisms targeting inflammatory proteins, as well as the histological changes in the intestinal tissue of mice, in addition, the bacterial strains that may be related to the health-enhancing properties. BALB/c mice were pre-treated with or without LBS via oral gavage, followed by mucositis induction with cisplatin. Our results revealed that the LBS-treated groups significantly attenuated proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α) compared to the CP group. Furthermore, LBS mitigated the damaged tight junction integrity caused by CP via up-regulating the levels of claudin, occludin, ZO-1, and mucin-2 protein (MUC-2). Finally, the 16S rRNA fecal microbiome genomic analysis showed that LBS administration enhanced the growth of beneficial bacteria, i.e., Firmicutes and Lachnospiraceae, while the relative abundance of the opportunistic bacteria Bacteroides and Proteobacteria decreased. Collectively, LBS was found to beneficially modulate microbial composition structure and functions and enrich the ecological diversity in the gut. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a persistent, lifelong inflammation of the digestive system. Dextran sulfate sodium is commonly used to induce colitis in experimental animal models, which causes epithelial damage, intestinal inflammation, mucin depletion, and dysbiosis of the gut microbiota. Various prebiotics, polysaccharides, and polypeptides are used for IBD treatment. In this study, we used a murine model utilizing BALB/c mice, with 10 mice per group, to investigate the treatment effect of sea conch peptide hydrolysate (CPH) on DSS-induced colitis mice. Colitis was induced through the administration of 2.5% DSS in drinking water over a seven-days period. Furthermore, on the eighth day of the experiment, sea conch peptide hydrolysate (CPH) at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, which were continued for 14 days, were assessed for medicinal purposes in DSS-induced colitis mice. Our results showed that CPH treatment significantly alleviated the severity and symptoms of colitis. The epithelial integrity and histological damage were improved. Intestinal inflammation and inflammatory cell infiltration were improved. Furthermore, the expression of pro-inflammatory cytokines was reduced, and intestinal barrier integrity was restored by elevating the tight junction proteins. Moreover, 16s RNA sequencing revealed dysbiosis of the gut microbiota was observed upon DSS treatment, which was reinstated after CPH treatment. An increased level of Firmicutes and Lactobacillus was observed in the treatment groups. Finally, our results suggest that CPH would be recommended as a functional food source and also have the potential to be used as a medicinal product for different gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Cobalt hydroxide is a widely studied electrode material for supercapacitor and alkaline zinc ion batteries. The large interlayer spacing of Co(OH)2 is also attractive to store Zn ions. However, Co(OH)2 is quite unstable in the acidic ZnSO4 electrolyte due to its amphoteric nature. Herein, we synthesized a mixed phase of Co(OH)2/CoOOH via a two-step electrochemical preparation. As the cathode material for an aqueous zinc ion battery (AZIB), Co(OH)2/CoOOH delivered a maximum capacity of 164 mAh g−1 at 0.05 A g−1 and a high energy density of 275 Wh kg−1. Benefiting from the low charge-transfer resistance, a capacity of 87 mAh g−1 was maintained at 1.6 A g−1, showing a good rate performance of the mixed phase. Various spectroscopy analyses and simulations based on the density functional theory (DFT) suggested a higher thermal stability of the mixed phase than pure Co(OH)2, due to its less local structural disorder. The reduced Co-Co and Co-O shells increased the mechanical strength of the mixed phase to accommodate Zn2+ ions and endure the electrostatic repulsion, resulting in an enhanced cycling stability. The mixed phased also delivered a good stability at the current density of 0.05 A g−1. After 200 cycles, a capacity retention of 78% was retained, with high Coulombic efficiencies. These results provide a new route to synthesize high-performance LDH for aqueous zinc ion batteries. [ABSTRACT FROM AUTHOR]

Bacterial pneumonia is the main cause of illness and death in children under 5 years old. We isolated and cultured pathogenic bacteria LE from the intestines of children with pneumonia and replicated the pediatric pneumonia model using an oral gavage bacterial animal model. Interestingly, based on 16srRNA sequencing, we found that the gut and lung microbiota showed the same imbalance trend, which weakened the natural resistance of this area. Further exploration of its mechanism revealed that the disruption of the intestinal mechanical barrier led to the activation of inflammatory factors IL-6 and IL-17, which promoted the recruitment of ILC-3 and the release of IL-17 and IL-22, leading to lung inflammation. The focus of this study is on the premise that the gut and lung microbiota exhibit similar destructive changes, mediating the innate immune response to promote the occurrence of pneumonia and providing a basis for the development and treatment of new drugs for pediatric pneumonia. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer is by far the most lethal gynecological malignancy. The exploration of promising immunomarkers to predict prognosis in ovarian cancer patients remains challenging. In our research, we carried out an integrated bioinformatic analysis of genome expressions and their immune characteristics in the ovarian cancer microenvironment with validation in different experiments. We filtrated 332 differentially expressed genes with 10 upregulated hub genes from the Gene Expression Omnibus database. These genes were closely related to ovarian tumorigenesis. Subsequently, the survival and immune infiltration analysis demonstrated that the upregulation of five candidate genes, ITGB2, VEGFA, CLDN4, OCLN, and SPP1, were correlated with an unfavorable clinical outcome and increased immune cell infiltration in ovarian cancer. Of these genes, ITGB2 tended to be the gene most correlated with various immune cell infiltrations and had a strong correlation with significant M2 macrophages infiltration (r = 0.707, p = 4.71 × 10−39), while it had a moderate correlation with CD4+/CD8+ T cells and B cells. This characteristic explains why the high expression of ITGB2 was accompanied by immune activation but did not reverse carcinogenesis. Additionally, we confirmed that ITGB2 was over-expressed in ovarian cancer tissues and was mainly located in cytoplasm, detected by Western blotting and the immunohistochemical method. In summary, ITGB2 may serve as a prognostic immunomarker for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8+ T and NKT (natural killer T) cells and inhibiting CD25+ Foxp3+ Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment. [ABSTRACT FROM AUTHOR]

Objective: Polyetheretherketone (PEEK) is widely used as an orthopedic implant material owing to its good biocompatibility and mechanical strength; however, PEEK implants are biologically inert, resulting in suboptimal cellular responses after implantation. The aim of this study was to enhance the biological activity of PEEK through sulfonation treatment. Methods: In this study, distal phalangeal implants of PEEK were customized by fused deposition modeling (FDM) printing technology and soaked in concentrated sulfuric acid at different times to obtain sulfonated PEEK (SPEEK). The groups were divided into five groups according to the sulfonation time as follows: 0 min (control group), 1 min (group SPEEK1), 2 min (group SPEEK2), 4 min (group SPEEK4), and 8 min (group SPEEK8). Then the physicochemical characteristics of implants were determined by SEM, XRD, EDS, etc. The implants were co-cultured with stem cells from human exfoliated deciduous teeth (SHED), and then the cell proliferation, adhesion, alkaline phosphatase (ALP) activity, and alizarin red staining were performed to detect the biological activity, biocompatibility, and osteogenic activity of the SPEEK implants. Results: The sulfonation time range of 1 to 8 min could promote the formation of micropores on the surface of PEEK implants, while slightly affecting the composition and compression performance of the implants. Compared with the control group, the hydrophilicity of PEEK materials was not improved after sulfonation treatment. Tests for adhesion and proliferation of SHED indicated that SPEEK2 showed superior biocompatibility. Furthermore, ALP activity and semi-quantitative analysis of Alizarin red staining showed that the osteogenic activity of SPEEK2 phalanges exhibited significantly stronger osteogenic activity than the other groups. Conclusions: The method presented here provides a promising approach to improve the surface bioactivity of PEEK implants prepared by FDM, providing a shred of primary evidence to support the application of SPEEK in orthopedics. [ABSTRACT FROM AUTHOR]

Prefabricated steel box girders (SBGs) are widely adopted in bridge engineering due to their light weight and low lifecycle cost. To smoothly assemble SBG components on a construction site, it is necessary to inspect their geometric quality and ensure that all the as-is SBG components have the correct dimensions. However, the traditional inspection method is time-consuming and error-prone. This study developed a non-contact geometric quality assessment technique based on 3D laser scanning to accurately assess the locations and dimensions of SBG components. First, a robust normal-based region-growing algorithm was developed to divide the SBG components into segments with different labels. The scanned data related to the T ribs were then extracted through the proposed subtraction algorithm after the identification of the steel cabin. Lastly, the required items for geometric quality inspection were calculated based on the extracted as-is SBG components. The feasibility of the proposed geometric quality assessment method was validated through a real SBG project. Field test results showed that the developed inspection technique could assess the geometric quality of prefabricated SBG components in a more accurate and efficient manner compared to traditional measurement approaches. [ABSTRACT FROM AUTHOR]

Acylglycerophosphate acyltransferases (AGPATs) are the rate-limiting enzymes for the de novo pathway of triacylglycerols (TAG) synthesis. Although AGPATs have been extensively explored by evolution, expression and functional studies, little is known on functional characterization of how many members of the AGPAT family are involved in TAG synthesis and their impact on the cell proliferation and apoptosis. Here, 13 AGPAT genes in buffalo were identified, of which 12 AGPAT gene pairs were orthologous between buffalo and cattle. Comparative transcriptomic analysis and real-time quantitative reverse transcription PCR (qRT-PCR) further showed that both AGPAT1 and AGPAT6 were highly expressed in milk samples of buffalo and cattle during lactation. Knockdown of AGPAT1 or AGPAT6 significantly decreased the TAG content of buffalo mammary epithelial cells (BuMECs) and bovine mammary epithelial cells (BoMECs) by regulating lipogenic gene expression (p < 0.05). Knockdown of AGPAT1 or AGPAT6 inhibited proliferation and apoptosis of BuMECs through the expression of marker genes associated with the proliferation and apoptosis (p < 0.05). Our data confirmed that both AGPAT1 and AGPAT6 could regulate TAG synthesis and growth of mammary epithelial cells in buffalo. These findings will have important implications for understanding the role of the AGPAT gene in buffalo milk performance. [ABSTRACT FROM AUTHOR]

The adsorption and desorption characteristics of cadmium (Cd) in uncontaminated soils have been investigated in numerous studies. However, similar studies on Cd-polluted soils from different sources, which exhibit complex physicochemical characteristics and internal interactions between Cd and the soil particles, are scarce. Therefore, in order to elucidate the adsorption and desorption characteristics of Cd in Cd polluted soils, six representative Cd-contaminated paddy soil samples were collected from farmlands in the vicinity of a steel plant (Soil 1), a smelter (Soil 2), a thermal power plant (Soil 3), two mining areas (Soil 4, the Dabaoshan mine, Shaoguan; Soil 5, a lead-zinc mine located at Lechang), and a paddy field irrigated with sewage at Zhongshan (Soil 6) in Guangdong Province, China. The analysis of the six soil samples showed that Cd adsorption fitted well to pseudo-second order as well as pseudo-first order kinetics; however, the pseudo-second order equation showed a better fit (R2 = 0.860–0.962), while Elovich and intraparticle kinetic models fitted the adsorption kinetics poorly. Further, the adsorption isotherms fitted well to both the Langmuir and Freundlich models, with the Freundlich model showing a better fit (R2 = 0.96–0.98). The following order was observed for the Cd(II) adsorption amount and rate: S5 > S6 > S1 > S3 > S2 > S4; meanwhile, the desorption amount and rate followed the opposite trend. Furthermore, the pH and soil organic matter were identified as the soil characteristics with the most significant impact on the adsorption and desorption behaviors of Cd(II) in the Cd-polluted soils. [ABSTRACT FROM AUTHOR]

Polymeric dielectrics exhibit remarkable dielectric characteristics and wide applicability, rendering them extensively employed within the domain of electrical insulation. Nevertheless, the electrical strength has always been a bottleneck, preventing its further utilization. Nanocomposite materials can effectively improve insulation strength, but uniform doping of nanofillers in engineering applications is a challenge. Consequently, a nanocomposite interfacial coating was meticulously designed to interpose between the electrode and the polymer, which can significantly improve DC breakdown performance. Subsequently, the effects of filler concentration and coating duration on DC breakdown performance, high field conductivity, and trap distribution characteristics were analyzed. The results indicate that the composite coating introduces deep traps between the electrode-polymer interface, which enhances the carrier confinement, resulting in reduced conductivity and enhanced DC breakdown strength. The incorporation of a composite coating at the interface between the electrode and polymer presents novel avenues for enhancing the dielectric insulation of polymers.