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IntroductionChimeric antigen receptor (CAR) T cell therapy has achieved unprecedented efficacy recently. However, the factors related to responses and durable remission are elusive. This study was to investigate the impact of pre-lymphodepletion (pre-LD) absolute lymphocyte count (ALC) on CAR T cell therapy outcomes.MethodsWe conducted a retrospective study of 84 patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who underwent CAR T cell treatment at the Affiliated Hospital of Xuzhou Medical University between March 1,2016 and December 31, 2021. The enrolled patients were divided into high group and low group according to the optimal cutoff value of pre-LD ALC. The Kaplan-Meier analyses was used to calculate survival curves. The Cox proportional hazards model was used for univariate and multivariate analysis to assess the prognostic factors.ResultsThe ROC showed that the optimal cutoff value of pre-LD ALC was 1.05 x 109/L. The overall response (defined as partial response or complete response) rate was significantly higher in patients with a high pre-LD ALC (75% versus 52.08%; P=0.032). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those having a high pre-LD ALC (median OS, 9.6 months versus 45.17 months [P=0.008]; median PFS, 4.07 months versus 45.17 months [P= 0.030]). Meanwhile, low pre-LD ALC is an independent risk factor for PFS and OS.DiscussionThe data suggested that pre-LD ALC may serve as a helpful indicator to predict the outcomes of CAR T cell therapy in patients with R/R DLBCL.

As a class of randomized learner model, stochastic configuration networks (SCNs) have been successfully applied in a few data analytics tasks. Given the industrial big data modeling tasks, however, the original SCNs potentially lead to excessive training time. To this end, this paper extends SCNs to a hybrid parallel version, termed HPSCNs. In the hybrid parallel learning algorithm, two SCNs are synchronously constructed. The difference between the two of them is that one employs a point-incremental algorithm, and another one adopts a block-incremental algorithm. Moreover, a data parallel method is established based on a dynamic block strategy to accelerate the establishment of candidate node pool for each SCN. Additionally, this paper proposes an adaptive hyperparameter adjustment method, which allows the hyperparameters in the supervisory mechanism to be automatically adjusted along with the learning process. Comparative experiments are first conducted through four large-scale benchmark datasets, followed by the fully discussion on the algorithm parameters. Finally, a practical industrial application case is made, where a grinding particle size soft sensor is developed based on HPSCN, showing the effectiveness of the proposed algorithm.

Synergistic effects of intumescent flame retardant and nano-CaCO3 on foamability and flame retardant property of polypropylene composites and their foams were carefully investigated. The differential scanning calorimetry results showed that the intumescent flame retardant played a plasticizing effect on the polypropylene/intumescent flame-retardant composites and accelerated the crystallization rate. The rheological properties and supercritical CO2-assisted molding foaming behaviors of the polypropylene/intumescent flame retardant/nano-CaCO3 composites showed that the nano-CaCO3 could enhance their foamability. Scanning electron microscopy pictures and mechanical properties of the polypropylene/intumescent flame-retardant composites foams indicated that the agglomeration of intumescent flame retardant would reduce the cell uniformity and even cause the cell collapse. Furthermore, the stress concentration, caused by the agglomeration, could reduce the mechanical properties of the PP composites foams. The synergistic effect of the nano-CaCO3 could improve the cell uniformity and reduce the stress concentration so that the mechanical properties of the polypropylene/intumescent flame retardant /nano-CaCO3 composites foams were improved. Moreover, the polypropylene/intumescent flame retardant/nano-CaCO3 composites foams had the higher limit oxygen index values than the polypropylene/intumescent flame-retardant foams. TGA results also showed that the nano-CaCO3 could improve the thermal stability of the polypropylene composites foams by forming compact carbon layer. The experimental results indicated that the foamability of the polypropylene composites and the flame-retardant property of their foams could be improved by the synergistic effects of intumescent flame retardant and nano-CaCO3.

Characterization and forecasting in fractured reservoirs is one of the most challenging topics in oil and gas industry. Due to significant difference of fluid flow mechanism in fracture and in matrix, managing such reservoirs requires construction of representative reservoir models. Dual porosity & dual permeability model (DPDP) is the first choice of fractured reservoirs, but history matching and plan prediction of this model facing poor convergence and long running time. Other models like dual porosity & single permeability model (DPSP), single porosity & single permeability model (SPSP) sometimes can replace DPDP and can be able to improve convergence and save calculation time, but lack of model equivalence criterion. In this study, 84 cases of 4 reservoir models has been built and simulated to study the equivalence criterion. Permeability difference and oil viscosity are considered to be the main influencing factors affecting model equivalence. With the application of the equivalence criterion, weak convergence and time consuming of fractured reservoir simulation can be improved.

This paper is devoted to the $L^p$ ($p>1$) solutions of one-dimensional backward stochastic differential equations (BSDEs for short) with general time intervals and generators satisfying some non-uniform conditions in $t$ and $��$. An existence and uniqueness result, a comparison theorem and an existence result for the minimal solutions are respectively obtained, which considerably improve some known works. Some classical techniques used to deal with the existence and uniqueness of $L^p$ ($p>1$) solutions of BSDEs with Lipschitz or linear-growth generators are also developed in this paper., 16 pages

(E)-4-Thio-5-(2-brominevinyl)uridine/2'-deoxyuridine(8a/8b) were efficiently and in an environmental friendly way synthesized from uridine/2'-deoxyuridine (1a/1b) that were first transformed to (E)-(2-brominevinyl) uridine / 2'-deoxyuridine(5a/5b) via iodination, selective oxidation, Heck reaction steps. The resulting products (5a/5b) were then converted to the targets (8a/8b) through esterification, thio-reaction of carbonyl, hydrolysis steps. Two new compounds (8a/8b) and three new intermediates (7a 7b 10) were obtained, and their structures have been fully characterized by 1H NMR, 13C NMR, IR, UV, HR-MS, X-Ray. The study of 8a and their derivatives regarding cytotoxicity was carried out by using MTT experiment method, and the initial findings suggest (E)-4-Thio-5-(2-brominevinyl) uridine/ 2'-deoxyuridine (8a / 8b) would be potential antitumor drugs.

Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of magnolol on acute lung injury induced by lipopolysaccharide in mice. Male BALB/c mice were pretreated with dexamethasone or magnolol 1 h before intranasal instillation of lipopolysaccharide (LPS). 7 h after LPS administration, the myeloperoxidase in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). The extent of phosphorylation of nuclear factor of inhibitory kappa B alpha (IκB-α), nuclear factor kappa-B (NF-κB) p65 and the expression of Toll-like receptor-4 (TLR4) were detected by western blot. The results showed that magnolol markedly attenuated the histological alterations in the lung; reduced the number of total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid; decreased the wet/dry weight ratio of lungs in the bronchoalveolar lavage fluid; down-regulated the level of pro-inflammatory mediators, including TNF-α, IL-1β and IL-6; inhibited the phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4, caused by LPS. Taken together, our results suggest that anti-inflammatory effects of magnolol against the LPS-induced acute lung injury may be due to its ability of inhibition TLR4 mediated NF-κB signaling pathways. Magnolol may be a promising potential therapeutic reagent for acute lung injury treatment.