Heat exchange characteristics of underground and pavement buried pipes for bridge deck heating conditions.

Geothermal energy is increasingly employed across diverse applications, with bridge deck snow melting emerging as a notable utilization scenario. In Jinan city, China, a project is underway to utilize ground source heat pumps (GSHPS) for heating bridges. However, essential operational parameters, including fluid medium, temperature, and heat exchange details, are currently lacking. This study addresses the thermal design challenges associated with ground heat exchangers (GHE) for bridge heating through a combination of numerical modeling and field experiments. Utilizing software Fluent, a refined three-dimensional multi-condition heat transfer numerical analysis was carried out. Field tests based on actual operating conditions were also conducted and the design parameters were verified. The results indicate that an inlet temperature of 5°C and an aqueous solution of ethylene glycol with a mass concentration of 35% as the heat exchange medium are suitable for the GSHPS in Jinan; Moreover, the influence of backfill material and operation time on the heat transfer efficiency was revealed and the suitable material with 10% bentonite and 90% SiO2 was suggested; Finally, based on the influence of the pipe spacing on the heating characteristics of bridge deck, the transition spacing of 0.2 m is given for the temperature response of the bridge deck. This comprehensive study contributes valuable insights through simulation and experimental analysis of the thermal environment variation, aiming to advance the development of GSHPS for bridge deck heating in Jinan, China.

Abnormally decreased functional connectivity of the right nucleus basalis of Meynert in Alzheimer's disease patients with depression symptoms.

Dysfunction of the basal forebrain is the main pathological feature in patients with Alzheimer's disease (AD). The aim of this study was to explore whether depressive symptoms cause changes in the functional network of the basal forebrain in AD patients. We collected MRI data from depressed AD patients (n = 24), nondepressed AD patients (n = 14) and healthy controls (n = 20). Resting-state functional magnetic resonance imaging data and functional connectivity analysis were used to study the characteristics of the basal forebrain functional network of the three groups of participants. The functional connectivity differences among the three groups were compared using ANCOVA and post hoc analyses. Compared to healthy controls, depressed AD patients showed reduced functional connectivity between the right nucleus basalis of Meynert and the left supramarginal gyrus and the supplementary motor area. These results increase our understanding of the neural mechanism of depressive symptoms in AD patients.

Suppression of NLRP3 inflammasome activation by astragaloside IV via promotion of mitophagy to ameliorate radiation-induced renal injury in mice.

Background: Irradiation (IR) promotes inflammation and apoptosis by inducing oxidative stress and/or mitochondrial dysfunction (MD). The kidneys are rich in mitochondria, and mitophagy maintains normal renal function by eliminating damaged mitochondria and minimizing oxidative stress. However, whether astragaloside IV (AS-IV) can play a protective role through the mitophagy pathway is not known. Methods: We constructed a radiation injury model using hematoxylin and eosin (HE) staining, blood biochemical analysis, immunohistochemistry, TdT-mediated dUTP nick end labeling (TUNEL) staining, ultrastructural observation, and Western blot analysis to elucidate the AS-IV resistance mechanism for IR-induced renal injury. Results: IR induced mitochondrial damage; the increase of creatinine (SCr), blood urea nitrogen (BUN) and uric acid (UA); and the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome and apoptosis in renal tissue. AS-IV administration attenuated the IR-induced MD and reactive oxygen species (ROS) levels in the kidney; enhanced the levels of mitophagy-associated protein [PTEN-induced putative kinase 1 (PINK1)], parkin proteins, and microtubule-associated protein 1 light 3 (LC3) II/I ratio in renal tissues; diminished NLRP3 inflammasome activation-mediated proteins [cleaved cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1ß (IL-1ß)] and apoptosis-related proteins [cleaved caspase-9, cleaved caspase-3, BCL2-associated X (Bax)]; reduced SCr, BUN, and UA levels; and attenuated the histopathological alterations in renal tissue. Conversely, mitophagy inhibitor cyclosporin A (CsA) suppressed the AS-IV-mediated protection of renal tissue. Conclusions: AS-IV can strongly diminish the activation and apoptosis of NLRP3 inflammasome, thus attenuating the renal injury induced by radiation by promoting the PINK1/parkin-mediated mitophagy. These findings suggest that AS-IV is a promising drug for treating IR-induced kidney injury.

Radiological evaluation of effectiveness of PCCP fixation for femoral neck fracture: med-term effectiveness in a retrospective multicenter.

Background It has been reported in the literature that the complication rate of percutaneous compression plate (PCCP) is the lowest among the new internal fixators for the treatment of femoral neck fracture (FNS). However, no multicenter studies of PCCP for FNS have been reported. This study aimed to evaluate the med-term effectiveness of PCCP in a multicenter mainly through radiology. Methods 265 patients with FNF treated with PCCP fixation in our five hospitals between January 2011 and December 2020 were retrospectively analyzed. 140 men and 125 women; aged 19-79 (mean 51.6）years. The follow-up time was 2-5 years (mean 3.1). Radiological evaluation of the therapeutic effect was the main outcome, and the function was the secondary outcome. Results One case of screw cutting out, 3 cases of screw back out, 25 cases of neck shortening, 2 cases of nonunion, 8 cases of delayed healing, and 29 cases of avascular necrosis (AVN). Bivariate correlation showed that shortening healing was correlated with age, Singh index, and Garden alignment index, poor healing was correlated with garden alignment index, and AVN was correlated with Pauwels and Garden classifications and operation timing. Further pairwise comparison analysis showed that age of > 65 and Singh index IV were dangerous factors for neck shortening, and the operation timing > 3 days, Pauwels II and III, and Garden III and IV were dangerous factors for AVN. The excellent and good rate of function in 198 patients who were readmitted for internal fixator removal or other surgery was 90.9%. Conclusion PCCP for FNS has satisfactory med-term efficacy with a low complication rate. The main complication is AVN, which is prone to occur in patients with displaced Pauwels II or III FNF and operation timing > 3 days. Another main complication is shortening healing, which is prone to occur in patients with an age of > 65 and Singh index IV.

Varying degrees of spontaneous osteogenesis of Masquelet's induced membrane: experimental and clinical observations.

BACKGROUND: Masquelet's induced membrane (IM) has osteogenesis activity, but IM spontaneous osteogenesis (SO) has not been described previously. OBJECTIVES: To report on varying degrees of IMSO and analyze its possible causes. METHODS: Twelve eight-week-old male Sprague-Dawley rats with 10 mm right femoral bone defects who received the first stage of IM technique (IMT) were used to observe the SO. In addition, clinical data from patients with bone defects who received the first stage of IMT with an interval of > 2 months post-operatively and exhibited SO between January 2012 and June 2020 were retrospectively analyzed. The SO was divided into four grades according to the amount and characteristics of the new bone formation. RESULTS: At twelve weeks, grade II SO was observed in all rats, and more new bone was formed in the IM near the bone end forming an uneven margin. Histology revealed bone and cartilage foci in the new bone. Four of the 98 patients treated with the first stage of IMT exhibited IMSO, including one female and three males with a median age of 40.5 years (range 29-52 years). The bone defects were caused by severe fractures and infection in two cases and by infection or tumor in one case each. Partial or segmental defects occurred in two cases. The time interval between inserting a cement spacer and diagnosis of SO ranged from six months to nine years. Two cases were grade I, and one case each of grades III and IV. CONCLUSION: Varying degrees of SO confirm the existence of the IMSO phenomenon. Bioactive bone tissue or local inflammation and a long time interval are the primary reasons underlying enhancement of the osteogenic activity of IM and leading to SO, which tends to take place as endochondral osteogenesis.

Astragaloside IV ameliorates radiation-induced nerve cell damage by activating the BDNF/TrkB signaling pathway.

Radiation can induce nerve cell damage. Synapse connectivity and functionality are thought to be the essential foundation of all cognitive functions. Therefore, treating and preventing damage to synaptic structure and function is an urgent challenge. Astragaloside IV (AS-IV) is a glycoside extracted from Astragalus membranaceus (Fisch.). Bunge is a widely used traditional Chinese medicine in China with various pharmacological properties, including protective effects on the central nervous system (CNS). In this study, the effect of AS-IV on synapse damage and BDNF/TrkB signaling pathway in radiated C57BL/6 mice with X-rays was investigated. PC12 cells and primary cortical neurons were exposed to UVA in vitro. Open field test and rotarod test were used to observe the effects of AS-IV on the motor and explore the abilities of radiated mice. The pathological changes in the brain were observed by hematoxylin and eosin and Nissl staining. Immunofluorescence analysis was used to detect the synapse damage. The expressions of the BDNF/TrkB pathway and neuroprotection-related molecules were detected by Western blotting and Quantitative-RTPCR, respectively. The results showed that AS-IV could improve the motor and explore abilities of radiated mice, reduce pathological damage to the cortex, enhance neuroprotection functions, and activate BDNF/TrkB pathway. In conclusion, AS-IV could relieve radiation-induced synapse damage, at least partly through the BDNF/TrkB pathway.

Construction of dual active sites for efficient alkaline hydrogen evolution: single-metal-atoms supported on BC2N monolayers.

Electrocatalytic water splitting suffers from sluggish kinetics towards the hydrogen evolution reaction (HER). Balancing the adsorption/desorption ability towards H* and OH* is considered to be an efficient way to enhance the HER efficiency, but it is too hard at one activity site. In this work, the HER activity of the single 3d transition metal atom-anchored BC2N monolayer (M@BC2N, M = Fe, Co, and Ni) was investigated by a density functional theory approach. Our calculation suggests that an efficient dual-active site is formed on M@BC2N towards the HER, i.e., the metal center M as the OH* active site and its adjacent C atoms as the H* active site. The combination of single M atoms with the BC2N monolayer can effectively tune the electronic structure of dual active sites to optimize the adsorption of H* and OH*, resulting in a HER activity sequence of Fe@BC2N < Co@BC2N < Ni@BC2N. Notably, the HER exchange current density of Ni@BC2N reaches up to 0.53 mA cm-2, which is close to the value for commercial Pt/C, suggesting its huge potential in the HER.

The Diagnosis of Early Gastric Cancer Based on Medical Imaging Technology and Mathematical Modeling.

The key to reducing the mortality of gastric cancer is early detection, early diagnosis, and early treatment of gastric cancer. Early diagnosis of gastric cancer is the key to early detection and diagnosis of gastric cancer. Early diagnosis and treatment of gastric cancer is of great significance for improving the curative effect and reducing mortality of gastric cancer. The purpose of this paper is to study the diagnosis of early gastric cancer based on medical imaging techniques and mathematical modeling. The effect of W-DeepLab network-assisted diagnosis of images under white light was analyzed, and the value of Narrow Band Imaging and Blue Laser Imaging in the diagnosis of early gastric cancer was compared. Because Blue Laser Imaging endoscopy can clearly observe the demarcation line and microvascular morphology; but when using Narrow Band Imaging observation, part of the demarcation line and microvascular morphology is not observed. The results show that Blue Laser Imaging is brighter than Narrow Band Imaging's endoscopic images, and it is easier to observe the microstructure of lesions under endoscopy, so as to accurately determine the nature of lesions.

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion.

Background: Multiple myeloma (MM) is the second most common hematological malignancy that still lacks effective clinical treatments. In particular, MM with central nervous system (CNS) invasion occurs rarely. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise for the treatment of relapsed/refractory MM, few studies have reported whether BCMA CAR-T could inhibit MM with CNS invasion. Case Presentation: In this study, we report a special case of a 63-year-old male patient who suffered MM with CNS invasion and presented rapid extramedullary disease (EMD) progression into multiple organs. Before CAR-T cell infusion, this patient received five cycles of bortezomib, Adriamycin, and dexamethasone (PAD) and an autologous transplant as the front-line treatment, followed by two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) as the second-line regimen, and daratumumab, bortezomib, dexamethasone (DVD) as the third-line regimen. Since the patient still showed rapid progressive disease (PD), BCMA CAR-T cells were infused, and 1 month later, a stringent complete response (sCR) was achieved, and the response lasted for 4 months. Meanwhile, only grade 1 cytokine release syndrome (CRS) was observed. Conclusion: This case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events, suggesting that CAR-T cell therapy could be a feasible therapeutic option for this kind of refractory disease. Clinical Trial Registration: https://ClinicalTrials.gov, identifier: NCT04537442.a.

[Innovation ability-driven optimization of the experimental teaching of human anatomy and animal physiology].

Innovation and entrepreneurship training through higher education sector is an important way to foster innovative talents and enhance their social adaptation abilities. We reformed and optimized the experimental teaching of human anatomy and animal physiology with the aim to promote the integration of students' theory learning with practice, to promote students' ability to apply anatomical and physiological knowledge to medicine, pharmacy, and life practice. Last but not least, students' innovative consciousness of applying scientific research to serve the society could also be enhanced. These practices would enhance the practical ability of the students through integrating the innovation education and professional education.

A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma.

Objective: Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor (CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells, especially the lower incidence rate of severe adverse events. However, the median progression-free survival (mPFS) of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta (2.9 monthsvs. 5.9 months), suggesting that Kymriah was limited in the long-term efficacy. Thus, a safe and durable 4-1BB-based CD19 CAR-T needs to be developed. Methods: We designed a CD19-targeted CAR-T (named as IM19) which consisted of an FMC63 scFv, 4-1BB and CD3ζ intracellular domain and was manufactured into a memory T-enriched formulation. A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory (r/r) B cell non-Hodgkin lymphoma (B-NHL). Dose-escalation investigation (at a dose of 5×105/kg, 1×106/kg and 3×106/kg) was performed in 22 r/r B-NHL patients. All patients received a single infusion of IM19 after 3-day conditional regimen. Results: At month 3, the overall response rate (ORR) was 59.1%, the complete response rate (CRR) was 50.0%. The mPFS was 6 months and the 1-year overall survival rate was 77.8%. Cytokine release syndrome (CRS) occurred in 13 patients (59.1%), with 54.5% of grade 1-2 CRS. Only one patient (4.5%) experienced grade 3 CRS and grade 3 neurotoxicity. Conclusions: These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T, IM19, which is promising for further development and clinical investigation.

What drives green development in China: public pressure or the willingness of local government?

With China already committing to peak carbon dioxide emissions before 2030 and achieving carbon neutrality before 2060, green development is urgent. It is necessary to clarify the driving mechanism of green development to design the path of green development scientifically. From the internal perspective of the green development system, this paper divides the green development power into external power and internal power. The external power is the political pressure formed by the public's green demands. The internal power is the endogenous power of green development transformed by the political promotion willingness of local government leaders. The research shows that (1) the green demands from the public and the accompanying political pressure can form the driving force of green development. (2) The political promotion intention has not been transformed into the endogenous driving force to promote green development in the research period. (3) The external driving force of public appeal is closely related to economic development, income and consumption levels, and education. This paper enriches the research literatures on the driving mechanism of green development and provides theoretical and practical exploration for the driving path of green development.

[Strengthening and application of science and education integration in experimental course of human anatomy and animal physiology].

Institutions of higher learning undertake the important responsibility of personnel training. Teaching and scientific research are two indispensable functions of colleges and universities, and the relationship between them is unbalanced and low integration in the current education and teaching. According to the existing problems in the experimental course of human anatomy and animal physiology, we explored how to apply the ideological and political education of scientific research to improve students' cognitive ability, develop experimental projects combined with scientific research practice, and strengthen the combination of classroom teaching and scientific research practice, aiming to establish the basic concept of the integration of science and education. These are favorable for the realization of the training goal of high-quality innovative talents.

Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies.

BACKGROUND: The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo. METHODS: NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry. RESULTS: CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7-21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients. CONCLUSIONS: CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects. TRIAL REGISTRATION: The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421 .

The Protective Effects of Peroxisome Proliferator-Activated Receptor Gamma in Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia-reperfusion injury (CI/RI) is a complex pathological process that often occurs secondary to trauma, surgery, and shock. Peroxisome proliferator activated receptor gamma (PPARγ) is a subunit of the PPAR and is a ligand-activated nuclear transcription factor. After being activated by its ligand, PPARγ can combine with specific DNA response elements to regulate the transcription and expression of genes. It has a wide range of biological functions, such as regulating lipid metabolism, improving insulin sensitivity, modulating anti-tumor mechanisms, and inhibiting inflammation. In recent years, some studies have shown that PPARγ exerts a protective effect during CI/RI. This article aims to summarize the research progress of studies that have investigated the protective effects of PPARγ in CI/RI and the cellular and molecular mechanisms through which these effects are modulated, including inhibition of excitatory amino acid toxicity, reduced Ca2+ overload, anti-oxidative stress, anti-inflammation, inhibition of microglial activation, maintain the BBB, promotion of angiogenesis, and neurogenesis and anti-apoptotic processes.

Production of lentiviral vectors in suspension cells using low proportion of supercoiled circular plasmid DNA.

The supercoiled circular (SC) topology form of plasmid DNA has been regarded to be advantageous over open circular or linearized analogue in transfection and expression efficiency, and therefore are largely demanded in the biopharmaceutical manufacturing. However, production of high-purity SC plasmid DNA would result in high manufacturing cost. The effect of SC proportion in plasmid DNA on the quality of packaged lentiviral vectors has never been reported. In this study, we established an efficient system for production of high-titer lentiviral vectors using suspension HEK293SF cells in serum-free media, and the lentiviral titer was not associated with the proportion of SC plasmid DNA. Plasmids DNA with different proportion of SC, open-circular, and linearized forms were prepared using the thermal denaturation method, and were transfected to adherent HEK293T or suspension HEK293SF cells for packaging of lentiviral vectors. The titer of lentiviral vectors from HEK293T cells, but not from HEK293SF cells, was significantly impaired when the proportion of SC plasmid DNA decreased from 60-80% to 30-40%. Further decrease of SC plasmid proportion to 3% led to a dramatic reduction of lentiviral titer no matter the packaging cell line was. However, lentiviral vectors from HEK293SF cells still showed a high titer even when the proportion of SC plasmid DNA was 3%. This study demonstrated that extremely high proportion of SC plasmid DNA was not required for packaging of high-titer lentiviral vector in HEK293SF cells, at least under our manufacturing process.

Preliminary study on the anti-apoptotic mechanism of Astragaloside IV on radiation-induced brain cells.

With multiple targets and low cytotoxicity, natural medicines can be used as potential neuroprotective agents. The increase in oxidative stress levels and inflammatory responses in the brain caused by radiation affects cognitive function and neuronal structure, and ultimately leads to abnormal changes in neurogenesis, differentiation, and apoptosis. Astragaloside Ⅳ (AS-Ⅳ), one of the main active constituents of astragalus, is known for its antioxidant, antihypertensive, antidiabetic, anti-infarction, anti-inflammatory, anti-apoptotic and wound healing, angiogenesis, and other protective effects. In this study, the mechanism of AS-IV against radiation-induced apoptosis of brain cells in vitro and in vivo was explored by radiation modeling, which provided a theoretical basis for the development of anti-radiation Chinese herbal active molecules and brain health products. In order to study the protective mechanism of AS-IV on radiation-induced brain cell apoptosis in mice, the paper constructed a radiation-induced brain cell apoptosis model, using TUNEL staining, flow cytometry, Western blotting to analyze AS-IV resistance mechanism to radiation-induced brain cell apoptosis. The results of TUNEL staining and flow cytometry showed that the apoptosis rate of radiation group was significantly increased. The results of Western blotting indicated that the expression levels of p-JNK, p-p38, p53, Caspase-9 and Caspase-3 protein, and the ratio of Bax to Bcl-2 in radiation group were significantly increased. There was no significant difference in the expression levels of JNK and p38. After AS-IV treatment, the apoptosis was reduced and the expression of apoptosis related proteins was changed. These data suggested that AS-IV can effectively reduce radiation-induced apoptosis of brain cells, and its mechanism may be related to the phosphorylation regulation of JNK-p38.

The clinical outcomes of fresh versus cryopreserved CD19-directed chimeric antigen receptor T cells in non-Hodgkin lymphoma patients.

CD19-directed chimeric antigen receptor T (CAR-T) cells have been widely reported in the therapy of relapsed/refractory non-Hodgkin lymphoma (NHL). Both cryopreserved and fresh formulations of CAR-T have been used in previous studies. However, quite a few studies investigated the effects of cryopreservation on the clinical outcomes of CAR-T cells. Here we retrospectively analyzed a phase I/II clinical trial of CD19-directed CAR-T cells in NHL patients, and compared the safety and efficacy of cryopreserved and fresh CAR-T products. All CAR-T cells were prepared using the same manufacturing process except the formulation step. Fifteen patients were infused with cryopreserved/thawed CAR-T cells, and 8 patients were treated with fresh CAR-T cells. Comparative overall response rates and in vivo expansion kinetics of CAR-T cells were observed between the cryopreserved cohort and fresh cohort. The occurrence rates of cytokine release syndrome and neurotoxicity were also similar in both groups. Patients in the fresh cohort showed higher incidence of acute hematological toxicity including anemia, hypoleukemia, and thrombocytopenia. This study demonstrated that cryopreservation showed negligible effects on the efficacy of CD19-directed CAR-T cells, but endowed CAR-T cells with higher safety in NHL patients, supporting the application of cryopreserved CAR-T products for NHL therapy.

Efficacy and Safety of CD28- or 4-1BB-Based CD19 CAR-T Cells in B Cell Acute Lymphoblastic Leukemia.

CD19-directed chimeric antigen receptor-T (CAR-T) cells with a 4-1BB or CD28 co-stimulatory domain have shown impressive antitumor activity against relapsed or refractory B cell acute lymphoblastic leukemia (r/r B-ALL). However, a parallel comparison of their performances in r/r B-ALL therapy has not been sufficiently reported. Here, we manufactured 4-1BB- and CD28-based CD19 CAR-T cells using the same process technology and evaluated their efficacy and safety in r/r B-ALL therapy based on pre-clinical and exploratory clinical investigations. In B-ALL-bearing mice, a similar antitumor effect and CAR-T kinetics in peripheral blood were observed at the CAR-T dose of 1 × 107/mouse. However, when the dose was decreased to 1 × 106/mouse, 4-1BB CAR-T cells were more potent in eradicating tumor cells and showed longer persistence than CD28 CAR-T cells. Retrospective analysis of an exploratory clinical study that used 4-1BB- or CD28-based CAR-T cells to treat r/r B-ALL was performed. Compared with CD28 CAR-T cells, 4-1BB CAR-T cells resulted in higher antitumor efficacy and less severe adverse events. This study demonstrated that the performance of 4-1BB CAR-T cells was superior to that of CD28 CAR-T cells in suppressing CD19+ B-ALL, at least under our manufacturing process.