Schiff base and coordinate bonds cross-linked chitosan-based eutectogels with ultrafast self-healing, self-adhesive, and anti-freezing capabilities for motion detection.

Ion conductors offer great potential for diverse electric applications. However, most of the ion conductors were fabricated from non - degradable petroleum-based polymers with non or low biodegradability, which inevitably leads to resource depletion and waste accumulation. Fabricating ion conductors based on renewable, and sustainable materials is highly desirable and valuable. Herein, a series of eutectogels were designed through dual-dynamic-bond cross-linking among ferric iron (Fe3+), protocatechualdehyde (PA), and chitosan (CS) in 1 - allyl-3 - methylimidazole chloride ionic liquid/urea (AmimCl/urea) eutectic-based ionic liquid. Due to the presence of AmimCl/urea eutectic-based ionic liquid, the obtained CS - PA@Fe eutectogels showed excellent ionic conductivity, superior anti-freezing properties that could maintain flexibility and high electrical properties at -20 °C. Dual-dynamic-bond cross-linking of catechol-Fe coordinate and dynamic Schiff base bonds equip CS - PA@Fe eutectogels with excellent injectable, and self-healing abilities. Additionally, due to the presence of phenolic hydroxyl groups of PA, the obtained CS - PA@Fe eutectogels present good adhesiveness. Based on the CS - PA@Fe eutectogels, multifunctional flexible strain sensors with high sensitivity, stability, as well as rapid response speed at wide operating temperature ranges were successfully fabricated. Thus, this study offers a promising strategy for fabricating naturally occurring biopolymers based eutectogels, which show great potential as high-performance flexible strain sensors for next-generation wearable electronic devices.

Analysis of 60 patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma treated with CD7-targeted chimeric antigen receptor-T cell therapy.

While the use of chimeric antigen receptor-T (CAR-T) therapy for T-cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long-term remission for patients with refractory/relapsed (R/R) T-cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T-ALL 35, T-LBL 25) received a single dose of naturally selected anti-CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105 /kg), a medium dose (1 to 1.5 × 106 /kg), and a high dose (2 × 106 /kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2-year overall survival and progression-free survival (PFS) were 63.5% (95% CI 47.7-79.4) and 53.7% (95% CI, 38.9-68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1-year PFS 67.2% (95% CI 51.9-82.4) versus 15.0% (95% CI 0-40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR-T therapy is effective in treating R/R T-ALL/LBL patients with promising PFS while maintaining a manageable safety profile.

Expansion Dynamics of a Shell-Shaped Bose-Einstein Condensate.

We report the creation of a shell BEC in the presence of Earth's gravity with immiscible dual-species BECs of sodium and rubidium atoms. After minimizing the displacement between the centers of mass of the two BECs with a magic-wavelength optical dipole trap, the interspecies repulsive interaction ensures the formation of a closed shell of sodium atoms with its center filled by rubidium atoms. Releasing the double BEC together from the trap, we observe explosion of the filled shell accompanied by energy transfer from the inner BEC to the shell BEC. With the inner BEC removed, we obtain a hollow shell BEC that shows self-interference as a manifestation of implosion. Our results pave an alternative way for investigating many of the intriguing physics offered by shell BECs.

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study.

To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and preliminary efficacy of CD19 F-CAR-T in B-cell acute lymphoblastic leukemia (B-ALL). CD19 F-CAR-T cells demonstrated excellent proliferation with a younger cellular phenotype, less exhaustion, and more effective tumor elimination compared to conventional CAR-T cells in the preclinical study. In our phase I study (NCT03825718), F-CAR-T cells were successfully manufactured and infused in all of the 25 enrolled pediatric and adult patients with B-ALL. CD19 F-CAR-T safety profile was manageable with 24% grade 3 cytokine release syndrome (CRS) and 28% grade 3/4 neurotoxicity occurring predominantly in pediatric patients. On day 14, 23/25 patients achieved minimal residual disease (MRD)-negative complete remission (CR), and 20 subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 months post F-CAR-T therapy. Fifteen of 20 patients were disease-free with a median remission duration of 734 days. One patient relapsed and 4/20 died from transplant-related mortality. Of the three patients who did not undergo allo-HSCT, two remained in CR until 10 months post-F-CAR-T. Our data indicate that anti-CD19 FasT CAR-T shows promising early efficacy for B-ALL. Further evaluations in larger clinical studies are needed.

Investigation of migration rule of rainwater for sponge city roads under different rainfall intensities.

Urban development and climate change have led to severe waterlogging in cities. To study the degree of mitigation of urban waterlogging using the design of sponge city roads, this study employed No. 9 Road in the Sino-German Eco-park. By establishing the scaled physical model, the pavement structure of the sponge city road was optimized. Furthermore, water migration (seepage, impoundment, and drainage) rule was obtained under different rainfall intensities using the optimal pavement scheme. The following conclusions were drawn from the studies. Good permeability of the sidewalk surface structure is conducive for rainwater collection. The sponge urban road rainwater collection and utilization system could absorb up to 88% of rainwater under the rainfall intensity of 173 mm (extra heavy rain), and could absorb up to 100% of rainwater under heavy rain conditions. The seepage volume increased exponentially with the rise in rainfall intensity, and the amount of water storage increased linearly with the rainfall intensity. These results can provide guidance for safety early warning of urban waterlogging on No. 9 Road in the Sino-German Eco-park and deeper insights in the design of sponge city roads.

Joint equalization scheme of ultra-fast RSOP and large PMD compensation in presence of residual chromatic dispersion.

Polarization demultiplexing is generally carried out by a multiple-input multiple-output (MIMO) based algorithm in polarization division multiplexing (PDM) coherent systems. However, in some extreme environments, the MIMO algorithm becomes inapplicable due to the ultra-fast rotation of the state of polarization (RSOP) and large polarization mode dispersion (PMD). In addition, the residual chromatic dispersion (RCD) is always present because of the mismatch of the compensated chromatic dispersion and real value induced in the optical fiber channel. According to the literature, the Kalman filter-based polarization demultiplexing algorithms possess very weak RCD tolerance. Faced with this dilemma, in this paper, a new Kalman filter structure is proposed, which can jointly compensate ultra-fast RSOP, large PMD and RCD. This Kalman filter structure enables the equalization of the RSOP in the time domain and compensation for RCD and PMD in the frequency domain. We verified the performance of the proposed Kalman scheme in the 28 Gbaud PDM-QPSK/16 QAM coherent system, with a comparison to constant modulus algorithm/multiple modulus algorithm (CMA/MMA). The simulation results confirm that, compared with CMA/MMA, the proposed Kalman scheme can provide a significant performance enhancement to cope with ultra-fast RSOP (up to 3 Mrad/s) and large PMD (more than 200 ps) with a large tolerance to RCD (over the range of ± 820 ps/nm in PDM-QPSK and ± 500 ps/nm in PDM-16 QAM).

[Screening, identification and optimization of fermentation conditions of an antagonistic endophyte to mulberry bacterial blight].

OBJECTIVE: Antagonistic endophytic strains with strongly inhibitory activity to mulberry bacterial blight (P. syringae pv. mori) were isolated from mulberry endophytes, we identified the antagonistic endophyte and optimized the fermentation conditions. METHOD: Streak plate method was used to separate the endophytes from healthy mulberry tissues after strict surface disinfection. Antagonistic endophytes were screened out through inhibition zone method. Strain SWg2 was identified by morphological, physiological and biochemical characteristics and 16S rDNA sequence analysis. The conditions of fermentation and medium composition were optimized through single factor and orthogonal experiment. RESULT: In total 77 endophytic strains have been isolated from healthy mulberry. SWg2 showed strong and stable antagonistic activity to mulberry bacterial blight. The morphological, cultural, physiological, and biochemical characteristics assays indicated that SWg2 belongs to Pantoea sp. The 16S rDNA sequence phylogenetic analysis reveals that SWg2 appeared a sister lineage to P. agglomerans. The optimized culture conditions of strain SWg2 were liquid volume 20 mL in 100 mL flask, 170 r/min at 28 degrees C, inoculation size of 4% for 5 d with a medium of 2.0% glycerol, 2.0% NH4NO3, 0.1% KH2PO4, 0.15% MgSO4 x 7H2O at initial pH of 7.5. CONCLUSION: The antagonistic endophytic strain SWg2 to mulberry bacterial blight was identified as P. agglomerans. SWg2 strain shows stronger antagonistic action to mulberry bacterial blight under optimized fermentation conditions.

Transplantation of co-microencapsulated hepatocytes and HUVECs for treatment of fulminant hepatic failure.

PURPOSE: Microencapsulated hepatocytes might solve immunological rejection, broadening a new perspective for the treatment of fulminant hepatic failure (FHF). However, the transplantation of microcapsulated hepatocytes is limited by low cell viability. Nevertheless, the co-microencapsulation of hepatocytes and human umbilical vein endothelial cells (HUVECs) may make the treatment of FHF more promising. METHODS: We prepared the microcapsules using the high-voltage electrostatic droplet spray method, transplanted the empty microcapsules, isolated hepatocytes, microcapsulated hepatocytes, and co-microencapsulated hepatocytes and HUVEC intraperitoneally into rat models of FHF induced by D-aminogalactose (D-gal). After 1, 3, and 7 days, and 2, 3, and 4 weeks posttransplantation, we calculated the mortality and assessed alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) levels in the serum of the model; evaluated the integrality and recovery of microcapsules; and stained with hematoxylin and eosin (H&E) the recovered microcapsules as well as the liver of the FHF rats. RESULTS: Hepatocyte-specific functions, including the levels of ALT, AST, and ALB in the serum of the co-microencapsulation group, were significantly better than those in the other groups (p<0.05) from 2 to 4 weeks after transplantation. Moreover, cotransplantation of the microencapsulated hepatocytes and HUVECs decreased the mortality rate of the FHF rats. The recovered microcapsules were intact, and recovery was up to 90%. H&E staining showed that the microencapsulated cells were still alive, and the liver tissues had started to recover after 4 weeks posttransplantation. CONCLUSION: The microcapsules have good biocompatibility and immunoprotection to protect the hepatocytes from immunological rejection. Cotransplantation of the microencapsulated hepatocytes and HUVECs could decrease mortality rates and improve liver function in FHF.

The reconstruction of lung alveolus-like structure in collagen-matrigel/microcapsules scaffolds in vitro.

This study attempted to use collagen-Matrigel as extracellular matrix (ECM) to supply cells with three-dimensional (3D) culture condition and employ alginate-poly-l-lysine-alginate (APA) microcapsules to control the formation of alveolus-like structure in vitro. We tested mice foetal pulmonary cells (FPCs) by immunohistochemistry after 2D culture. The alveolus-like structure was reconstructed by seeding FPCs in collagen-Matrigel mixed with APA microcapsules 1.5 ml. A self-made mould was used to keep the structure from contraction. Meanwhile, it provided static stretch to the structure. After 7, 14 and 21 days of culture, the alveolus-like structure was analysed histologically and immunohistochemically, or by scanning transmission electron microscopy (TEM). We also observed these structures under inverted phase contrast microscope. The expression of pro-surfactant protein C (SpC) was detected by reverse transcription-polymerase chain reaction (RT-PCR). We obtained fibroblasts, epithelial cells and alveolar type II (AE2) cells in FPCs. In the reconstructed structure, seeding cells surrounding the APA microcapsules constructed alveolus-like structures, the size of them ranges from 200 to 300 µm. In each reconstructed lung tissue sheet, microcapsules had integrity. Pan-cytokeratin, vimentin and SpC positive cells were observed in 7- and 14-day cultured structures. TEM showed lamellar bodies of AE2 cells in the reconstructed tissues whereas RT-PCR expressed SpC gene. Primary mice FPCs could form alveolus-like structures in collagen-Matrigel/APA microcapsules engineered scaffolds, which could maintain a differentiated state of AE2 cells.

Transplantation of sertoli-islet cell aggregates formed by microgravity: prolonged survival in diabetic rats.

Transplantation of pancreatic islets is a potentially attractive treatment for type I diabetes. We generated the transplantable, tissue-like aggregates composed of Sertoli cells and islets in rotating wall vessel bioreactors, SICA (Sertoli-islet cell aggregates), to improve their biological function in vitro and in vivo. The isolated islet equivalent and Sertoli cells were purified from Wistar rats and cocultured for 5 days in bioreactor to generate SICA. The SICA, islets aggregates, and fresh isolated islets were transplanted under the kidney capsule of diabetic Sprague-Dawley (SD) rats, respectively. The functions of different grafts were ascertained by blood glucose level measurements and an in vivo glucose tolerance test. In response to elevated glucose, insulin secretion from SICA was 1.4-fold higher (P<0.05, n=5) than islet aggregates cultured alone. Of the rats that received SICA, 90% (9/10) remained normoglycemic at 60 days post-transplantation, and the survival significantly increased compared with recipients bearing homotypic islets aggregates or freshly isolated islets. The former responded similarly with healthy rats to the glucose tolerance test. Our results support the usefulness of SICA for the treatment of type 1 diabetes without any immunosuppressive agents.