Two Birds with One Stone: V4 C3 MXene Synergistically Promoted VS2 Cathode and Zinc Anode for High-Performance Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) are considered to be a rising star in the large-scale energy storage area because of their low cost and environmental friendliness properties. However, the limited electrochemical performance of the cathode and severe zinc dendrite of the anode severely hinder the practical application of AZIBs. Herein, a novel 3D interconnected VS2 ⊥V4 C3 Tx heterostructure material is prepared via one-step solvothermal method. Morphological and structural characterizations show that VS2 nanosheets are uniformly and dispersedly distributed on the surface of the V4 C3 MXene substrate, which can effectively suppress volume change of the VS2 . Owing to the open heterostructure along with the high conductivity of V4 C3 MXene, the VS2 ⊥V4 C3 Tx cathode shows a high specific capacity of 273.9 mAh g-1 at 1 A g-1 and an excellent rate capability of 143.2 mAh g-1 at 20 A g-1 . The V4 C3 MXene can also effectively suppress zinc dendrite growth when used as protective layer for the Zn anode, making the V4 C3 Tx @Zn symmetric cell with a stable voltage profile for ≈1700 h. Benefitting from the synergistic modification effect of V4 C3 MXene on both the cathode and anode, the VS2 ⊥V4 C3 Tx ||V4 C3 Tx @Zn battery exhibits a long cycling lifespan of 5000 cycles with a capacity of 157.1 mAh g-1 at 5A g-1 .

Amino Group-Aided Efficient Regeneration Targeting Structural Defects and Inactive FePO4 Phase for Degraded LiFePO4 Cathodes.

It is urgent to develop efficient recycling methods for spent LiFePO4 cathodes to cope with the upcoming peak of power battery retirement. Compared with the traditional metallurgical recovery methods that lack satisfactory economic and environmental benefits, the direct regeneration seems to be a promising option at present. However, a simple direct lithium replenishment cannot effectively repair and regenerate the cathodes due to the serious structural damage of the spent LiFePO4. Herein, the spent LiFePO4 cathodes are directly regenerated by a thiourea-assisted solid-phase sintering process. The density functional theory calculation indicates that thiourea has a targeted repair effect on the antisite defects and inactive FePO4 phase in the spent cathode due to the associative priority of amino group (─NH2) in thiourea with Fe ions: Fe3+─N > Fe2+─N. Meanwhile, the pyrolysis products of thiourea can also create an optimal reducing atmosphere and inhibit the agglomeration of particles in the high temperature restoration process. The regenerated LiFePO4 exhibits an excellent electrochemical performance, which is comparable to that of commercial LiFePO4. This targeted restoration has improved the efficiency of direct regeneration, which is expected to achieve large-scale recycling of spent LiFePO4.

Ca/Li Synergetic-Doped Na0.67Ni0.33Mn0.67O2 to Realize P2-O2 Phase Transition Suppression for High-Performance Sodium-Ion Batteries.

P2-type layered transition metal oxide Na0.67Ni0.33Mn0.67O2 is considered as a promising cathode for advanced sodium-ion batteries due to its high theoretical specific capacity. However, the P2-type cathode suffers severe P2-O2 phase transition during cycling process, resulting unsatisfactory cyclic stability and rate capability. Herein, a Ca/Li co-doped P2-type Na0.62Ca0.05Ni0.33Mn0.57Li0.10O2 (NCNMLO) cathode material was synthesized through a simple sol-gel method. With the synergistic effect of Ca-doping at Na sites and Li substitution at transition metal (TM) sites, the cathode achieves an excellent electrochemical performance due to the inhibited P2-O2 phase transition and improved ion diffusion with Na+/vacancy disordering arrangement. The NCNMLO cathode exhibits a good cyclic stability with 70.8% of capacity retention at 1 C after 200 cycles and excellent rate capability with 40.1 mAh g-1 at 20 C. The dual sites doping strategy provides an effective and simple approach for designing high-performance layered oxide cathode materials for sodium-ion batteries.

The crucial role of transient tri-coordinated oxygen in the flow of silicate melts.

The transport properties of high-temperature silicate melts control magma flow and are crucial for a wide variety of industrial processes involving minerals. However, anomalous melt properties have been observed that cannot be explained by the traditional polymerization degree theory, which was derived based on quenched melts. Ab initio molecular dynamics (AIMD) simulations were conducted to investigate the flow mechanism of CaO-Al2O3-SiO2 melts under high temperature atmospheric conditions. By analyzing the dynamic structure of melted silicates and employing molecular orbital theory, we gained a fundamental understanding of the flow mechanism from a chemistry perspective. Transient tri-coordinated oxygen (TO) bonded with one Si and two Al atoms (SiOAl2) was found to be a pivotal intermediate in melt flow and atomic diffusion processes. Frequent chemical transition between TO in SiOAl2 and bridging oxygen (BO) dominated the fluidity of melted silicates. The presence of such transitions is facilitated by the unstable nature of [SiAlO2] 4-membered rings, which are susceptible to instability due to the intense repulsion between the O 2p lone pairs and the excessively bent O-Al-O angle. Additionally, the density of SiOAl2 type TO motif could serve as an indicator to determine the relationship between structure and fluidity. Our results challenge the traditional polymerization degree theory and suggest the need to reassess high-temperature liquid properties that govern processes in the Earth and industry by monitoring transient motifs.

Rational design of anthocyanidins-directed near-infrared two-photon fluorescent probes.

Recently, two-photon fluorescent probes based on anthocyanidin molecules have attracted extensive attention due to their outstanding photophysical properties. However, there are only a few two-photon excited fluorescent probes that really meet the requirements of relatively long emission wavelengths (>600 nm), large two-photon absorption (TPA) cross-sections (300 GM), significant Stokes shift (>80 nm), and high fluorescence intensity. Herein, the photophysical properties of a series of anthocyanidins with the same substituents but different fluorophore skeletons are investigated in detail. Compared with b-series molecules, a-series molecules with a six-membered ring in the backbone have a slightly higher reorganization energy. This results in more energy loss upon light excitation, enabling the reaction products to detect NTR through a larger Stokes shift. More importantly, there is very little decrease in fluorescence intensity as the Stokes shift increases. These features are extremely valuable for high-resolution NTR detection. In light of this, novel 2a-n (n = 1-5) compounds are designed, which are accomplished by inhibiting the twisted intramolecular charge transfer (TICT) effect through alkyl cyclization, azetidine ring and extending π conjugation. Among them, 2a-3 gains a long emission spectrum (λem = 691.4 nm), noticeable TPA cross-section (957 GM), and large Stokes shift (110 nm), indicating that it serves as a promising candidate for two-photon fluorescent dyes. It is hoped that this work will offer some insightful theoretical direction for the development of novel high performance anthocyanin fluorescent materials.

FBXO22 inhibits proliferation and metastasis of cervical cancer cells by mediating ubiquitination-dependent degradation of GAK.

Cervical cancer is one of the recognized malignant tumors of female reproductive system. At present, the research and development of biomarkers has attracted increasing attention, and the wide application of clinical cervical cancer screening strategies has significantly reduced its morbidity and mortality. A member of the F-box protein family, FBXO22, is involved in cell cycle, DNA damage repair and many other processes. Dysregulation of FBXO22 plays an important role in the occurrence and development of various tumors, including ovarian cancer, liver cancer and lung cancer. Nevertheless, the effect of FBXO22 in cervical cancer needs further investigation. We found that FBXO22 inhibited cervical cancer cell proliferation, migration and invasion. The results of proteomics studies suggested FBXO22 appears to target the Cyclin G Associated Kinase (GAK) for degradation. The combined results of analysis of cultured cells with altered abundance of FBXO22 by depletion or over-expression in the presence or absence of proteasomal inhibitor, comparison of protein decay rate, as well as cellular ubiquitination, support a hypothesis that FBXO22 mediates the ubiquitin-dependent degradation of GAK. Taken together, our data suggest that FBXO22 has a protective role in cervical cancer.

Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study.

OBJECTIVES: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. RESULTS: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). CONCLUSIONS: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.

Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.

Improvement of SAW Resonator Performance by Petal-like Topological Insulator.

This article introduces a novel petal-like SAW topology insulator, which can transmit sound waves with low loss and high flexibility in an ultra-wide frequency band by simultaneously adjusting multiple structural parameters of phononic crystals. Using finite element analysis, it was found that adjusting these parameters can generate a broadband gap of 55.8-65.7 MHz. This structure can also achieve defect immunity and sharp bending in waveguide transmission. When this topology insulator is applied to resonators, compared to traditional designs, the insertion loss is reduced by 22 dB, the on-load quality factor is increased by 227%, the off-load quality factor is increased by 1024.5%, and the quality sensitivity is improved by 3.7 times compared to bare devices.

Adaptive Sensing Data Augmentation for Drones Using Attention-Based GAN.

Drones have become essential tools across various industries due to their ability to provide real-time data and perform automated tasks. However, integrating multiple sensors on a single drone poses challenges such as payload limitations and data management issues. This paper proposes a comprehensive system that leverages advanced deep learning techniques, specifically an attention-based generative adversarial network (GAN), to address data scarcity in drone-collected time-series sensor data. By adjusting sensing frequency based on operational conditions while maintaining data resolution, our system ensures consistent and high-quality data collection. The spatiotemporal The attention mechanism within the GAN enhances the generation of synthetic data, filling gaps caused by reduced sensing frequency with realistic data. This approach improves the efficiency and performance of various applications, such as precision agriculture, environmental monitoring, and surveillance. The experimental results demonstrated the effectiveness of our methodology in extending the operational range and duration of drones and providing reliable augmented data utilizing a variety of evaluation metrics. Furthermore, the superior performance of the proposed system was verified by comparing it with various comparative GAN models.

Misdiagnosis of ß-Thalassemia Major Due to Chinese Gγ+(Aγδß)0-Thalassemia Combined with ß0-Thalassemia.

δß-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese Gγ(Aγδß)0-thalassemia, Yunnanese Gγ(Aγδß)0-thalassemia, Cantonese Gγ(Aγδß)0-thalassemia in China. Due to the low rate of δß-thalassemia carriers, there are few reports of δß-thalassemia combined with ß-thalassemia causing ß-thalassemia major. Herein, we described the combination of Chinese Gγ(Aγδß)0-thalassemia and ß-thalassemia leading to ß-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with ßCD17M/ßCD17M using routine genetic analysis. However, her father was heterozygous for CD17 in ß-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese Gγ(Aγδß)0-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from ßCD17M/ßCD17M to ßCD17M/ßGγ(Aγδß)0. This is the first report of Chinese Gγ(Aγδß)0-thalassemia combined with ß-thalassemia resulting in ß-thalassemia major in China. Screening for δß-thalassemia by Hb analysis could be an effective method.

Immobilization mechanism of heavy metals by crystals and liquid phase during melting treatment of MSWI fly ash.

Melting treatment has emerged as a promising technology for managing municipal solid waste incineration (MSWI) fly ash owing to its advantageous features of effective detoxification and volume reduction. The melting treatment of MSWI fly ash involves the immobilization of heavy metals by crystals and liquid phase. Herein, the immobilization mechanism of heavy metals (Cu, Pb and Cd) by the crystals and the liquid phase was investigated using melting experiments, thermodynamic calculations and density functional theory (DFT) calculations. Results demonstrate that the immobilization of heavy metals is influenced by a combination of factors: the reaction of heavy metals, physical encapsulation ability of the liquid phase and chemical fixation ability of both the crystals and the liquid phase. An increase in the content of SiO2 and Al2O3 promotes the conversion of heavy metals oxides into heavy metals chlorides. Furthermore, an increase in the content and polymerization degree of the liquid phase facilitates the physical encapsulation of heavy metals chlorides. The chemical fixation ability of the crystals and the liquid phase differs for Cu and Pb, while Cd cannot be immobilized through chemical fixation. To enhance the immobilization of heavy metals during melting treatment, the chemical composition of MSWI fly ash should be adjusted within the anorthite region of the ternary phase diagram. This study provides valuable insights into the immobilization mechanism of heavy metals by the crystals and the liquid phase during the melting treatment of MSWI fly ash.

Modular Access to meta-Substituted Benzenes via Mo-Catalyzed Intermolecular Deoxygenative Benzene Formation.

The substituted benzene derivatives are essential to organic synthesis, medicinal chemistry, and material science. However, the 1,3-di- and 1,3,5-trisubstituted benzenes are far less prevalent in small-molecule drugs than other substitution patterns, likely due to the lack of robust, efficient, and convenient synthetic methods. Here, we report a Mo-catalyzed intermolecular deoxygenative benzene-forming reaction of readily available ynones and allylic amines. A wide range of unsymmetric and unfunctionalized 1,3-di- and 1,3,5-trisubstituted benzenes were obtained in up to 88% yield by using a commercially available molybdenum catalyst. The synthetic potential of the method was further illustrated by synthetic transformations, a scale-up synthesis, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this benzene-forming process might proceed through a Mo-catalyzed aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization cascade. This strategy not only provided a facile, robust, and modular approach to various meta-substituted benzene derivatives but also demonstrated the potential of molybdenum catalysis in the challenging intermolecular deoxygenative cross-coupling reactions.

Catalytic Asymmetric Deoxygenative Cyclopropanation Reactions by a Chiral Salen-Mo Catalyst.

The catalytic asymmetric cyclopropanation reaction of alkenes with diazo compounds is a direct and powerful method to construct chiral cyclopropanes that are essential to drug discovery. However, diazo compounds are potentially explosive and often require hazardous reagents for their preparation. Here, we report on the use of 1,2-dicarbonyl compounds as safe and readily available surrogates for diazo compounds in the direct catalytic asymmetric deoxygenative cyclopropanation reaction. Enabled by a class of simple and readily accessible chiral salen-Mo catalysts, the reaction proceeded with generally good enantioselectivities and yields toward a wide range of substrates (80 examples). Preliminary mechanistic studies suggested that the proposed µ-oxo bridged dinuclear Mo(III)-species was the catalytically active species. This strategy not only provides a promising route for the synthesis of chiral cyclopropanes but also opens a new window for the potential applications of chiral salen-Mo complexes in asymmetric catalysis.

Regulation of Sulfur Atoms in MoSx by Magneto-Electrodeposition for Hydrogen Evolution Reaction.

Compared with crystalline molybdenum sulfide (MoS2 ) employed as an efficient hydrogen evolution reaction (HER) catalyst, amorphous MoSx exhibits better activity. To synthesize amorphous MoSx , electrodeposition serving as a convenient and time-saving method is successfully applied. However, the loading mass is hindered by limited mass transfer efficiency and the available active sites require further improvement. Herein, magneto-electrodeposition is developed to synthesize MoSx with magnetic fields up to 9 T to investigate the effects of a magnetic field in the electrodeposition processing, as well as the induced electrochemical performance. Owing to the magneto-hydrodynamic effect, the loading mass of MoSx is obviously increased, and the terminal S2- serving as the active site is enhanced. The optimized MoSx catalyst delivers outstanding HER performance, achieving an overpotential of 50 mV at a current density of 10 mA cm-2 and the corresponding Tafel slope of 59 mV dec-1 . The introduction of a magnetic field during the electrodeposition process will provide a novel route to prepare amorphous MoSx with improved electrochemical performance.

Carbon Foam-Supported VS2 Cathode for High-Performance Flexible Self-Healing Quasi-Solid-State Zinc-Ion Batteries.

As the new generation of energy storage systems, the flexible battery can effectively broaden the application area and scope of energy storage devices. Flexibility and energy density are the two core evaluation parameters for the flexible battery. In this work, a flexible VS2 material (VS2 @CF) is fabricated by growing the VS2 nanosheet arrays on carbon foam (CF) using a simple hydrothermal method. Benefiting from the high electric conductivity and 3D foam structure, VS2 @CF shows an excellent rate capability (172.8 mAh g-1 at 5 A g-1 ) and cycling performance (130.2 mAh g-1 at 1 A g-1 after 1000 cycles) when it served as cathode material for aqueous zinc-ion batteries. More importantly, the quasi-solid-state battery VS2 @CF//Zn@CF assembled by the VS2 @CF cathode, CF-supported Zn anode, and a self-healing gel electrolyte also exhibits excellent rate capability (261.5 and 149.8 mAh g-1 at 0.2 and 5 A g-1 , respectively) and cycle performance with a capacity of 126.6 mAh g-1 after 100 cycles at 1 A g-1 . Moreover, the VS2 @CF//Zn@CF full cell also shows good flexible and self-healing properties, which can be charged and discharged normally under different bending angles and after being destroyed and then self-healing.

GSK3326595 is a promising drug to prevent SARS-CoV-2 Omicron and other variants infection by inhibiting ACE2-R671 di-methylation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 epidemic is worsening. Binding of the Spike1 protein of SARS-CoV-2 with the angiotensin-converting enzyme 2 (ACE2) receptor mediates entry of the virus into host cells. Many reports show that protein arginine methylation by protein arginine methyltransferases (PRMTs) is important for the functions of these proteins, but it remains unclear whether ACE2 is methylated by PRMTs. Here, we show that PRMT5 catalyses ACE2 symmetric dimethylation at residue R671 (meR671-ACE2). We indicate that PRMT5-mediated meR671-ACE2 promotes SARS-CoV-2 receptor-binding domain (RBD) binding with ACE2 probably by enhancing ACE2 N-glycosylation modification. We also reveal that the PRMT5-specific inhibitor GSK3326595 is able to dramatically reduce ACE2 binding with RBD. Moreover, we discovered that meR671-ACE2 plays an important role in ACE2 binding with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants; and we found that GSK3326595 strongly attenuates ACE2 interaction with Spike1 of the SARS-CoV-2 Omicron, Delta, and Beta variants. Finally, SARS-CoV-2 pseudovirus infection assays uncovered that PRMT5-mediated meR671-ACE2 is essential for SARS-CoV-2 infection in human cells, and pseudovirus infection experiments confirmed that GSK3326595 can strongly suppress SARS-CoV-2 infection of host cells. Our findings suggest that as a clinical phase II drug for several kinds of cancers, GSK3326595 is a promising candidate to decrease SARS-CoV-2 infection by inhibiting ACE2 methylation and ACE2-Spike1 interaction.

B2(OH)4-Mediated Reductive Transamidation of N-Acyl Benzotriazoles with Nitro Compounds En Route to Aqueous Amide Synthesis.

We herein developed a reductive transamidation reaction between N-acyl benzotriazoles (AcBt) and organic nitro compounds or NaNO2 under mild conditions. This protocol employed the stable and readily available B2(OH)4 as the reducing agent and H2O as the ideal solvent. N-Deuterated amides can be synthesized when conducting the reaction in D2O. A reasonable reaction mechanism involving bond metathesis between the AcBt amide and amino boric acid intermediate was proposed to explain the unique nature of AcBt.

GPC3-IL7-CCL19-CAR-T primes immune microenvironment reconstitution for hepatocellular carcinoma therapy.

BACKGROUND: Chimeric antigen receptor (CAR)-T-cell therapy is a revolutionary treatment that has become a mainstay of advanced cancer treatment. Conventional glypican-3 (GPC3)-CAR-T cells have not produced ideal clinical outcomes in advanced hepatocellular carcinoma (HCC), and the mechanism is unclear. This study aims to investigate the clinical utility of novel GPC3-7-19-CAR-T cells constructed by our team and to explore the mechanisms underlying their antitumor effects. METHODS: We engineered a novel GPC3-targeting CAR including an anti-GPC3 scFv, CD3ζ, CD28 and 4-1BB that induces co-expression of IL-7 at a moderate level (500 pg/mL) and CCL19 at a high level (15000 pg /mL) and transduced it into human T cells. In vitro, cell killing efficacy was validated by the xCELLigence RTCA system, LDH nonradioactive cytotoxicity assay and was confirmed in primary HCC organoid models employing a 3D microfluid chip. In vivo, the antitumor capacity was assessed in a humanized NSG mouse xenograft model. Finally, we initiated a phase I clinical trial to evaluate the safety and effect of GPC3-7-19-CAR-T cells in the clinic. RESULTS: GPC3-7-19-CAR-T cells had 1.5-2 times higher killing efficiency than GPC3-CAR-T cells. The tumor formation rates in GPC3-7-19-CAR-T cells treated model were reduced (3/5vs.5/5), and the average tumor volumes were 0.74 cm3 ± 1.17 vs. 0.34 cm3 ± 0.25. Of note, increased proportion of CD4+ TEM and CD8+ TCM cells was infiltrated in GPC3-7-19-CAR-T cells group. GPC3-7-19-CAR-T cells obviously reversed the immunosuppressive tumor microenvironment (TME) by reducing polymorphonuclear (PMN)-myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells infiltration and recruiting more dendritic cells (DCs) to HCC xenograft tumor tissues. In one patient with advanced HCC, GPC3-7-19-CAR-T-cell treatment resulted in tumor reduction 56 days after intravenous infusion. CONCLUSIONS: In conclusion, GPC3-7-19-CAR-T cells achieved antitumor effects superior to those of conventional GPC3-CAR-T cells by reconstructing the TME induced by the dominant CD4+ TEM and CD8+ TCM cell subsets. Most importantly, GPC3-7-19-CAR-T cells exhibited good safety and antitumor efficacy in HCC patients in the clinic. ► Novel GPC3-7-19-CAR-T cells designed with mediate level of IL-7 secretion and high level of CCL19 secretion, which could recruit more mature DCs to assist killing on GPC3+HCCs. ►DC cells recruited by CCL19 could interact with CD4+ T cells and promote the differentiation of CD4+TEFF cells into CD4+TEM and CD8+TCM subsets, leading a better anti-tumor effect on GPC3+HCCs. ►Compared with conventional GPC3-CAR-T, GPC3-7-CCL19-CAR-T cells could reverse tumor immunosuppressive microenvironment by reducing PMN-MDSC and Treg cell infiltration.

Real-world evidence for the use of subcutaneous implantable cardioverter-defibrillators in China: A single-center experience.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have been shown to be non-inferior to transvenous ICDs in the prevention of sudden cardiac death (SCD), but there is still a lack of evidence from clinical trials in China. We investigated whether S­ICD implantation in the Chinese population is safe and feasible and should be promoted in the future. METHODS: Consecutive patients undergoing S­ICD implantation at our center were enrolled in this retrospective study. Data were collected within the median follow-up period of 554 days. Data concerning patient selection, implantation procedures, complications, and episodes of shock were analyzed. RESULTS: In total, 70.2% of all 47 patients (median age = 39 years) were included for secondary prevention of SCD with different etiologies. Vector screening showed that 98% of patients were with > 1 appropriate vector in all postures. An intraoperative defibrillation test was not performed on six patients because of the high risk of disease deterioration, while all episodes of ventricular fibrillation induced post implantation were terminated by one shock. As expected, no severe complications (e.g., infection and device-related complications) were observed, except for one case of delayed healing of the incision. Overall, 15 patients (31.9%) experienced appropriate shocks (AS) with all episodes terminated by one shock. Two patients (4.3%) experienced inappropriate shocks (IAS) due to noise oversensing, resulting in a high Kaplan-Meier IAS-free rate of 95.7%. CONCLUSION: Based on appropriate patient selection and standardized implantation procedures, this real-world study confirmed the safety and efficacy of S­ICD in Chinese patients, indicating that it may help to promote the prevention of SCD in China.