METTL14 regulates CD8+T-cell activation and immune responses to anti-PD-1 therapy in lung cancer.

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.

Balancing Polarization and Breakdown for High Capacitive Energy Storage by Microstructure Design.

The compromise of contradictive parameters, polarization, and breakdown strength, is necessary to achieve a high energy storage performance. The two can be tuned, regardless of material types, by controlling microstructures: amorphous states possess higher breakdown strength, while crystalline states have larger polarization. However, how to achieve a balance of amorphous and crystalline phases requires systematic and quantitative investigations. Herein, the trade-off between polarization and breakdown field is comprehensively evaluated with the evolution of microstructure, i.e., grain size and crystallinity, by phase-field simulations. The results indicate small grain size (≈10-35 nm) with moderate crystallinity (≈60-80%) is more beneficial to maintain relatively high polarization and breakdown field simultaneously, consequently contributing to a high overall energy storage performance. Experimentally, therefore an ultrahigh energy density of 131 J cm-3 is achieved with a high efficiency of 81.6% in the microcrystal-amorphous dual-phase Bi3NdTi4O12 films. This work provides a guidance to substantially enhance dielectric energy storage by a simple and effective microstructure design.

miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39.

Exosomes are emerging mediators of cell-cell communication, which are secreted from cells and may be delivered into recipient cells in cell biological processes. Here, we examined microRNA (miRNA) expression in esophageal squamous cell carcinoma (ESCC) cells. We performed miRNA sequencing in exosomes and cells of KYSE150 and KYSE450 cell lines. Among these differentially expressed miRNAs, 20 of the miRNAs were detected in cells and exosomes. A heat map indicated that the level of miR-451a was higher in exosomes than in ESCC cells. Furthermore, miRNA pull-down assays and combined exosomes proteomic data showed that miR-451a interacts with YWHAE. Over-expression of YWHAE leads to miR-451a accumulation in the exosomes instead of the donor cells. We found that miR-451a was sorted into exosomes. However, the biological function of miR-451a remains unclear in ESCC. Here, Dual-luciferase reporter assay was conducted and it was proved that CAB39 is a target gene of miR-451a. Moreover, CAB39 is related to TGF-ß1 from RNA-sequencing data of 155 paired of ESCC tissues and the matched tissues. Western Blot and qPCR revealed that CAB39 and TGF-ß1 were positively correlated in ESCC. Over-expression of CAB39 were cocultured with PBMCs from the blood from healthy donors. Flow cytometry assays showed that apoptotic cells were significantly reduced after CAB39 over-expression and significantly increased after treated with TGF-ß1 inhibitors. Thus, our data indicate that CAB39 weakens antitumor immunity through TGF-ß1 in ESCC. In summary, YWHAE selectively sorted miR-451a into exosomes and it can weaken antitumor immunity promotes tumor progression through CAB39.

Dry-processed technology for flexible and high-performance FeS2-based all-solid-state lithium batteries at low stack pressure.

All-solid-state lithium batteries (ASSLBs) are considered promising energy storage systems due to their high energy density and inherent safety. However, scalable fabrication of ASSLBs based on transition metal sulfide cathodes through the conventional powder cold-pressing method with ultrahigh stacking pressure remains challenging. This article elucidates a dry process methodology for preparing flexible and high-performance FeS2-based ASSLBs under low stack pressure by utilizing polytetrafluoroethylene (PTFE) binder. In this design, fibrous PTFE interweaves Li6PS5Cl particles and FeS2 cathode components, forming flexible electrolyte and composite cathode membranes. Beneficial to the robust adhesion, the composite cathode and Li6PS5Cl membranes are tightly compacted under a low stacking pressure of 100 MPa which is a fifth of the conventional pressure. Moreover, the electrode/electrolyte interface can sustain adequate contact throughout electrochemical cycling. As expected, the FeS2-based ASSLBs exhibit outstanding rate performance and cyclic stability, contributing a reversible discharged capacity of 370.7 mAh g-1 at 0.3C after 200 cycles. More importantly, the meticulous dQ/dV analysis reveals that the three-dimensional PTFE binder effectively binds the discharge products with sluggish kinetics (Li2S and Fe) to the ion-electron conductive network in the composite cathode, thereby preventing the electrochemical inactivation of products and enhancing electrochemical performance. Furthermore, FeS2-based pouch-type cells are fabricated, demonstrating the potential of PTFE-based dry-process technology to scale up ASSLBs from laboratory-scale mold cells to factory-scale pouch cells. This feasible dry-processed technology provides valuable insights to advance the practical applications of ASSLBs.

Long-term postoperative outcomes of spinal cellular schwannoma: study of 93 consecutive cases.

BACKGROUND CONTEXT: Cellular schwannoma (CS) is a rare tumor that accounts for 2.8%-5.2% of all benign schwannomas. There is a dearth of up-to-date information on spinal CS in the literature. PURPOSE: The aims of this study were to identify the proportion of CS cases amongst spinal benign schwannoma, describe the clinical features of spinal CS, and identify prognostic factors for local recurrence by analyzing data from 93 consecutive CS cases. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: We analyzed 93 PSGCT screened from 1,706 patients with spine CS who were treated at our institute between 2008 and 2021. OUTCOME MEASURES: Demographic, radiographic, operative and postoperative data were recorded and analyzed. METHODS: We compared the clinical features of spinal CS from the cervical, thoracic, lumbar and sacral segments. Prognostic factors for local recurrence-free survival (RFS) were identified by the Kaplan-Meier method. Factors with p≤.05 in univariate analysis were subjected to multivariate analysis by Cox regression analysis. RESULTS: The proportion of spinal CS in all benign schwannomas was 6.7%. The mean and median follow-up times for the 93 patients in this study were 92.2 and 91.0 months respectively (range 36-182 months). Local recurrence was detected in 11 cases, giving an overall recurrence rate of 11.7%, with one patient death. Statistical analysis revealed that tumor size ≥5 cm, intralesional resection, and Ki-67 ≥5% were independent negative prognostic factors for RFS in spinal CS. CONCLUSIONS: Whenever possible, en bloc resection is recommended for spinal CS. Long-term follow-up should be carried out for patients with tumor size ≥5 cm and postoperative pathological Ki-67 ≥5%.

PASS-ALL study of paediatric-inspired versus adult chemotherapy regimens on survival of high-risk Philadelphia-negative B-cell acute lymphoblastic leukaemia with allogeneic haematopoietic stem cell transplantation.

This PASS-ALL study was designed to explore the effect of paediatric-inspired versus adult chemotherapy regimens on survival of adolescents and young adults (AYA) with high-risk Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia (HR PH-ve B-cell ALL) eligible for allogeneic haematopoietic stem cell transplantation (allo-HSCT). The PASS-ALL study is a multicentre, observational cohort study, and 143 patients with HR B-cell PH-ve ALL were enrolled from five centres-77 patients allocated in the paediatric-inspired cohort and 66 in the adult cohort with comparable baseline characteristics. Of the 143 patients, 128 cases underwent allo-HSCT. Three-year leukaemia-free survival (LFS) in the paediatric-inspired cohort was 72.2% (95% CI 60.8%-83.6%) compared with 44.6% (95% CI 31.9%-57.3%; p = 0.001). Furthermore, time-to-positive minimal residual disease (TTP-MRD) post-HSCT was marked different, 3-year cumulative incidence of relapse was 25.9% (95% CI 15.8%-37.2%) in paediatric cohort and 45.4% (95% CI 40.0%-57.9%) in adult cohort (p = 0.026). Finally, the 3-year OS rate was 75.3% (95% CI 64.9%-85.7%) for the paediatric-inspired cohort and 64.1% (95% CI 51.8%-76.4%) for the adult cohort (p = 0.074). On a multivariate analysis, paediatric-inspired regimen is a predictive factor for LFS (HR = 2.540, 95% CI 1.327-4.862, p = 0.005). Collectively, our data suggest that paediatric-inspired chemotherapy pre-HSCT results in deeper and durable MRD response reduces relapse post-HSCT and improves survival in HR B-cell PH-ve ALL patients with allo-HSCT.

Unraveling the multifaceted role of EpCAM in colorectal cancer: an integrated review of its function and interplay with non-coding RNAs.

The epithelial cell adhesion molecule (EpCAM) is a critical glycoprotein involved in cell cycle progression, proliferation, differentiation, migration, and immune evasion. Its role as a target for bispecific antibodies has shown promise in annihilating cancer cells. EpCAM's potential as a biomarker for tumor-initiating cells, characterized by self-renewal and tumorigenic capabilities, underscores its value in early cancer detection, immunotherapy, and targeted drug delivery. While EpCAM monotherapies have been met with limited success, bispecific antibodies targeting both EpCAM and other proteins have exhibited encouraging results in colorectal cancer (CRC) research. The integration of EpCAM-directed nanotechnology in drug delivery systems has emerged as a pivotal innovation in CRC treatment. Moreover, developing chimeric antigen receptor (CAR) T-cell and CAR natural killer (NK) cell therapies opens promising therapeutic avenues for EpCAM-positive CRC patients. Although preliminary, this review sets the stage for future advances. Additionally, this study advances our understanding of the role of non-coding RNAs in CRC, which may be pivotal in gene regulation and could provide insights into the molecular underpinning. The findings suggest that lncRNA, miRNA, and circRNA could serve as novel therapeutic targets or biomarkers, further enriching the landscape of CRC diagnostics and therapeutics.

Construction of Synchronous-Deposition K Metal Anodes Via Modulation of Ion/Electron Transport Kinetics for High-Rate and Low-Temperature K Metal Batteries.

The construction of conductive scaffolds is demonstrated to be an ideal strategy to alleviate the volume expansion and dendrite growth of K metal anodes. Nevertheless, the heterogeneous top-bottom deposition behavior caused by incompatible electronic/ionic conductivity of three-dimensional (3D) skeleton severely hinders its application. Here, a K2 Se/Cu conducting layer is fabricated on the Cu foam so as to enhance ionic transport and weaken electronic conductivity of the skeleton. Then, an excellent simultaneous deposition behavior of K metal inside the host is obtained for the first time via tuning fast ionic transport and low electronic conductivity. The simultaneous deposition mode can not only utilize the entire 3D structure to accommodate the volume expansion during K deposition but also avoid the formation of K dendrites at high current and ultra-low temperature. Consequently, the symmetric cells present a long cycle lifespan over 1000 h with a low deposition overpotential of 80 mV at 1 mA cm-2 . Furthermore, the full cell matching with the perylene-tetracarboxylic dianhydride (PTCDA) cathode presents an outstanding cycle lifespan over 600 cycles at 5 C at -20°C. The proposed simultaneous deposition strategy provides a new design direction for the construction of dendrite-free K metal anodes.

Facile and High-Efficiency Chemical Presodiation Strategy on the SnS2/rGO Composite Anode for Stable Sodium-Ion Batteries.

SnS2/reduced graphite oxide (rGO) composite materials show great potential as high-performance anode candidates in sodium-ion batteries (SIBs) owing to their high specific capacities and power densities. However, the repeated formation/decomposition of the solid electrolyte interface (SEI) layer around composite anodes usually consumes additional sodium cations, resulting in poor Coulombic efficiency and decreasing specific capacity upon cycling. Therefore, in order to compensate for the large irreversible sodium loss of the SnS2/rGO anode, this study has proposed a facile strategy by implementing organic solutions of sodium-biphenyl/tetrahydrofuran (Na-Bp/THF) and sodium-naphthylamine/dimethoxyethane (Na-Naph/DME) as chemical presodiation reagents. Particularly, the storage stability of Na-Bp/THF and Na-Naph/DME in ambient air accompanied by their presodiation behavior on the SnS2/rGO anode has been investigated, and both reagents exhibited desirable ambient air-tolerant storage stability with favorable sodium supplement effects even after 20 days of storage. More importantly, the initial Coulombic efficiency (ICE) of SnS2/rGO electrodes could be controllably increased by immersing in a presodiation reagent for different durations. Consequently, with a facile chemical presodiation strategy of immersion in Na-Bp/THF solution for only 3 min in ambient air, the presodiated SnS2/rGO anode has exhibited an outstanding electrochemical performance with a high ICE of 95.6% as well as an ultrahigh specific capacity of 879.2 mAh g-1 after 300 cycles (83.5% of its initial capacity), highly superior to the pristine SnS2/rGO anode. This efficient and scalable presodiation strategy provides a new avenue for the prevailing application of other anode candidates in high-energy SIBs.

In-situ cross-linked multifunctional polymer electrolyte buffer layers for high-performance garnet solid-state lithium metal batteries.

The garnet Li6.75La3Zr1.75Ta0.25O12 (LLZTO) is one of the most promising electrolytes for commercial application since of its high ionic conductivity and good stability to Li. Nevertheless, the poor electrolyte/electrode interface contact enlarges the interface impedance of all-solid-state battery (ASSB). Herein, a multifunctional polymer electrolyte (MPE) interface buffer layers are formed on both sides of LLZTO surface through an in-situ crosslinking strategy to improve the interface contact with electrodes, which can facilitate uniform Li+ deposition/exfoliation and inhibit the growth of lithium dendrites as evidenced by the reduced interface impedance (103.4 Ω cm2), the increased critical current density (CDD, 1.2 mA cm-2) and 950 h stable cycle of Li symmetric cells at 0.7 mA cm-2, 0.7 mA h cm-2. Besides, the MPE layer can reduce the magnitude of electric field at the interface and widen the electrochemical window (0∼5.2 V). The stable interface of the LLZTO@MPE/cathode enables the full cells matching with the LiFePO4 (LFP) and LiNi0.5Co0.2Mn0.3O2 (NCM523) cathodes to deliver superior electrochemical performances. Specifically, the Li/MPE@LLZTO@MPE/LFP delivers a capacity retention rate of 87% after 200 cycles at 1 C. When it's matched with the NCM523 cathode, a capacity retention rate of 98% is retained after 100 cycles at 1 C. This work provides an effective and simple way to build good-interface-contact and long-lifespan garnet solid-state lithium metal batteries (SSLMBs).

Potential markers of cancer stem-like cells in ESCC: a review of the current knowledge.

In patients with esophageal squamous cell carcinoma (ESCC), the incidence and mortality rate of ESCC in our country are also higher than those in the rest of the world. Despite advances in the treatment department method, patient survival rates have not obviously improved, which often leads to treatment obstruction and cancer repeat. ESCC has special cells called cancer stem-like cells (CSLCs) with self-renewal and differentiation ability, which reflect the development process and prognosis of cancer. In this review, we evaluated CSLCs, which are identified from the expression of cell surface markers in ESCC. By inciting EMTs to participate in tumor migration and invasion, stem cells promote tumor redifferentiation. Some factors can inhibit the migration and invasion of ESCC via the EMT-related pathway. We here summarize the research progress on the surface markers of CSLCs, EMT pathway, and the microenvironment in the process of tumor growth. Thus, these data may be more valuable for clinical applications.

Dynamics of minimal residual disease defines a novel risk-classification and the role of allo-HSCT in adult Ph-negative B-cell acute lymphoblastic leukemia.

The prognosis of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients is well established. However, the implementation of dynamic MRD for risk classification and decision-making for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains vague. In this study, we collected multiparameter flow cytometry (MFC)-MRD data of Ph-negative B-ALL patients (n = 134) from the Precision-Classification-Directed-Target-Total-Therapy-ALL-2016 (PDT-ALL-2016) cohort and stratified it into high-(HR), medium-(MR), and standard-risk (SR) groups. With a median of 3.65 years follow-up (95% CI: 3.037-4.263), 3-year OS rate was 51.8 ± 8.3% in HR, compared with MR 61.5 ± 10.8% (p = 0.472), and SR 73.3 ± 5.9% (p = 0.006). Multivariate analysis shows that integrated dynamic MRD is an independent factor for overall survival. Compared to pediatric-inspired chemotherapy, allo-HSCT significantly improves the survival of the HR cohort (p < 0.001), but not in MR and SR. Finally, our study suggests that integrated dynamic MRD defines a novel risk-classification criteria and highlights the benefits of allo-HSCT in adult patients with Ph-negative ALL.

High-entropy enhanced capacitive energy storage.

Electrostatic dielectric capacitors are essential components in advanced electronic and electrical power systems due to their ultrafast charging/discharging speed and high power density. A major challenge, however, is how to improve their energy densities to effectuate the next-generation applications that demand miniaturization and integration. Here, we report a high-entropy stabilized Bi2Ti2O7-based dielectric film that exhibits an energy density as high as 182 J cm-3 with an efficiency of 78% at an electric field of 6.35 MV cm-1. Our results reveal that regulating the atomic configurational entropy introduces favourable and stable microstructural features, including lattice distorted nano-crystalline grains and a disordered amorphous-like phase, which enhances the breakdown strength and reduces the polarization switching hysteresis, thus synergistically contributing to the energy storage performance. This high-entropy approach is expected to be widely applicable for the development of high-performance dielectrics.

Enhanced oil removal from oily sand by injecting micro-macrobubbles in swirl elution.

Environmental contamination by petroleum hydrocarbons was exacerbated by oil pipeline breaks, marine oil spills and discharges from industrial production. To further improve the removal performance of petroleum hydrocarbons in solid particles, the deoiling experiments of swirl elution with micro-macrobubbles on oily sands were carried out in this paper. Experiment results indicated that when particles fell from the center of the bubble, the collision efficiency was 99.3%. The instantaneous contact angle (ICA) between the macrobubbles and the oil layer was improved in the presence of microbubbles. Furthermore, the maximum ICA of bubbles attaching to the oil layer was found to occur at pH 9 in the system of oily sand mixtures ranging from pH 5 to pH 14. This finding indicated that the slightly alkaline solution was more advantageous for bubbles to attach to the oil layer than the highly alkaline solution. The optimum condition for the elution of oily sand in the mixture of pH 7-14 was pH 12, and the oil removal efficiency was 85.4% for 10 min. The oil removal efficiency of swirl elution (SE) with bubbles on oily sand at pH 12 for 10 min was superior to either SE without bubbles or air flotation (AF). The results show that the swirl elution with bubbles can effectively enhance the oil removal efficiency of oily sands and provide guidance for controlling the environmental petroleum hydrocarbon contamination and reducing the usage of surfactants.

One-pot synthesis and multifunctional surface modification of lithium-rich manganese-based cathode for enhanced structural stability and low-temperature performance.

High-energy-density lithium-rich Li1.2Ni0.13Co0.13Mn0.54O2 is regarded as one of the most promising cathode materials for lithium-ion batteries. However, its practical application is restricted by critical kinetics drawbacks and poor low-temperature electrochemical performances. In this research, Li1.2Ni0.13Co0.13Mn0.54O2 submicron particles coated by a Li7La3Zr2O12 (LLZO) layer and co-doped by La/Zr cations has been fabricated via a facile one-pot sol-gel technique and subsequent heat treatment. The coating LLZO layer with a few nanometers is able to build a rapid lithium-ion transport channel for adjacent particles and suppress severe side reactions between active material and the electrolyte. Moreover, large-radius La/Zr cations co-doping can broaden the diffusion paths of lithium ions, hinder the detrimental structural transformation, and improve the electrochemical structure stability of the cathode during repeated cycles. Owing to numerous merits from this multifunctional surface modification strategy, the modified Li1.2Ni0.13Co0.13Mn0.54O2 composite exhibits the significantly decreased interface impedance, enhanced Li+ diffusion kinetics and mitigated phase transformation, as well as excellent low-temperature electrochemical performance. It can contribute ultrahigh capacities of 173.8 mAh g-1 at -10 ℃ and 134.1 mAh g-1 at -20 ℃, respectively, displaying great application prospects of Li-rich cathode materials.

Phase-Field Simulations of Tunable Polar Topologies in Lead-Free Ferroelectric/Paraelectric Multilayers with Ultrahigh Energy-Storage Performance.

Dielectric capacitors are emerging energy-storage components that require both high energy-storage density and high efficiency. The conventional approach to energy-storage enhancement is polar nanodomain engineering via chemical modification. Here, a new approach of domain engineering is proposed by exploiting the tunable polar topologies that have been observed recently in ferroelectric/paraelectric multilayer films. Using phase-field simulations, it is demonstrated that vortex, spiral, and in-plane polar structures can be stabilized in BiFeO3 /SrTiO3 (BFO/STO) multilayers by tailoring the strain state and layer thickness. Various switching dynamics are realized in these polar topologies, resulting in relaxor-ferroelectric-, antiferroelectric-, and paraelectric-like polarization behaviors, respectively. Ultrahigh energy-storage densities above 170 J cm-3 and efficiencies above 95% are achievable in STO/BFO/STO trilayers. This strategy should be generally implementable in other multilayer dielectrics and offers a new avenue to enhancing energy storage by tuning the polar topology and thus the polarization characteristics.

Two new triterpenoid glycosides from leaves of Cyclocarya paliurus.

Two dammarane glycosides (1-2) were isolated from the leaves of Cyclocarya paliurus. The structures of new compounds were established by application of spectroscopic methods, including one-dimensional and two-dimensional NMR, HRESIMS, and chemical hydrolysis. When evaluated against seven human cancer cell lines, the two compounds exhibited selective cytotoxicity to MCF-7 cells.[Formula: see text].

Afatinib combined with anlotinib in the treatment of lung adenocarcinoma patient with novel HER2 mutation: a case report and review of the literature.

BACKGROUND: HER2 is a member of the ERBB family of receptor tyrosine kinases, and HER2 mutations occur in 1-4% of non-small cell lung cancer (NSCLC) as an oncogenic driver mutation. We found a rare mutation of HER2 p.Asp769Tyr in NSCLC. CASE PRESENTATION: We presented a case of a 68-year-old nonsmoking male patient with brain metastasis from lung adenocarcinoma harboring a rare mutation of HER2 p.Asp769Tyr. After multiple lines of treatment, he obtained a durable response (10 months) to afatinib and anlotinib. CONCLUSION: We reported for the first time that afatinib and anlotinib have successfully treated lung adenocarcinoma with HER2 p.Asp769Tyr mutation. This finding can provide an insight into the optimal treatment of lung adenocarcinoma patients with novel mutations. Additionally, we summarized the efficacy of targeted therapy for HER2 mutant lung cancer in this article.