TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair in back pain conditions.

Poor intervertebral disc (IVD) healing causes IVD degeneration (IVDD) and progression to herniation and back pain. This study identified distinct roles of TNFα-receptors (TNFRs) in contributing to poor healing in painful IVDD. We first isolated IVDD tissue of back pain subjects and determined the complex pro-inflammatory mixture contained many chemokines for recruiting inflammatory cells. Single-cell RNA-sequencing of human IVDD tissues revealed these pro- inflammatory cytokines were dominantly expressed by a small macrophage-population. Human annulus fibrosus (hAF) cells treated with IVDD-conditioned media (CM) underwent senescence with greatly reduced metabolic rates and limited inflammatory responses. TNFR1 inhibition partially restored hAF cell metabolism sufficiently to enable a robust chemokine and cytokine response to CM. We showed that the pro-reparative TNFR2 was very limited on hIVD cell membranes so that TNFR2 inhibition with blocking antibodies or activation using Atsttrin had no effect on hAF cells with CM challenge. However, TNFR2 was expressed in high levels on macrophages identified in scRNA-seq analyses, suggesting their role in repair responses. Results therefore point to therapeutic strategies for painful IVDD involving immunomodulation of TNFR1 signaling in IVD cells to enhance metabolism and enable a more robust inflammatory response including recruitment or delivery of TNFR2 expressing immune cells to enhance IVD repair. SUMMARY STATEMENT: TNFR1 signaling drives cells towards senesce and muted inflammatory response in painful intervertebral disc degeneration, while limited TNFR2 signaling may limit disc cell repair responses.

A novel signature constructed by mitochondrial function and cell death-related gene for the prediction of prognosis in bladder cancer.

Bladder urothelial carcinoma (BLCA) presents a persistent challenge in clinical management. Despite recent advancements demonstrating the BLCA efficacy of immune checkpoint inhibitors (ICI) in BLCA patients, there remains a critical need to identify and expand the subset of individuals who benefit from this treatment. Mitochondria, as pivotal regulators of various cell death pathways in eukaryotic cells, exert significant influence over tumor cell fate and survival. In this study, our objective was to investigate biomarkers centered around mitochondrial function and cell death mechanisms to facilitate prognostic prediction and guide therapeutic decision-making in BLCA. Utilizing ssGSEA and LASSO regression, we developed a prognostic signature termed mitochondrial function and cell death (mtPCD). Subsequently, we evaluated the associations between mtPCD score and diverse clinical outcomes, including prognosis, functional pathway enrichment, immune cell infiltration, immunotherapy response analysis and drug sensitivity, within high- and low-risk subgroups. Additionally, we employed single-cell level functional assays, RT-qPCR, and immunohistochemistry to validate the differential expression of genes comprising the mtPCD signature. The mtPCD signature comprises a panel of 10 highly influential genes, strongly correlated with survival outcomes in BLCA patients and exhibiting robust predictive capabilities. Importantly, individuals classified as high-risk according to mtPCD score displayed a subdued overall immune response, characterized by diminished immunotherapeutic efficacy. In summary, our findings highlight the development of a novel prognostic signature, which not only holds promise as a biomarker for BLCA prognosis but also offers insights into the immune landscape of BLCA. This paradigm may pave the way for personalized treatment strategies in BLCA management.

Tannic acid protects against colitis by regulating the IL17 - NFκB and microbiota - methylation pathways.

Tannic acid, a bioactive polyphenol found in various phytogenic foods and medicinal plants, has potential prevention effects on colitis, though more evidence and mechanistic studies are required to substantiate this. In this study, we investigated the effects of different doses from 0 to 3 mg/mL of tannic acid on mice, ultimately selecting a dose of 3 mg/mL for the anti-colitis trial based on growth and intestinal morphology assessments. Using the DSS-induced colitis model, we found that tannic acid may alleviate colitis by inhibiting the IL-17 - NF-κB p65 signaling pathway and modulating epigenetic pathways, particularly methylation modifications. Additionally, tannic acid altered the gut microbiota, increasing the abundances of Prevotella, Eubacterium_siraeum_group, and Enterorhabdus in the colon. Supplementation with Eubacterium siraeum via gavage also inhibited colitis, accompanied by increased folate and methylation regulators in the colon. These findings suggest that tannic acid may inhibit colitis through the suppression of the IL-17 - NF-κB pathway and the enhancement of microbiota-mediated methylation pathways.

Ultrahigh precision laser nanoprinting based on defect-compensated digital holography for fast-fabricating optical metalenses.

The 3D structured light field manipulated by a digital-micromirror-device (DMD)-based digital hologram has demonstrated its superiority in fast-fabricating stereo nanostructures. However, this technique intrinsically suffers from defects of light intensity in generating modulated focal spots, which prevents from achieving high-precision micro/nanodevices. In this Letter, we have demonstrated a compensation approach based on adapting spatial voxel density for fabricating optical metalenses with ultrahigh precision. The modulated focal spot experiences intensity fluctuations of up to 3% by changing the spatial position, leading to a 20% variation of the structural dimension in fabrication. By altering the voxel density to improve the uniformity of the laser cumulative exposure dosage over the fabrication region, we achieved an increased dimensional uniformity from 94.4% to 97.6% in fabricated pillars. This approach enables fast fabrication of metalenses capable of sub-diffraction focusing of 0.44λ/NA with the increased mainlobe-sidelobe ratio from 1:0.34 to 1:0.14. A 6 × 5 supercritical lens array is fabricated within 2 min, paving a way for the fast fabrication of large-scale photonic devices.

Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis.

OBJECTIVE: The aim of this study was to explore the pathogenesis of CLCN6-related disease and to assess whether its Cl-/H+-exchange activity is crucial for the biological role of ClC-6. METHODS: We performed whole-exome sequencing on a girl with development delay, intractable epilepsy, behavioral abnormities, retinal dysfunction, progressive brain atrophy, suggestive of neuronal ceroid lipofuscinoses (NCLs). We generated and analyzed the first knock-in mouse model of a patient variant (p.E200A) and compared it with a Clcn6-/- mouse model. Additional functional tests were performed with heterologous expression of mutant ClC-6. RESULTS: We identified a de novo heterozygous p.E200A variant in the proband. Expression of disease-causing ClC-6E200A or ClC-6Y553C mutants blocked autophagic flux and activated transcription factors EB (TFEB) and E3 (TFE3), leading to autophagic vesicle and cholesterol accumulation. Such alterations were absent with a transport-deficient ClC-6E267A mutant. Clcn6E200A/+ mice developed severe neurodegeneration with typical features of NCLs. Mutant ClC-6E200A, but not loss of ClC-6 in Clcn6-/- mice, increased lysosomal biogenesis by suppressing mTORC1-TFEB signaling, blocked autophagic flux through impairing lysosomal function, and increased apoptosis. Carbohydrate and lipid deposits accumulated in Clcn6E200A/+ brain, while only lipid storage was found in Clcn6-/- brain. Lysosome dysfunction, autophagy defects, and gliosis were early pathogenic events preceding neuron loss. INTERPRETATION: CLCN6 is a novel genetic cause of NCLs, highlighting the importance of considering CLCN6 mutations in the diagnostic workup for molecularly undefined forms of NCLs. Uncoupling of Cl- transport from H+ countertransport in the E200A mutant has a dominant effect on the autophagic/lysosomal pathway. ANN NEUROL 2024.

Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia.

BACKGROUND AND AIMS: Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. METHODS AND RESULTS: A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were -72.7% (3.9%) for PFS and -71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CLINICAL TRIAL REGISTRATION: CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

Deletion of the alr gene in Brucella suis S2 attenuates virulence by enhancing TLR4-NF-κB-NLRP3- mediated host inflammatory responses.

Brucella is an intracellular parasitic bacterium lacking typical virulence factors, and its pathogenicity primarily relies on replication within host cells. In this study, we observed a significant increase in spleen weight in mice immunized with a Brucella strain deleted of the gene for alanine racemase (Alr), the enzyme responsible for alanine racemization (Δalr). However, the bacterial load in the spleen markedly decreased in the mutant strain. Concurrently, the ratio of white pulp to red pulp in the spleen was increased, serum IgG levels were elevated, but no significant damage to other organs was observed. In addition, the inflammatory response was potentiated and the NF-κB-NLRP3 signaling pathway was activated in macrophages (RAW264.7 Cells and Bone Marrow-Derived Cells) infect ed with the Δalr mutant. Further investigation revealed that the Δalr mutant released substantial amounts of protein in a simulated intracellular environment which resulted in heightened inflammation and activation of the TLR4-NF-κB-NLRP3 pathway in macrophages. The consequent cytoplasmic exocytosis reduced intracellular Brucella survival. In summary, cytoplasmic exocytosis products resulting from infection with a Brucella strain deleted of the alr gene effectively activated the TLR4-NFκB-NLRP3 pathway, triggered a robust inflammatory response, and reduced bacterial survival within host cells. Moreover, the Δalr strain exhibits lower toxicity and stronger immunogenicity in mice.

Gastrodin Ameliorates Post-Stroke Depressive-Like Behaviors Through Cannabinoid-1 Receptor-Dependent PKA/RhoA Signaling Pathway.

Post-stroke depression (PSD) is a significant complication in stroke patients, increases long-term mortality, and exaggerates ischemia-induced brain injury. However, the underlying molecular mechanisms and effective therapeutic targets related to PSD have remained elusive. Here, we employed an animal behavioral model of PSD by combining the use of middle cerebral artery occlusion (MCAO) followed by spatial restraint stress to study the molecular underpinnings and potential therapies of PSD. Interestingly, we found that sub-chronic application of gastrodin (Gas), a traditional Chinese medicinal herb Gastrodia elata extraction, relieved depression-related behavioral deficits, increased the impaired expression of synaptic transmission-associated proteins, and restored the altered spine density in hippocampal CA1 of PSD animals. Furthermore, our results indicated that the anti-PSD effect of Gas was dependent on membrane cannabinoid-1 receptor (CB1R) expression. The contents of phosphorated protein kinase A (p-PKA) and phosphorated Ras homolog gene family member A (p(ser188)-RhoA) were decreased in the hippocampus of PSD-mice, which was reversed by Gas treatment, and CB1R depletion caused a diminished efficacy of Gas on p-PKA and p-RhoA expression. In addition, the anti-PSD effect of Gas was partially blocked by PKA inhibition or RhoA activation, indicating that the anti-PSD effect of Gas is associated with the CB1R-mediated PKA/RhoA signaling pathway. Together, our findings revealed that Gas treatment possesses protective effects against the post-stroke depressive-like state; the CB1R-involved PKA/RhoA signaling pathway is critical in mediating Gas's anti-PSD potency, suggesting that Gas application may be beneficial in the prevention and adjunctive treatment of PSD.

Divergent landscapes of A-to-I editing in postmortem and living human brain.

Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.

MOF-derived low Ru-loaded high entropy alloy as an efficient and durable self-supporting electrode in rechargeable liquid/flexible Zn-air batteries.

Exploiting the high-entropy alloy (HEA) electrocatalysts with the synergistic effect of multi-metal components is an effective approach to address the slow kinetics and undesirable stability of the oxygen evolution reaction (OER) in Zn-air batteries (ZABs), but still faces many challenges. In this study, a multimetallic Metal-organic framework (MOF)-derived HEA catalyst was successfully fabricated on carbon fiber as a flexible self-supporting electrode (denoted as CC@FeCoNiMoRu-HEA/C) for high-performance liquid/flexible ZABs using a facile and cost-effective strategy. The three-dimensional (3D) highly open network framework and hierarchical porous structure accelerate the mass transport of OH-/O2 and charge transfer. The electronic structure adjustment, lattice defects and high entropy effects enable the CC@FeCoNiMoRu-HEA/C catalysts to perform high OER catalytic activity and strong durability while reducing the Ru content and lowering the economic cost. In situ Raman spectra and XPS results reveal the generation of metal-OOH intermediates on the HEA surface during the OER process. In a practical demonstration, the liquid ZAB assembled with CC@FeCoNiMoRu-HEA/C + Pt/C as the air electrode offers stable open-circuit voltage, large power density, excellent specific capacity and satisfactory cycle life, outperforming the commercial RuO2 + Pt/C-based reference ZAB. More attractively, the flexible solid-state ZAB also achieves fast dynamic response, high peak power density, robust cycling stability as well as favorable mechanical flexibility, indicating a promising application prospect in future flexible electronics and wearable devices. This work provides a viable pathway to develop low precious metal-loaded HEAs as advanced OER self-supporting electrocatalysts and realize high-performance flexible energy storage devices.

Large-scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial and ethnic groups. Methods: Dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (998 unique individuals), 333 were from African American donors, 223 from Latino Americans, 529 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG tissue samples (244 unique individuals), 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag mass spectrometry (TMT-MS). Results: As a Quality control (QC) measure, proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. After QC, 9,180 and 9,734 proteins remained in the DLPC and STG proteome, respectively, of which approximately 9,000 proteins were shared between regions. Protein levels of microtubule-associated protein tau (MAPT) and amyloid-precursor protein (APP) demonstrated AD-related elevations in DLPFC tissues with a strong association with CERAD and Braak across racial groups. APOE4 protein levels in brain were highly concordant with APOE genotype of the individuals. Discussion: This comprehensive region resolved large-scale proteomic dataset provides a resource for the understanding of ethnoracial-specific protein differences in AD brain.

Divergent landscapes of A-to-I editing in postmortem and living human brain.

Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR1 and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries illuminate the nuanced functions and intricate regulatory mechanisms of RNA editing within the human brain.

The FGF6 amplification mutation plays an important role in the progression and treatment of malignant meningioma.

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

Building Flame-Retardant Polymer Electrolytes via Microcapsule Technology for Stable Lithium Batteries.

Flame retardants could improve the safety properties of lithium batteries (LBs) with the sacrifice of electrochemical performance due to parasitic reactions. To concur with this, we designed thermal-response clothes for hexachlorophosphazene (HCP) additives by the microcapsule technique with urea-formaldehyde (UF) resin as the shell. HCP@UF combines with polyacrylonitrile (PAN) by hydrogen bonds successfully to form PAN-HCP@UF as the flame-retardant solid polymer electrolyte. The hydrogen bonds ensure excellent mechanical properties of the polymer electrolyte. The multiscale free radical-annihilating agent HCP effectively eliminates hydrogen free radicals of electrolytes under high temperature, showing excellent flame retardation. During the operation of the battery, functional groups on the UF resin act as active sites to promote the migration of lithium ions, while the internal HCP is protected from electrochemical reaction. With 25% HCP@UF addition, the limiting oxygen index of the PAN-HCP@UF increases to 28% and the Li+ transfer number up to 0.80. By UF protection, the initial capacity retention rate of the Li||LFP battery that assembles with PAN-HCP@UF is 88.8% after 500 cycles at 0.5 C. Thus, the microcapsule-encapsulated approach is deemed to provide an innovative strategy to prepare high-safety solid-state LB with a stable long cycle life.

Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer's disease.

Communication between glial cells has a profound impact on the pathophysiology of Alzheimer's disease (AD). We reveal here that reactive astrocytes control cell distancing in peri-plaque glial nets, which restricts microglial access to amyloid deposits. This process is governed by guidance receptor Plexin-B1 (PLXNB1), a network hub gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes. Plexin-B1 deletion in a mouse AD model led to reduced number of reactive astrocytes and microglia in peri-plaque glial nets, but higher coverage of plaques by glial processes, along with transcriptional changes signifying reduced neuroinflammation. Additionally, a reduced footprint of glial nets was associated with overall lower plaque burden, a shift toward dense-core-type plaques and reduced neuritic dystrophy. Altogether, our study demonstrates that Plexin-B1 regulates peri-plaque glial net activation in AD. Relaxing glial spacing by targeting guidance receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD.

Posterior cingulate epilepsy: Seizure semiology and intracranial electrical stimulation using SEEG.

PURPOSE: This study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE). METHODS: This study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified. RESULTS: Analysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC. CONCLUSION: The manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC.

Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.

Neurodegenerative diseases are debilitating nervous system disorders attributed to various conditions such as body aging, gene mutations, genetic factors, and immune system disorders. Prominent neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Insulin resistance refers to the inability of the peripheral and central tissues of the body to respond to insulin and effectively regulate blood sugar levels. Insulin resistance has been observed in various neurodegenerative diseases and has been suggested to induce the occurrence, development, and exacerbation of neurodegenerative diseases. Furthermore, an increasing number of studies have suggested that reversing insulin resistance may be a critical intervention for the treatment of neurodegenerative diseases. Among the numerous measures available to improve insulin sensitivity, exercise is a widely accepted strategy due to its convenience, affordability, and significant impact on increasing insulin sensitivity. This review examines the association between neurodegenerative diseases and insulin resistance and highlights the molecular mechanisms by which exercise can reverse insulin resistance under these conditions. The focus was on regulating insulin resistance through exercise and providing practical ideas and suggestions for future research focused on exercise-induced insulin sensitivity in the context of neurodegenerative diseases.

A Study on the Effect and Suppression of Hydrogen Permeation Behavior on the Friction Characteristics of PEEK/PTFE Composites via Molecular Dynamics Simulation.

To research the effect of hydrogen permeation on the friction characteristics of the seal materials on the hydrogen equipment, the molecular models of 10% PEEK/PTFE composites and its frictional models were established, respectively, and molecular dynamics (MDs) and giant canonical Monte Carlo (GCMC) methods were used to simulate the diffusion coefficient, dissolution coefficient and permeability coefficient of the hydrogen in PEEK/PTFE composites. The effect of a different amount of hydrogen on the friction and wear of PEEK/PTFE composites was also studied. The results showed that few permeations of the hydrogen gas mainly demonstrated having a positive effect on the surface of the PEEK/PTFE composites, and the wear rate of the PEEK/PTFE composites showed a slight decreasing trend. The wear rate of the PEEK/PTFE composites gradually decreased when more hydrogen molecules penetrated the matrix. With the further penetration of the hydrogen molecules, the wear rate and friction coefficient of the PEEK/PTFE composites rapidly increased, showing a negative effect. With the further penetration of the hydrogen molecule, the friction coefficient of the composite displayed a small fluctuation and then a rapid decreasing trend. Meanwhile, effective improvement measures were proposed, and the introduction of the graphene was verified to be effective to reduce the negative effect of the hydrogen permeation, thereby improving the friction performance of the PEEK/PTFE composites.

Novel CAR T-cell therapies for relapsed/refractory B-cell malignancies: latest updates from 2023 ASH annual meeting.

Chimeric antigen receptors (CAR) are engineered fusion proteins that target T-cells to specific surface antigens of tumor cells to generate effective anti-tumor responses. CAR T-cell therapy is playing an increasingly important role in the treatment of relapsed/refractory B-cell malignancies (R/R BCM). Attempting to make CAR T-cells safer and more effective in treating R/R BCM, various novel engineered CAR T-cell agents are currently in the research and development or clinical trial stages. We have summarized here the latest reports on the novel CAR T-cell therapies for R/R BCM presented at the 2023 ASH Annual Meeting as well as the latest updates in related clinical trials.