Macgregorjohannsen9966
Recycling spent lithium-ion batteries (LIBs) is promising for resource reuse and environmental conservation but suffers from complex processing and loss of embedded value of spent LIBs in conventional metallurgy-based recycling routes. Herein, we selected a eutectic LiI-LiOH salt with the lowest eutectic point among binary eutectic lithium salt systems to provide a Li-rich molten environment, not only offering excess lithium but benefiting ion diffusion compared with that in the solid environment. Hence, the highly degraded LiNi0.5Co0.2Mn0.3O2 in spent LIBs which suffers high Li-deficiency and serious structural defects with harmful phase transitions is directly regenerated. A facile one-step heating strategy in the presence of a combination of the eutectic lithium salt and Co2O3 and MnO2 additives not only simplifies the recycling process but also endows the cathode materials with lithium supplementation and structural ordering, which contributes to a restoration of the capacity and stable cycling performance. In particular, this eutectic salt with a low eutectic point helps decrease the temperature and time of the direct recycling process and shows good adaptability for other layer oxide cathode materials (LiCoO2 and LiNi0.6Co0.2Mn0.2O2) in spent LIBs with varying cathode chemistry. As such, the feasibility of the direct recycling route is improved and broadened with simple and efficient processing, providing an idea for energy-saving cathode regeneration in future LIB recycling.
Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. C-176 price Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.
We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity.
The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively.
The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
Gallbladder carcinoma (GBC) is an uncommon and aggressive disease, which remains poorly defined at a molecular level. Here, we aimed to characterize the molecular landscape of GBC and identify markers with potential prognostic and therapeutic implications.
GBC samples were analyzed using the MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) platform (targeted NGS assay that analyzes 505 cancer-associated genes). Variants with therapeutic implications were identified using OncoKB database. The associations between recurrent genetic alterations and clinicopathologic characteristics (Fisher exact tests) or overall survival (univariate Cox regression) were evaluated. P values were adjusted for multiple testing.
Overall, 244 samples (57% primary tumors and 43% metastases) from 233 patients were studied (85% adenocarcinomas, 10% carcinomas with squamous differentiation, and 5% neuroendocrine carcinomas). The most common oncogenic molecular alterations appeared inprovides guidance for the development of targeted therapies.
The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutations to enhance their immunogenicity.
Exome and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides. Subsequently, in silico HLA-anchor placements were used to deduce putative T-cell receptor (TCR) contacts of peptides. Single amino acids of TCR contacting residues were then mutated by amino acid replacements. Overall, 175 peptides were synthesized and sets of 25 each containing both peptides designed to bind to HLA class I and II molecules applied in the vaccination. Upon development of a tumor recurrence, the tumor-infiltrating lymphocytes (TIL) were characterized in detail both at the bulk and clonal level.
The immune response of peripheral blood T cells to vaccine peptides, including natural peptides and designed neopeptides, gradually increased with repetitive vaccination, but remained low. In contrast, at the time of tumor recurrence, CD8+ TILs and CD4+ TILs responded to 45% and 100%, respectively, of the vaccine peptides. Furthermore, TIL-derived CD4+ T-cell clones showed strong responses and tumor cell lysis not only against the designed neopeptide but also against the unmutated natural peptides of the tumor.
Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T-cell responses in a cold tumor like glioblastoma.
Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T-cell responses in a cold tumor like glioblastoma.High levels of psychological distress present a major public health issue among LGBTQ+ youth and adults; however, research has repeatedly identified community connectedness as an important protective factor for mental health in LGBTQ+ populations. The aim of the present study was to examine whether age moderates the association of community connectedness on psychological distress in a community sample of LGBTQ+ people. In the present exploratory study, we analyzed secondary cross-sectional data from a sample of LGBTQ+ youth and adults (n = 292) in a semi-rural community in the Western United States. Participants completed a measure of community connectedness, the K6, and the PHQ-4. The results of two moderation models showed that the negative association of community connectedness on psychological distress was strongest among youth, weaker among young adults, and nonsignificant among older middle-aged adults and older adults. These results provide further evidence for the potential buffering role of community connectedness on psychological distress for LGBTQ+ youth and young adults.
The aim of this study was to determine the ophthalmologic involvement in patients with hereditary transthyretin amyloidosis and its correlation with the mutations described in the literature.
Cross-sectional, noninterventional study. Fifty-two eyes of 26 consecutive patients diagnosed with hereditary transthyretin amyloidosis who visited the Puerta de Hierro-Majadahonda University Hospital from September 2019 to March 2022. All patients underwent complete ophthalmologic examination and multimodal imaging. Cardiologic, neurologic, digestive, and renal examinations were also recorded.
Eighteen eyes of the total (34.61%) showed amyloid-related ocular involvement, vitreous amyloid deposits being the most common ocular manifestation (18/52). Statistically significant differences were found for the presence of vitreous amyloid deposits ( P < 0.01), crystalline amyloid deposits ( P < 0.05), parenchymal amyloid deposits ( P < 0.01), and vascular alterations ( P < 0.01) when comparing affected and unf amyloidosis' ophthalmologic involvement.
The treatment outcome for locally advanced or metastatic soft-tissue sarcoma (STS) remains unsatisfactory. Anlotinib had demonstrated impressive activity in the subsequent-line treatment of STS. This study investigated the combination of anlotinib and epirubicin followed by anlotinib maintenance as first-line treatment for patients with advanced STS.
This prospective, open-label, single-arm, phase II trial was conducted in Zhongshan Hospital, Fudan University. Eligible patients were ages 18 years or older and had previously untreated, pathologically confirmed, unresectable locally advanced or metastatic STS. All patients received up to six cycles of anlotinib plus epirubicin followed by anlotinib maintenance until disease progression, unacceptable toxicity, or death. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The study was registered on chictr.org (identifier ChiCTR1900024928).
From June 2019 to August 2020, 30 patients were enrolled. By December 2021, the median PFS was 11.5 months [95% confidence interval (CI) 8.6-14.4 months], while the median overall survival was not reached (95% CI NE-NE). The objective response rate was 13.33% and the disease control rate was 80.0%. The most common adverse events (AE) included anemia (43.3%), nausea/vomiting (40.0%), fatigue (36.7%), leukopenia (30.0%), and proteinuria (10.0%), which were mainly of grade 1 or 2. The most frequent grade 3 or 4 AEs were anemia (10.0%), febrile neutropenia (33.3%), hypothyroidism (3.3%), and leukopenia (3.3%). No treatment-related death occurred.
The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.
The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.Flexible multidirectional strain sensors capable of simultaneously detecting strain amplitudes and directions have attracted tremendous interest. Herein, we propose a flexible multidirectional strain sensor based on a newly designed single-layer hierarchical aligned micro-/nanowire (HAMN) network. The HAMN network is efficiently fabricated using a one-step femtosecond laser patterning technology based on a modulated line-shaped beam. The anisotropic performance is attributed to the significantly different morphological changes caused by an inhomogeneous strain redistribution among the HAMN network. The fabricated strain sensor exhibits high sensitivity (gauge factor of 65 under 2.5% strain and 462 under larger strains), low response/recovery time (140 and 322 ms), and good stability (over 1000 cycles). Moreover, this single-layer strain sensor with high selectivity (gauge factor differences of ∼73 between orthogonal strains) is capable of distinguishing multidimensional strains and exhibits decoupled responses under low strains ( less then 1%).
