Bismuth oxychloride nanosheets anchored aramid separator with sponge-like structure for improved lithium-ion battery performance.

Functional modification of inorganic particles is an effective approach to tackle the issue of Li+ transport and the lithium dendrites formation in lithium-ion batteries (LIBs). In this study, PMIA/BiOCl composite separators are prepared by nonsolvent induce phase separation (NIPS) method using P-type semiconductor bismuth oxychloride (BiOCl) functionalized poly (m-phenylene isophthalamide) (PMIA) separators. Compared with the polypropylene (PP) separator, PMIA has superior thermal stability and the addition of BiOCl further enhances its flame retardancy. And the prepared PMIA/BiOCl separator presents improved porosity (66.47 %), enhanced electrolyte uptake rate (863 %) and higher ionic conductivity (0.49 mS∙cm-1). Besides, the incorporation of BiOCl can anchor PF6- to the three-dimensional network skeleton of the PMIA/BiOCl separators, enabling the desolvation of Li+ and selectively facilitating Li+ transport (the Li+ transfer number is 0.79). Moreover, the uniform porous structure of the PMIA/BiOCl separators and the efficient transport of Li+ uniformly deposite Li+, and minimize the growth of lithium dendrites. Batteries assembled with PMIA/BiOCl separators have a discharge specific capacity of 124.4 mAh∙g-1 and capacity retention of 96.7 % after 200 cycles at 0.2C. Therefore, this work provides an effective route in the design strategy of separators for LIBs.

Arthroscopic and open approaches for autologous matrix-induced chondrogenesis repair of the knee have similar results: a meta-analysis.

BACKGROUND: Cartilage defects are debilitating injuries that can reduce quality of life in patients. However, the poor regenerative properties of cartilage mean that cartilage repair remains challenging, and many methods have arisen to address that. Autologous matrix-induced chondrogenesis (AMIC®) is a popular technique to manage cartilage defects. Recent advances have allowed AMIC® to be done arthroscopically, instead of a mini-open arthrotomy approach. This systematic review and meta-analysis aims to investigate whether the arthroscopic approach to AMIC® provides better clinical outcomes than does the mini-open approach, in hopes of delineating a gold standard in cartilage repair. METHODS: With reference to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search of the following databases (PubMed, Embase, Scopus, and Cochrane Library) was performed on 26th October 2022 using a combination of the following search terms: "autologous matrix induced", "chondrogenesis", and "knee". A total of 390 studies were identified, of which, 24 studies were included in our final analysis. RESULTS: The arthroscopic approach achieves lower Visual Analogue Scale for pain scores. The International Knee documentation Committee) score and Knee Injury and Osteoarthritis Outcome Score were comparable between arthroscopic and open approaches. The open approach achieves a higher Magnetic Resonance Observation of Cartilage Repair Tissue score. Incidence of reported postoperative complications of revision surgery and knee stiffness was higher for the open approach than for the arthroscopic approach, whereas deep vein thrombosis was higher in the arthroscopic approach. CONCLUSION: The AMIC® repair outcomes indicate that the arthroscopic approach does not hold a distinct advantage over the open approach. The choice of approach should consider surgeon expertise, location of lesion, and patient-specific factors. LEVEL OF EVIDENCE: Systematic review and meta-analysis; Level III.

An adverse tumor-protective effect of IDO1 inhibition.

By restoring tryptophan, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors aim to reactivate anti-tumor T cells. However, a phase III trial assessing their clinical benefit failed, prompting us to revisit the role of IDO1 in tumor cells under T cell attack. We show here that IDO1 inhibition leads to an adverse protection of melanoma cells to T cell-derived interferon-gamma (IFNγ). RNA sequencing and ribosome profiling shows that IFNγ shuts down general protein translation, which is reversed by IDO1 inhibition. Impaired translation is accompanied by an amino acid deprivation-dependent stress response driving activating transcription factor-4 (ATF4)high/microphtalmia-associated transcription factor (MITF)low transcriptomic signatures, also in patient melanomas. Single-cell sequencing analysis reveals that MITF downregulation upon immune checkpoint blockade treatment predicts improved patient outcome. Conversely, MITF restoration in cultured melanoma cells causes T cell resistance. These results highlight the critical role of tryptophan and MITF in the melanoma response to T cell-derived IFNγ and uncover an unexpected negative consequence of IDO1 inhibition.

Anti-tumour immunity induces aberrant peptide presentation in melanoma.

Extensive tumour inflammation, which is reflected by high levels of infiltrating T cells and interferon-γ (IFNγ) signalling, improves the response of patients with melanoma to checkpoint immunotherapy1,2. Many tumours, however, escape by activating cellular pathways that lead to immunosuppression. One such mechanism is the production of tryptophan metabolites along the kynurenine pathway by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which is induced by IFNγ3-5. However, clinical trials using inhibition of IDO1 in combination with blockade of the PD1 pathway in patients with melanoma did not improve the efficacy of treatment compared to PD1 pathway blockade alone6,7, pointing to an incomplete understanding of the role of IDO1 and the consequent degradation of tryptophan in mRNA translation and cancer progression. Here we used ribosome profiling in melanoma cells to investigate the effects of prolonged IFNγ treatment on mRNA translation. Notably, we observed accumulations of ribosomes downstream of tryptophan codons, along with their expected stalling at the tryptophan codon. This suggested that ribosomes bypass tryptophan codons in the absence of tryptophan. A detailed examination of these tryptophan-associated accumulations of ribosomes-which we term 'W-bumps'-showed that they were characterized by ribosomal frameshifting events. Consistently, reporter assays combined with proteomic and immunopeptidomic analyses demonstrated the induction of ribosomal frameshifting, and the generation and presentation of aberrant trans-frame peptides at the cell surface after treatment with IFNγ. Priming of naive T cells from healthy donors with aberrant peptides induced peptide-specific T cells. Together, our results suggest that IDO1-mediated depletion of tryptophan, which is induced by IFNγ, has a role in the immune recognition of melanoma cells by contributing to diversification of the peptidome landscape.

Nondestructive monitoring of polyphenols and caffeine during green tea processing using Vis-NIR spectroscopy.

Increasing consumption of green tea is attributed to the beneficial effects of its constituents, especially polyphenols, on human health, which can be varied during leaf processing. Processing technology has the most important effect on green tea quality. This study investigated the system dynamics of eight catechins, gallic acid, and caffeine in the processing of two varieties of tea, from fresh leaves to finished tea. It was found that complex biochemical changes can occur through hydrolysis under different humidity and heating conditions during the tea processing. This process had a significant effect on catechin composition in the finished tea. The potential application of visible and near-infrared (Vis-NIR) spectroscopy for fast monitoring polyphenol and caffeine contents in tea leaves during the processing procedure has been investigated. It was found that a combination of PCA (principal component analysis) and Vis-NIR spectroscopy can successfully classify the two varieties of tea samples and the five tea processing procedures, while quantitative determination of the constituents was realized by combined regression analysis and Vis-NIR spectra. Furthermore, successive projections algorithm (SPA) was proposed to extract and optimize spectral variables that reflected the molecular characteristics of the constituents for the development of determination models. Modeling results showed that the models had good predictability and robustness based on the extracted spectral characteristics. The coefficients of determination for all calibration sets and prediction sets were higher than 0.862 and 0.834, respectively, which indicated high capability of Vis-NIR spectroscopy for the determination of the constituents during the leaf processing. Meanwhile, this analytical method could quickly monitor quality characteristics and provide feedback for real-time controlling of tea processing machines. Furthermore, the study on complex biochemical changes that occurred during the tea processing would provide a theoretical basis for improving the content of quality components and effective controlling processes.

Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold.

New opportunities are needed to increase immune checkpoint blockade (ICB) benefit. Whereas the interferon (IFN)γ pathway harbors both ICB resistance factors and therapeutic opportunities, this has not been systematically investigated for IFNγ-independent signaling routes. A genome-wide CRISPR/Cas9 screen to sensitize IFNγ receptor-deficient tumor cells to CD8 T cell elimination uncovered several hits mapping to the tumor necrosis factor (TNF) pathway. Clinically, we show that TNF antitumor activity is only limited in tumors at baseline and in ICB non-responders, correlating with its low abundance. Taking advantage of the genetic screen, we demonstrate that ablation of the top hit, TRAF2, lowers the TNF cytotoxicity threshold in tumors by redirecting TNF signaling to favor RIPK1-dependent apoptosis. TRAF2 loss greatly enhanced the therapeutic potential of pharmacologic inhibition of its interaction partner cIAP, another screen hit, thereby cooperating with ICB. Our results suggest that selective reduction of the TNF cytotoxicity threshold increases the susceptibility of tumors to immunotherapy.

Hepatocellular Carcinoma: Retrospective Evaluation of the Correlation Between Gadobenate Dimeglumine-Enhanced Magnetic Resonance Imaging and Pathologic Grade.

OBJECTIVE: The aim of this study was to evaluate the usefulness of gadobenate dimeglumine-enhanced magnetic resonance imaging in characterizing the grade of hepatocellular carcinoma (HCC) using the signal intensity (SI) of the erector spinae as internal reference. MATERIALS AND METHODS: Clinical data of 40 patients (a total of 44 lesions) confirmed by pathology for HCC were retrospectively reviewed. Gadobenate dimeglumine-enhanced magnetic resonance imaging was performed in all patients, and SI of lesions (SIles), liver parenchyma around the lesions (SIhep), erector spinae (SImus) and standard deviation of SI of the surrounding noise (SDnoi) on nonenhanced T2WI, nonenhanced T1WI, and contrast-enhanced T1WI (in both arterial and hepatobiliary phase [AP and HBP]) were measured, respectively. Contrast-to-noise ratio (CNR) were separately defined as CNR1 ([SIles - SIhep]/SDnoi) and CNR2 ([SIles - SImus]/SDnoi). Statistical analyses were performed using one-way analysis of variance, least significant difference test, logistic regression analysis, Spearman rank correlation, and receiver operating characteristic curves analysis. RESULTS: Forty-four HCCs, including 3 well-differentiated HCCs, 26 moderately differentiated HCCs, and 15 poorly differentiated (PD) HCCs, were confirmed. On logistic regression analysis, only CNR2 in the HBP was predictor of PD HCCs (P = 0.015, odds ratio = 1.040). The size of lesions, CNR1 in the AP, CNR2 in the AP, and CNR2 in the HBP, showed significant correlations with the degree of differentiation (correlation coefficients = -0.371, 0.435, 0.503, and 0.512, respectively; P = 0.013, 0.003, 0.001, and 0.000, respectively). Contrast-to-noise ratio 2 in the HBP with the cutoff of less than 4.56 could distinguish moderately differentiated HCCs from PD HCC with the sensitivity and specificity of 84.6% and 60.0%, respectively. CONCLUSIONS: Relatively low arterial enhancement and low CNR2 value in the HBP are predictive for poor histological grade of HCCs.

Parallel in vivo and in vitro melanoma RNAi dropout screens reveal synthetic lethality between hypoxia and DNA damage response inhibition.

To identify factors preferentially necessary for driving tumor expansion, we performed parallel in vitro and in vivo negative-selection short hairpin RNA (shRNA) screens. Melanoma cells harboring shRNAs targeting several DNA damage response (DDR) kinases had a greater selective disadvantage in vivo than in vitro, indicating an essential contribution of these factors during tumor expansion. In growing tumors, DDR kinases were activated following hypoxia. Correspondingly, depletion or pharmacologic inhibition of DDR kinases was toxic to melanoma cells, including those that were resistant to BRAF inhibitor, and this could be enhanced by angiogenesis blockade. These results reveal that hypoxia sensitizes melanomas to targeted inhibition of the DDR and illustrate the utility of in vivo shRNA dropout screens for the identification of pharmacologically tractable targets.