Despite their higher capacity compared to common intercalation- and conversion-type anodes, black phosphorus (BP) based anodes suffer from significant capacity fading attributed to the large volume expansion (∼300%) during lithiation. Downsizing BP into nanosheets has been proposed to mitigate this issue, and various methods, particularly mechanical mixing with graphitic materials (BP-C), have been explored to enhance electrochemical performance. However, the understanding of BP-C hybridization is hindered by the lack of studies focusing on fundamental degradation mechanisms within operational battery environments. Here we address this challenge by employing electrochemical atomic force microscopy (EC-AFM) to study the morphological and mechanical evolution of BP-C composite anodes during lithiation. The results reveal that BP-C binding interactions alone are insufficient to withstand the structural reorganization of BP during its alloying reaction with lithium. Furthermore, the study emphasizes the critical role of the solid electrolyte interphase (SEI) and BP-C interface evolution in determining the long-term performance of these composites, shedding light on the disparity in final electrode morphologies between binder-inclusive and binder-free BP-C composites. These findings provide crucial insights into the challenges associated with BP-based anodes and underscore the need for a deeper understanding of the dynamic behavior within operating cells for the development of stable and high-performance battery materials.

The importance of the DNA damage response in mediating effects of radiotherapy (RT) has galvanized efforts to target this pathway with radiosensitizers. Yet early clinical trials of this approach have failed to yield a benefit in unselected populations. We hypothesized that ataxia-telangiectasia mutated (Atm)-null tumors would demonstrate genotype-specific synergy between RT and an inhibitor of the DNA damage response protein ataxia-telangiectasia and Rad3-related (ATR) kinase. We investigated the synergistic potential of the ATR inhibitor (ATRi) RP-3500 and RT in two Atm-null and isogenic murine models, both in vitro and in vivo. Staining of γ-H2AX foci, characterization of the immune response via flow cytometry, and tumor rechallenge experiments were performed to elucidate the mechanism of interaction. To examine genotype specificity, we tested the interaction of ATRi and RT in a Brca1-null model. Finally, patients with advanced cancer with ATM alterations were enrolled in a phase I/II clinical trial to validate preclinical findings. Synergy between RP-3500 and RT was confirmed in Atm-null lines in vitro, characterized by an accumulation of DNA double-strand breaks. In vivo, Atm-null tumor models had higher rates of durable control with RT and ATRi than controls. In contrast, there was no synergy in tumors lacking Brca1. Analysis of the immunologic response indicated that efficacy is largely mediated by cell-intrinsic mechanisms. Lastly, early results from our clinical trial showed complete responses in patients. Genotype-directed radiosensitization with ATRi and RT can unleash significant therapeutic benefit and could represent a novel approach to develop more effective combinatorial synthetic cytotoxic RT-based treatments.

Traditional applications of mechanically robust bamboo are mostly confined to flat and straight components. Here, we investigated the tunable bending characteristics of bamboo strips by regulating the moisture content as a means to achieve efficient fabrication of single-layer and multi-layer bamboo curved components (SBCCs and MBCCs). Under the two opposite radial bending modes, the bending strength of bamboo strips decreased while their ductility and toughness increased as the moisture content increased from 0 % to 35 %, and the asymmetry of the bending properties became more pronounced. Moisture in bamboo strips was a double-edged sword for curved component manufacturing. Bamboo strips with high moisture content had higher bendability, which was conducive to improving the bending pass rate of SBCCs. At a bending radius of 70 mm, the total bending pass rate of SBCCs made from bamboo strips with 35 % moisture content was 85.9 % higher than that of SBCCs made from bamboo strips with 0 % moisture content. However, excessive moisture content could easily reduce the bending stability of the SBCCs and affect the bonding properties of the MBCCs. The optimal moisture content of bamboo strips for manufacturing curved components was 10–18 %, and increasing the moisture content of bamboo strips could produce components with complex shapes. The results can provide more possibilities for innovative bamboo product design and engineering applications, thereby promoting the utilization of sustainable and eco-friendly bamboo.

To decide what programming parameters to use for cochlear implants (CIs) in partial deaf patients can be challenging. The processor programming form, categorised as electrical complement (EC), electro-acoustic-stimulation (EAS) or electric stimulation (ES), and difficulties switching programming form were investigated. A retrospective investigation of medical records and audiograms was conducted in adult patients intended for EC and EAS. Eighty-four ears (80 patients) were included. Twenty ears were initially fitted with EC, 32 with EAS, 30 with ES and 2 with both EC and EAS. Sixty-four ears met the criteria to use EC or EAS at initial fitting, however only 54 ears were fitted with EC or EAS initially. Twenty-eight patients altered between at least two programming forms and six of those experienced difficulties to adapt to a new form when their low-frequency hearing deteriorated. Twenty-five percent of patients initially fitted with EC or EAS switched programming form within two years. Further studies on how to choose the most beneficial sound processor programming parameters for EC and EAS, and when to change between programming forms, are warranted as well as clear guidance on choosing the right candidates for EC and EAS.

BackgroundIn non-small cell lung cancer (NSCLC) the efficacy of chemo-immunotherapy is affected by the high expression of drug efflux transporters as ABCC1 and by the low expression of ABCA1, mediating the isopentenyl pyrophosphate (IPP)-dependent anti-tumor activation of Vγ9Vδ2 T-lymphocytes. In endothelial cells ABCA1 is a predicted target of the transcription factor EB (TFEB), but no data exists on the correlation between TFEB and ABC transporters involved in the chemo-immuno-resistance in NSCLC.MethodsThe impact of TFEB/ABCC1/ABCA1 expression on NSCLC patients’ survival was analyzed in the TCGA-LUAD cohort and in a retrospective cohort of our institution. Human NSCLC cells silenced for TFEB (shTFEB) were analyzed for ABC transporter expression, chemosensitivity and immuno-killing. The chemo-immuno-sensitizing effects of nanoparticles encapsulating zoledronic acid (NZ) on shTFEB tumors and on tumor immune-microenvironment were evaluated in Hu-CD34+ mice by single-cell RNA-sequencing.ResultsTFEBlowABCA1lowABCC1high and TFEBhighABCA1highABCC1low NSCLC patients had the worst and the best prognosis, respectively, in the TCGA-LUAD cohort and in a retrospective cohort of patients receiving platinum-based chemotherapy or immunotherapy as first-line treatment. By silencing shTFEB in NSCLC cells, we demonstrated that TFEB was a transcriptional inducer of ABCA1 and a repressor of ABCC1. shTFEB cells had also a decreased activity of ERK1/2/SREBP2 axis, implying reduced synthesis and efflux via ABCA1 of cholesterol and its intermediate IPP. Moreover, TFEB silencing reduced cholesterol incorporation in mitochondria: this event increased the efficiency of OXPHOS and the fueling of ABCC1 by mitochondrial ATP. Accordingly, shTFEB cells were less immuno-killed by the Vγ9Vδ2 T-lymphocytes activated by IPP and more resistant to cisplatin. NZ, which increased IPP efflux but not OXPHOS and ATP production, sensitized shTFEB immuno-xenografts, by reducing intratumor proliferation and increasing apoptosis in response to cisplatin, and by increasing the variety of anti-tumor infiltrating cells (Vγ9Vδ2 T-lymphocytes, CD8+T-lymphocytes, NK cells).ConclusionsThis work suggests that TFEB is a gatekeeper of the sensitivity to chemotherapy and immuno-killing in NSCLC, and that the TFEBlowABCA1lowABCC1high phenotype can be predictive of poor response to chemotherapy and immunotherapy. By reshaping both cancer metabolism and tumor immune-microenvironment, zoledronic acid can re-sensitize TFEBlow NSCLCs, highly resistant to chemo- and immunotherapy.

Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease of wheat globally. However, the molecular mechanisms underlying the interactions between F. graminearum and wheat remain unclear. Here, we identified a secreted effector protein, FgEC1, that is induced during wheat infection and is required for F. graminearum virulence. FgEC1 suppressed flg22- and chitin-induced callose deposition and reactive oxygen species (ROS) burst in Nicotiana benthamiana. FgEC1 directly interacts with TaGF14b, which is upregulated in wheat heads during F. graminearum infection. Overexpression of TaGF14b increases FHB resistance in wheat without compromising yield. TaGF14b interacts with NADPH oxidase respiratory burst oxidase homolog D (TaRBOHD) and protects it against degradation by the 26S proteasome. FgEC1 inhibited the interaction of TaGF14b with TaRBOHD and promoted TaRBOHD degradation, thereby reducing TaRBOHD-mediated ROS production. Our findings reveal a novel pathogenic mechanism in which a fungal pathogen acts via an effector to reduce TaRBOHD-mediated ROS production.

We investigated the effect of the NaCl concentration (0.3-2M) on the structure and dynamics of hen egg yolk at room temperature and during thermal gelation at temperatures in the range of 66-90 °C utilizing low-dose x-ray photon correlation spectroscopy in ultra-small angle x-ray scattering geometry. With an increase in the salt concentration, we observe progressive structural and dynamic changes at room temperature, indicating the disruption of yolk components such as yolk-granules and yolk-plasma proteins. Temperature- and salt-dependent structural and dynamic investigations suggest a delay in the gel formation and aggregation of yolk low-density lipoproteins with increasing ionic strength. However, the time-temperature superposition relationship observed in all samples suggests an identical mechanism underlying protein aggregation-gelation with a temperature-dependent reaction rate. The sol-gel transition time extracted from kinetic and dynamic information follows Arrhenius's behavior, and the activation energy (460kJ/mol) is found to be independent of the salt concentration.

Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β Abs from PBMCs of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.

Ultrathin nanofibrous films with unique properties, such as controlled thickness, structures, and excellent mechanical robustness, play a vital role in flexible wearable devices, electronic skin, and rechargeable batteries. However, nanofibrous films are always facing limitations in their mechanical properties, even though they are strong when used as textiles, mainly owing to their structural shortcomings by using conventional fabrication methods. Herein, we present the fabrication of free-standing ultrathin nanofibrous films with good mechanical properties by using a microfluidic-based continuous printing strategy. Owing to the precisely controllable microfluidic flow in the micrometre-scale, the resulting aramid nanofibre (ANF) films can reach thicknesses as low as 140 ± 25 nm. Specifically, the tensile strength of such ultrathin ANF films is recorded at an impressive value of 667 ± 40 MPa, representing a 120% improvement compared to the films prepared by using casting method. Such excellent mechanical robustness comes from the double-sided protonation, which shows a symmetrically dense structure compared to the asymmetric structure of cast films. Furthermore, we demonstrate the continuous fabrication of thin regenerated cellulose nanofiber (RCNF) and cellulose diacetate (CDA) films using the microfluidic-based printing strategy. Both microfluidic-based films show significant enhancements in strength, with a 42% increase for RCNF and a 94% increase for CDA compared to their cast films. We envision that this microfluidic-based continuous printing strategy provides a promising pathway for the development of advanced ultrathin nanofibrous films towards practical applications.

The dynamics of lysozyme is probed by attaching -SCN to all alanine residues. The one-dimensional infrared spectra exhibit frequency shifts in the position of the maximum absorption of 4 cm-1, which is consistent with experiments in different solvents and indicates moderately strong interactions of the vibrational probe with its environment. Isotopic substitution 12C → 13C leads to a redshift by -47 cm-1, which agrees quantitatively with experiments for CN-substituted copper complexes in solution. The low-frequency, far-infrared part of the protein spectra contains label-specific information in the difference spectra when compared with the wild type protein. Depending on the position of the labels, local structural changes are observed. For example, introducing the -SCN label at Ala129 leads to breaking of the α-helical structure with concomitant change in the far-infrared spectrum. Finally, changes in the local hydration of SCN-labeled alanine residues as a function of time can be related to the reorientation of the label. It is concluded that -SCN is potentially useful for probing protein dynamics, both in the high-frequency part (CN-stretch) and in the far-infrared part of the spectrum.