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Background Radiotherapy (RT) is a highly effective multimodal nonsurgical treatment that is essential for patients with advanced colorectal cancer (CRC). Nevertheless, cell subpopulations displaying intrinsic radioresistance survive after RT. The reactivation of their proliferation and successful colonization at local or distant sites may increase the risk of poor clinical outcomes. Recently, radioresistant cancer cells surviving RT were reported to exhibit a more aggressive phenotype than parental cells, although the underlying mechanisms remain unclear. Methods By investigating public databases containing CRC patient data, we explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts. Results Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was activated in radioresistant CRC tissues in correlation with local and distant metastases. JAK2 was preferentially overexpressed in the CRC stem cell subpopulation, which was accompanied by the phosphorylation of STAT proteins, especially STAT3. JAK2/STAT3 signaling played an essential role in promoting tumor initiation and radioresistance by limiting apoptosis and enhancing clonogenic potential. Mechanistically, the direct binding of STAT3 to the cyclin D2 (CCND2) promoter increased CCND2 transcription. CCND2 expression was required for persistent cancer stem cell (CSC) growth via the maintenance of an intact cell cycle and proliferation with low levels of DNA damage accumulation. Conclusion Herein, we first identified JAK2/STAT3/CCND2 signaling as a resistance mechanism for the persistent growth of CSCs after RT, suggesting potential biomarkers and regimens for improving outcomes among CRC patients.

In the adult hippocampus, synapses are constantly formed and eliminated 1 , 2 . However, the exact function of synapse elimination in the adult brain, and how it is regulated, are largely unknown. Here we show that astrocytic phagocytosis 3 is important for maintaining proper hippocampal synaptic connectivity and plasticity. By using fluorescent phagocytosis reporters, we find that excitatory and inhibitory synapses are eliminated by glial phagocytosis in the CA1 region of the adult mouse hippocampus. Unexpectedly, we found that astrocytes have a major role in the neuronal activity-dependent elimination of excitatory synapses. Furthermore, mice in which astrocytes lack the phagocytic receptor MEGF10 show a reduction in the elimination of excitatory synapses; as a result, excessive but functionally impaired synapses accumulate. Finally, Megf10- knockout mice show defective long-term synaptic plasticity and impaired formation of hippocampal memories. Together, our data provide strong evidence that astrocytes eliminate unnecessary excitatory synaptic connections in the adult hippocampus through MEGF10, and that this astrocytic function is crucial for maintaining circuit connectivity and thereby supporting cognitive function. In adult mice, astrocytes carry out phagocytosis of excitatory hippocampal synapses through MEGF10 to maintain synaptic and circuit homeostasis.

Lithium–sulfur (Li–S) batteries have a high specific capacity, but lithium polysulfide (LPS) diffusion and lithium dendrite growth drastically reduce their cycle life. High discharge rates also necessitate their resilience to high temperature. Here we show that biomimetic self-assembled membranes from aramid nanofibers (ANFs) address these challenges. Replicating the fibrous structure of cartilage, multifactorial engineering of ion-selective mechanical, and thermal properties becomes possible. LPS adsorption on ANF surface creates a layer of negative charge on nanoscale pores blocking LPS transport. The batteries using cartilage-like bioinspired ANF membranes exhibited a close-to-theoretical-maximum capacity of 1268 mAh g −1 , up to 3500+ cycle life, and up to 3C discharge rates. Essential for safety, the high thermal resilience of ANFs enables operation at temperatures up to 80 °C. The simplicity of synthesis and recyclability of ANFs open the door for engineering high-performance materials for numerous energy technologies. Lithium–sulfur batteries have a high specific capacity, but lithium polysulfide diffusion (LPS) and dendrite growth reduce their cycle life. Here, the authors show a biomimetic aramid nanofiber membrane for effectively suppressing LPS diffusion as well as lithium dendrites while allowing lithium ions to be transported. The membranes resists performance degradation at high temperatures and can be produced at scale by Kevlar recycling.

Chiral phonons are concerted mirror-symmetric movements of atomic groups connected by covalent and intermolecular bonds. Such lattice vibrations in crystals of biomolecules should be highly specific to their short- and long-range organizations, but their chiroptical signatures and structure–property relationships remain uncertain. Here we show that terahertz chiroptical spectroscopy enables the registration and attribution of chiral phonons for microscale and nanoscale crystals of amino acids and peptides. Theoretical analysis and computer simulations indicate that sharp mirror-symmetric bands observed for left- and right-handed enantiomers originate from the collective vibrations of biomolecules interconnected by hydrogen bonds into helical chains. The sensitivity of chiral phonons to minute structural changes can be used to identify physical and chemical differences in seemingly identical formulations of dipeptides used in health supplements. The generality of these findings is demonstrated by chiral phonons observed for amyloid nanofibrils of insulin. Their spectral signatures and polarization rotation strongly depend on their maturation stage, which opens a new door for medical applications of terahertz photonics.Chiral phonons—long-range lattice vibrations with rotational motion of atoms—are observed by terahertz chiroptical spectroscopy in biocrystals. Terahertz circular dichroism peaks between 0.2 and 2.0 THz clearly identify the chirality of these phonons in various microcrystalline and nanofibrils of biomolecules.

In this experimental study, we compared the outcomes between anterior-tenting and wrapping techniques in prepectoral breast reconstruction using an acellular dermal matrix (ADM). Fifteen rats were divided into control, anterior-tenting, and whole-wrapping groups, each receiving two silicone implants. In the control group, only silicone implants were placed, whereas in the anterior-tenting and whole-wrapping groups, the anterior surface of the implants and the entire implants were covered with ADM, respectively. The Animals were irradiated on one side of the back 3 weeks postoperatively and sacrificed 3 months postoperatively. The range of change in tonometry values with or without irradiation in the whole-wrapping group tended to be larger than that in the anterior-tenting group ( p  < 0.05). The cellular capsule was significantly thinner on the side covered by ADM ( p  < 0.05). There were no significant differences in other microscopic features of the cellular capsule. Microscopic analysis of the ADM revealed significant increases in thickness and collagen density with radiation exposure, whereas a significant decrease was observed in the α-smooth muscle actin-positive area, CD3-positive cell counts, and F4/80 positive area ( p  < 0.05). In our rat model, the whole wrapping technique led to a greater increase in intraprosthetic pressure due to radiation-related structural changes in ADM, compared to the anterior-tenting technique.

The quality of recovery (QoR) of remimazolam-based and propofol-based total intravenous anesthesia was compared as measured by QoR-15 scores. A prospective, double-blind, randomized controlled, non-inferiority trial. An operating room, a post-anesthesia care unit (PACU), and a hospital ward. Female patients (n = 140; 20–65 years) scheduled for open thyroidectomy were enrolled and randomly assigned to the remimazolam or propofol group. The remimazolam group received continuous remimazolam infusions and effect-site target-controlled remifentanil infusions. The propofol group received effect-site target-controlled infusions of propofol and remifentanil. The primary outcome was QoR-15 on postoperative day 1 (POD1). The mean difference between the groups was compared against a non-inferiority margin of −8. Secondary outcomes were QoR-15 on POD2, hemodynamic data, time to lose and recover consciousness, sedation score upon PACU admission, pain, and postoperative nausea and vomiting profiles at the PACU and ward. Group-time interaction effects in hemodynamic data and QoR-15 were analyzed using a linear mixed model. The total QoR-15 score on POD1 in the remimazolam group was non-inferior to that in the propofol group (mean [SD] 111.2 [18.8] vs. 109.1 [18.9]; mean difference [95% CI] 2.1 [−4.2, 8.5]; p = 0.002 for non-inferiority). The QoR-15 score on POD2 was comparable between the groups, and no group-time interaction was observed. At the end of anesthesia, after extubation, and upon arrival at the PACU, mean arterial pressure was significantly higher in the remimazolam group. Remimazolam group was more sedated at the time of admission to PACU. Pain intensity and the requirement for analgesics were lower in the remimazolam group than in the propofol group. Remimazolam-based total intravenous anesthesia provided a similar QoR to propofol. Remimazolam and propofol can be used interchangeably for general anesthesia in female patients undergoing thyroid surgery. •Evidence regarding quality of recovery after remimazolam-based total intravenous anesthesia has been limited.•Remimazolam-based total intravenous anesthesia was explored in female patients undergoing open thyroidectomy.•Remimazolam-based total intravenous anesthesia demonstrated similar quality of recovery to propofol.•Hypotensive incidence at cessation of anesthetics was lower in patients administered with remimazolam compared to propofol.•Remimazolam-based total intravenous anesthesia was associated with reduced pain intensity and analgesic requirement.

Oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect that impairs the quality of life of patients treated with the chemotherapeutic agent, oxaliplatin. The underlying pathophysiology of OIPN remains unclear, and there are no effective therapeutics. This study aimed to investigate the causal relationship between spinal microglial activation and OIPN and explore the analgesic effects of syringaresinol, a phytochemical from the bark of Cinnamomum cassia, on OIPN symptoms. The causality between microglial activation and OIPN was investigated by assessing cold and mechanical allodynia in mice after intrathecal injection of the serum supernatant from a BV-2 microglial cell line treated with oxaliplatin. The microglial inflammatory response was measured based on inducible nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated nuclear factor-kappa B (p-NF-κB) expression in the spinal dorsal horn. The effects of syringaresinol were tested using behavioral and immunohistochemical assays. We found that oxaliplatin treatment activated the microglia to increase inflammatory responses, leading to the induction of pain. Syringaresinol treatment significantly ameliorated oxaliplatin-induced pain and suppressed microglial expression of inflammatory signaling molecules. Thus, we concluded that the analgesic effects of syringaresinol on OIPN were achieved via the modulation of spinal microglial inflammatory responses.

In the adult brain, neural circuit homeostasis depends on the constant turnover of synapses via astrocytic phagocytosis mechanisms. However, it remains unclear whether this process occurs in a circuit-specific manner. Here, we reveal that astrocytes target and eliminate specific type of excitatory synapses in the striatum. Using model mice lacking astrocytic phagocytosis receptors in the dorsal striatum, we found that astrocytes constantly remove corticostriatal synapses rather than thalamostriatal synapses. This preferential elimination suggests that astrocytes play a selective role in modulating corticostriatal plasticity and functions via phagocytosis mechanisms. Supporting this notion, corticostriatal long-term potentiation and the early phase of motor skill learning are dependent on astrocytic phagocytic receptors. Together, our findings demonstrate that astrocytes contribute to the connectivity and plasticity of the striatal circuit by preferentially engulfing a specific subset of excitatory synapses within brain regions innervated by multiple excitatory sources. Neural circuit homeostasis depends on astrocytic phagocytosis, but its circuit specificity remains unclear. Here, the authors show that astrocytes selectively eliminate corticostriatal synapses, regulating striatal plasticity and motor learning.

The biological effects of circularly polarized light on living cells are considered to be negligibly weak. Here, we show that the differentiation of neural stem cells into neurons can be accelerated by circularly polarized photons when DNA-bridged chiral assemblies of gold nanoparticles are entangled with the cells’ cytoskeletal fibres. By using cell-culture experiments and plasmonic-force calculations, we demonstrate that the nanoparticle assemblies exert a circularly-polarized-light-dependent force on the cytoskeleton, and that the light-induced periodic mechanical deformation of actin nanofibres with a frequency of 50 Hz stimulates the differentiation of neural stem cells into the neuronal phenotype. When implanted in the hippocampus of a mouse model of Alzheimer’s disease, neural stem cells illuminated following a polarity-optimized protocol reduced the formation of amyloid plaques by more than 70%. Our findings suggest that circularly polarized light can guide cellular development for biomedical use. Chiral photons can accelerate the differentiation of neural stem cells into neurons in vitro and in vivo when DNA-bridged chiral assemblies of gold nanoparticles are tightly entangled with the cells’ cytoskeletal fibres.

Blood vessels support tumours by providing nutrients and oxygen, while also acting as conduits for the dissemination of cancer 1 . Here we use mouse models of breast and lung cancer to investigate whether endothelial cells also have active ‘instructive’ roles in the dissemination of cancer. We purified genetically tagged endothelial ribosomes and their associated transcripts from highly and poorly metastatic tumours. Deep sequencing revealed that metastatic tumours induced expression of the axon-guidance gene Slit2 in endothelium, establishing differential expression between the endothelial (high Slit2 expression) and tumoural (low Slit2 expression) compartments. Endothelial-derived SLIT2 protein and its receptor ROBO1 promoted the migration of cancer cells towards endothelial cells and intravasation. Deleting endothelial Slit2 suppressed metastatic dissemination in mouse models of breast and lung cancer. Conversely, deletion of tumoural Slit2 enhanced metastatic progression. We identified double-stranded RNA derived from tumour cells as an upstream signal that induces expression of endothelial SLIT2 by acting on the RNA-sensing receptor TLR3. Accordingly, a set of endogenous retroviral element RNAs were upregulated in metastatic cells and detected extracellularly. Thus, cancer cells co-opt innate RNA sensing to induce a chemotactic signalling pathway in endothelium that drives intravasation and metastasis. These findings reveal that endothelial cells have a direct instructive role in driving metastatic dissemination, and demonstrate that a single gene ( Slit2 ) can promote or suppress cancer progression depending on its cellular source. Expression of the axon-guidance gene Slit2 in endothelium, induced by endothelial sensing of tumour-derived double-stranded RNA, promotes metastatic dissemination in mouse models of breast and lung cancer.