We study mechanical cooling in systems of coupled passive (lossy) and active (with gain) optical resonators. We find that for a driving laser which is red-detuned with respect to the cavity ...frequency, the supermode structure of the system is radically changed, featuring the emergence of genuine high-order exceptional points. This in turn leads to giant enhancement of both the mechanical damping and the spring stiffness, facilitating low-power mechanical cooling in the vicinity of gain-loss balance. This opens up new avenues of steering micromechanical devices with exceptional points beyond the lowest-order two.
The question as to why some hosts can eradicate their tumors while others succumb to tumor‐progression remains unanswered. Here, a provocative concept is proposed that intrinsic differences in the T ...cell receptor (TCR) repertoire of individuals may influence the outcome of anti‐tumor immunity by affecting the frequency and/or variety of tumor‐reactive CD8 and/or CD4 tumor‐infiltrating lymphocytes. This idea implicates that the TCR repertoire in a given patient might not provide sufficiently different TCR clones that can recognize tumor antigens, namely, “a hole in the TCR repertoire” might exist. This idea may provide a novel perspective to further dissect the mechanisms underlying heterogeneous anti‐tumor immune responses in different hosts. Besides tumor‐intrinsic heterogeneity and host microbiome, the various factors that may constantly shape the dynamic TCR repertoire are also discussed. Elucidating mechanistic differences in different individuals’ immune systems will allow to better harness immune system to design new personalized cancer immunotherapy.
Underlying mechanisms that dictate the immunological heterogeneity in cancers remain elusive. Besides tumor‐intrinsic heterogeneity and environmental factors, intrinsic differences in the T cell receptor (TCR) repertoire may play a role. “A hole in the TCR repertoire” hypothesis is proposed to explain heterogeneity of anti‐tumor responses that may significantly impact cancer immunotherapy.
Optomechanically-induced transparency (OMIT) and the associated slowing of light provide the basis for storing photons in nanoscale devices. Here we study OMIT in parity-time (PT)-symmetric ...microresonators with a tunable gain-to-loss ratio. This system features a sideband-reversed, non-amplifying transparency, i.e., an inverted-OMIT. When the gain-to-loss ratio is varied, the system exhibits a transition from a PT-symmetric phase to a broken-PT-symmetric phase. This PT-phase transition results in the reversal of the pump and gain dependence of the transmission rates. Moreover, we show that by tuning the pump power at a fixed gain-to-loss ratio, or the gain-to-loss ratio at a fixed pump power, one can switch from slow to fast light and vice versa. These findings provide new tools for controlling light propagation using nanofabricated phononic devices.
Recent research has shown that TOP2A plays an important role in the tumorigenesis of many malignancies, such as breast cancer, ovarian cancer, and prostate cancer. However, few studies have been ...conducted on TOP2A expression and functions in colon cancer. In the present study, we found that TOP2A expression was obviously elevated in colon cancer tissues compared to adjacent non‐cancerous tissues. Depletion of TOP2A in HCT116 and SW480 colon cancer cells by transfection of specific small interfering RNA significantly suppressed proliferation and inhibited invasion of cells, even induced apoptosis as indicated by both MTT assay, Annexin V/propidium iodide staining, and Transwell assay. Furthermore, we explored the underlying mechanisms. Knockdown of TOP2A not only affects the expression of cell apoptosis‐related (Bcl‐2 and Bax) and invasion‐related proteins (MMP‐2 and MMP‐9), but also reduced the phosphorylation levels of ERK and AKT. In conclusion, we showed that TOP2A was upregulated in colon cancer tissue samples and that TOP2A may serve as an oncogene in colon cancer.
1. Upregulation of TOP2A in colon cancer tissues, 2. Increased TOP2A expression in colon cancer is associated with tumor stage, and 3. Downregulation of TOP2A expression inhibits colon cancer cell proliferation.
We study optomechanically induced transparency (OMIT) in a compound system consisting of coupled optical resonators and a mechanical mode, focusing on the unconventional role of loss. We find that ...optical transparency can emerge at the otherwise strongly absorptive regime in the OMIT spectrum, by using an external nanotip to enhance the optical loss. In particular, loss-induced revival of optical transparency and the associated slow-to-fast light switch can be identified in the vicinity of an exceptional point. These results open up a counterintuitive way to engineer micro-mechanical devices with tunable losses for e.g., coherent optical switch and communications.
We study the nonlinear optomechanically induced transparency (OMIT) with gain and loss. We find that (i) for a single active cavity, significant enhancement can be achieved for the higher-order ...sidebands, including the transmission rate and the group delay; (ii) for active-passive-coupled cavities, hundreds of microsecond of optical delay or advance are attainable for the nonlinear sideband pulses in the parity-time-symmetric regime. The active higher-order OMIT effects, as firstly revealed here, open up the way to make a low-power optomechaical amplifier, which can amplify both the strength and group delay of not only the probe light but also its higher-order sidebands.
Head and neck cancers are a heterogeneous group of tumors that are highly aggressive and collectively represent the sixth most common cancer worldwide. Ninety percent of head and neck cancers are ...squamous cell carcinomas (HNSCCs). The tumor microenvironment (TME) of HNSCCs consists of many different subsets of cells that infiltrate the tumors and interact with the tumor cells or with each other through various networks. Both innate and adaptive immune cells play a crucial role in mediating immune surveillance and controlling tumor growth. Here, we discuss the different subsets of immune cells and how they contribute to an immunosuppressive TME of HNSCCs. We also briefly summarize recent advances in immunotherapeutic approaches for HNSCC treatment. A better understanding of the multiple factors that play pivotal roles in HNSCC tumorigenesis and tumor progression may help define novel targets to develop more effective immunotherapies for patients with HNSCC.
The BCR recognizes foreign Ags to initiate humoral immunity that needs isotype-switched Abs generated via class switch recombination (CSR); however, stimulating the BCR in the absence of ...costimulation (e.g., CD40) does not induce CSR; thus, it remains elusive whether and how the BCR induces CSR mechanistically. Autoreactive B cells can maintain anergy via unresponsiveness of their BCRs to self-antigens. However, it remains unknown what molecule(s) restrict BCR signaling strength for licensing BCR-induced CSR and whether deficiency of such molecule(s) disrupts autoreactive B cell anergy and causes B cell-mediated diseases by modulating BCR signaling. In this study, we employ mouse models to show that the BCR's capacity to induce CSR is restrained by B cell-intrinsic checkpoints TRAF3 and TRAF2, whose deletion in B cells enables the BCR to induce CSR in the absence of costimulation. TRAF3 deficiency permits BCR-induced CSR by elevating BCR-proximal signaling intensity. Furthermore, NF-κB2 is required for BCR-induced CSR in TRAF3-deficient B cells but not for CD40-induced or LPS-induced CSR, suggesting that TRAF3 restricts NF-κB2 activation to specifically limit the BCR's ability to induce CSR. TRAF3 deficiency also disrupts autoreactive B cell anergy by elevating calcium influx in response to BCR stimulation, leading to lymphoid organ disorders and autoimmune manifestations. We showed that TRAF3 deficiency-associated autoimmune phenotypes can be rectified by limiting BCR repertoires or attenuating BCR signaling strength. Thus, our studies highlight the importance of TRAF3-mediated restraint on BCR signaling strength for controlling CSR, B cell homeostasis, and B cell-mediated disorders.
Highlights ► We assessed the role of autophagy in endovascular perforation SAH model. ► Autophagy has a beneficial role in early brain injury following SAH. ► This neuroprotective effect was ...associated with inhibition of apoptotic cell death. ► The mitochondrial pathway was involved in autophagy-modulated apoptosis after SAH.
Mature B cells express B cell antigen receptor (BCR), toll-like receptors (TLR) and TNF family receptors including CD40 and B-cell activating factor receptor (BAFFR). These receptors transduce ...cellular signals to govern the physiological and pathological processes in B cells including B cell development and differentiation, survival, proliferation, and antibody-mediated immune responses as well as autoimmune diseases and B cell lymphomagenesis. Effective antibody-mediated immune responses require class switch recombination (CSR), a somatic DNA recombination event occurring at the immunoglobulin heavy chain (
) gene locus. Mature B cells initially express IgM as their BCR, and CSR enables the B cells to switch from expressing IgM to expressing different classes of antibodies including IgG, IgA or IgE that exhibit distinct effector functions. Here, we briefly review recent findings about how the signaling crosstalk of the BCR with TLRs, CD40 and BAFFR regulates CSR, antibody-mediate immune responses, and B cell anergy.
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