Layer Hall effect induced by hidden Berry curvature in antiferromagnetic insulators.

The layer Hall effect describes electrons spontaneously deflected to opposite sides at different layers, which has been experimentally reported in the MnBi2Te4 thin films under perpendicular electric fields. Here, we reveal a universal origin of the layer Hall effect in terms of the so-called hidden Berry curvature, as well as material design principles. Hence, it gives rise to zero Berry curvature in momentum space but non-zero layer-locked hidden Berry curvature in real space. We show that, compared to that of a trivial insulator, the layer Hall effect is significantly enhanced in antiferromagnetic topological insulators. Our universal picture provides a paradigm for revealing the hidden physics as a result of the interplay between the global and local symmetries, and can be generalized in various scenarios.

Finite-size effect on quantum percolation in topological insulators.

We study the finite-size effect on quantum percolation in two-dimensional topological insulators. We demonstrate that the percolation threshold in topological insulators strongly depends on the localization length of the edge states in small clusters due to the finite-size effect. Also, we explain why the percolation threshold in the corresponding classical model determines the lower bound of the quantum percolation threshold in topological insulators. In addition, we extend the percolation model to a more general scenario, where the system is composed of both topological and trivial clusters. We find that the quantum percolation threshold can be less than the classical percolation threshold due to quantum tunneling of the edge states.

With two episodes of right retromandibular angle subcutaneous emphysema during right upper molar crown preparation: A case report.

BACKGROUND: Subcutaneous emphysema is a well-known complication of oral surgery, especially during mandibular wisdom tooth extraction. However, subcutaneous emphysema secondary to dental procedures such as crown preparation is rare. The main symptom of emphysema is swelling and crepitus on palpation. Uncontrolled emphysema may spread along the fascial planes and cause deep space infections or a pneumomediastinum. CASE SUMMARY: In this paper, we report a 34-year-old female who underwent upper molar tooth preparation for crowns and subsequently developed extensive subcutaneous emphysema on the retromandibular angle on two different occasions. The treatment plan for this patient involved close observation of the airway, and administration of dexamethasone and antibiotics via intravenous drip or orally. Ice bag compression was quickly applied and medication was prescribed to alleviate discomfort and promote healing. Although the main reason is unclear, the presence of a fissure in the molar is an important clue which may contribute to the development of subcutaneous emphysema during crown preparation. It is imperative for dental professionals to recognize such pre-disposing factors in order to minimize the risk of complications. CONCLUSION: This case highlights the need for prompt diagnosis and management of subcutaneous emphysema because of the risk of much more serious complications. Awareness of relatively "benign" subcutaneous emphysema during any dental procedure is critical not only for inexperienced dentists, but also for those who work in rural and remote settings as members of surgical teams. In this study, we review the clinical presentation, mechanism, and differential diagnosis of subcutaneous emphysema.

Accumulation of branched-chain amino acids reprograms glucose metabolism in CD8+ T cells with enhanced effector function and anti-tumor response.

Branched-chain amino acids (BCAAs) provide nutrient signals for cell survival and growth. How BCAAs affect CD8+ T cell functions remains unexplored. Herein, we report that accumulation of BCAAs in CD8+ T cells due to the impairment of BCAA degradation in 2C-type serine/threonine protein phosphatase (PP2Cm)-deficient mice leads to hyper-activity of CD8+ T cells and enhanced anti-tumor immunity. CD8+ T cells from PP2Cm-/- mice upregulate glucose transporter Glut1 expression in a FoxO1-dependent manner with more glucose uptake, as well as increased glycolysis and oxidative phosphorylation. Moreover, BCAA supplementation recapitulates CD8+ T cell hyper-functions and synergizes with anti-PD-1, in line with a better prognosis in NSCLC patients containing high BCAAs when receiving anti-PD-1 therapy. Our finding thus reveals that accumulation of BCAAs promotes effector function and anti-tumor immunity of CD8+ T cells through reprogramming glucose metabolism, making BCAAs alternative supplementary components to increase the clinical efficacy of anti-PD-1 immunotherapy against tumors.

Developing Single-Atomic Manganese Nanozymes for Synergistic Mild Photothermal/Multienzymatic Therapy.

Synergistic mild photothermal/nanozyme therapy with outstanding hyperthermia performance and excellent multienzyme properties is highly needed for osteosarcoma treatment. Herein, we have developed efficient single-atom nanozymes (SANs) consisting of Mn sites atomically dispersed on nitrogen-doped carbon nanosheets (denoted as Mn-SANs) for synergistic mild photothermal/multienzymatic therapy against osteosarcoma. Benefiting from their black N-doped carbon nanosheet matrices, Mn-SANs showed an excellent NIR-II-triggered photothermal effect. On the other hand, Mn-SANs with atomically dispersed Mn sites have outstanding multienzyme activities. Mn-SANs can catalyze endogenous H2O2 in osteosarcoma into O2 by catalase (CAT)-like activity, which can effectively ease osteosarcoma hypoxia and trigger the oxidase (OXD)-like catalysis that converts O2 to the cytotoxic superoxide anion radical (•O2-). At the same time, Mn-SANs can also mimic glutathione oxidase (GSHOx) to effectively consume the antioxidant glutathione (GSH) in osteosarcoma and inhibit intracellular glutathione peroxidase 4 (GPX4) expression. Such intratumoral •O2- production, GSH depletion, and GPX4 inactivation mediated by Mn-SANs can create a large accumulation of lipid peroxides (LPO) and •O2-, leading to oxidative stress and disrupting the redox homeostasis in osteosarcoma cells, which can ultimately induce osteosarcoma cell death. More importantly, heat shock proteins (HSPs) can be significantly destroyed via Mn-SAN-mediated plentiful LPO and •O2- generation, thus effectively impairing osteosarcoma cells resistant to mild photothermal therapy. Overall, through the cooperative effect of chemical processes (boosting •O2-, consuming GSH, and enhancing LPO) and biological processes (inactivating GPX4 and hindering HSPs), collaborative mild photothermal/multienzymatic therapy mediated by Mn-SANs is a promising strategy for efficient osteosarcoma treatment.

Quantum theory of the nonlinear Hall effect.

The nonlinear Hall effect is an unconventional response, in which a voltage can be driven by two perpendicular currents in the Hall-bar measurement. Unprecedented in the family of the Hall effects, it can survive time-reversal symmetry but is sensitive to the breaking of discrete and crystal symmetries. It is a quantum transport phenomenon that has deep connection with the Berry curvature. However, a full quantum description is still absent. Here we construct a quantum theory of the nonlinear Hall effect by using the diagrammatic technique. Quite different from nonlinear optics, nearly all the diagrams account for the disorder effects, which play decisive role in the electronic transport. After including the disorder contributions in terms of the Feynman diagrams, the total nonlinear Hall conductivity is enhanced but its sign remains unchanged for the 2D tilted Dirac model, compared to the one with only the Berry curvature contribution. We discuss the symmetry of the nonlinear conductivity tensor and predict a pure disorder-induced nonlinear Hall effect for point groups C3, C3h, C3v, D3h, D3 in 2D, and T, Td, C3h, D3h in 3D. This work will be helpful for explorations of the topological physics beyond the linear regime.

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1.

BACKGROUND/AIMS: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. METHODS: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. RESULTS: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. CONCLUSION: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

3D Quantum Hall Effect of Fermi Arcs in Topological Semimetals.

The quantum Hall effect is usually observed in 2D systems. We show that the Fermi arcs can give rise to a distinctive 3D quantum Hall effect in topological semimetals. Because of the topological constraint, the Fermi arc at a single surface has an open Fermi surface, which cannot host the quantum Hall effect. Via a "wormhole" tunneling assisted by the Weyl nodes, the Fermi arcs at opposite surfaces can form a complete Fermi loop and support the quantum Hall effect. The edge states of the Fermi arcs show a unique 3D distribution, giving an example of (d-2)-dimensional boundary states. This is distinctly different from the surface-state quantum Hall effect from a single surface of topological insulator. As the Fermi energy sweeps through the Weyl nodes, the sheet Hall conductivity evolves from the 1/B dependence to quantized plateaus at the Weyl nodes. This behavior can be realized by tuning gate voltages in a slab of topological semimetal, such as the TaAs family, Cd_{3}As_{2}, or Na_{3}Bi. This work will be instructive not only for searching transport signatures of the Fermi arcs but also for exploring novel electron gases in other topological phases of matter.

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis.

OBJECTIVE: To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). METHODS: Three groups of PlGF-2/BMP-2-loaded heparin-N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 µg PlGF-2; with 1.0 µg BMP-2; and with 0.5 µg PlGF-2 combined with 1.0 µg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. RESULTS: The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%-84% of PlGF-2 and 89%-91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. CONCLUSION: PlGF-2-loaded heparin-HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone.

Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector.

Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.

Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells.

AIM: The mitochondrial targeted 2C-type serine/threonine protein phosphatase (PP2Cm) is encoded by the gene PPM1K and is highly conserved among vertebrates. PP2Cm plays a critical role in branched-chain amino acid catabolism and regulates cell survival. Its expression is dynamically regulated by the nutrient environment and pathological stresses. However, little is known about the molecular mechanism underlying the regulation of PPM1K gene expression. In this study, we aimed to reveal how PPM1K expression is affected by miRNA-mediated post-transcriptional regulation. METHODS: Computational analysis based on conserved miRNA binding motifs was applied to predict the candidate miRNAs that potentially affect PPM1K expression. Dual-luciferase reporter assay was performed to verify the miRNAs' binding sites in the PPM1K gene and their influence on PPM1K 3'UTR activity. We further over-expressed the mimics of these miRNAs in human and mouse cells to examine whether miRNAs affected the mRNA level of PPM1K. RESULTS: Computational analysis identified numerous miRNAs potentially targeting PPM1K. Luciferase reporter assays demonstrated that the 3'UTR of PPM1K gene contained the recognition sites of miR-204 and miR-211. Overexpression of these miRNAs in human and mouse cells diminished the 3'UTR activity and the endogenous mRNA level of PPM1K. However, the miR-22 binding site was found only in human and not mouse PPM1K 3'UTR. Accordingly, PPM1K 3'UTR activity was suppressed by miR-22 overexpression in human but not mouse cells. CONCLUSION: These data suggest that different miRNAs contribute to the regulation of PP2Cm expression in a species-specific manner. miR-204 and miR-211 are efficient in both mouse and human cells, while miR-22 regulates PP2Cm expression only in human cells.