Universal Spin Superconducting Diode Effect from Spin-Orbit Coupling.

We propose a universal spin superconducting diode effect (SDE) induced by spin-orbit coupling (SOC) in systems with spin-triplet correlations, where the critical spin supercurrents in opposite directions are unequal. By analysis from both the Ginzburg-Landau theory and energy band analysis, we show that the spin-↑↑ and spin-↓↓ Cooper pairs possess opposite phase gradients and opposite momenta from the SOC, which leads to the spin SDE. Two superconductors with SOC, a p-wave superconductor as a toy model and a practical superconducting nanowire, are numerically studied and they both exhibit spin SDE. In addition, our theory also provides a unified picture for both spin and charge SDEs.

Visualizing a single wavefront dislocation induced by orbital angular momentum in graphene.

Phase singularities are phase-indeterminate points where wave amplitudes are zero, which manifest as phase vertices or wavefront dislocations. In the realm of optical and electron beams, the phase singularity has been extensively explored, demonstrating a profound connection to orbital angular momentum. Direct local imaging of the impact of orbital angular momentum on phase singularities at the nanoscale, however, remains challenging. Here, we study the role of orbital angular momentum in phase singularities in graphene, particularly at the atomic level, through scanning tunneling microscopy and spectroscopy. Our experiments demonstrate that the scatterings between different orbital angular momentum states, which are induced by local rotational symmetry-breaking potentials, can generate additional phase singularities, and result in robust single-wavefront dislocations in real space. Our results pave the way for exploring the effects of orbital degree of freedom on quantum phases in quasiparticle interference processes.

D-beta-hydroxybutyrate up-regulates Claudin-1 and alleviates the intestinal hyperpermeability in lipopolysaccharide-treated mice.

The hyperpermeability of intestinal epithelium is a key contributor to the occurrence and development of systemic inflammation. Although D-beta-hydroxybutyrate (BHB) exhibits various protective effects, whether it affects the permeability of intestinal epithelium in systemic inflammation has not been clarified. In this study, we investigated the effects of BHB on the intestinal epithelial permeability, the epithelial marker E-cadherin and the tight junction protein Claudin-1 in colon in the lipopolysaccharide (LPS)-induced systemic inflammation mouse model. Intraperitoneal injection of LPS was used to induce systemic inflammation and BHB was given by oral administration. The permeability of intestinal epithelium, the morphological changes of colonic epithelium, the distribution and generation of colon E-cadherin, and the Claudin-1 generation and its epithelial distribution in colon were detected. The results confirmed the intestinal epithelial hyperpermeability and inflammatory changes in colonic epithelium, with disturbed E-cadherin distribution in LPS-treated mice. Besides, colon Claudin-1 generation was decreased and its epithelial distribution in colon was weakened in LPS-treated mice. However, BHB treatments alleviated the LPS-induced hyperpermeability of intestinal epithelium, attenuated the colonic epithelial morphological changes and promoted orderly distribution of E-cadherin in colon. Furthermore, BHB up-regulated colon Claudin-1 generation and promoted its colonic epithelial distribution and content in LPS-treated mice. In conclusion, BHB may alleviate the hyperpermeability of intestinal epithelium via up-regulation of Claudin-1 in colon in LPS-treated mice.

Thermal dissipation of the quantum spin Hall edge states in HgTe/CdTe quantum well.

Quantum spin Hall effect is characterized by topologically protected helical edge states. Here we study the thermal dissipation of helical edge states by considering two types of dissipation sources. The results show that the helical edge states are dissipationless for normal dissipation sources with or without Rashba spin-orbit coupling in the system, but they are dissipative for spin dissipation sources. Further studies on the energy distribution show that electrons with spin-up and spin-down are both in their own equilibrium without dissipation sources. Spin dissipation sources can couple the two subsystems together to induce voltage drop and non-equilibrium distribution, leading to thermal dissipation, while normal dissipation sources cannot. With the increase of thermal dissipation, the subsystems of electrons with spin-up and spin-down evolve from non-equilibrium finally to mutual equilibrium. In addition, the effects of disorder on thermal dissipation are also discussed. Our work provides clues to reduce thermal dissipation in the quantum spin Hall systems.

Upregulation of Microglial Sirt6 and Inhibition of Microglial Activation by Vitamin D3 in Lipopolysaccharide-stimulated Mice and BV-2 Cells.

Vitamin D3 may suppress microglial activation and neuroinflammation, which play a central role in the pathophysiology of many neurological disorders. Sirt6 can remove histone 3 lysine 9 acetylation (H3K9ac) to repress expression of pathological genes and produce anti-inflammatory effects. However, whether vitamin D3 upregulates microglial Sirt6 to exert its protective effects against microglial activation and neuroinflammation is unclear. The effects of lower, normal, and higher dosages (1, 10 and 100 µg/kg/day) of vitamin D3 on behavioral and neuromorphological changes, brain inflammatory factors, Sirt6 and H3K9ac levels, and microglial Sirt6 distribution in hippocampus were evaluated in lipopolysaccharide (LPS)-stimulated mice. In addition, the effects of vitamin D3 on inflammatory factors, reactive oxygen species, Sirt6, and H3K9ac were confirmed in LPS-stimulated BV-2 cells. We verified that vitamin D3 ameliorated the impaired sociability of LPS-stimulated mice by three-chamber test. In addition, vitamin D3 upregulated brain Sirt6 generation, reduced H3K9ac levels and inhibited generation of brain inflammatory factors. Moreover, vitamin D3 promoted microglial Sirt6 distribution and attenuated microglia displaying an activated morphology in the hippocampus of LPS-stimulated mice. Similarly, vitamin D3 upregulated Sirt6 generation and intensity, reduced H3K9ac levels, and inhibited the inflammatory activation of LPS-stimulated BV-2 cells. In conclusion, vitamin D3 may upregulate microglial Sirt6 to reduce H3K9ac and inhibit microglial activation, thereby antagonizing neuroinflammation.

Molecular Collapse States in Graphene/WSe_{2} Heterostructure Quantum Dots.

In relativistic physics, both atomic collapse in a heavy nucleus and Hawking radiation in a black hole are predicted to occur through the Klein tunneling process that couples particles and antiparticles. Recently, atomic collapse states (ACSs) were explicitly realized in graphene because of its relativistic Dirac excitation with a large "fine structure constant." However, the essential role of the Klein tunneling in the ACSs remains elusive in experiment. Here we systematically study the quasibound states in elliptical graphene quantum dots (GQDs) and two coupled circular GQDs. Bonding and antibonding molecular collapse states formed by two coupled ACSs are observed in both systems. Our experiments supported by theoretical calculations indicate that the antibonding state of the ACSs will change into a Klein-tunneling-induced quasibound state revealing deep connection between the ACSs and the Klein tunneling.

Magnetic-Field-Tunable Valley-Contrasting Pseudomagnetic Confinement in Graphene.

Introducing quantum confinement has uncovered a rich set of interesting quantum phenomena and allows one to directly probe the physics of confined (quasi-)particles. In most experiments, however, an electrostatic potential is the only available method to generate quantum dots in a continuous system to confine (quasi-)particles. Here we demonstrate experimentally that inhomogeneous pseudomagnetic fields in strained graphene can introduce exotic quantum confinement of massless Dirac fermions. The pseudomagnetic fields have opposite directions in the two distinct valleys of graphene. By adding and tuning real magnetic fields, the total effective magnetic fields in the two valleys are imbalanced. By that we realized valley-contrasting spatial confinement, which lifts the valley degeneracy and results in field-tunable valley-polarized confined states in graphene. Our results provide a new avenue to manipulate the valley degree of freedom.

Coexistence of electron whispering-gallery modes and atomic collapse states in graphene/WSe2 heterostructure quantum dots.

The relativistic massless charge carriers with a Fermi velocity of about c/300 in graphene enable us to realize two distinct types of resonances (here, c is the speed of light in vacuum). One is the electron whispering-gallery mode in graphene quantum dots arising from the Klein tunneling of the massless Dirac fermions. The other is the atomic collapse state, which has never been observed in experiment with real atoms due to the difficulty of producing heavy nuclei with charge Z > 170; however, they can be realized near a Coulomb impurity in graphene with a charge Z ≥ 1 because of the "small" velocity of the Dirac excitations. Here we demonstrate that both the electron whispering-gallery modes and atomic collapse states coexist in graphene/WSe2 heterostructure quantum dots due to the Coulomb-like potential near their edges. By applying a perpendicular magnetic field, we explore the evolution from the atomic collapse states to unusual Landau levels in the collapse regime.

Risk factors and prediction model of level II lymph node metastasis in papillary thyroid carcinoma.

Introduction: Surgical management of lateral lymph nodes in papillary thyroid carcinoma, especially at level II, remains controversial. This study aimed to investigate the risk factors for level II lymph node metastasis in patients with papillary thyroid carcinoma and establish a prediction model to estimate the metastatic risk. Materials and methods: A total of 768 patients with papillary thyroid carcinoma underwent thyroidectomy and central plus lateral lymph node dissection, including levels VI, II, III, and IV, at the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2018. Data on the clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to identify risk factors for level II lymph node metastasis. Subsequently, a predictive model was established based on the results of the multivariate analyses. Results: The level II lymph node metastatic rate was 34.11% with the following features: largest tumor diameter >20 mm (Odds ratio=1.629, P=0.026), located in the upper pole (Odds ratio=4.970, P<0.001), clinical lymph node-positive (clinical central lymph node-positive: Odds ratio=1.797; clinical lateral lymph node-positive: Odds ratio=1.805, P=0.008), vascular invasion (Odds ratio=6.759, P=0.012), and rate of central lymph node metastasis (Odds ratio=2.498, P<0.001). Level III lymph node metastasis (Odds ratio=2.749, P<0.001) and level IV lymph node metastasis (Odds ratio=1.732, P=0.007) were independent of level II lymph node metastasis predictors. The prediction model's areas under the receiver operating characteristic curve were 0.815 and 0.804, based on bootstrapping validation. Level II lymph node metastasis was associated with the tumor-free survival rate of patients with papillary thyroid carcinoma (P<0.001). Conclusions: Largest tumor diameter >20 mm, located in the upper pole, clinical lymph node-positive, vascular invasion, rate of central lymph node metastasis, and levels III and IV lymph node metastases were independent level II lymph node metastasis predictors. We developed a prediction model for level II lymph node metastasis. Overall, level II lymph node metastasis dissection should be individualized according to clinicopathological data both preoperatively and intraoperatively.

Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk.

Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through activation of epidermal TLR4/IL-36R crosstalk. This activation is dependent upon NETs formation and integrity, as targeting NETs with DNase I or CI-amidine in vivo improves disease in the imiquimod (IMQ)-induced psoriasis-like mouse model, decreasing IL-17A, lipocalin2 (LCN2), and IL-36G expression. Proinflammatory activity of NETs, and LCN2 induction, is dependent upon activation of TLR4/IL-36R crosstalk and MyD88/nuclear factor-kappa B (NF-κB) down-stream signaling, but independent of TLR7 or TLR9. Notably, both TLR4 inhibition and LCN2 neutralization alleviate psoriasis-like inflammation and NETs formation in both the IMQ model and K14-VEGF transgenic mice. In summary, these results outline the mechanisms for the proinflammatory activity of NETs in skin and identify NETs/TLR4 as novel therapeutic targets in psoriasis.

Dysregulation of Akt-FOXO1 Pathway Leads to Dysfunction of Regulatory T Cells in Patients with Psoriasis.

Psoriasis is a T lymphocyte-driven systemic inflammatory disease. Regulatory T cells (Tregs) are essential for establishing and maintaining immune tolerance. In this study, we found that patients with psoriasis and healthy controls had comparable percentages of circulating CD4+CD25+FOXP3+ Tregs, but psoriatic Tregs had reduced suppressive function. Thereafter, mRNA arrays were performed to study the gene expression profile of psoriatic Tregs. Psoriatic Tregs expressed high levels of a T helper type 1-like transcription factor and cytokines such as T-bet and IFN-γ. Furthermore, we found that FOXO1 can bind to the promoter of TBX21 to inhibit its expression, thus keeping the suppressive function of Tregs. However, an increase in protein kinase B-mediated phosphorylation of FOXO1 was observed in psoriatic Tregs, which subsequently caused FOXO1 inactivation by nuclear exclusion. In addition, incubation of healthy Tregs with psoriatic serum led to the activation of protein kinase B, nuclear exclusion of FOXO1, and the loss of FOXO1 transcription activity. The role of FOXO1 in regulating the function of Tregs was corroborated using a psoriasis-like mouse model in which Foxo1-deficient Tregs failed to protect mice from developing psoriasis. In conclusion, our findings reveal that the dysregulation of the protein kinase B-FOXO1 pathway may be a critical cause of Treg dysfunction in psoriasis.

Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production.

Psoriasis is a chronic inflammatory autoimmune skin disease that often occurs in rubbed areas undergoing a strong mechanical stretch, such as the elbows and knees. However, the pathologic role of mechanical tension in psoriasis remains unclear. In this study, we investigated the contribution of keratinocyte mechanical stretch to the clinical features of psoriasis. We found that keratinocyte proliferation and skin barrier-associated gene expression increased significantly after 24 hours of continuous stretching. Additionally, continuous stretching induced the production of psoriasis-associated proinflammatory cytokines, antibacterial peptides, and chemokines in primary human keratinocytes. Furthermore, we established a murine model of skin expansion by implanting a dilator into the dorsum of BALB/c mice to assess the effect of mechanical stretch on the epidermis in vivo. The dilator-implanted mice displayed prominent epidermal hyperproliferation, impaired skin barrier function, and up-regulation of psoriasis-associated cytokines in epidermal keratinocytes. Most importantly, the dilator-implanted psoriatic mice treated with imiquimod or IL-23 displayed an aggravated psoriatic phenotype compared with mice without dilator implantation. Collectively, our results suggest that mechanical stretch can exacerbate psoriatic lesions by promoting cell proliferation and amplifying the production of proinflammatory cytokines by keratinocytes. Thus, our findings provide new insights into the pathogenesis of psoriasis.

NB-UVB irradiation downregulates keratin-17 expression in keratinocytes by inhibiting the ERK1/2 and STAT3 signaling pathways.

Keratin-17 (K17) is a cytoskeletal protein produced by keratinocytes (KCs), which is overexpressed in psoriasis and may play a pivotal role in its pathogenesis. Narrow-band ultraviolet B (NB-UVB) irradiation is used as a general treatment for psoriasis, although its impact on K17 expression has yet to be determined. In this study, we aimed to investigate the effect of NB-UVB irradiation on K17 expression and its signaling pathways. After exposure to NB-UVB irradiation, immortalized human keratinocytes (HaCaT cells) were analyzed by flow cytometry, CCK-8 assays and transmission electron microscopy to examine proliferation. Meanwhile, K17 expression in primary human epithelial keratinocytes was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis and immunofluorescence. HaCaT cells pre-incubated with PD-98059 and piceatannol were subjected to western blot analysis to examine ERK1/2 and STAT3 phosphorylation. The ears of mice treated with imiquimod (IMQ) and irradiated by NB-UVB were taken to examine K17 expression by qRT-PCR, western blot analysis, and immunofluorescence. Our results showed that 400 mJ/cm2 of NB-UVB irradiation was the maximum tolerable dose for HaCaT cells and could cause inhibited HaCaT cell proliferation and moderate increase of the early apoptosis. Furthermore, NB-UVB irradiation could downregulate K17 expression by inhibiting the ERK1/2 and STAT3 signaling pathways. In experiments conducted in vivo, NB-UVB irradiation with doses of MED or higher could eliminate the IMQ-induced psoriasis-like dermatitis and inhibit K17 expression. These results indicated that NB-UVB irradiation may eliminate chronic psoriatic plaques by suppressing K17 expression via the ERK1/2 and STAT3 signaling pathways.