Probing PT-Symmetry Breaking of Non-Hermitian Topological Photonic States via Strong Photon-Magnon Coupling.

Light-matter interaction is crucial to both understanding fundamental phenomena and developing versatile applications. Strong coupling, robustness, and controllability are the three most important aspects in realizing light-matter interactions. Topological and non-Hermitian photonics have provided frameworks for robustness and control flexibility, respectively. How to engineer the properties of the edge state such as photonic density of state by using non-Hermiticity while ensuring topological protection has not been fully studied. Here we construct a parity-time-symmetric dimerized photonic lattice and probe the spontaneous PT-symmetry breaking of the edge states by utilizing the strong coupling between the photonic mode and a spin ensemble. Our Letter presents an accurate and almost noninvasive approach for investigating non-Hermitian topological states, while also offering methodologies for the implementation and manipulation of topological light-matter interactions.

Identification of a novel thermostable transaminase and its application in L-phosphinothricin biosynthesis.

Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase (PtTA) from Pseudomonas thermotolerans was mined and characterized. The PtTA showed a high specific activity (28.63 U/mg) towards 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. Two cascade systems driven by PtTA were developed for L-PPT biosynthesis, including asymmetric synthesis of L-PPT from PPO and deracemization of D, L-PPT. For the asymmetric synthesis of L-PPT from PPO, a three-enzyme cascade was constructed as a recombinant Escherichia coli (E. coli G), by co-expressing PtTA, glutamate dehydrogenase (GluDH) and D-glucose dehydrogenase (GDH). Complete conversion of 400 mM PPO was achieved using only 40 mM amino donor L-glutamate. Furthermore, by coupling D-amino acid aminotransferase (Ym DAAT) from Bacillus sp. YM-1 and PtTA, a two-transaminase cascade was developed for the one-pot deracemization of D, L-PPT. Under the highest reported substrate concentration (800 mM D, L-PPT), a 90.43% L-PPT yield was realized. The superior catalytic performance of the PtTA-driven cascade demonstrated that the thermodynamic limitation was overcome, highlighting its application prospect for L-PPT biosynthesis. KEY POINTS: • A novel thermostable transaminase was mined for L-phosphinothricin biosynthesis. • The asymmetric synthesis of L-phosphinothricin was achieved via a three-enzyme cascade. • Development of a two-transaminase cascade for D, L-phosphinothricin deracemization.

Deep quantum neural networks on a superconducting processor.

Deep learning and quantum computing have achieved dramatic progresses in recent years. The interplay between these two fast-growing fields gives rise to a new research frontier of quantum machine learning. In this work, we report an experimental demonstration of training deep quantum neural networks via the backpropagation algorithm with a six-qubit programmable superconducting processor. We experimentally perform the forward process of the backpropagation algorithm and classically simulate the backward process. In particular, we show that three-layer deep quantum neural networks can be trained efficiently to learn two-qubit quantum channels with a mean fidelity up to 96.0% and the ground state energy of molecular hydrogen with an accuracy up to 93.3% compared to the theoretical value. In addition, six-layer deep quantum neural networks can be trained in a similar fashion to achieve a mean fidelity up to 94.8% for learning single-qubit quantum channels. Our experimental results indicate that the number of coherent qubits required to maintain does not scale with the depth of the deep quantum neural network, thus providing a valuable guide for quantum machine learning applications with both near-term and future quantum devices.

Squeezing microwaves by magnetostriction.

Squeezed light finds many important applications in quantum information science and quantum metrology, and has been produced in a variety of physical systems involving optical non-linear processes. Here, we show how a non-linear magnetostrictive interaction in a ferrimagnet in cavity magnomechanics can be used to reduce quantum noise of the electromagnetic field. We show optimal parameter regimes where a substantial and stationary squeezing of the microwave output field can be achieved. Realization of the scheme is within reach of current technology in cavity electromagnonics and magnomechanics. Our work provides a new and practicable approach for producing squeezed vacuum states of electromagnetic fields, and may find promising applications in quantum information processing and quantum metrology.

Quantum Control of a Single Magnon in a Macroscopic Spin System.

Nonclassical quantum states are the pivotal features of a quantum system that differs from its classical counterpart. However, the generation and coherent control of quantum states in a macroscopic spin system remain an outstanding challenge. Here we experimentally demonstrate the quantum control of a single magnon in a macroscopic spin system (i.e., 1 mm-diameter yttrium-iron-garnet sphere) coupled to a superconducting qubit via a microwave cavity. By tuning the qubit frequency in situ via the Autler-Townes effect, we manipulate this single magnon to generate its nonclassical quantum states, including the single-magnon state and the superposition of single-magnon state and vacuum (zero magnon) state. Moreover, we confirm the deterministic generation of these nonclassical states by Wigner tomography. Our experiment offers the first reported deterministic generation of the nonclassical quantum states in a macroscopic spin system and paves a way to explore its promising applications in quantum engineering.

Development of an aminotransferase-driven biocatalytic cascade for deracemization of d,l-phosphinothricin.

2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) is the essential precursor keto acid for the asymmetric biosynthesis of herbicide l-phosphinothricin (l-PPT). Developing a biocatalytic cascade for PPO production with high efficiency and low cost is highly desired. Herein, a d-amino acid aminotransferase from Bacillus sp. YM-1 (Ym DAAT) with high activity (48.95 U/mg) and affinity (Km = 27.49 mM) toward d-PPT was evaluated. To circumvent the inhibition of by-product d-glutamate (d-Glu), an amino acceptor (α-ketoglutarate) regeneration cascade was constructed as a recombinant Escherichia coli (E. coli D), by coupling Ym d-AAT, d-aspartate oxidase from Thermomyces dupontii (TdDDO) and catalase from Geobacillus sp. CHB1. Moreover, the regulation of the ribosome binding site was employed to overcome the limiting step of expression toxic protein TdDDO in E. coli BL21(DE3). The aminotransferase-driven whole-cell biocatalytic cascade (E. coli D) showed superior catalytic efficiency for the synthesis of PPO from d,l-phosphinothricin (d,l-PPT). It revealed the production of PPO exhibited high space-time yield (2.59 g L-1 h-1 ) with complete conversion of d-PPT to PPO at high substrate concentration (600 mM d,l-PPT) in 1.5 L reaction system. This study first provides the synthesis of PPO from d,l-PPT employing an aminotransferase-driven biocatalytic cascade.

Giant spin ensembles in waveguide magnonics.

The dipole approximation is usually employed to describe light-matter interactions under ordinary conditions. With the development of artificial atomic systems, 'giant atom' physics is possible, where the scale of atoms is comparable to or even greater than the wavelength of the light they interact with, and the dipole approximation is no longer valid. It reveals interesting physics impossible in small atoms and may offer useful applications. Here, we experimentally demonstrate the giant spin ensemble (GSE), where a ferromagnetic spin ensemble interacts twice with the meandering waveguide, and the coupling strength between them can be continuously tuned from finite (coupled) to zero (decoupled) by varying the frequency. In the nested configuration, we investigate the collective behavior of two GSEs and find extraordinary phenomena that cannot be observed in conventional systems. Our experiment offers a new platform for 'giant atom' physics.

Mechanical Bistability in Kerr-modified Cavity Magnomechanics.

Bistable mechanical vibration is observed in a cavity magnomechanical system, which consists of a microwave cavity mode, a magnon mode, and a mechanical vibration mode of a ferrimagnetic yttrium-iron-garnet sphere. The bistability manifests itself in both the mechanical frequency and linewidth under a strong microwave drive field, which simultaneously activates three different kinds of nonlinearities, namely, magnetostriction, magnon self-Kerr, and magnon-phonon cross-Kerr nonlinearities. The magnon-phonon cross-Kerr nonlinearity is first predicted and measured in magnomechanics. The system enters a regime where Kerr-type nonlinearities strongly modify the conventional cavity magnomechanics that possesses only a radiation-pressure-like magnomechanical coupling. Three different kinds of nonlinearities are identified and distinguished in the experiment. Our Letter demonstrates a new mechanism for achieving mechanical bistability by combining magnetostriction and Kerr-type nonlinearities, and indicates that such Kerr-modified cavity magnomechanics provides a unique platform for studying many distinct nonlinearities in a single experiment.

Flexible nano-liposomes-based transdermal hydrogel for targeted delivery of dexamethasone for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that can lead to synovitis, cartilage destruction, and even joint damage. Dexamethasone (DEX) is a commonly used agent for RA therapy on inflammation manage. However, the traditional administering DEX is hampered by low efficiency and obvious adverse effects. Therefore, in order to efficiently deliver DEX to RA inflamed joints and overcome existing deficiencies, we developed transdermal formation dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel), validated their transdermal efficiency, evaluated its ability to target activated macrophages, and its anti-inflammatory effect. The DS-FLs/DEX exhibited excellent biocompatibility, sustainable drug release, and high uptake by lipopolysaccharide (LPS)-activated macrophages. Furthermore, the DS-FLs/DEX hydrogel showed desired skin permeation as compared with regular liposome hydrogel (DS-RLs/DEX hydrogel) due to its good deformability. In vivo, when used the AIA rats as RA model, the DS-FLs/DEX hydrogel can effectively penetrate and accumulate in inflamed joints, significantly improve joint swelling in RA rats, and reduce the destructive effect of RA on bone. Importantly, the expression of inflammatory cytokines in joints was inhibited and the system toxicity did not activate under DS-FLs/DEX hydrogel treatment. Overall, these data revealed that the dextran sulfate (DS) modified DEX-loaded flexible liposome hydrogel (DS-FLs/DEX hydrogel) can prove to be an excellent drug delivery vehicle against RA.

Pulmonary toxicity in driver gene positive non-small cell lung cancer therapy.

Molecular targeted therapy significantly improved the therapeutic efficacy in non-small cell lung cancer (NSCLC) patients with driver gene mutations but also with new toxicity profiles. Although most patients treated with these drugs developed relatively controllable toxicity, significant pulmonary toxicity events, including interstitial lung disease, occurred in a small proportion of patients and can lead to discontinuation or even be life-threatening. Pulmonary toxicity associated with these anti-tumor drugs is a problem that cannot be ignored in clinical practice. The prompt diagnosis of drug-related lung injury and the consequent differential diagnosis with other forms of pulmonary disease are critical in the management of pulmonary toxicity. Current knowledge of the pathophysiology and management of pulmonary toxicity associated with these targeted drugs is limited, and participants should be able to identify and respond to the development of drug-induced pulmonary toxicity. This review offers information about the potential pathogenesis, risk factors and management for the development of these events based on the available literature. This review focused on pulmonary toxicities in driver gene-positive NSCLC therapy by describing the related adverse events to promote the awareness and management of this important toxicity related to antitumor-targeted therapy.

LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion.

LAG1 longevity assurance homolog 2 (LASS2), a highly conserved transmembrane protein, has been reported in several cancer types. However, the roles of LASS2 in glioma biology remain elusive. In the present study, we investigated the expression of LAAS2 in human glioma tissues and the effects of LASS2 on glioma stem cell (GSC) proliferation. Roles of LASS2 in glioma cell migration and invasion were also researched both in vitro and in vivo. Our results demonstrated that the level of LASS2 is gradually reduced with the increase of glioma grade. The level of LASS2 is significantly lower in GSCs than in non GSCs, whereas LASS2 overexpression reduced the sphere formation and promoted the differentiation of CD133+ glioblastoma cells, as was indicated by reduced levels of CD133 and Nestin. In addition, LASS2 overexpression significantly reduced colony formation, migration, and invasion of glioma cells by promoting tumor cell apoptosis and inhibiting epithelial-mesenchymal transition (EMT). Overexpression of LASS2 inhibited U-87 MG cell-derived glioma xenograft growth in nude mice in a manner similar to in vitro. Our findings indicate that LASS2 can function as a suppressor of glioma growth, suggesting that modulation of LASS2 expression may contribute to a novel strategy for the management of glioma via inhibition of GSCs.

Long-Time Memory and Ternary Logic Gate Using a Multistable Cavity Magnonic System.

Multistability is an extraordinary nonlinear property of dynamical systems and can be explored to implement memory and switches. Here we experimentally realize the tristability in a three-mode cavity magnonic system with Kerr nonlinearity. The three stable states in the tristable region correspond to the stable solutions of the frequency shift of the cavity magnon polariton under specific driving conditions. We find that the system staying in which stable state depends on the history experienced by the system, and this state can be harnessed to store the history information. In our experiment, the memory time can reach as long as 5.11 s. Moreover, we demonstrate the ternary logic gate with good on-off characteristics using this multistable hybrid system. Our new findings pave a way towards cavity magnonics-based information storage and processing.

Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review.

BACKGROUND: Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). CASE PRESENTATIONS: Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. CONCLUSIONS: LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.

Lipoprotein(a) is associated with coronary atheroma progression: analysis from a serial coronary computed tomography angiography study.

BACKGROUND: Lipoprotein(a) [Lp(a)] has been closely related to coronary atherosclerosis and might affect perivascular inflammation due to its proinflammatory properties. However, there are limited data about Lp(a) and related perivascular inflammation on coronary atheroma progression. Therefore, this study aimed to investigate the associations between Lp(a) and the perivascular fat attenuation index (FAI) with coronary atheroma progression detected by coronary computed tomography angiography (CCTA). METHODS: Patients who underwent serial CCTA examinations without a history of revascularization and with available data for Lp(a) within one month before or after baseline and follow-up CCTA imaging scans were considered to be included. CCTA quantitative analyses were performed to obtain the total plaque volume (TPV) and the perivascular FAI. Coronary plaque progression (PP) was defined as a ≥ 10% increase in the change of the TPV at the patient level or the presence of new-onset coronary atheroma lesions. The associations between Lp(a) or the perivascular FAI with PP were examined by multivariate logistic regression. RESULTS: A total of 116 patients were ultimately enrolled in the present study with a mean CCTA interscan interval of 30.80 ± 13.50 months. Among the 116 patients (mean age: 53.49 ± 10.21 years, males: 83.6%), 32 patients presented PP during the follow-up interval. Lp(a) levels were significantly higher among PP patients than those among non-PP patients at both baseline [15.80 (9.09-33.60) mg/dLvs. 10.50 (4.75-19.71) mg/dL,P = 0.029] and follow-up [20.60 (10.45-34.55) mg/dLvs. 8.77 (5.00-18.78) mg/dL,P = 0.004]. However, there were no differences in the perivascular FAI between PP group and non-PP group at either baseline or follow-up. Multivariate logistic regression analysis showed that elevated baseline Lp(a) level (OR = 1.031, 95% CI: 1.005-1.058,P = 0.019) was an independent risk factor for PP after adjustment for other conventional variables. CONCLUSIONS: Lp(a) was independently associated with coronary atheroma progression beyond low-density lipoprotein cholesterol and other conventional risk factors. Further studies are warranted to identify the inflammation effect exhibited as the perivascular FAI on coronary atheroma progression.

Unconventional Singularity in Anti-Parity-Time Symmetric Cavity Magnonics.

By engineering an anti-parity-time (anti-PT) symmetric cavity magnonics system with precise eigenspace controllability, we observe two different singularities in the same system. One type of singularity, the exceptional point (EP), is produced by tuning the magnon damping. Between two EPs, the maximal coherent superposition of photon and magnon states is robustly sustained by the preserved anti-PT symmetry. The other type of singularity, arising from the dissipative coupling of two antiresonances, is an unconventional bound state in the continuum (BIC). At the settings of BICs, the coupled system exhibits infinite discontinuities in the group delay. We find that both singularities coexist at the equator of the Bloch sphere, which reveals a unique hybrid state that simultaneously exhibits the maximal coherent superposition and slow light capability.

SMRT sequencing revealed to be an effective method for ADTKD-MUC1 diagnosis through follow-up analysis of a Chinese family.

We reported a large Chinese family diagnosed with autosomal dominant tubulointerstitial kidney disease caused by MUC1 mutation (ADTKD-MUC1). Cytosine duplication within a string of 7 cytosines in the variable-number tandem repeats (VNTR) region of the MUC1 gene was detected by long-read single-molecule real-time (SMRT) sequencing. MUC1 frameshift protein (MUC1fs) was found to be expressed in renal tubules and urinary exfoliated cells by pathological examination. The family, which consisted of 5 generations including 137 individuals, was followed for 5 years. Genetic testing was performed in thirty-four individuals, 17 of whom carried MUC1 mutations. The ADTKD-MUC1-affected individuals had an elevated incidence of hyperuricaemia without gout attack. Within five years, higher baseline levels of urinary α1-microglobulin were detected in affected individuals with rapidly progressing renal failure than in affected individuals with stable renal function, and the increases manifested even before increases in serum creatinine. This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function.

Instant ghost imaging: algorithm and on-chip implementation.

Ghost imaging (GI) is an imaging technique that uses the correlation between two light beams to reconstruct the image of an object. Conventional GI algorithms require large memory space to store the measured data and perform complicated offline calculations, limiting practical applications of GI. Here we develop an instant ghost imaging (IGI) technique with a differential algorithm and an implemented high-speed on-chip IGI hardware system. This algorithm uses the signal between consecutive temporal measurements to reduce the memory requirements without degradation of image quality compared with conventional GI algorithms. The on-chip IGI system can immediately reconstruct the image once the measurement finishes; there is no need to rely on post-processing or offline reconstruction. This system can be developed into a realtime imaging system. These features make IGI a faster, cheaper, and more compact alternative to a conventional GI system and make it viable for practical applications of GI.

Nonreciprocity and Unidirectional Invisibility in Cavity Magnonics.

We reveal the cooperative effect of coherent and dissipative magnon-photon couplings in an open cavity magnonic system, which leads to nonreciprocity with a considerably large isolation ratio and flexible controllability. Furthermore, we discover unidirectional invisibility for microwave propagation, which appears at the zero-damping condition for hybrid magnon-photon modes. A simple model is developed to capture the generic physics of the interference between coherent and dissipative couplings, which accurately reproduces the observations over a broad range of parameters. This general scheme could inspire methods to achieve nonreciprocity in other systems.

IgG4-related sialadenitis complicated with type III mixed cryoglobulinemia: A case report.

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice.

OBJECTIVE: Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice. DATA SOURCES: All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019. STUDY SELECTION: This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia. RESULTS: Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances. CONCLUSIONS: Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.