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Abstract Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

Objective(s): To investigate the protective effect of N-acetylcysteine (NAC) on septic acute kidney injury (SAKI) via regulating Sirtuin3 (SIRT3)-mediated mitochondrial dysfunction and apoptosis.Materials and Methods: By constructing SIRT3 knockout mice and culturing kidney tubular epithelial cells (KTECs), we assessed the changes of renal function and detected the protein expression of adenine nucleotide translocator (ANT), cyclophilin (CypD) and voltage-dependent anion channel (VDAC) using western-blotting, and simultaneously detected toll-like receptor 4 (TLR4), inhibitor of kappa B kinase (IKKβ), inhibitor of Kappa Bα (IκBα), and p65 protein expression. We observed mitochondrial damage of KTECs using a transmission electron microscope and assessed apoptosis by TdT-mediated dUTP Nick-End Labeling and flow cytometry. Results: SIRT3 deficiency led to the deterioration of renal function, and caused a significant increase in inducible nitric oxide synthase production, a decrease in mitochondrial volume, up-regulation of TLR4, IκBα, IKKβ, and p65 proteins, and up-regulation of ANT, CypD and VDAC proteins. However, NAC significantly improved renal function and down-regulated the expression of TLR4, IκBα, IKKβ, and p65 proteins. Furthermore, SIRT3 deficiency led to a significant increase in KTEC apoptosis, while NAC up-regulated the expression of SIRT3 and inhibited apoptosis.Conclusion: NAC has a significant protective effect on SAKI by inhibiting SIRT3-mediated mitochondrial dysfunction and apoptosis of KTECs.

The concept of Maxwell demon plays an essential role in connecting thermodynamics and information theory, while entanglement and nonlocality are fundamental features of quantum theory. Given the rapid advancements in the field of quantum information science, there is a growing interest and significance in investigating the connection between Maxwell demon and quantum correlation. The majority of research endeavors thus far have been directed toward the extraction of work from quantum correlation through the utilization of Maxwell demon. Recently, a novel concept called Maxwell demon-assisted Einstein-Podolsky-Rosen (EPR) steering has been proposed, which suggests that it is possible to simulate quantum correlation by doing work. This seemingly counterintuitive conclusion is attributed to the fact that Alice and Bob need classical communication during EPR steering task, a requirement that does not apply in the Bell test. In this study, we demonstrate Maxwell demon-assisted EPR steering with superconducting quantum circuits. By compiling and optimizing a quantum circuit to be implemented on a 2D superconducting chip, we were able to achieve a steering parameter of S_{2}=0.770±0.005 in the case of two measurement settings, which surpasses the classical bound of 1/sqrt[2] by 12.6 standard deviations. In addition, experimental observations have revealed a linear correlation between the nonlocality demonstrated in EPR steering and the work done by the demon. Considering the errors in practical operation, the experimental results are highly consistent with theoretical predictions. Our findings not only suggest the presence of a Maxwell demon loophole in the EPR steering, but also contribute to a deeper comprehension of the interplay between quantum correlation, information theory, and thermodynamics.

Abstract The mechanisms underlying glucocorticoid (GC)-induced obesity are poorly understood. Macrophages are the primary targets by which GCs exert pharmacological effects and perform critical functions in adipose tissue homeostasis. Here, we show that macrophages are essential for GC-induced obesity. Dexamethasone (Dex) strongly induced Krüppel-like factor 9 (Klf9) expression in macrophages. Similar to Dex, lentivirus-mediated Klf9 overexpression inhibits M1 and M2a markers expression, causing macrophage deactivation. Furthermore, the myeloid-specific Klf9 transgene promotes obesity. Conversely, myeloid-specific Klf9-knockout (mKlf9KO) mice are lean. Moreover, myeloid Klf9 knockout largely blocks obesity induced by chronic GC treatment. Mechanistically, GC-inducible KLF9 recruits the SIN3A/HDAC complex to the promoter regions of Il6, Ptgs2, Il10, Arg1, and Chil3 to inhibit their expression, subsequently reducing thermogenesis and increasing lipid accumulation by inhibiting STAT3 signaling in adipocytes. Thus, KLF9 in macrophages integrates the beneficial anti-inflammatory and adverse metabolic effects of GCs and represents a potential target for therapeutic interventions.

Object detection in Unmanned Aerial Vehicle (UAVs) faces a significant challenge in computer vision. Traditional methods are difficult to model object appearance feature with large scale variations and viewpoint differences, when drones fly at different altitudes and capture images from diverse shooting angles. To address this issue, we propose a Learnable Cross-scale Sparse Attention (LCSA) guided feature fusion method to improve the performance of UAV object detection. Specifically, the LCSA feature fusion module enables each point in a feature map to aggregate discriminative information from a set of points with learnable offsets in neighbor feature maps. It enhances local discriminative features of the object by facilitating semantic information interaction across multiple feature maps. The LCSA can function as a novel neck method that complements the existing neck methods and is also transplantable to different object detection frameworks. Moreover, we also employ a scale-aware loss function to integrate the normalized Wasserstein distance with CIoU in order to improve the incompatibility of IoU for objects with large scale variance. Experimental results on the SeaDroneSeev2 and VisDrone2019-DET datasets show that the proposed method achieves superior performance. At a resolution of 640*640, our method achieves 81.9% AP50 and 47.4% AP on SeaDroneSeev2, surpassing baseline 4.9% and 4.8%, achieves state-of-the-art performance. Furthermore, our method outperforms baseline by 5% AP on VisDrone2019-DET. Code will be available at https://github.com/qch777/LSACF.

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD’s inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

Abstract Background Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. Aims In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. Methods SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. Results In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. Conclusions In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

Abstract Although originally predicted in relativistic quantum mechanics, Zitterbewegung can also appear in some classical systems, which leads to the important question of whether Zitterbewegung of Dirac particles is underlain by a more fundamental and universal interference behavior without classical analogs. We here reveal such an interference pattern in phase space, which underlies but goes beyond Zitterbewegung, and whose nonclassicality is manifested by the negativity of the phase space quasiprobability distribution, and the associated pseudospin-momentum entanglement. We confirm this discovery by numerical simulation and an on-chip experiment, where a superconducting qubit and a quantized microwave field respectively emulate the internal and external degrees of freedom of a Dirac particle. The measured quasiprobability negativities agree well with the numerical simulation. Besides being of fundamental importance, the demonstrated nonclassical effects are useful in quantum technology.

Abstract The quantum Hall effect, fundamental in modern condensed matter physics, continuously inspires new theories and predicts emergent phases of matter. Here we experimentally demonstrate three types of Chern insulators with synthetic dimensions on a programable 30-qubit-ladder superconducting processor. We directly measure the band structures of the 2D Chern insulator along synthetic dimensions with various configurations of Aubry-André-Harper chains and observe dynamical localisation of edge excitations. With these two signatures of topology, our experiments implement the bulk-edge correspondence in the synthetic 2D Chern insulator. Moreover, we simulate two different bilayer Chern insulators on the ladder-type superconducting processor. With the same and opposite periodically modulated on-site potentials for two coupled chains, we simulate topologically nontrivial edge states with zero Hall conductivity and a Chern insulator with higher Chern numbers, respectively. Our work shows the potential of using superconducting qubits for investigating different intriguing topological phases of quantum matter.

Objective(s): We aimed to study the effect of S-nitroso glutathione (SNG) on acute kidney injury (AKI) in septic rats by regulating nucleotide oligomerization domain-like receptor protein 3 (NLRP3).Materials and Methods: Sprague Dawley rats were used to construct the AKI model, and biochemical methods were used to detect the levels of inflammatory factors and anti-oxidant enzymes in renal tissue. We observed the ultrastructural changes of renal tissue by transmission electron microscopy and detected the protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain foci (ASC) and Caspase-1 by western-blotting and RT-qPCR. Results: Cecal ligation and puncture induced renal tubular epithelial tissue damage in septic rats, resulting in decreased renal function, increased levels of inflammation and decreased levels of anti-oxidant enzymes in renal tissue, and aggravated mitochondrial damage, significantly decreased mitochondrial density and enzyme complex I/II/III/IV levels (all P

Abstract Hawking radiation is one of the quantum features of a black hole that can be understood as a quantum tunneling across the event horizon of the black hole, but it is quite difficult to directly observe the Hawking radiation of an astrophysical black hole. Here, we report a fermionic lattice-model-type realization of an analogue black hole by using a chain of 10 superconducting transmon qubits with interactions mediated by 9 transmon-type tunable couplers. The quantum walks of quasi-particle in the curved spacetime reflect the gravitational effect near the black hole, resulting in the behaviour of stimulated Hawking radiation, which is verified by the state tomography measurement of all 7 qubits outside the horizon. In addition, the dynamics of entanglement in the curved spacetime is directly measured. Our results would stimulate more interests to explore the related features of black holes using the programmable superconducting processor with tunable couplers.

Abstract Quantum entanglement between an interfering particle and a detector for acquiring the which-path information plays a central role for enforcing Bohr’s complementarity principle. However, the quantitative relation between this entanglement and the fringe visibility remains untouched upon for an initial mixed state. Here we find an equality for quantifying this relation. Our equality characterizes how well the interference pattern can be preserved when an interfering particle, initially carrying a definite amount of coherence, is entangled, to a certain degree, with a which-path detector. This equality provides a connection between entanglement and interference in the unified framework of coherence, revealing the quantitative entanglement-interference complementarity. We experimentally demonstrate this relation with a superconducting circuit, where a resonator serves as a which-path detector for an interfering qubit. The measured fringe visibility of the qubit’s Ramsey signal and the qubit-resonator entanglement exhibit a complementary relation, in well agreement with the theoretical prediction.

Abstract Quantum simulation enables study of many-body systems in non-equilibrium by mapping to a controllable quantum system, providing a powerful tool for computational intractable problems. Here, using a programmable quantum processor with a chain of 10 superconducting qubits interacted through tunable couplers, we simulate the one-dimensional generalized Aubry-André-Harper model for three different phases, i.e., extended, localized and critical phases. The properties of phase transitions and many-body dynamics are studied in the presence of quasi-periodic modulations for both off-diagonal hopping coefficients and on-site potentials of the model controlled respectively by adjusting strength of couplings and qubit frequencies. We observe the spin transport for initial single- and multi-excitation states in different phases, and characterize phase transitions by experimentally measuring dynamics of participation entropies. Our experimental results demonstrate that the recently developed tunable coupling architecture of superconducting processor extends greatly the simulation realms for a wide variety of Hamiltonians, and can be used to study various quantum and topological phenomena.

It has been predicted that entanglement phase diagrams of Haar-measure random states can show interesting phenomenology, including entanglement phase transitions. Here, the authors confirm these predictions using up to 15 qubits in a fully-connected superconducting quantum processor.

Utilizing quantum computer to investigate quantum chemistry is an important research field nowadays. In addition to the ground-state problems that have been widely studied, the determination of excited-states plays a crucial role in the prediction and modeling of chemical reactions and other physical processes. Here, we propose a non-variational full circuit-based quantum algorithm for obtaining the excited-state spectrum of a quantum chemistry Hamiltonian. Compared with previous classical-quantum hybrid variational algorithms, our method eliminates the classical optimization process, reduces the resource cost caused by the interaction between different systems, and achieves faster convergence rate and stronger robustness against noise without barren plateau. The parameter updating for determining the next energy-level is naturally dependent on the energy measurement outputs of the previous energy-level and can be realized by only modifying the state preparation process of ancillary system, introducing little additional resource overhead. Numerical simulations of the algorithm with hydrogen, LiH, H2O and NH3 molecules are presented. Furthermore, we offer an experimental demonstration of the algorithm on a superconducting quantum computing platform, and the results show a good agreement with theoretical expectations. The algorithm can be widely applied to various Hamiltonian spectrum determination problems on the fault-tolerant quantum computers.

AIM: To report a case which keratitis is the first clinical manifestation of COVID-19 that occurred 3d earlier than the common COVID-19 symptoms. METHODS: Regular slit lamp examination, corneal scraping test, and chest computed tomography (CT) were performed for patients with COVID-19 infection. The ophthalmologic treatment included ganciclovir eye drop (50 mg/mL, 6 times/d). The treatment for diarrhea included Guifu Lizhong pills (TID). The antiviral therapy consisted of oseltamivir (75 mg capsule Q12H); therapy preventing bacterial infection consisted of azithromycin (250 mg tablet QD) and moxifloxacin (0.4 g tablet Q12H); and therapy for cough relief and fever prevention consisted of Chinese herbal decoction. RESULTS: A 35-year-old male suddenly suffered pain, photophobia, and tears in his right eye for one day without systemic COVID-19 symptoms. Patient was diagnosed with keratitis, which was seemingly different from common keratitis. Ganciclovir eye drop was initiated. The corneal scraping test for COVID-19 was positive. The chest CT images were abnormal confirming the diagnosis of COVID-19 infection. The antiviral and antibacterial therapies were initiated. Chinese herbal therapy was used for cough relief and fever prevention. After roughly two weeks, patient recovered from COVID-19. CONCLUSION: A new type of keratitis, atypical keratitis, is a clinical manifestation of COVID-19, and this clinical manifestation could appear 3d earlier than fever and cough. The earlier a COVID-19 clinical manifestation is identified, the earlier can a patient be directed to stay at home, and significantly fewer people would be infected.

Abstract We illustrate two linear configurations (one-side model and two-side model) for implementing a non-Markovian speedup evolution of a massive particle gravitationally coupled with a controllable environment: multiple massive particles. By controlling the environment, for instance by choosing a judicious the mass of the environmental particles or by changing the separation distance of each massive particle, two dynamical crossover behaviors from Markovian to non-Markovian and from no-speedup to speedup are achieved due to the gravitational interactions between the system particle and each environmental particle. Numerical calculation also shows that the critical mass of the environmental particles or the critical separation distance for these two dynamical crossover behaviors restrict each other directly. The larger the value of the mass of the environmental particles is, the smaller the value of the critical separation distance should be requested. In this work, the non-Markovian dynamics is the principal physical reason for the speedup evolution of a quantum system. Particularly, the non-Markovianity of the system mass particle in the two-side model has better correspondence with the quantum speed limit time than that in the one-side model.

Objective(s): Acute lung injury (ALI) is a common comorbidity in patients with sepsis, and finding drugs that can effectively reduce its mortality is a hot spot in current research. The purpose of this study is to explore the protective mechanism of N-acetylcysteine (NAC) on ALI in septic rats.Materials and Methods: We used NAC to intervene in septic rats to evaluate the plasma inflammatory factors and lung tissue pathological damage. Biochemical methods were used to determine the levels of oxidases in lung tissue, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) proteins, and observed lung tissue cell apoptosis.Results: NAC pretreatment decreased the mortality of septic rats, improved lung tissue pathological damage, reduced the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, and malondialdehyde, and increased activity of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, NAC pretreatment significantly decreased iNOS protein expression and increased eNOS protein expression in lung tissue. Meanwhile, NAC significantly decreased the number of apoptosis and the levels of Bax and Caspase-3 mRNA and increased the level of Bcl-2 mRNA in the lung tissue of septic rats. Conclusion: NAC protects ALI in septic rats by inhibiting inflammation, oxidative stress, and apoptosis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Efficient preparation of spin-squeezed states is important for quantum-enhanced metrology. Current protocols for generating strong spin squeezing rely on either high dimensionality or long-range interactions. A key challenge is how to generate considerable spin squeezing in one-dimensional systems with only nearest-neighbor interactions. Here, we develop variational spin-squeezing algorithms to solve this problem. We consider both digital and analog quantum circuits for these variational algorithms. After the closed optimization loop of the variational spin-squeezing algorithms, the generated squeezing can be comparable to the strongest squeezing created from two-axis twisting. By analyzing the experimental imperfections, the variational spin-squeezing algorithms proposed in this paper are feasible in recently developed noisy intermediate-scale quantum computers.

Abstract Generative adversarial networks are an emerging technique with wide applications in machine learning, which have achieved dramatic success in a number of challenging tasks including image and video generation. When equipped with quantum processors, their quantum counterparts—called quantum generative adversarial networks (QGANs)—may even exhibit exponential advantages in certain machine learning applications. Here, we report an experimental implementation of a QGAN using a programmable superconducting processor, in which both the generator and the discriminator are parameterized via layers of single- and two-qubit quantum gates. The programmed QGAN runs automatically several rounds of adversarial learning with quantum gradients to achieve a Nash equilibrium point, where the generator can replicate data samples that mimic the ones from the training set. Our implementation is promising to scale up to noisy intermediate-scale quantum devices, thus paving the way for experimental explorations of quantum advantages in practical applications with near-term quantum technologies.

Abstract Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder significantly decreasing patients’ lives of quality and placing huge economic burden on our society. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued. It is clinically important to assess these post-treatment therapeutic effects (PTTE), which prevent IBS from relapsing. To assess the PTTE in pinaverium treatment and obtain high-quality evidence to justify the use of PTTE for long-term IBS management, we performed this controlled, double blind study on patients with IBS who were randomized to pinaverium 50 mg (n = 132) or placebo (n = 132), three times daily, for 4 weeks, and were followed up for 57 weeks after the treatments. The primary endpoints were abdominal pain and stool consistency. The secondary endpoints were pain frequency and stool frequency. The tertiary endpoints were global overall symptom and adverse events. Three days after pinaverium was discontinued, endpoints rebounded only 23.2–42.8% (P 0.05)], during which an average of 51.5–56.4% of patients (pool pinaverium and placebo data together) had IBS symptoms. These results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment. Trial registration number: NCT02330029 (16/08/2016).

Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17–25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P

Objective(s): To explore the regulation mechanism of Sirtuin 3 (SIRT3) on the mitochondrial function and apoptosis of acute kidney injury (AKI) in septic mice.Materials and Methods: The sepsis-induced AKI model was constructed in the wild-type and SIRT3 knockout (KO) mice, and the levels of serum creatinine (Scr) and plasma kidney injury molecule 1 (pKIM-1) in mice were detected by ELISA. The mitochondrial damage of kidney tubular epithelial cells (KTEC) was observed by electron microscopy, the apoptosis of KTEC was detected by TUNEL assay, and the mRNA levels of SIRT3, Bax, Caspase-3, and Bcl-2 were detected by RT-qPCR.Results: SIRT3 KO caused increased expression of Scr, pKIM-1, and inducible nitric oxide synthase protein in the kidneys of septic mice, and decreased the levels of superoxide dismutase, catalase, and mitochondrial complex enzymes I/II/III/IV. SIRT3 deficiency exacerbated histopathological and mitochondrial damage to the proximal tubules of the kidney. In addition, SIRT3 KO resulted in a significantly increased apoptosis of KTEC, increased the mRNA levels of Bax and Caspase-3, and decreased the mRNA levels of Bcl-2. Conclusion: Our study suggests that SIRT3 deficiency promotes sepsis-induced AKI via increasing oxidative stress, mitochondrial dysfunction, and inducing apoptosis.

Abstract Background The bone marrow mesenchymal stem cell (BMSCs)-derived extracellular vesicles (EVs) open up a new avenue for ulcerative colitis (UC) treatment recently, but they are not selectively enriched in targeted tissues. EphB2, a cell-to-cell signaling receptor, is identified as a regulator for inflammatory response, immune homeostasis and cell migration. In this study, we investigated the therapeutic potential and underlying mechanism for EphB2 over-expressing BMSCs derived EVs (EphB2-EVs) in the treatment of UC. Methods BMSCs and EVs were obtained and characterized by a series of experiments. Lentivirus vector encoding EphB2 was transfected into BMSCs and verified by qRT-PCR. We analyzed the EphB2-EVs ability of colonic targeting in a DSS-induced colitis model by using confocal microscope and WB. The protective effect of EphB2-EVs in vivo was systematically evaluated by using a series of function experiments. Results We successfully constructed EphB2-overexpressing BMSCs derived EVs (EphB2-EVs). Overexpression of EphB2 significantly enhanced the homing of EVs to the damaged colon. In addition, EphB2-EVs were effective to attenuate inflammation in intestinal mucosa and restore the damaged colon tissue by inhibiting the release of proinflammatory cytokines and upregulating the anti-inflammatory mediators. EphB2-EVs effectively reduced the oxidative stress and repaired the intestinal mucosal barrier in the UC rats. Moreover, EphB2-EVs demonstrated a robust immunomodulatory effect to restore immune homeostasis via modulating Th17/Treg balance and restraining STAT3 activation. Conclusions Our results suggest that EphB2-EVs have high colonic targeting ability and could mitigate DSS-induced colitis via maintaining colonic immune homeostasis. These findings provide an effective therapeutic strategy for UC treatment in clinic.

Abstract The Bloch oscillation (BO) and Wannier-Stark localization (WSL) are fundamental concepts about metal-insulator transitions in condensed matter physics. These phenomena have also been observed in semiconductor superlattices and simulated in platforms such as photonic waveguide arrays and cold atoms. Here, we report experimental investigation of BOs and WSL simulated with a 5-qubit programmable superconducting processor, of which the effective Hamiltonian is an isotropic X Y spin chain. When applying a linear potential to the system by properly tuning all individual qubits, we observe that the propagation of a single spin on the chain is suppressed. It tends to oscillate near the neighborhood of their initial positions, which demonstrates the characteristics of BOs and WSL. We verify that the WSL length is inversely correlated to the potential gradient. Benefiting from the precise single-shot simultaneous readout of all qubits in our experiments, we can also investigate the thermal transport, which requires the joint measurement of more than one qubits. The experimental results show that, as an essential characteristic for BOs and WSL, the thermal transport is also blocked under a linear potential. Our experiment would be scalable to more superconducting qubits for simulating various of out-of-equilibrium problems in quantum many-body systems.

Abstract No-cloning theorem forbids perfect cloning of an unknown quantum state. A universal quantum cloning machine (UQCM), capable of producing two copies of any input qubit with the optimal fidelity, is of fundamental interest and has applications in quantum information processing. This is enabled by delicately tailored nonclassical correlations between the input qubit and the copying qubits, which distinguish the UQCM from a classical counterpart, but whose experimental demonstrations are still lacking. We here implement the UQCM in a superconducting circuit and investigate these correlations. The measured entanglements well agree with our theoretical prediction that they are independent of the input state and thus constitute a universal quantum behavior of the UQCM that was not previously revealed. Another feature of our experiment is the realization of deterministic and individual cloning, in contrast to previously demonstrated UQCMs, which either were probabilistic or did not constitute true cloning of individual qubits.

Lattice gauge theories (LGTs) are one of the most fundamental subjects in many-body physics, and has recently attracted considerable research interests in quantum simulations. Here we experimentally investigate the emergent Z_{2} gauge invariance in a 1D superconducting circuit with 10 transmon qubits. By precisely adjusting staggered longitudinal and transverse fields to each qubit, we construct an effective Hamiltonian containing an LGT and gauge-broken terms. The corresponding matter sector can exhibit a localization, and there also exists a 3-qubit operator, of which the expectation value can retain nonzero for a long time in low-energy regimes. The above localization can be regarded as the confinement of matter fields, and the 3-body operator is the Z_{2} gauge generator. These experimental results demonstrate that, despite the absence of gauge structure in the effective Hamiltonian, Z_{2} gauge invariance can still emerge in low-energy regimes. Our work provides a method for both theoretically and experimentally studying the rich physics in quantum many-body systems with emergent gauge invariance.

Objective(s): To investigate the protective effect of S-nitrosoglutathione (SNG) pretreatment on acute lung injury (ALI) in septic rats. Materials and Methods: We constructed a rat model of sepsis by cecal ligation and perforation (CLP), and randomly divided into Sham, CLP, and CLP+SNG (0.25 and 0.5 mg/kg) groups. We used H&E staining and lung wet/dry ratio to assess the severity of lung injury, detected the levels of protein and cells in bronchoalveolar lavage fluid (BALF) and the levels of TNF-α, IL-1β, TLR4 mRNA, and NF-κB p65 mRNA in the lung tissue, and assessed the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in the lung tissue.Results: A rat model of sepsis was successfully constructed by CLP, and pretreatment of SNG significantly increased the survival of septic rats (PConclusion: SNG pretreatment has a protective effect on ALI in septic rats, and the specific mechanism may be related to anti-endotoxic, anti-inflammatory, and anti-oxidative properties.

Oxidative stress, caused by excessive production of reactive oxygen species (ROS), plays a crucial role in the occurrence and development of ulcerative colitis (UC). We developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against UC with oral administration. The NPs were fabricated with a d-α-tocopherol polyethylene glycol succinate-b-poly(β-thioester) copolymer (TPGS-PBTE) for ROS cleavage via the colitis-targeted delivery of luteolin (LUT), a natural flavonoid with good anti-inflammation and radical-scavenging activity. Owing to the thioether bond in the polymer main chain, the TPGS-PBTE NPs exhibited an ROS-responsive size change and drug release, which benefited the ROS-scavenging and selective accumulation of LUT in the inflamed colon. In a dextran sulfate sodium-induced acute colitis murine model, LUT@TPGS-PBTE NPs alleviated body weight loss, colon length shortening, and damage to the colonic tissues due to the suppression of ROS and proinflammatory cytokines (e.g., IL-17A, IL-6, interferon-γ, tumor necrosis factor-α), as well as upregulation of glutathione and anti-inflammatory factors (e.g., IL-10, IL-4). More importantly, LUT@TPGS-PBTE NPs regulated the inflammatory microenvironment by modulating the T helper (Th)1/Th2 and Th17/regulatory T cell (Treg) balance (i.e., increased numbers of Tregs and Th2 cells and decreased numbers of Th1 and Th17 ​cells), thus resolving inflammation and accelerating the healing of the intestinal mucosa. Additionally, the LUT@TPGS-PBTE NPs formulation enabled the reduction of the effective dose of LUT and showed excellent biosafety in the mouse model, demonstrating its potential as a targeted UC therapeutic oral preparation.

The variational preparation of complex quantum states using the quantum approximate optimization algorithm (QAOA) is of fundamental interest, and becomes a promising application of quantum computers. Here, we systematically study the performance of QAOA for preparing ground states of target Hamiltonians near the critical points of their quantum phase transitions, and generating Greenberger–Horne–Zeilinger (GHZ) states. We reveal that the performance of QAOA is related to the translational invariance of the target Hamiltonian: without the translational symmetry, for instance due to the open boundary condition (OBC) or randomness in the system, the QAOA becomes less efficient. We then propose a generalized QAOA assisted by the parameterized resource Hamiltonian (PRH-QAOA), to achieve a better performance. In addition, based on the PRH-QAOA, we design a low-depth quantum circuit beyond one-dimensional geometry, to generate GHZ states with perfect fidelity. The experimental realization of the proposed scheme for generating GHZ states on Rydberg-dressed atoms is discussed. Our work paves the way for performing QAOA on programmable quantum processors without translational symmetry, especially for recently developed two-dimensional quantum processors with OBC.

The SARS-CoV-2 and its variants are still hitting the world. Ever since the outbreak, neurological involvements as headache, ageusia, and anosmia in COVID-19 patients have been emphasized and reported. But the pathogenesis of these new-onset neurological manifestations in COVID-19 patients is still obscure and controversial. As difficulty always lay in the diagnosis of neurological infection, current reports to validate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) almost relied on the basic methods and warranted improvement. Here we reported a case series of 8 patients with prominent new-onset neurological manifestations, who were screened out from a patch of 304 COVID-19 confirmed patients. Next-generation sequencing (NGS) and proteomics were conducted in the simultaneously obtained CSF and serum samples of the selected patients, with three non-COVID-19 patients with matched demographic features used as the controls for proteomic analysis. SARS-CoV-2 RNA was detected in the CSF of four COVID-19 patients and was suspicious in the rest four remaining patients by NGS, but was negative in all serum samples. Proteomic analysis revealed that 185 and 59 proteins were differentially expressed in CSF and serum samples, respectively, and that only 20 proteins were shared, indicating that the proteomic changes in CSF were highly specific. Further proteomic annotation highlighted the involvement of complement system, PI3K-Akt signaling pathway, enhanced cellular interaction, and macrophages in the CSF proteomic alterations. This study, equipped with NGS and proteomics, reported a high detection rate of SARS-CoV-2 in the CSF of COVID-19 patients and the proteomic alteration of CSF, which would provide insights into understanding the pathological mechanism of SARS-CoV-2 CNS infection.

We demonstrate that multipartite entanglement, witnessed by the quantum Fisher information, can characterize topological quantum phase transitions in the spin-1/2 toric code model (TCM) on a square lattice with external fields. We show that the quantum Fisher information density of the ground state can be written in terms of the expectation values of gauge-invariant Wilson loops for different sizes of square regions and identify Z_{2} topological order by its scaling behavior. Furthermore, we use this multipartite entanglement witness to investigate thermalization and disorder-assisted stabilization of topological order after a quantum quench. Moreover, with an upper bound of the quantum Fisher information, we demonstrate the absence of finite-temperature topological order in the two-dimensional TCM in the thermodynamic limit. Our results provide insights to topological phases, which are robust against external disturbances and are candidates for topologically protected quantum computation.

Aloperine, a quinolizidine-type alkaloid, was first isolated from the seeds and leaves of herbal plant, Sophora alopecuroides L. Empirically, Sophora alopecuroides L. is appreciated for its anti-dysentry effect, a property that is commonly observed in other Sophora Genus phytomedicines. Following the rationale of reductionism, subsequent biochemical analyses attribute such anti-dysentry effect to the bactericidal activity of aloperine. From then on, the multiple roles of aloperine are gradually revealed. Accumulating evidence suggests that aloperine possesses multiple pharmacological activities and holds a promising potential in clinical conditions including skin hyper-sensitivity, tumor and inflammatory disorders etc.; however, the current knowledge on aloperine is interspersed and needs to be summarized. To facilitate further investigation, herein, we conclude the key pharmacological functions of aloperine, and most importantly, the underlying cellular and molecular mechanisms are clarified in detail to explain the functional mode of aloperine.

BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity.MethodsDemographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19.ResultsThe counts and percentages of NK cells, CD4+ T cells, CD8+ T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3-CD56dimCD16+ cell population significantly decreased, while the CD3-CD56dimCD16- part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3-CD56dimCD16- cells were screened out as an influential factor in severe cases by LASSO logistic regression.ConclusionsThe functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.

Objective We aimed to investigate the diagnostic value of microRNA-155 (miR-155) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) in patients with sepsis. Methods In this prospective study, we used Spearman correlation analysis to investigate relationships between miR-155 expression and inflammatory factors, oxygenation ratio (PaO 2 /FiO 2 ), and ALI/ARDS score, and used area under the receiver operating characteristic curve (AU-ROC) to evaluate miR-155's diagnostic accuracy for ALI/ARDS in patients with sepsis. Results In total, 156 patients with sepsis were enrolled in our study, of which 41 had ALI and 32 had ARDS. miR-155 expression in plasma of patients with sepsis and ALI/ARDS was significantly higher than that of patients with sepsis but no ALI/ARDS. The miR-155 level in patients with sepsis and ALI/ARDS was positively correlated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels and ALI/ARDS score, but negatively correlated with PaO 2 /FiO 2 . The AU-ROC of plasma miR-155 for diagnosis of sepsis with ALI/ARDS was 0.87, and plasma miR-155, IL-1β, and TNF-α had high sensitivity and specificity for the diagnosis of sepsis with ALI/ARDS. Conclusion miR-155 is highly expressed in plasma of patients with septic ALI/ARDS; it is positively correlated with lung function and can be used for early diagnosis.

Objective We aimed to assess the effects of physical activity (PA) on depression symptoms in patients with IgA nephropathy (IgAN). Methods We developed a 6-month personalized PA training program for patients with IgAN. At the beginning and after completion of the training intervention, patients’ cardiopulmonary function was assessed via a spiroergometric study. Prior to the start of and after the intervention, we administered the Beck Depression Inventory-II (BDI-II), Eysenck Personality Questionnaire (EPQ), Quality of Life Index (QLI), Life Satisfaction Index, and Short Form-36 (SF-36) to all participants. Scores of the QLI were used as the dependent variable. Results A total of 216 patients were included in our analysis. After completing the PA training program, cardiopulmonary function and depressive symptoms were significantly improved in patients with IgAN, as compared with baseline values. Multiple logistic regression analysis showed that regular PA; extended hemodialysis interval; decreased scores of the BDI-II, EPQ, and SF-36 Mental Component Scale; and increased SF-36 Physical Component Scale scores were independently associated with improved QLI. Conclusions Regular PA may improve cardiopulmonary function, depression symptoms, and health-related quality of life in patients with IgAN.

In this Letter, we study the quantum nature of non-Bunch–Davies states in de Sitter space by evaluating CHSH inequality on a localized two-atom system. We show that quantum nonlocality can be generated through the Markovian evolution of two-atom, witnessed by a violation of CHSH inequality on its final equilibrium state. We find that the upper bound of inequality violation is determined by different choices of de Sitter-invariant vacua sectors. In particular, with growing Gibbons–Hawking temperature, the CHSH bound degrades monotonously for Bunch–Davies vacuum sector. Due to the intrinsic correlation of non-Bunch–Davies vacua, we find that the related violation of inequality can however drastically increase after certain turning point, and may persist for arbitrarily large environment decoherence. This implies that the CHSH inequality is useful to classify the initial quantum state of the Universe. Finally, we clarify that the witnessed intrinsic correlation of non-Bunch–Davies vacua can be utilized for quantum information applications, e.g., surpassing the Heisenberg uncertainty bound of quantum measurement in de Sitter space.

Abstract We investigate the behavior of coherence in scattering quantum walk search on complete graph under the condition that the total number of vertices of the graph is significantly larger than the marked number of vertices we are searching, N ≫ v. We find that the consumption of coherence represents the increase of the success probability for the searching, also it is related to the efficiency of the algorithm in oracle queries. If no coherence is consumed or an incoherent state is utilized, the algorithm will behave as the classical blind search, implying that coherence is responsible for the speed-up in this quantum algorithm over its classical counterpart. The effect of noises, in particular of photon loss and random phase shifts, on the performance of algorithm is studied. Two types of noise are considered because they arise in the optical network used for experimental realization of scattering quantum walk. It is found that photon loss will reduce the coherence and random phase shifts will hinder the interference between the edge states, both leading to lower success probability compared with the noise-free case. We then conclude that coherence plays an essential role and is responsible for the speed-up in this quantum algorithm.

Abstract One unique feature of quantum mechanics is the Heisenberg uncertainty principle, which states that the outcomes of two incompatible measurements cannot simultaneously achieve arbitrary precision. In an information-theoretic context of quantum information, the uncertainty principle can be formulated as entropic uncertainty relations with two measurements for a quantum bit (qubit) in two-dimensional system. New entropic uncertainty relations are studied for a higher-dimensional quantum state with multiple measurements, and the uncertainty bounds can be tighter than that expected from two measurements settings and cannot result from qubits system with or without a quantum memory. Here we report the first room-temperature experimental testing of the entropic uncertainty relations with three measurements in a natural three-dimensional solid-state system: the nitrogen-vacancy center in pure diamond. The experimental results confirm the entropic uncertainty relations for multiple measurements. Our result represents a more precise demonstrating of the fundamental uncertainty principle of quantum mechanics.

Tertiary lymphoid organs (TLOs) frequently develop locally in adults in response to non-resolving inflammation. Chronic inflammation leads to the differentiation of stromal fibroblast cells toward lymphoid tissue organizer-like cells, which interact with lymphotoxin α1β2+ immune cells. The interaction initiates lymphoid neogenesis by recruiting immune cells to the site of inflammation and ultimately leads to the formation of TLOs. Mature TLOs harbor a segregated T-cell zone, B-cell follicles with an activated germinal center, follicular dendritic cells, and high endothelial venules, which architecturally resemble those in secondary lymphoid organs. Since CXCL13 and LTα1β2 play key roles in TLO neogenesis, they might constitute potential biomarkers of TLO activity. The well-developed TLOs actively regulate local immune responses and influence disease progression, and they are thereby regarded as the powerhouses of local immunity. In this review, we recapitulated the determinants for TLOs development, with great emphasis on the fundamental role of chronic inflammation and tissue-resident stromal cells for TLO neogenesis, hence offering guidance for therapeutic interventions in TLO-associated diseases.

Objective To explore the protective effects and mechanisms of salidroside on myocardial injury induced by heat stroke (HS) in mice. Methods We pretreated mice with salidroside for 1 week and then established an HS model by exposure to 41.2°C for 1 hour. We then examined the effects of salidroside on survival. We also assessed the severity of cardiac injury by pathology, and analyzed changes in levels of myocardial injury markers, inflammatory cytokines, and oxidative stress. Results Salidroside pretreatment significantly reduced HS-induced mortality and improved thermoregulatory function. Salidroside also provided significant protection against HS-induced myocardial damage, and decreased the expression levels of cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase. Moreover, salidroside attenuated HS-induced changes in the inflammation markers tumor necrosis factor-α, interleukin (IL)-6, and IL-10, and down-regulated the oxidative stress response indicated by thiobarbituric acid reactant substances, malondialdehyde, reduced glutathione, and superoxide dismutase. Conclusions Salidroside pretreatment protected against HS-induced myocardial damage, potentially via a mechanism involving anti-inflammatory and anti-oxidative effects.

Background: Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) as the commonly used renin-angiotensin aldosterone system inhibitor are widely used in patients with IgA nephropathy (IgAN), but the effect is controversy. In this study, we used a meta-analysis to evaluate the efficacy and safety of ACEI and/or ARB for the patients with IgAN. Methods: Two investigators independently searched the PubMed, EMBASE, the Cochrane Library, EBSCO, and Wiley databases without language restrictions. We collected the clinical randomized controlled trials (RCTs) on “ACEI and/or ARB for the patients with IgAN” published before December 31, 2018, and performed data extraction and quality analysis on the included studies, and analyzed data using RevMan 5.2 software. Results: A total of 10 RCTs (635 patients) were included in our analysis. Alone use of ACEI (MD=-0.75, 95%CI: -1.28-0.21, P=0.006) or ARB (MD=-0.56, 95%CI: -0.82-0.30, P< 0.001) or a combination of ACEI and ARB (MD=-0.63, 95%CI: -0.87-0.38, P

Glucomannan, long recognized as the active ingredient of the traditional Chinese medicinal herb Konjac glucomannan, is a naturally occurring polysaccharide existing in certain plant species and fungi. Due to its special property to also serve as a dietary supplement, glucomannan has been widely applied in clinic to lower body weight and circulation cholesterol level and to treat constipation, diabetes, and arterial sclerosis. Besides the regulatory role engaged with gastroenterological and metabolic syndrome, recently, its therapeutic effect and the underlying mechanisms in treating cancerous diseases have been appreciated by mounting researches. The present review aims to emphasize the multifaceted aspects of how glucomannan exerts its anti-tumor function.

BackgroundEvidence on adverse effects of maternal macrolide use during pregnancy is inconsistent. We conducted a systematic review and meta-analysis to investigate the association between macrolide use during pregnancy and adverse fetal and child outcomes.Methods and findingsWe included observational studies and randomised controlled trials (RCTs) that recorded macrolide use during pregnancy and child outcomes. We prioritized comparisons of macrolides with alternative antibiotics (mainly penicillins or cephalosporins) for comparability of indication and effect. Random effects meta-analysis was used to derive pooled odds ratios (OR) for each outcome. Subgroup analyses were performed according to specific types (generic forms) of macrolide. Of 11,186 citations identified, 19 (10 observational, 9 RCTs) studies were included (21 articles including 228,556 participants). Macrolide prescribing during pregnancy was associated with an increased risk of miscarriage (pooled ORobs 1·82, 95% CI 1·57-2·11, three studies, I2 = 0%), cerebral palsy and/or epilepsy (ORobs 1·78, 1·18-2·69; one study), epilepsy alone (ORobs 2·02, 1·30-3·14, one study; ORRCT 1.03, 0.79-1.35, two studies), and gastrointestinal malformations (ORobs 1·56, 1·05-2·32, two studies) compared with alternative antibiotics. We found no evidence of an adverse effect on 12 other malformations, stillbirth, or neonatal death. Results were robust to excluding studies with high risk of bias.ConclusionsConsistent evidence of an increased risk of miscarriage in observational studies and uncertain risks of cerebral palsy and epilepsy warrant cautious use of macrolide in pregnancy with warnings in drug safety leaflets and use of alternative antibiotics where appropriate. As macrolides are the third most commonly used class of antibiotics, it is important to confirm these results with high quality studies.