Search

Abstract A foundational assumption of quantum error correction theory is that quantum gates can be scaled to large processors without exceeding the error-threshold for fault tolerance. Two major challenges that could become fundamental roadblocks are manufacturing high-performance quantum hardware and engineering a control system that can reach its performance limits. The control challenge of scaling quantum gates from small to large processors without degrading performance often maps to non-convex, high-constraint, and time-dynamic control optimization over an exponentially expanding configuration space. Here we report on a control optimization strategy that can scalably overcome the complexity of such problems. We demonstrate it by choreographing the frequency trajectories of 68 frequency-tunable superconducting qubits to execute single- and two-qubit gates while mitigating computational errors. When combined with a comprehensive model of physical errors across our processor, the strategy suppresses physical error rates by ~3.7× compared with the case of no optimization. Furthermore, it is projected to achieve a similar performance advantage on a distance-23 surface code logical qubit with 1057 physical qubits. Our control optimization strategy solves a generic scaling challenge in a way that can be adapted to a variety of quantum operations, algorithms, and computing architectures.

Soil thermal conductivity in the near-phase-transition zone is a key parameter affecting the thermal stability of permafrost engineering and its catastrophic thermal processes. Therefore, accurately determining the soil thermal conductivity in this specific temperature zone has important theoretical and engineering significance. In the present work, a method for testing the thermal conductivity of fine sandy soil in the near-phase-transition zone was proposed by measuring thermal conductivity with the transient plane heat source method and determining the volumetric specific heat capacity by weighing unfrozen water contents. The unfrozen water content of sand specimens in the near-phase-transition zone was tested, and a corresponding empirical fitting formula was established. Finally, based on the testing results, temperature variation trends and parameter influence laws of thermal conductivity in the near-phase-transition zone were analyzed, and thermal conductivity prediction models based on multiple regression (MR) and a radial basis function neural network (RBFNN) were also established. The results show the following: (1) The average error of the proposed test method in this work and the reference steady-state heat flow method is only 7.25%, which validates the reliability of the proposed test method. (2) The variation in unfrozen water contents in fine sandy soil in the range of 0~−3 °C accounts for over 80% of the variation in the entire negative temperature range. The unfrozen water content and thermal conductivity curves exhibit a similar trend, and the near-phase-transition zone can be divided into a drastic phase transition zone and a stable phase transition zone. (3) Increases in the thermal conductivity of fine sandy soil mainly occur the drastic phase transition zone, where these increases account for about 60% of the total increase in thermal conductivity in the entire negative temperature region. With the increase in density and total water content, the rate of increase in thermal conductivity in the drastic phase transition zone gradually decreases. (4) The R2, MAE, and RSME of the RBFNN model in the drastic phase transition zone are 0.991, 0.011, and 0.021, respectively, which are better than those of the MR prediction model.

Abstract Fast, high-fidelity operations between microwave resonators are an important tool for bosonic quantum computation and simulation with superconducting circuits. An attractive approach for implementing these operations is to couple these resonators via a nonlinear converter and actuate parametric processes with RF drives. It can be challenging to make these processes simultaneously fast and high fidelity, since this requires introducing strong drives without activating parasitic processes or introducing additional decoherence channels. We show that in addition to a careful management of drive frequencies and the spectrum of environmental noise, leveraging the inbuilt symmetries of the converter Hamiltonian can suppress unwanted nonlinear interactions, preventing converter-induced decoherence. We demonstrate these principles using a differentially-driven DC-SQUID as our converter, coupled to two high-Q microwave cavities. Using this architecture, we engineer a highly-coherent beamsplitter and fast (~100 ns) swaps between the cavities, limited primarily by their intrinsic single-photon loss. We characterize this beamsplitter in the cavities’ joint single-photon subspace, and show that we can detect and post-select photon loss events to achieve a beamsplitter gate fidelity exceeding 99.98%, which to our knowledge far surpasses the current state of the art.

Abstract Background and Aim Dengue fever, transmitted by Aedes mosquitoes, is a significant public health concern in tropical and subtropical regions. With the end of the COVID-19 pandemic and the reopening of the borders, dengue fever remains a threat to mainland China, Zhejiang province of China is facing a huge risk of importing the dengue virus. This study aims to analyze and predict the current and future potential risk regions for Aedes vectors distribution and dengue prevalence in Zhejiang province of China. Method We collected occurrence records of DENV and DENV vectors globally from 2010 to 2022, along with historical and future climate data and human population density data. In order to predict the probability of DENV distribution in Zhejiang province of China under future conditions, the ecological niche of Ae. aegypti and Ae. albopictus was first performed with historical climate data based on MaxEnt. Then, predicted results along with a set of bioclimatic variables, elevation and human population density were included in MaxEnt model to analyze the risk region of DENV in Zhejiang province. Finally, the established model was utilized to predict the spatial pattern of DENV risk in the current and future scenarios in Zhejiang province of China. Results Our findings indicated that approximately 89.2% (90,805.6 KM2) of Zhejiang province of China is under risk, within about 8.0% (8,144 KM2) classified as high risk area for DENV prevalence. Ae. albopictus were identified as the primary factor influencing the distribution of DENV. Future predictions suggest that sustainable and “green” development pathways may increase the risk of DENV prevalence in Zhejiang province of China. Conversely, Fossil-fueled development pathways may reduce the risk due to the unsuitable environment for vectors. Conclusions The implications of this research highlight the need for effective vector control measures, community engagement, health education, and environmental initiatives to mitigate the potential spread of dengue fever in high-risk regions of Zhejiang province of China.

In traditional Chinese medicine (TCM), the liver is the “general organ” that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang–xiang theory, yin–yang theory, meridians and collaterals theory, and the five–viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother–child relationships between the liver and the heart, and the yin–yang and exterior–interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex “pan-hepatic network” model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.

The recent emergence of COVID-19 variants has necessitated the development of new vaccines that stimulate the formation of high levels of neutralizing antibodies against S antigen variants. A new strategy involves the intradermal administration of heterologous vaccines composed of one or two doses of inactivated vaccine and a booster dose with the mutated S1 protein (K-S). Such vaccines improve the immune efficacy by increasing the neutralizing antibody titers and promoting specific T cell responses against five variants of the RBD protein. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that both administration schedules (i.e. “1 + 1” and “2 + 1”) ensured protection against this strain. These results suggest that the aforementioned strategy is effective for protecting against new variants and enhances the anamnestic immune response in the immunized population.

Type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), cardio-cerebrovascular diseases (CCVDs), hyperuricemia and gout, and metabolic-related sexual dysfunction are metabolic diseases that affect human health in modern society. Scientists have made great efforts to investigate metabolic diseases using cell models in vitro or animal models in the past. However, the findings from cells or animals are difficult to translate into clinical applications due to factors such as the in vitro and in vivo differences; the differences in anatomy, physiology, and genetics between humans and animals; and the differences in microbiome–host interaction. The Chinese have extensively used the medicated diet of traditional Chinese medicine (TCM) (also named as Yao-Shan of TCM, Chinese Yao-Shan et al.) to maintain or improve cardiometabolic health for more than 2,200 years. These ancient classic diets of TCM are essential summaries of long-term life and clinical practices. Over the past 5 years, our group has made every effort to collect and sort out the classic Yao-Shan of TCM from the ancient TCM literature since Spring and Autumn and Warring States Period, especially these are involved in the prevention and treatment of metabolic diseases, such as diabetes, NAFLD, CCVDs, hyperuricemia and gout, and sexual dysfunction. Here, we summarized and discussed the classic Yao-Shan of TCM for metabolic diseases according to the time recorded in the ancient literature, and revised the Latin names of the raw materials in these Yao-Shan of TCM. Moreover, the modern medicine evidences of some Yao-Shan of TCM on metabolic diseases have also been summarized and emphasized in here. However, the exact composition (in terms of ratios), preparation process, and dosage of many Yao-Shan are not standardized, and their main active ingredients are vague. Uncovering the mystery of Yao-Shan of TCM through modern biological and chemical strategies will help us open a door, which is ancient but now looks new, to modulate metabolic homeostasis and diseases.

Leptin (Lep) plays a crucial role in controlling food intake and maintaining energy balance in mammals. While several studies have shown the presence of multiple leptin genes in teleosts, limited information is currently available on how sex steroid hormones regulate the expression of these genes in fish. In this study, we used two previously expressed and purified leptin proteins to incubate four tissues in vitro (hypothalamic-pituitary-gonadal axis and liver) and used the RT-qPCR method to detect the expression of genes related to growth and reproduction in tongue sole (Cynoglossus semilaevis). The results showed that both recombinant LepA and LepB proteins of tongue sole almost entirely suppressed the expression of genes related to growth and reproduction in the hypothalamic-pituitary-gonadal axis and liver, while LepB may have had a positive role on steroid synthesis in gonads. Further, a high concentration of LepA facilitated the expression of IGF-Ι in liver. At the same time, we utilized human leptin to incubate four tissues in vitro; although most of them had trends similar to those stimulated with tongue sole leptins, there were still some differences, indicating differences among leptin homologs between humans and fishes. To our knowledge, this is the first study to explore the function of tongue sole LepA and LepB within the hypothalamic-pituitary-gonadal axis and liver in vitro. Our results provide a valuable resource and foundation for future studies.

LPXRFa, also known as gonadotropin-inhibitory hormone (GnIH), and kisspeptin (Kiss) are two major hypothalamic peptides that modulate the reproductive axis of vertebrates, including teleosts. However, little information is available regarding the actions of nutritional status on the regulation of these two neuroendocrine systems in fish. Herein, we assessed the effects of starvation and refeeding on the expression of lpxrfa, kiss2 and their receptors (lpxrfa-r and kiss2r respectively) at the brain-pituitary level of half-smooth tongue sole (Cynoglossus semilaevis). Food deprivation for 4 weeks induced a rise in brain lpxrfa as well as brain and pituitary lpxrfa-r mRNA levels, and refeeding restored brain lpxrfa and lpxrfa-r expression back to normal. However, pituitary lpxrfa-r mRNA levels still remained high after 1 week of refeeding. Neither lpxrfa nor kiss2 transcripts in the pituitary were altered by fasting, but their mRNA levels increased significantly after 1 week of refeeding, and declined back to the control levels after 2 weeks of refeeding. None of brain kiss2 and kiss2r along with pituitary kiss2r transcripts were modified by the nutritional status. In summary, our results revealed an interaction between energy status and the elements of LPXRFa and Kiss systems in the brain-pituitary axis of half-smooth tongue sole. Food deprivation and refeeding differentially regulated the two systems, which provided additional evidence for the involvement of the LPXRFa and Kiss systems in the regulation of reproduction by energy balance in non-mammalian species.

Encoding a qubit in a high-quality superconducting microwave cavity offers the opportunity to perform the first layer of error correction in a single device but presents a challenge: how can quantum oscillators be controlled while introducing a minimal number of additional error channels? We focus on the two-qubit portion of this control problem by using a three-wave-mixing coupling element to engineer a programmable beam-splitter interaction between two bosonic modes separated by more than an octave in frequency, without introducing major additional sources of decoherence. Combining this with single-oscillator control provided by a dispersively coupled transmon provides a framework for quantum control of multiple encoded qubits. The beam-splitter interaction g_{bs} is fast relative to the time scale of oscillator decoherence, enabling over 10^{3} beam-splitter operations per coherence time and approaching the typical rate of the dispersive coupling χ used for individual oscillator control. Further, the programmable coupling is engineered without adding unwanted interactions between the oscillators, as evidenced by the high on-off ratio of the operations, which can exceed 10^{5}. We then introduce a new protocol to realize a hybrid controlled-swap operation in the regime g_{bs}≈χ, in which a transmon provides the control bit for the swap of two bosonic modes. Finally, we use this gate in a swap test to project a pair of bosonic qubits into a Bell state with measurement-corrected fidelity of 95.5%±0.2%.

Background : Epithelial ovarian cancer (EOC) remains the leading cause of gynecologic cancer death worldwide due to the high recurrence rate. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality for platinum-sensitive recurrent EOC. The latest studies demonstrate homologous recombination-related (HRR) mutation status increases the sensitivity to platinum-based chemotherapy drugs in EOC. However, the molecular analysis of recurrent EOC patient benefits from HIPEC is unknown. Thus, we aimed to evaluate the efficacy and safety of CRS combined with HIPEC for platinum-sensitive in recurrent EOC with HRR mutation. Methods: This is a phase III randomized controlled clinical trial in patients with platinum-sensitive recurrent EOC. Participants were divided into 2 groups based on the HRR mutation status and randomized to receive CRS + HIPEC. The patients then received periodic chemotherapy and follow-up. Results: The primary objective of this study was to evaluate the effect of CRS + HIPEC compared to CRS alone in patients with a platinum-sensitive recurrent EOC stratified for HRD status. We hypothesize that the addition of HIPEC to CRS improves the progression-free survival (PFS) of platinum-sensitive recurrent EOC patients with HRR mutation compared with patients without HRR mutation. Conclusion: Recurrent EOC has a poor prognosis due to implantation and metastasis in the abdominal cavity. Intraperitoneal chemotherapy reduced seeding by removing free tumor cells. HIPEC utilizes physical and biological properties to significantly increase the clearance rate of tumors. Van Driel WJ et al proposed that HIPEC using platinum-based chemotherapy improves the survival of patients with ovarian cancer. HRR mutation, as a common pathogenic mutation in ovarian cancer, has a predictive effect on the platinum sensitivity of ovarian cancer patients. Whether lobaplatin-based HIPEC will play a greater role in ovarian cancer patients with HRR mutations is currently unknown.

Cardiocerebrovascular diseases (CCVDs) are the leading cause of death worldwide; therefore, to deeply explore the pathogenesis of CCVDs and to find the cheap and efficient strategies to prevent and treat CCVDs, these are of great clinical and social significance. The discovery of nitric oxide (NO), as one of the endothelium-derived relaxing factors and its successful utilization in clinical practice for CCVDs, provides new ideas for us to develop drugs for CCVDs: “gas medicine” or “medical gases.” The endogenous gas molecules such as carbon monoxide (CO), hydrogen sulfide (H2S), sulfur dioxide (SO2), methane (CH4), and hydrogen (H2) have essential biological effects on modulating cardiocerebrovascular homeostasis and CCVDs. Moreover, it has been shown that noble gas atoms such as helium (He), neon (Ne), argon (Ar), krypton (Kr), and xenon (Xe) display strong cytoprotective effects and therefore, act as the exogenous pharmacologic preventive and therapeutic agents for CCVDs. Mechanistically, besides the competitive inhibition of N-methyl-D-aspartate (NMDA) receptor in nervous system by xenon, the key and common mechanisms of noble gases are involved in modulation of cell death and inflammatory or immune signals. Moreover, gases interaction and reduction in oxidative stress are emerging as the novel biological mechanisms of noble gases. Therefore, to investigate the precise actions of noble gases on redox signals, gases interaction, different cell death forms, and the emerging field of gasoimmunology, which focus on the effects of gas atoms/molecules on innate immune signaling or immune cells under both the homeostatic and perturbed conditions, these will help us to uncover the mystery of noble gases in modulating CCVDs.

The nonanesthetic noble gas helium (He) can protect many organs against ischemia and reperfusion injury, such as liver and heart. However, the role of He on cardiac dysfunction during sepsis is not clear. In this study, we established a lipopolysaccharide (LPS)-induced cardiac dysfunction mouse model to examine the influence of He on the impaired cardiac function, and further investigated the possible innate immune mechanisms that may be involved. LPS induced left ventricular dysfunction and cavity enlargement, as indicated by decreased percent ejection fraction, percent fractional shortening, left ventricular anterior wall thickness in systole, and left ventricular posterior wall thickness in systole, while increased left ventricular end-systolic diameter and left ventricular end-systolic volume. He improved the impaired left ventricular function and cavity enlargement in a dose-dependent manner, and it was beneficial at 1.0 mL/100 g. Mechanistically, He inhibited toll-like receptor 4 (TLR4) expression, reduced the phosphorylation of nuclear factor κB (NF-κB), and subsequently alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) expression in heart. Therefore, He protects against LPS-induced cardiac dysfunction in mice partially via inhibiting myocardial TLR4-NF-κB-TNF-α/IL-18 signaling.

Although recent studies have revealed its involvement in fish reproduction, the physiological role of neurokinin B (NKB), which is encoded by the tachykinin 3 (tac3) gene, is still largely unclear in teleosts, with most researches on the orders Perciformes and Cypriniformes. In the current study we identified the tac3 gene in a representative species of Pleuronectiformes, the half-smooth tongue sole. The full-length cDNA sequence of tongue sole tac3 was 742 base pairs (bp) in length with an open reading frame of 372 bp that encoded a 123-amino acids preprohormone. The TAC3 precursor contained NKB and an additional peptide NKB-related peptide (NKBRP), both of which had an –FVGLM motif at the C-termini. Tissue distribution analysis indicated that tac3 transcripts were highly expressed in the brain, intestine and gonads of both sexes, and to a lesser extent in other tissues. Among various brain regions, tac3 transcripts were most abundant in the hypothalamus. In addition, the expression profiles of tac3 mRNA were also evaluated along the brain-pituitary-gonadal axis during tongue sole ovarian maturation. The brain tac3 mRNA levels remained unchanged, however, in both pituitary and ovary, the mRNA expression of tac3 increased significantly to the maximal levels at stage III and then declined back to basal levels. Taken together, our results encompass the first study reporting the existence of tac3 gene in a flatfish species and suggest its possible involvement in the control of reproduction in the half-smooth tongue sole.

The nucleosome assembly protein 1 (NAP1) family is the main histone chaperone of histone H2A–H2B. To explore the function of NAP1 family genes in moso bamboo (Phyllostachys edulis), characterized by extremely rapid growth and a long flowering cycle, we originally conducted a genome-wide analysis of the PheNAP1 gene. The phylogenetic relationship, gene expression pattern, DNA methylation, and histone modification were analyzed. Eventually, 12 PheNAP1 genes were recognized from the Phyllostachys edulis genome, divided into two sorts: the NRP subfamily (four members) and the NAP subfamily (eight members). Highly conserved motifs exist in each subfamily, which are distinct between subfamilies. PheNAP1 was distributed homogeneously on 10 out of 24 chromosomes, and gene duplication contributed significantly to the enhancement of the PheNAP1 gene in the genome. Cis-acting element analysis showed that PheNAP1 family genes are involved in light, hormone, and abiotic stress responses and may play an important role in the rapid growth and flowering. PheNAP1 exhibited the highest expression level in fast-growing shoots, indicating it is closely associated with the rapid growth of moso bamboo. Besides, PheNAP1 can rescue the early-flowering phenotype of nrp1-1 nrp2-2, and it affected the expression of genes related to the flowering pathway, like BSU1, suggesting the vital role that PheNAP1 may take in the flowering process of moso bamboo. In addition, histone modification results showed that PheNAP1 could bind to phosphorylation-, acetylation-, and methylation-modified histones to further regulate gene expression. A sketch appears: that PheNAP1 can accompany histones to regulate fast-growth- and flowering-related genes in moso bamboo. The consequences of this study enrich the understanding of the epigenetic regulation mechanism of bamboo plants and lays a foundation for further studies on the role of the NAP1 gene in Phyllostachys edulis and the function of chromatin regulation in forest growth and development.

In continuous-variable quantum computing with qubits encoded in the infinite-dimensional Hilbert space of bosonic modes, it is a difficult task to realize strong and on-demand interactions between the qubits. One option is to engineer a beamsplitter interaction for photons in two superconducting cavities by driving an intermediate superconducting circuit with two continuous-wave drives, as demonstrated in a recent experiment [Gao et al., Phys. Rev. X 8, 021073 (2018)10.1103/PhysRevX.8.021073]. Here we show how quantum optimal control theory (OCT) can be used in a systematic way to improve the beamsplitter interaction between the two cavities. We find that replacing the two-tone protocol by a three-tone protocol accelerates the effective beamsplitter rate between the two cavities. The third tone's amplitude and frequency are determined by gradient-free optimization and make use of cavity-transmon sideband couplings. We show how to further improve the three-tone protocol via gradient-based optimization while keeping the optimized drives experimentally feasible. Our work exemplifies how to use OCT to systematically improve practical protocols in quantum information applications.

Spexin (SPX) is a newly identified peptide hormone of 14 amino acids (aa) with pleiotropic functions in vertebrates, and recently a second paralog of SPX (named SPX2) has been only found in some non-mammalian species (the previous form of SPX is now designated as SPX1). Results of previous studies have revealed the existence of a functional SPX1 in the half-smooth tongue sole. To clarify the divergence of the spexin family, we further isolated the spx2 gene from the same flatfish species in the current study. The open reading frame of tongue sole spx2 was 378 nucleotides in size that encoded a 125-aa preprohormone, and the tongue sole SPX2 precursor included a 17-aa mature peptide that may be amidated at the C-terminus, rather than a tetradecapeptide reported in most other vertebrates. Tissue distribution analysis showed that spx2 transcripts were found in a wide array of tissues of both sexes with the highest expression in the ovary. In addition, the spx2 mRNA abundance was also ubiquitously detected in different brain regions. Food deprivation for 4 weeks stimulated spx2 mRNA levels at the brain-pituitary-ovary axis, and refeeding of starved fish restored the spx2 mRNA levels back to normal. Taken together, this study provides initial evidence for the existence of a novel spexin gene (spx2) in Pleuronectiformes and suggest its possible involvement in the regulation of energy balance in the female tongue sole.

Cell migration plays a critical role in vascular homeostasis. Under noxious stimuli, endothelial cells (ECs) migration always contributes to vascular repair, while enhanced migration of vascular smooth muscle cells (VSMCs) will lead to pathological vascular remodeling. Moreover, vascular activities are involved in communication between ECs and VSMCs, between ECs and immune cells, et al. Recently, Ma et al. (2015) discovered a novel migration-dependent organelle “migrasome,” which mediated release of cytoplasmic contents, and this process was defined as “migracytosis.” The formation of migrasome is precisely regulated by tetraspanins (TSPANs), cholesterol and integrins. Migrasomes can be taken up by neighboring cells, and migrasomes are distributed in many kinds of cells and tissues, such as in blood vessel, human serum, and in ischemic brain of human and mouse. In addition, the migrasome elements TSPANs are wildly expressed in cardiovascular system. Therefore, TSPANs, migrasomes and migracytosis might play essential roles in regulating vascular homeostasis. In this review, we will discuss the discoveries of migration-dependent migrasome and migracytosis, migrasome formation, the basic differences between migrasomes and exosomes, the distributions and functions of migrasome, the functions of migrasome elements TSPANs in vascular biology, and discuss the possible roles of migrasomes and migracytosis in vascular homeostasis.

Basic and clinical studies have shown that hydrogen (H2), the lightest gas in the air, has significant biological effects of anti-oxidation, anti-inflammation, and anti-apoptosis. The mammalian cells have no abilities to produce H2 due to lack of the expression of hydrogenase. The endogenous H2 in human body is mainly produced by anaerobic bacteria, such as Firmicutes and Bacteroides, in gut and other organs through the reversible oxidation reaction of 2 H+ + 2 e- ⇌ H2. Supplement of exogenous H2 can improve many kinds of liver injuries, modulate glucose and lipids metabolism in animal models or in human beings. Moreover, hepatic glycogen has strong ability to accumulate H2, thus, among the organs examined, liver has the highest concentration of H2 after supplement of exogenous H2 by various strategies in vivo. The inadequate production of endogenous H2 play essential roles in brain, heart, and liver disorders, while enhanced endogenous H2 production may improve hepatitis, hepatic ischemia and reperfusion injury, liver regeneration, and hepatic steatosis. Therefore, the endogenous H2 may play essential roles in maintaining liver homeostasis.

Revealing the variation law of thermal diffusivity of sandy soil can provide a theoretical basis for the engineering design and construction in cold and arid regions. Based on experimental data of sandy soil samples, the distribution characteristics and influence of dry density and moisture content on thermal diffusivity are analyzed in this work. Then, the prediction model based on the empirical fitting formula and RBF neural network method for thermal diffusivity of frozen and unfrozen sandy soil is established, and the prediction accuracy of different prediction methods is compared. The results show that (1) thermal diffusivity of sandy soil is positively correlated with the particle size. With the increase of sand size, thermal diffusivity of sandy soil increases significantly. (2) Partial correlation among natural moisture content, dry density, and thermal diffusivity varies with different frozen and unfrozen conditions. (3) For unfrozen sandy soil, the binary RBF neural network prediction model is obviously better than that of the binary empirical fitting formula model. (4) The ternary prediction model has significantly higher prediction accuracy than that of the binary prediction model for frozen sandy soil, and the ternary RBF neural network model has the best prediction effect among the four methods.

Hydrogen (H2) is colorless, odorless, and the lightest of gas molecules. Studies in the past ten years have indicated that H2 is extremely important in regulating the homeostasis of the cardiovascular system and metabolic activity. Delivery of H2 by various strategies improves cardiometabolic diseases, including atherosclerosis, vascular injury, ischemic or hypertrophic ventricular remodeling, intermittent hypoxia- or heart transplantation-induced heart injury, obesity and diabetes in animal models or in clinical trials. The purpose of this review is to summarize the physical and chemical properties of H2, and then, the functions of H2 with an emphasis on the therapeutic potential and molecular mechanisms involved in the diseases above. We hope this review will provide the future outlook of H2-based therapies for cardiometabolic disease.

Microwave photons are used to wire up modular quantum processors, but mitigating the effects of loss between modules remains a crucial challenge. We use a low-loss bus resonator to couple bosonic qubits across a superconducting network with protocols made robust to photon loss in the bus. We transfer a multiphoton qubit and track loss events, improving the fidelity to the break-even point with respect to the best uncorrectable encoding. We also demonstrate a entanglement protocol using Hong-Ou-Mandel interference and error detection to prepare a two-photon Bell state with fidelity 94% and success probability 0.79, halving the error obtained with a single photon. This network link also presents new opportunities for resource-efficient direct gates between modules.

Background and Purpose: Septic cardiomyopathy, which is one of the features of multi-organ dysfunction in sepsis, is characterized by ventricular dilatation, reduced ventricular contractility, and reduction in ejection fraction and, if severe, can lead to death. To date, there is no specific therapy that exists, and its treatment represents a large unmet clinical need. Herein, we investigated the effects and underlying anti-inflammatory mechanisms of hydrogen gas in the setting of lipopolysaccharide (LPS)-induced cardiomyocytes injury.Experimental Approach: Hydrogen gas was intraperitoneally injected to mice in LPS plus hydrogen group and hydrogen group for 4 days. On fourth, LPS was given by intraperitoneal injection to mice in LPS group and to mice in LPS plus hydrogen group. In addition, H9c2 cardiomyocytes were treated with hydrogen-rich medium for 30 min before LPS. The transthoracic echocardiography was performed at 6 h post‐LPS to assess left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (EF%), fractional shortening (FS%), left ventricular mass average weight (LV mass AW), and LV mass AW (Corrected). The histological and morphological analyses of left ventricular were performed by hematoxylin and eosin (H&E) staining and Masson’s trichrome staining. The mRNA levels of ANP and BNP were examined by PCR in vitro. The expression of cytokines were assayed by Enzyme Linked Immunosorbent Assay (ELISA) and PCR. Moreover, Western blotting was performed to examine the expression of TLR4, the activation of ERK1/2, p38, JNK, and the expression of NF-κB in nucleus after 6 h of LPS challenge in vivo and in vitro.Key Results: LPS induced cardiac dysfunction; hydrogen therapy improved cardiac function after LPS challenge. Furthermore, pretreatment with hydrogen resulted in cardioprotection during septic cardiomyopathy via inhibiting the expression of pro-inflammatory cytokines TNFα, IL-1β, and IL-18; suppressing the phosphorylation of ERK1/2, p38, and JNK; and reducing the nuclear translocation of NF-κB and the expression of TLR4 by LPS.Conclusion and Implications: Hydrogen therapy prevents LPS-induced cardiac dysfunction in part via downregulation of TLR4-mediated pro-inflammatory cytokines expression.

ObjectiveAs a high-level nerve center that regulates visceral and endocrine activity, the hypothalamus plays an important role in regulating the body’s stress response. Previous studies have shown that stress can cause damage to hypothalamic neurons. The present study aimed to further clarify the mechanism of endoplasmic reticulum stress (ERS) involvement in hypothalamic neuronal injury.MethodsA 7-day stressed rat model was established with daily restraining for 8 h and forced ice-water swimming for 5 min. The rats were randomly divided into control, stress, stress + GSK2606414 (PERK phosphorylation inhibitor), stress + KIRA6 (IRE1 phosphokinase activity inhibitor), GSK2606414, and KIRA6 groups. The pathological changes of hypothalamic neurons were observed by thionine staining. Expression of ERS proteins GRP78, ATF4, ASK1, JNK, and CHOP in the hypothalamic neurons were observed by immunohistochemical staining. The expression of JNK and CHOP mRNA in the hypothalamic neurons were observed by RNA in situ hybridization (RNA Scope) and the expression of related proteins and mRNA was semiquantitatively analyzed by microscopy-based multicolor tissue cytometry (MMTC).ResultsThionine staining revealed that stress exposure resulted in edema, a lack of Nissl bodies, and pyknosis in hypothalamic neurons. Immunohistochemistry and RNA Scope showed that stress exposure significantly increased the expression of GRP78, ATF4, ASK1, CHOP, JNK, JNK mRNA, and CHOP mRNA. Treatment with PERK and IRE1 inhibitors attenuated pathological damage and downregulated the expression of ATF4, ASK1, JNK, CHOP, JNK mRNA, and CHOP mRNA.ConclusionStress caused pathological changes in rat hypothalamic neurons. ERS PERK-ATF4-CHOP and IRE1-ASK1-JNK pathways were involved in the injury process.

Education systems worldwide have shown much interest in "21st Century Competencies." In response to the call for better assessment of these competencies, we draw on a 4Cs framework (Communication, Collaboration, Creativity, and Critical Thinking) and develop the 21st Century Competencies Scale-4C on a sample of 5857 Grades Four to Nine Chinese students. The Scale demonstrates good validity and reliability, yet statistical variance exists across the urban and the rural subsamples. Our discussion revolves around rural-urban disparity. Our findings provide insights into policy, practice, and research regarding 21st Century Competencies that account for sociocultural dynamics within student populations. These findings may have implications for understanding 21st Century Competencies elsewhere.

The efficient simulation of quantum systems is a primary motivating factor for developing controllable quantum machines. For addressing systems with underlying bosonic structure, it is advantageous to utilize a naturally bosonic platform. Optical photons passing through linear networks may be configured to perform quantum simulation tasks, but the efficient preparation and detection of multiphoton quantum states of light in linear optical systems are challenging. Here, we experimentally implement a boson sampling protocol for simulating molecular vibronic spectra [J. Huh et al., Nat. Photonics 9, 615 (2015)NPAHBY1749-488510.1038/nphoton.2015.153] in a two-mode superconducting device. In addition to enacting the requisite set of Gaussian operations across both modes, we fulfill the scalability requirement by demonstrating, for the first time in any platform, a high-fidelity single-shot photon number resolving detection scheme capable of resolving up to 15 photons per mode. Furthermore, we exercise the capability of synthesizing non-Gaussian input states to simulate spectra of molecular ensembles in vibrational excited states. We show the reprogrammability of our implementation by extracting the spectra of photoelectron processes in H_{2}O, O_{3}, NO_{2}, and SO_{2}. The capabilities highlighted in this work establish the superconducting architecture as a promising platform for bosonic simulations, and by combining them with tools such as Kerr interactions and engineered dissipation, enable the simulation of a wider class of bosonic systems.

We investigate the quantum transition to a correlated state of coupled oscillators in the regime where they display period tripling in response to a drive at triple the eigenfrequency. Correlations are formed between the discrete oscillation phases of individual oscillators. The evolution toward the ordered state is accompanied by the transient breaking of the symmetry between seemingly equivalent configurations. We attribute this to the nontrivial geometric phase that characterizes period tripling. We also show that the Wigner distribution of a single damped quantum oscillator can display a minimum at the classically stable zero-amplitude state.

The ventral tegmental area (VTA), a critical portion of the mesencephalic dopamine system, is thought to be involved in the development and maintenance of addiction. It has been proposed that the dopaminergic regulatory factors TH, Nurr1, and Pitx3 are crucial for determining the survival and maintenance of dopaminergic neurons. Thus, the present study investigated whether abnormalities in these dopaminergic regulatory factors in the VTA were associated with neuronal injury induced by chronic morphine dependence. Rat models with different durations of morphine dependence were established. Thionine staining was used to observe morphological changes in the VTA neurons. Immunohistochemistry and western blot were used to observe changes in the expression of the dopaminergic regulatory proteins TH, Nurr1, and Pitx3. Thionine staining revealed that prolonged morphine dependence resulted in dopaminergic neurons with edema, a lack of Nissl bodies, and pyknosis. Immunohistochemistry showed that the number of TH+, Nurr1+, and Pitx3+ cells, and the number of TH+ cells expressing Nurr1 or Pitx3, significantly decreased in the VTA after a long period of morphine dependence. Western blot results were consistent with the immunohistochemistry findings. Chronic morphine exposure resulted in abnormalities in dopaminergic regulatory factors and pathological changes in dopaminergic neurons in the VTA. These results suggest that dysregulation of dopaminergic regulatory factors in the VTA are associated with neuronal injury induced by chronic morphine dependence.

Background & Purpose: Hydrogen (H2) has been shown to have a strong antioxidant effect on preventing oxidative stress-related diseases. The goal of the present study is to determine the pharmacodynamics of H2 in a model of isoproterenol (ISO)-induced cardiac hypertrophy.Methods: Mice (C57BL/6J; 8-10 weeks of age) were randomly assigned to four groups: Control group (n=10), ISO group (n=12), ISO plus H2 group (n=12), H2 group (n=12). Mice received H2 (1ml/100g/day, intraperitoneal injection) for 7 days before ISO (0.5mg/100g/day, subcutaneous injection) infusion, and then administered ISO with or without H2 for another 7 days. Then, cardiac function was evaluated by echocardiography. Cardiac hypertrophy was reflected by heart weight/body weight, gross hearts and heart sections stained with H&E, and relative ANP and BNP mRNA levels. Cardiac reactive oxygen species (ROS), 3-nitrotyrosine and p67 (phox) levels were analyzed by Dihydroethidium staining, immunohistochemistry and western blotting, respectively. For in vitro study, H9c2 cardiomyocytes were pretreated with hydrogen rich medium for 30 minutes, and then administrated with ISO (10 μM) for the indicated time. The medium and ISO were re-changed every 24 hours. Cardiomyocyte surface areas, relative ANP and BNP mRNA levels, the expression of 3-nitrotyrosine, and the dissipation of mitochondrial membrane potential (MMP) were examined. Moreover, the expression of ERK1/2, p-ERK1/2, p38, p-p38, JNK, p-JNK were measured by western blotting both in vivo and in vitro.Results: Intraperitoneal injection of hydrogen prevents cardiac hypertrophy and improves cardiac function in ISO-infused mice. Hydrogen rich medium blocks ISO-mediated cardiomyocytes hypertrophy in vitro. Hydrogen blocked the excessive expression of NADPH oxidase and the accumulation of ROS, attenuated the decrease of MMP, and inhibited ROS-sensitive ERK1/2, p38, JNK1/2 signaling pathways.Conclusions: H2 inhibited ISO-induced cardiac/cardiomyocytes hypertrophy both in vivo and in vitro, and improved the impaired left ventricular function. H2 exerts its protective effects partially through blocking ROS-sensitive ERK1/2, p38, JNK1/2 signaling pathways.

Interference experiments provide a simple yet powerful tool to unravel fundamental features of quantum physics. Here we engineer a driven, time-dependent bilinear coupling that can be tuned to implement a robust 50∶50 beam splitter between stationary states stored in two superconducting cavities in a three-dimensional architecture. With this, we realize high-contrast Hong-Ou-Mandel interference between two spectrally detuned stationary modes. We demonstrate that this coupling provides an efficient method for measuring the quantum state overlap between arbitrary states of the two cavities. Finally, we showcase concatenated beam splitters and differential phase shifters to implement cascaded Mach-Zehnder interferometers, which can control the signature of the two-photon interference on demand. Our results pave the way toward implementation of scalable boson sampling, the application of linear optical quantum computing protocols in the microwave domain, and quantum algorithms between long-lived bosonic memories.

We show that in periodically driven systems, along with the delta-peak at the driving frequency, the spectral density of fluctuations displays extra features. These can be peaks or dips with height quadratic in the driving amplitude, for weak driving. For systems where inertial effects can be disregarded, the peaks/dips are generally located at zero frequency and at the driving frequency. The shape and intensity of the spectra very sensitively depend on the parameters of the system dynamics. To illustrate this sensitivity and the generality of the effect, we study three types of systems: an overdamped Brownian particle (e.g., an optically trapped particle), a two-state system that switches between the states at random, and a noisy threshold detector. The analytical results are in excellent agreement with numerical simulations.