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Abstract Urbanization is one of the milestones in the development of human society. Many regions in the southern parts of ‘the old world’ demonstrating an early emergence of agriculture also witnessed the flourishing of some of the earliest cities. Recent, yet still sparse, archaeological evidence appears to indicate a relatively later time for early urbanism in central Eurasia. However, given its vital geographic location and cultural nexus between East and West, more attention should be paid to the sedentary communities and their cities in oases amid the vast droughty desert, particularly in light of the rapidly increasing number of publications on early pastoralism and related communication routes along mountain chains and rivers. This study reveals the trajectory of urbanization and its role in the establishment of an exchange network in Xinjiang’s oasis region via reconstruction of the chronological sequence of the local societal history of the Baiyang River Basin along the southern piedmont of the Eastern Tianshan Mountains. A thorough archaeological investigation and refined radiocarbon dating programme was carried out and coupled with information from historical documentation within a Bayesian statistical framework. The results indicate three pulses of local urbanization during: the Early Iron Age, Tang–Yuan period, and Qing Dynasty, respectively. Combining this with evidence from other parts of Xinjiang, we re-evaluate the role of oasis urbanism in the promotion of trans-regional exchange.

Abstract Background Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD’s genetic background. Methods Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated. Results We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype “HLA-DR expression on CD14 + monocytes” showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%. Conclusion Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future.

Abstract Entanglement and coherence are fundamental properties of quantum systems, promising to power near-future quantum technologies, such as quantum computation, quantum communication, and quantum metrology. Yet, their quantification, rather than mere detection, generally requires reconstructing the spectrum of quantum states, i.e., experimentally challenging measurement sets that increase exponentially with the system size. Here, we demonstrate quantitative bounds to operationally useful entanglement and coherence that are universally valid, analytically computable, and experimentally friendly. Specifically, our main theoretical results are lower and upper bounds to the coherent information and the relative entropy of coherence in terms of local and global purities of quantum states. To validate our proposal, we experimentally implement two purity detection methods in an optical system: shadow estimation with random measurements and collective measurements on pairs of state copies. The experiment shows that both the coherent information and the relative entropy of coherence of pure and mixed unknown quantum states can be bounded by purity functions. Our research offers an efficient means of verifying large-scale quantum information processing.

The cut surface of fresh-cut taro tends to yellowing and browning even stored at low temperatures, leading to a decrease in commercial values. In this study, to confirm the preservative effects of vacuum packaging (VP) combined with cold storage on fresh-cut taro, the effects of VP treatment on the browning and total microbial counts in fresh-cut taro during cold storage were studied. The results showed that VP treatment delayed the decrease of L* values and the increase of a*, b*, color differences (△E), and browning index (BI) values, indicating that VP treatment significantly prevented the browning of fresh-cut taro during cold storage. Furthermore, VP treatment effectively restrained the growth and reproduction of microbials, reducing the total number of bacteria by 94.31% and the total number of yeast by 65.02% at 12 d, suggesting that VP combined with cold storage had a good preservative effect on fresh-cut taro. VP treatment led to decreased PAL and PPO activities, as well as reduced levels of total phenolics, total flavonoids, and total soluble quinones, suggesting that VP treatment hindered the browning by reducing the biosynthesis and oxidation of phenolic compounds of fresh-cut taro. Moreover, VP treatment restrained the decline in CAT activity, increased POD activity at early storage, and reduced LOX activity, H2O2 contents and MDA contents, suggesting that VP treatment alleviated cutting-induced oxidative damages by maintaining the antioxidant activity of fresh-cut taro, thus restraining the quality deterioration during cold storage. This study demonstrates that VP treatment combined with cold storage is a physical preservative technology with good preservation effects, simple and easy to use, laying a foundation for the application of VP method in the preservation of fresh-cut taro.

Abstract Metasurface enables the generation and manipulation of multiphoton entanglement with flat optics, providing a more efficient platform for large-scale photonic quantum information processing. Here, we show that a single metasurface optical device would allow more efficient characterizations of multiphoton entangled states, such as shadow tomography, which generally requires fast and complicated control of optical setups to perform information-complete measurements, a demanding task using conventional optics. The compact and stable device here allows implementations of general positive operator valued measures with a reduced sample complexity and significantly alleviates the experimental complexity to implement shadow tomography. Integrating self-learning and calibration algorithms, we observe notable advantages in the reconstruction of multiphoton entanglement, including using fewer measurements, having higher accuracy, and being robust against experimental imperfections. Our work unveils the feasibility of metasurface as a favorable integrated optical device for efficient characterization of multiphoton entanglement, and sheds light on scalable photonic quantum technologies with ultra-thin optical devices.

Abstract Entanglement serves as the resource to empower quantum computing. Recent progress has highlighted its positive impact on learning quantum dynamics, wherein the integration of entanglement into quantum operations or measurements of quantum machine learning (QML) models leads to substantial reductions in training data size, surpassing a specified prediction error threshold. However, an analytical understanding of how the entanglement degree in data affects model performance remains elusive. In this study, we address this knowledge gap by establishing a quantum no-free-lunch (NFL) theorem for learning quantum dynamics using entangled data. Contrary to previous findings, we prove that the impact of entangled data on prediction error exhibits a dual effect, depending on the number of permitted measurements. With a sufficient number of measurements, increasing the entanglement of training data consistently reduces the prediction error or decreases the required size of the training data to achieve the same prediction error. Conversely, when few measurements are allowed, employing highly entangled data could lead to an increased prediction error. The achieved results provide critical guidance for designing advanced QML protocols, especially for those tailored for execution on early-stage quantum computers with limited access to quantum resources.

Abstract How to efficiently encode classical data is a fundamental task in quantum computing. While many existing works treat classical data encoding as a black box in oracle-based quantum algorithms, their explicit constructions are crucial for the efficiency of practical algorithm implementations. Here, we unveil the mystery of the classical data encoding black box and study the Clifford + T complexity in constructing several typical quantum access models. For general matrices (even including sparse ones), we prove that sparse-access input models and block-encoding both require nearly linear circuit complexities relative to the matrix dimension. We also give construction protocols achieving near-optimal gate complexities. On the other hand, the construction becomes efficient with respect to the data qubit when the matrix is a linear combination of polynomial terms of efficiently implementable unitaries. As a typical example, we propose improved block-encoding when these unitaries are Pauli strings. Our protocols are built upon improved quantum state preparation and a select oracle for Pauli strings, which hold independent values. Our access model constructions provide considerable flexibility, allowing for tunable ancillary qubit numbers and offering corresponding space-time trade-offs.

Abstract Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.

Background: To evaluate the efficacy and safety of allogenic CD8 + natural killer T (CD8+ NKT) immunotherapy combined with gefitinib in the treatment of advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). Methods: This study is prospective. The NSCLC patients with exon 19 (Ex19del) or exon 21 L858R point mutations, and response to gefitinib treatment were enrolled into the trial to be randomly assigned into the gefitinib arm and the gefitinib/NKT arm. Allogenic CD8+ NKT cells were cultured in vitro and adaptive transferred into the patients via vein in the gefitinib/NKT arm. The primary endpoint was progression-free survival (PFS). Secondary endpoint analysis included time to disease progression (TTP), overall survival (OS), levels of serum tumour markers for carcinoembryonic antigen (CEA) and alanine aminotransferase (ALT) in the blood, the response rate and safety. From July 2017 to June 2021, 19 patients were randomly assigned to the gefitinib arm (n = 8) and the gefitinib/NKT arm (n = 11). Results: The estimated median survival PFS in the gefitinib/NKT arm was significantly longer than that of the gefitinib arm (12 months vs 7 months). Similar results were also observed for the median TTP. Moreover, the gefitinib/NKT arm had better CEA control than the gefitinib arm. Clinical grade 3 adverse reactions occurred in 64% and 39% of patients in the gefitinib/NKT arm and the gefitinib arm, respectively. The most common grade 3 adverse events in the gefitinib/NKT arm included abnormal liver function in 8 cases (73%) and diarrhoea in 1 case (9%), both of which resolved after drug intervention. Conclusion: The PFS of EGFR-mutated advanced NSCLC treated with allogenic CD8+ NKT cells combined with gefitinib was longer than that of gefitinib alone. No obvious serious adverse reactions occurred, and the patients compliance and survival status were good.

Abstract Implantable medical devices have played an important role in human medicine in recent decades. However, traditional implanted devices require battery replacement and a second surgery for device removal, which can cause pain to the patient. This work presents a biodegradable triboelectric nanogenerator (BI-TENG) made from both natural and synthetic biodegradable materials that is utilized to collect mechanical energy in vivo and transduce it into electricity. Reed film and polylactic acid were chosen among different biodegradable materials as the triboelectric layers due to having the best generator output performance by providing voltages that reached 368 V. The biocompatibility of the friction layer and the device was verified via a blood test. After implantation in mice, the BI-TENG exhibited an open-circuit voltage of 0.176 V and a short-circuit current of 192 nA as generated from body movement. The BI-TENG was connected to an interdigital electrode to generate an electric field, which stimulated the accelerated release of doxorubicin (DOX) from red blood cells in targeted drug delivery systems. After stopping the electric field, the release of DOX normalized, facilitating the precise killing of cancer cells. Our work demonstrates the broad potential of BI-TENGs in the field of cancer treatment.

Abstract Phenotype-guided gene prioritizers have proved a highly efficient approach to identifying causal genes for Mendelian diseases. In our previous study, we preliminarily evaluated the performance of ten prioritizers. However, all the selected software was run based on default settings and singleton mode. With a large-scale family dataset from Deciphering Developmental Disorders (DDD) project (N = 305) and an in-house trio cohort (N = 152), the four optimal performers in our prior study including Exomiser, PhenIX, AMELIE, and LIRCIAL were further assessed through parameter optimization and/or the utilization of trio mode. The in-depth assessment revealed high diagnostic yields of the four prioritizers with refined preferences, each alone or together: (1) 83.3–91.8% of the causal genes were presented among the first ten candidates in the final ranking lists of the four tools; (2) Over 97.7% of the causal genes were successfully captured within the top 50 by either of the four software. Exomiser did best in directly hitting the target (ranking the causal gene at the very top) while LIRICAL displayed a predominant overall detection capability. Besides, cases affected by low-penetrance and high-frequency pathogenic variants were found misjudged during the automated prioritization process. The discovery of the limitations shed light on the specific directions of future enhancement for causal-gene ranking tools.

Abstract Alzheimer's disease (AD) constitutes a neurodegenerative disorder marked by a progressive decline in cognitive function and memory capacity. The accurate diagnosis of this condition predominantly relies on cerebrospinal fluid (CSF) markers, notwithstanding the associated burdens of pain and substantial financial costs endured by patients. This study encompasses subjects exhibiting varying degrees of cognitive impairment, encompassing individuals with subjective cognitive decline, mild cognitive impairment, and dementia, constituting a total sample size of 82 participants. The primary objective of this investigation is to explore the relationships among brain atrophy measurements derived from magnetic resonance imaging, atypical electroencephalography (EEG) patterns, behavioral assessment scales, and amyloid β‐protein (Aβ) indicators. The findings of this research reveal that individuals displaying reduced Aβ1‐42/Aβ‐40 levels exhibit significant atrophy in the frontotemporal lobe, alongside irregularities in various parameters related to EEG frequency characteristics, signal complexity, inter‐regional information exchange, and microstates. The study additionally endeavors to estimate Aβ1‐42/Aβ‐40 content through the application of a random forest algorithm, amalgamating structural data, electrophysiological features, and clinical scales, achieving a remarkable predictive precision of 91.6%. In summary, this study proposes a cost‐effective methodology for acquiring CSF markers, thereby offering a valuable tool for the early detection of AD.

This study fabricated the in-situ Cu(OH)2 hierarchical nanograss surface (HNS) via immersion method for simultaneous enhancement of the critical heat flux (CHF) and heat transfer coefficient (HTC) in diverse experimental conditions. Nanograss stripes were patterned, and then in-situ grown on the copper substrate through the chemical modification. The effect of the Cu(OH)2 HNS on the pool boiling heat transfer performance was systematically examined. Furthermore, the optimized HNS which can exhibit the highest CHF and HTC was identified based on comparative experiments. It is found that the numerous nanoscale cavities existing in the HNS can act as the active nucleation sites for facilitating the boiling process. Experimental results reveal that the HNS can reduce the independent bubble departure diameter, increase the bubble departure frequency and significantly delay the bubble mergence due to much improved capillary pumping and replenishment of cooling liquid. According to the experiments, the CHF on the optimized HNS sample, were improved by 97.8% compared with the smooth surface and the HTC is enhanced to 2.4 W/cm2K, which is equivalent to an augmentation of 25.7% compared to that on smooth surface. Meanwhile, the HNS can improve the heat transfer uniformity and stability with temporal temperature variations less than 1 K at CHF, which is pivotal to the efficient thermal management of miniaturized devices.

【Objective】Fresh-cut taro is prone to turning yellow and brown during storage, even stored at low temperature, which greatly diminishes its commercial values. In order to identify the important functional genes involved in the browning process of fresh-cut taro, the allene oxide synthase (AOS) gene AOS1 was cloned from fresh-cut taros.The correlation between the expression of AOS1 and the browning development of fresh-cut taro was analyzed, with a view to offering references for the study of taro browning mechanism.【Method】With cDNA of fresh-cut taro as a template, the coding sequence (CDS) of AOS1 gene was cloned by the RT-PCR method. The expression patterns of AOS1 during the browning of fresh-cut taro were analyzed by using qRT-PCR, the impact of exogenous browning inhibitors on AOS1 expression was examined by using transcriptome sequencing data, and the promoter subsequence was analyzed.【Result】Fresh-cut taros showed obvious yellowing and browning symptoms on the cut surface after 24 hours of storage at 20 ℃, while the obvious browning symptoms were occurred after 12 d of cold storage at 4 ℃. These results suggested that storage temperature was a crucial factor influencing the browning process of fresh-cut taros, with low temperature storage effectively inhibiting the browning. The CDS of taro AOS1 gene had a total length of 1 560 bp and encoded 519 amino acid residues. The molecular weight of the protein encoded by AOS1 gene was 57.63 kD, with an isoelectric point of 8.68, and located in chloroplast. The similarity of AOS1 protein sequences across different plant species was relatively low, with notable differences observed between taro, tomato, and Arabidopsis. However, high sequence homology was found among AOS1 proteins in Araceae family plants. The promoter region of taro AOS1 contained various plant hormone and stress response elements. The expression of AOS1 significantly increased after fresh-cut processing, indicating that the cutting treatment induced AOS1 expression. Moreover, as the browning of freshcut taro progressed, the expression of AOS1 gradually increased. Applications of exogenous glycolic acid and vanillic acid significantly decreased the expression of AOS1 in fresh-cut taros, showing its correlation with the browning process.【Conclusion】A significant positive correlation was observed between the browning of fresh-cut taros and the expression of AOS1 during cold storage. Treatments such as cutting and peeling may accelerate the browning process by inducing AOS1 expression.

In the context of resource utilization, the applications of waste biomass have attracted increasing attention.Previous studies have shown that forming biochar by heat treatment of sludge could replace the traditional sludge disposal methods, and sludge biochar is proved to be efficient in wastewater treatment. In this work, the pyrolysis, hydrothermal carbonization and microwave pyrolysis methods for preparing sludge biochar were reviewed, and the effects of different modification methods on the performance of sludge biochar in the synthesis process were comprehensively analyzed. This review also summarized the risk control of heavy metal leaching in sludge biochar, increasing the pyrolysis temperature and use of the fractional pyrolysis or co-pyrolysis were usually effectively meathods to reduce the leaching risk of heavy metal in the system, which is crucial for the wide application of sludge biochar in sewage treatment. At the same time, the adsorption mechanism of sludge biochar and the catalytic mechanism as the catalytic material in AOPs reaction, the process of radical and non-radical pathway and the possible impacts in the sludge biochar catalytic process were also analyzed in this paper

Abstract Quantum computing has shown great potential in various quantum chemical applications such as drug discovery, material design, and catalyst optimization. Although significant progress has been made in the quantum simulation of simple molecules, ab initio simulation of solid-state materials on quantum computers is still in its early stage, mostly owing to the fact that the system size quickly becomes prohibitively large when approaching the thermodynamic limit. In this work, we introduce an orbital-based multifragment approach on top of the periodic density matrix embedding theory, resulting in a significantly smaller problem size for the current near-term quantum computer. We demonstrate the accuracy and efficiency of our method compared with the conventional methodologies and experiments on solid-state systems with complex electronic structures. These include spin-polarized states of a hydrogen chain (1D-H), the equation of state of a boron nitride layer (h-BN) as well as the magnetic ordering in nickel oxide (NiO), a prototypical strongly correlated solid. Our results suggest that quantum embedding combined with a chemically intuitive fragmentation can greatly advance quantum simulation of realistic materials, thereby paving the way for solving important yet classically hard industrial problems on near-term quantum devices.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, often associated with a poor prognosis for patients. One of the major challenges in managing PDAC is the difficulty in early diagnosis, owing to the limited and invasive nature of current diagnostic methods. Recent studies have identified the oral microbiome as a potential source of non-invasive biomarkers for diseases, including PDAC. In this study, we focused on leveraging the differential expression of virulence factors (VFs) encoded by the oral microbiome to create a diagnostic tool for PDAC. We observed a higher alpha diversity in VF categories among PDAC patients compared to healthy controls. We then identified a panel of VF categories that were significantly upregulated in PDAC patients, these being associated with bacterial adherence, exoenzyme production, and nutritional/metabolic processes. Moreover, Streptococcus-derived VFs were notably enriched in PDAC patients. We developed a diagnostic model using random forest analysis based on the levels of these VFs. The model's diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.88, indicating high accuracy in differentiating PDAC patients from healthy controls. Our findings suggest that VFs encoded by the oral microbiome hold potential as diagnostic tools for PDAC, offering a non-invasive approach that could significantly enhance early detection and prognosis, ultimately leading to improved patient outcomes.

The rhizosphere of grown tea (Camellia sinensis (L.) O. Kuntze) becomes acidic, and aluminium (Al) toxicity has been identified as a key constraint on plant development in acidic soils. The current study investigated the composition and functions of rhizosphere bacteria as well as soil enzyme activity under different Al stress conditions. The effect of soil pH, soil enzyme activities, the diversity and structure of the rhizosphere bacterial population under various Al concentrations were studied by the pot experiment. All analyses demonstrated that substantial alterations in the activity of soil enzymes and the composition of the bacterial communities in the rhizosphere could only be seen under conditions of extreme Al stress. Soil enzymes were more concentrated in Al concentrations of 100, 150 and 250 µM, respectively. More than 82,000 valid reads were obtained for each replicate, and the abundance of certain genera in the aluminium treated groups were greater than the control group. Lower Al stress attracted Al-tolerant bacteria such as Burkholderia to increase Al stress resistance. These findings revealed that soil enzyme activities and the structure of the rhizosphere bacterial population in tea orchard soil provided tolerance or resistance capability to tea plants for their development under Al stress.

Abstract This study aims to investigate dietary exposure to acrylamide (AA) and also make an assessment of its effect on the neurobehavioral performance and oxidative stress in the serum of university students in Ningxia. The place primarily consists of arid, dry desert, and wheat‐based foods are the staple food there. A total of 803 university students in Ningxia participated in this cross‐sectional study. Diet intake of AA was estimated with FFQ. The AA risk was calculated as margin of exposure (MOE) values. NCTB questionnaires were used to assess neurobehavioral performance. The serum oxidative stress levels of the university students were measured as GSH, MDA, and SOD. The mean for AA exposure of university students was 0.515 μg kg−1 bw day−1. The highest contributor was traditional Chinese grain products, representing 34.71% of the total daily AA intake. Followed were deep‐fried potato products, traditional Western grain products, soft drinks, and nuts, which accounted for 23.87%, 16.59%, 11.15%, and 11%, respectively. The median AA exposure were 480 (BMDL10 = 0.18 mg kg−1 bw day−1) and 827 (BMDL10 = 0.31 mg kg−1 bw day−1), respectively. The results indicated that diet AA may have an effect on the emotional status and neurobehavior among this population. We observed no significant differences in oxidative stress under the three levels of AA exposure (p > .05). It suggests a health concern for university students in Northwest China that should get society's attention.

Abstract Background Erectile dysfunction is a common problem in males of couples experiencing pregnancy loss. Erectile dysfunction in males with couple infertile has been extensively investigated and found to be closely linked with semen quality impairment and psychological distress, but it is less clear if this relation exists in males of couples experiencing pregnancy loss. Method A cross-sectional analysis of 437 men who attended our outpatient clinic between June 2021 and October 2021 for couple pregnancy loss. All subjects underwent a complete physical examination, palpation, inspection of the male genitalia, and semen analysis. Validated assessment tools for erectile dysfunction (the International Index of Sexual Function5 -IIEF-5) and anxiety (the seven-item Generalized Anxiety Disorder Scale- GAD-7) were used. Results Among 437 men of couples with pregnancy loss, we found several relevant sperm parameters confirmed a significant correlation between IIEF-5 scores and sperm parameters, including: sperm progressive motility (r = 0.1627, p = 0.001), sperm normal morphology (r = 0.1373, p = 0.004) and sperm DNA fragmentation (r =—0.1248, p = 0.009). Males with an IIEF-5 scores range between 5–11 presented the worst results in terms of sperm progressive motility (p = 0.002), normal morphology (p = 0.001), and SDF levels (p = 0.003). GAD-7 score, as well as anxiety level, was significantly higher in those males with an IIEF-5 score between 5 and 11 (p = 0.000). Conclusion Although current evidence does not demonstrate the importance of spermatozoa in the etiology of pregnancy loss, significant correlations have been observed between impaired sperm quality and low IIEF-5 scores. Also, anxiety is more likely to occur in males with sexual dysfunction.

Glass frit used in conductive silver (Ag) pastes has a significant impact not only on the electrical performance but also on the long-term reliability of metallized electrodes in crystalline silicon (c-Si) solar cells. Here, we investigated the role of compositional changes on the metallization process of silver pastes by adjusting the SiO _2 , ZnO, Li _2 O, or Bi _2 O _3 in lead borate glass melts, and performed damp heat (DH) tests in an acidic damp heat environment. It was found that the addition of Bi _2 O _3 resulted in a decrease in conversion efficiency (Eta) of only 6.44% after the cell was treated with dilute acetic acid. Under scanning electron microscopy (SEM), it was observed that the cell with this glass frit had minimal changes in the microstructure of its silver-silicon contacts and silver electrodes. This finding helps to improve the performance and stability of solar cells in harsh environments.

Errors are common issues in quantum computing platforms, among which leakage is one of the most-challenging to address. This is because leakage, i.e., the loss of information stored in the computational subspace to undesired subspaces in a larger Hilbert space, is more difficult to detect and correct than errors that preserve the computational subspace. As a result, leakage presents a significant obstacle to the development of fault-tolerant quantum computation. In this paper, we propose an efficient and accurate benchmarking framework called leakage randomized benchmarking (LRB), for measuring leakage rates on multi-qubit quantum systems. Our approach is more insensitive to state preparation and measurement (SPAM) noise than existing leakage benchmarking protocols, requires fewer assumptions about the gate set itself, and can be used to benchmark multi-qubit leakages, which has not been achieved previously. We also extended the LRB protocol to an interleaved variant called interleaved LRB (iLRB), which can benchmark the average leakage rate of generic n-site quantum gates with reasonable noise assumptions. We demonstrate the iLRB protocol on benchmarking generic two-qubit gates realized using flux tuning and analyzed the behavior of iLRB under corresponding leakage models. Our numerical experiments showed good agreement with the theoretical estimations, indicating the feasibility of both the LRB and iLRB protocols.

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids.

Optical orbital angular momentum (OAM) holography provides a critical method for holographic information storage systems and experimentally demonstrates the feasibility of holographic multiplexation. Herein, the elliptic perfect optical vortex orbital angular momentum (EPOV-OAM) multiplexed holography is proposed and experimentally implemented. The mode selectivity of the ellipticity and rotation angle are investigated, respectively, which demonstrates that those parameters can be used as additional encoded degrees of freedom for the holographic multiplexing. The combination of the topological charge (TC), scaling factor, rotation angle, ellipticity can provide a four-dimensional multiplexed holography for information encryption. Furthermore, the minimum interval of TC for holographic multiplexing could reach 0.01. The method proposed here can enhance the information capacity and the security level of the holographic optical encryption systems.

IntroductionElectroencephalographic (EEG) abnormalities are seen in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance.MethodsWe recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function.Results and discussionMultiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.

Planting aromatic plant might be a promising strategy for safely utilizing heavy metal (HM)-contaminated soils, as HMs in essential oil could be completely excluded using some special technologies with ease. Clove basil (Ocimum gratissimum L.) is an important aromatic plant used in essential oil production. Improving cadmium (Cd) tolerance in clove basil can increase its production and improve the utilization efficiency of Cd-contaminated soils. However, the lack of genomic information on clove basil greatly restricts molecular studies and applications in phytoremediation. In this study, we demonstrated that high levels of Cd treatments (0.8, 1.6 and 6.5 mg/L) significantly impacted the growth and physiological attributes of clove basil. Cd contents in clove basil tissues increased with treatment concentrations. To identify Cd stress-responsive genes, we conducted a comparative transcriptomic analysis using seedlings cultured in the Hoagland’s solution without Cd ion (control) or containing 1.6 mg/L CdCl2 (a moderate concentration of Cd stress for clove basil seedlings). A total of 104.38 Gb clean data with high-quality were generated in clove basil under Cd stress through Illumina sequencing. More than 1,800 differential expressed genes (DEGs) were identified after Cd treatment. The reliability and reproducibility of the transcriptomic data were validated through qRT-PCR analysis and Sanger sequencing. KEGG classification analysis identified the “MAPK signaling pathway,” “plant hormone signal transduction” and “plant-pathogen interaction” as the top three pathways. DEGs were divided into five clusters based on their expression patterns during Cd stress. The functional annotation of DEGs indicated that downregulated DEGs were mainly involved in the “photosynthesis system,” whereas upregulated DEGs were significantly assigned to the “MAPK signaling pathway” and “plant-pathogen interaction pathway.” Furthermore, we identified a total of 78 transcription factors (TFs), including members of bHLH, WRKY, AP2/ERF, and MYB family. The expression of six bHLH genes, one WRKY and one ERF genes were significantly induced by Cd stress, suggesting that these TFs might play essential roles in regulating Cd stress responses. Overall, our study provides key genetic resources and new insights into Cd adaption mechanisms in clove basil.

Abstract Background Infertile men with higher sexual dysfunction risk and increased psychological burden, were also associated with more inclined to timed intercourse. Decreased semen quality may have adverse effects on male sexual function. However, it is also likely that many of these sequences do not play a direct role, those negative consequences may depend mainly on the later failed attempting pregnancy. Research is limited in this area. Methods This cross-sectional study was based on a group of 509 men who were assessed for couple’s infertility at the First Hospital of Jilin University between June 2021 and October 2021. All the men completed a comprehensive questionnaire, and then were divided in two groups. Group A included patients who either never received a routine infertility work-up or done so recently within the last 6 months. Group B included patients who previously received a sperm quality assessment at least 6 months or more prior. Patients were further categorized into three subgroups according to the severity of the decreases in their sperm parameters: severe, mild-moderate, and normozoospermic. Results The prevalence of erectile dysfunction was higher in Group B Mild-Moderate and Group B Severe in comparison to Group A (OR=1.86 [1.07–3.24], P = 0.027; OR=5.312 [2.69–10.49], P < 0.001, respectively). No significant differences were found between Group A and Group B-normozoospermic. Similar results were observed in the prevalence of premature ejaculation between the groups. Timed intercourse was seen in 11.8% (20/170) of men in Group A and 16.2% (19/117) in Group B-normozoospermic. It was more commonly practiced among infertile men in Group B-Mild-Moderate and Group B Severe, as 28.2% (44/156) and 25.7% (17/66) of these couples had attempted to conceive through timed intercourse (P < 0.001). Conclusions Our findings indicate that the severity of sperm quality impairment was negatively associated with sexual dysfunction only in infertile men who with known impairment of sperm quality for a long period. Timed intercourse was more common among these couples. For those individuals had never test their sperm quality, although more than half of these patients showed a decrease in sperm quality, the incidence of sexual dysfunction is relatively low and were comparable to those men examined previously known as normozoospermic.

Abstract In mitosis, accurate chromosome segregation depends on kinetochores that connect centromeric chromatin to spindle microtubules. The centromeres of budding yeast, which are relatively simple, are connected to individual microtubules via a kinetochore constitutive centromere associated network (CCAN). However, the complex centromeres of human chromosomes comprise millions of DNA base pairs and attach to multiple microtubules. Here, by use of cryo-electron microscopy and functional analyses, we reveal the molecular basis of how human CCAN interacts with duplex DNA and facilitates accurate chromosome segregation. The overall structure relates to the cooperative interactions and interdependency of the constituent sub-complexes of the CCAN. The duplex DNA is topologically entrapped by human CCAN. Further, CENP-N does not bind to the RG-loop of CENP-A but to DNA in the CCAN complex. The DNA binding activity is essential for CENP-LN localization to centromere and chromosome segregation during mitosis. Thus, these analyses provide new insights into mechanisms of action underlying kinetochore assembly and function in mitosis.

Fresh-cut taros are prone to browning even though they are stored at low temperatures, which leads to the quality deterioration and markedly limits the shelf life. The browning control of fresh-cut food with natural substances has received much attention. This study evaluated anti-browning potential of peppermint extracts in fresh-cut taro during cold storage. The results showed that both peppermint leaf and shoot extract (LE and SE) treatments could effectively retard the browning of fresh-cut taros. Furthermore, LE and SE treatments reduced the activities of phenylalanine ammonialyase and lipoxygenase, the contents of total phenolic compound (TPC), total flavonoids, soluble quinones, malondialdehyde and hydrogen peroxide, enhanced peroxidase activity and antioxidant capacity in taro slices. The TPC contents were reduced by 4.05 and 17.71%, and the T-AOC was enhanced by 28.73 and 28.82% as compared to the control at 12 d. These results together suggested that peppermint extract treatments reduced phenolic biosynthesis but enhanced antioxidant activity. However, LE and SE treatments did not inhibit polyphenol oxidase (PPO) activity, suggesting that peppermint extract treatments reduced taro browning was not through inhibition of phenolic oxidation. More than 240 phenolic-related compounds including caffeic acid, ferulic acid and p-Coumaric acid were identified in peppermint extracts through UPLC–MS/MS analysis, suggesting that phenolics may be bioactive substances reducing taro browning. In conclusion, this study demonstrates that peppermint extract is a promising natural anti-browning ingredient and phenolic compounds may function on taro browning inhibition.

Human infection with Chlamydia psittaci is rare but difficult to recognize. We report an outbreak of psittacosis among poultry processing workers in China. We applied metagenomic next-generation sequencing and identified Chlamydia psittaci reads from samples of all seven patients, four of which were subsequently confirmed by PCR. Epidemiological results suggested that the poultry processed in the factory was the possible source of human infection.

ObjectiveTo evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA).MethodsCNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software.ResultsA total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events.ConclusionDietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

Background and aimsHepatocellular carcinoma (HCC) is a common cause of cancer-related death in humans. Increasing evidence indicates that an imbalance in N6-methyladenosine (m6A) methylation is linked to the occurrence and development of cancer. We then developed a prognostic model as an independent risk factor with which predict the prognosis of HCC.MethodsWe obtained the gene expression and clinical data of HCC patients from the TCGA databases. The prognostic value of m6A methylation-related genes in patients who had HCC were subjected to comprehensive bioinformatics analysis. We use RiskScore=∑i=1nCoefi×Xi to construct the risk scoring formula. We collected pathological specimens from 68 patients who had HCC, and conducted immunohistochemical staining experiments on the specimens.ResultsThere was a significant correlation between candidate m6A methylation-related genes (YTHDF2, METTL14 and ZC3H13) overall survival of HCC patients. Among the 68 HCC patient specimens that underwent immunohistochemical staining, all cancer tissues were positive for METTL14, YTHDF2, and ZC3H13 staining in contrast to the adjacent tissues. We conducted a Kaplan-Meier survival analysis. The results showed that patients who had low METTL14 expression had a longer survival time than those of patients who had high METTL14 expression. Also, patients with low YTHDF2 expression had a longer survival time than patients with high YTHDF2 expression. Finally, patients with high ZC3H13 expression lived longer than those with low ZC3H13 expression. This result is consistent with the bioinformatics analysis conclusion above.ConclusionsGenerally, the prognostic model that was based on m6A methylation-related genes in this study can effectively predict the prognosis of HCC patients.

Neonicotinoid insecticides (NEOs) are widely used in many urban regions. Studies on NEOs residues in urban tidal streams and the associated ecological risks are limited. In this study, the occurrence, spatiotemporal distribution, and ecological risks of seven selected NEOs in the Wuchong Stream in Guangzhou, China were investigated. Moreover, the correlation between typical urban factors and the ecological risk of NEOs was discussed. In the Wuchong Stream, the concentrations of NEOs in the water samples ranged from 0.97 to 175.92 ng. L-1 in the dry season and 3.15 to 312.92 ng. L-1 in the wet season.The most commonly used neonicotionoids were acetamiprid and imidacloprid in the Wuchong Sream basin. The concentrations of NEOs in the midstream were higher than that in the downstream and upstream. The results of the ecological risk indicated that NEOs were likely to biologically impair the urban stream ecosystem, especially in the dry season. For three typical aquatic organisms, the current concentrations of NEOs posed a significant threat to aquatic insects. Compared to other urban factors, residentidal district and farmland area were the main socioeconomic factors affecting the ecological risk of NEOs in the Wuchong Stream basin. Therefore, the correct and reasonable application of NEOs and continuous improvement of the applicant methods can reduce the environmental risks of urban streams.

ObjectiveThe purpose of this study was to evaluate the curative effect of external therapies of traditional Chinese medicine on constipation in patients with chronic renal failure and to provide scientific theoretical basis for clinical practice.MethodWe searched the English database of PubMed, EMBASE, the Cochrane Library and the Web of Science and Chinese database of CNKI, Wan fang database, VIP Database and China Biomedical Literature Database up to December 2022. Randomized controlled trials (RCTs) involving constipation in patients with CRF that compared external therapies of traditional Chinese medicine and routine treatment to routine treatment were eligible for the analysis. A meta-analysis of the outcome indicators including total efficiency, weekly defecation times, defecation time, defecation difficulty score, patient-assessment of constipation quality of life and adverse events of treatment were performed. The analysis was performed by using Review Manager version 5.3.ResultA total of 23 studies were included, with 1764 patients. Meta-analysis results showed that compared with the control group, the test group could significantly increase weekly defecation times(MD = 0.94, 95%CI(0.70, 1.18), Z = 7.74, P < 0.00001), reduce defecation time(MD = -2.92, 95%CI(-3.69, -2.16), Z = 7.49, P < 0.00001), reduce defecation difficulty score(MD = -1.92, 95%CI(-2.45, -1.39), Z = 7.11, P < 0.00001), improve the quality of life in patients with constipation(MD = -7.57, 95%CI(-10.23, -4.91), Z = 5.58, P < 0.00001) and obtain a higher total effective rate of treatment(OR = 4.53, 95%CI(3.27, 6.29), Z = 9.07, P < 0.00001). In terms of safety, there was no statistical significance in the incidence of adverse events between two groups(OR = 0.35, 95%CI(0.04, 2.95), Z = 0.96, P = 0.34).ConclusionThe combination of external therapies of traditional Chinese medicine and routine treatment could achieve an excellent curative effect, and there was no specific adverse event. However because of the limited level of current evidence, more high-quality trials are needed in the future.5.

As one of the most toxic environmental pollutants, cadmium (Cd) has lastingly been considered to have negative influences on plant growth and productivity. Recently, increasing studies have shown that low level of Cd exposure could induce hormetic effect which benefits to plants. However, the underlying mechanisms of Cd-triggered hormesis are poorly understood. In this study, we found that Cd stress treatment showed a hormetic effect on peppermint and Cd treatment with 1.6 mg L-1 concertation manifested best stimulative effects. To explore the hormesis mechanisms of Cd treatment, comparative transcriptome analysis of peppermint young plants under low (1.6 mg L-1) and high (6.5 mg L-1) level of Cd exposure at 0 h, 24 h and 72 h were conducted. Twelve of differentially expressed genes (DEGs) were selected for qRT-PCR validation, and the expression results confirmed the credibility of transcriptome data. KEGG analysis of DEGs showed that the phenylpropanoid biosynthesis and photosynthesis were important under both low and high level of Cd treatments. Interestingly, GO and KEGG analysis of 99 DEGs specifically induced by low level of Cd treatment at 72 h indicated that these DEGs were mainly involved in the pathway of phenylpropanoid biosynthesis and their functions were associated with antioxidant activity. The expression pattern of those genes in the phenylpropanoid biosynthesis pathway and encoding antioxidant enzymes during 72 h of Cd exposure showed that low level of Cd treatment induced a continuation in the upward trend but high level of Cd treatment caused an inverted V-shape. The changes of physiological parameters during Cd exposure were highly consistent with gene expression pattern. These results strongly demonstrate that low level of Cd exposure constantly enhanced antioxidant activity of peppermint to avoid oxidative damages caused by Cd ion, while high level of Cd stress just induced a temporary increase in antioxidant activity which was insufficient to cope with lasting Cd toxicity. Overall, the results presented in this study shed a light on the underlying mechanisms of the Cd-mediated hormesis in plant. Moreover, our study provided a safe method for the efficient utilization of mild Cd-contaminated soil as peppermint is an important cash plant.

Ischemic stroke (IS) is one of the leading causes of death and disability. Its pathogenesis is not completely clear, and inflammatory cascade is one of its main pathological processes. The current clinical practice of IS is to restore the blood supply to the ischemic area after IS as soon as possible through thrombolytic therapy to protect the vitality and function of neurons. However, blood reperfusion further accelerates ischemic damage and cause ischemia-reperfusion injury. The pathological process of cerebral ischemia-reperfusion injury involves multiple mechanisms, and the exact mechanism has not been fully elucidated. Pyroptosis, a newly discovered form of inflammatory programmed cell death, plays an important role in the initiation and progression of inflammation. It is a pro-inflammatory programmed death mediated by caspase Caspase-1/4/5/11, which can lead to cell swelling and rupture, release inflammatory factors IL-1β and IL-18, and induce an inflammatory cascade. Recent studies have shown that pyroptosis and its mediated inflammatory response are important factors in aggravating ischemic brain injury, and inhibition of pyroptosis may alleviate the ischemic brain injury. Furthermore, studies have found that natural plant components may have a regulatory effect on pyroptosis. Therefore, this review not only summarizes the molecular mechanism of pyroptosis and its role in ischemic stroke, but also the role of natural plant components as regulator of pyroptosis, in order to provide reference information on pyroptosis for the treatment of IS in the future.

The low sensitivity of radiotherapy is the main cause of tumor tolerance against ionizing radiation (IR). However, the molecular mechanisms by which radiosensitivity is controlled remain elusive. Here, we observed that high expression of pellino E3 ubiquitin protein ligase 1 (PELI1) was correlated with improved prognosis in human esophageal squamous cell carcinoma stage III patients that received adjuvant radiotherapy. Moreover, we found PELI1‐mediated IR‐induced tumor cell apoptosis in vivo and in vitro. Mechanistically, PELI1 mediated the lysine 48 (Lys48)–linked polyubiquitination and degradation of NF‐κB–inducing kinase (NIK; also known as MAP3K14), the master kinase of the noncanonical NF‐κB pathway, thereby inhibiting IR‐induced activation of the noncanonical NF‐κB signaling pathway during radiotherapy. As a consequence, PELI1 inhibited the noncanonical NF‐κB–induced expression of the anti‐apoptotic gene BCL2 like 1 (Bclxl; also known as BCL2L1), leading to an enhancement of the IR‐induced apoptosis signaling pathway and ultimately promoting IR‐induced apoptosis in tumor cells. Therefore, Bclxl or NIK knockdown abolished the apoptosis‐resistant effect in PELI1‐knockdown tumor cells after radiotherapy. These findings establish PELI1 as a critical tumor intrinsic regulator in controlling the sensitivity of tumor cells to radiotherapy through modulating IR‐induced noncanonical NF‐κB expression.

Propylene/propane separations are generally performed by distillation which are energy intensive and costly to build and operate. There is therefore high interest to develop new separation technologies like membrane modules. In our previous paper, we collected, analyzed and reported data for neat polymers and mixed matrix membranes (MMM) based on flat and hollow fiber configurations for propylene/propane separations. In this second part, we collected the data for carbon molecular sieving (CMS) membranes from polymer pyrolysis reaction and metal-organic framework (MOF) membranes from different fabrication methods, as well as data on facilitated transport membrane-polymer electrolyte membranes (PEM). CMS membranes show great potential for C3H6/C3H8 separation with an optimum pyrolysis temperature around 500–600 ℃. However, physical aging is a concern as the micro-pores shrink over time leading to lower permeability. The performance of MOF membranes are above the 2020 upper bound of polymer-based membranes, but have limited commercial application because they are fragile and difficult to produce. Finally, facilitated transport membranes show excellent propylene/propane separation performance, but are less stable compared to commercial polymeric membranes limiting their long-term operation and practical applications. As usual, there is no universal membrane and the selection must be made based on the operating conditions.

Research on international students suggests they have a low sense of belonging at the U.S. institutions they attend. This study examined whether academic advisor's cultural empathy, advisor-advisee rapport, and international students' advising satisfaction influenced international students' perspectives of belonging to the institution. We further examined whether cultural empathy and advisor-advisee rapport mediated the effect of advising satisfaction on international students' sense of belonging. The cross-sectional quantitative study used a convenience sample of 209 international students enrolled in two institutions in the United States. Results indicated that cultural empathy and student advising satisfaction had a statistically significant influence on the sense of belonging, not advisor-advisee rapport, and cultural empathy mediated the effect of advising satisfaction on sense of belonging. We offered recommendations for institutions and academic advisors when working with international students.

Although the involvement of the ubiquitin-proteasome system (UPS) in several coronavirus-productive infections has been reported, whether the UPS is required for infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV) infections is unclear. In this study, the role of UPS in the IBV and PEDV life cycles was investigated. When the UPS was suppressed by pharmacological inhibition at the early infection stage, IBV and PEDV infectivity were severely impaired. Further study showed that inhibition of UPS did not change the internalization of virus particles; however, by using R18 and DiOC-labeled virus particles, we found that inhibition of UPS prevented the IBV and PEDV membrane fusion with late endosomes or lysosomes. In addition, proteasome inhibitors blocked the degradation of the incoming viral protein N, suggesting the uncoating process and genomic RNA release were suppressed. Subsequently, the initial translation of genomic RNA was blocked. Thus, UPS may target the virus-cellular membrane fusion to facilitate the release of incoming viruses from late endosomes or lysosomes, subsequently blocking the following virus uncoating, initial translation, and replication events. Similar to the observation of proteasome inhibitors, ubiquitin-activating enzyme E1 inhibitor PYR-41 also impaired the entry of IBV, enhanced the accumulation of ubiquitinated proteins, and depleted mono-ubiquitin. In all, this study reveals an important role of UPS in coronavirus entry by preventing membrane fusion and identifies UPS as a potential target for developing antiviral therapies for coronavirus.

PurposeThe advanced lung cancer inflammation index (ALI) is a novel inflammatory and nutritional index that exerts prognostic value in various types of cancer. A previous study demonstrated that ALI at discharge could predict the prognosis in patients with acute decompensated heart failure (ADHF). However, the long-term prognostic value of ALI on admission in elderly heart failure (HF) inpatients remains unclear.Materials and methodsWe retrospectively collected HF inpatients over 65-year-old who were hospitalized in our cardiology center during the whole year of 2015. ALI was calculated as body mass index (BMI) × serum albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR). Patients were divided into two groups by the optimal cutoff value of ALI for predicting all-cause mortality using time-dependent receiver operating characteristic (ROC) curves. The Spearman rank correlation coefficient was computed to evaluate the correlation between ALI and the geriatric nutritional risk index (GNRI). Kaplan–Meier curves, Cox survival analyses, time-dependent ROC analyses, and net reclassification improvement (NRI) analyses were used to assess the prognostic effect of ALI on all-cause mortality and cardiovascular mortality.ResultsOver a 28-month median follow-up, all-cause and cardiovascular mortality occurred in 192 (35.4%) and 132 (24.3%) out of 543 patients, respectively. The optimal cutoff value of ALI for predicting all-cause mortality at 2 years was 25.8. Spearman’s correlation coefficient showed a moderate positive linear correlation between ALI and GNRI (r = 0.44, p < 0.001). The Kaplan–Meier analysis revealed that the cumulative incidences of both all-cause and cardiovascular mortalities were significantly higher in patients with lower ALI (log-rank test, all-cause mortality: p < 0.0001; cardiovascular mortality: p < 0.0001). The multivariate Cox proportional hazard analyses indicated that ALI was an independent predictor for both all-cause mortality (HR 0.550, 95% CI 0.349–0.867, p = 0.01) and cardiovascular mortality (HR 0.536, 95% CI 0.302–0.953, p = 0.034). Time-dependent ROC analyses showed that ALI was comparable to GNRI in predicting long-term all-cause mortality (AUC: ALI 0.625, GNRI 0.641, p = 0.976) and cardiovascular mortality (AUC: ALI 0.632, GNRI 0.626, p = 0.999) at 2 years. However, the estimated NRI indicated that the addition of ALI could not significantly improve risk stratification of base models for all-cause mortality (categorical NRI 4.9%, p = 0.433, continuous NRI 25%, p = 0.022) or cardiovascular mortality (categorical NRI 6.5%, p = 0.223, continuous NRI 27.5%, p = 0.029).ConclusionHigher ALI was significantly associated with lower all-cause and cardiovascular mortalities in elderly HF patients. ALI on admission could be a competent nutrition-inflammation marker with independent predictive value for evaluating the long-term mortality of HF in elder population.

Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die of ischemia several hours after ischemic stroke, which activates the innate immune response in the brain, promotes the production of neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species and − nitrogen oxide, and mediates the destruction of blood-brain barrier and the occurrence of a series of inflammatory cascade reactions. Meanwhile, the expression of adhesion molecules in cerebral vascular endothelial cells increased, and immune inflammatory cells such as polymorphonuclear neutrophils, lymphocytes and mononuclear macrophages passed through vascular endothelial cells and entered the brain tissue. These cells recognize antigens exposed by the central nervous system in the brain, activate adaptive immune responses, and further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce the above-mentioned damage, the body induces peripheral immunosuppressive responses through negative feedback, which increases the incidence of post-stroke infection. This process is accompanied by changes in the immune status of the ischemic brain tissue in local and systemic systems. A growing number of studies implicate noncoding RNAs (ncRNAs) as novel epigenetic regulatory elements in the dysfunction of various cell subsets in the neurovascular unit after cerebral infarction/ischemia-reperfusion injury. In particular, recent studies have revealed advances in ncRNA biology that greatly expand the understanding of epigenetic regulation of immune responses and inflammation after cerebral infarction/ischemia-reperfusion injury. Identification of aberrant expression patterns and associated biological effects of ncRNAs in patients revealed their potential as novel biomarkers and therapeutic targets for cerebral infarction/ischemia-reperfusion injury. Therefore, this review systematically presents recent studies on the involvement of ncRNAs in cerebral infarction/ischemia-reperfusion injury and neuroimmune inflammatory cascades, and elucidates the functions and mechanisms of cerebral infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities for the discovery of disease biomarkers and targeted therapy. Furthermore, this review introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possible transformative tool for studying lncRNAs. In the future, ncRNA is expected to be used as a target for diagnosing cerebral infarction/ischemia-reperfusion injury, judging its prognosis and treatment, thereby significantly improving the prognosis of patients.

The Anjian chicken is a local breed in Hotan, Xinjiang, China. Herein, we studied the morphological characteristics and genetic diversity of the Anjian chicken population. The findings of this study could inform the genetic improvement strategy of this breed. Phenotypic characteristics investigated included the diversity in the general appearance, feather color, and crowing length of the Anjian cocks. The population structure of the Anjian chicken and its relationship with other chicken breeds were also assessed based on mitochondrial DNA (mtDNA) D-loop sequence analysis. Phenotypically, the feather color of the Anjian chicken varied considerably. The sequence diversity analysis revealed the following: nucleotide diversity (Pi) was 0.00618, haplotype diversity (Hd) was 0.776, the average number of nucleotide differences (k) was 7.631, and Tajima’s (D) was −0.00407, indicating that Anjian chicken is moderately genetically diverse. Further phylogenetic analysis revealed that the Anjian chicken breed has 10 haplotypes clustered into two branches. Genetic distance and median network analysis showed that the mtDNA D-loop sequence of the Anjian chicken was distributed in many different clusters of the tree. These data demonstrate that even though the Anjian chicken mainly originated from red jungle fowl, it has multiple maternal origins. In conclusion, the Anjian chicken is highly genetically diverse.

Objective: To explore the role of Wnt/β-catenin signaling pathway in the pathogenesis and progression of temporomandibular joint osteoarthritis (TMJ OA) caused by overloaded force. Materials and methods: We generated a rat model of forward mandibular extension device to induce TMJ OA by overloaded force. Condylar cartilage samples were collected at 2wk, 4wk, and 8wk after appliances were installed. Changes of the condylar cartilage and subchondral bone were evaluated by hematoxylin and eosin (HE), Safranin O and Fast Green staining (SO&FG), micro-CT, tartrate resistant acid phosphatase (TRAP) staining. The expression levels of β-catenin, COL-2, MMP3 and sclerostin (SOST) were detected by immunohistochemistry (IHC) and PCR. Results: HE, SO&FG, micro-CT, OARSI and Mankin scores showed that the condyle cartilage layer was significantly thinner and proteoglycan loss in the overloded group. TRAP staining exhibited that the number of positive osteoclasts increased and OPG level decreased in the overload group. IHC, PCR showed that the expression of COL2 and SOST decreased, while MMP3 and β-catenin increased in the overload group. Conclusion: Wnt/β-catenin signaling pathway is activated in the progress of mandibular condylar cartilage degeneration and subchondral bone loss induced by overloaded functional orthopedic force (OFOF)

Cerebrovascular diseases, such as ischemic stroke, pose serious medical challenges worldwide due to their high morbidity and mortality and limitations in clinical treatment strategies. Studies have shown that reactive oxygen species (ROS)-mediated inflammation, excitotoxicity, and programmed cell death of each neurovascular unit during post-stroke hypoxia and reperfusion play an important role in the pathological cascade. Ferroptosis, a programmed cell death characterized by iron-regulated accumulation of lipid peroxidation, is caused by abnormal metabolism of lipids, glutathione (GSH), and iron, and can accelerate acute central nervous system injury. Recent studies have gradually uncovered the pathological process of ferroptosis in the neurovascular unit of acute stroke. Some drugs such as iron chelators, ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) can protect nerves after neurovascular unit injury in acute stroke by inhibiting ferroptosis. In addition, combined with our previous studies on ferroptosis mediated by natural compounds in ischemic stroke, this review summarized the progress in the regulation mechanism of natural chemical components and herbal chemical components on ferroptosis in recent years, in order to provide reference information for future research on ferroptosis and lead compounds for the development of ferroptosis inhibitors.

Abstract Quantum key distribution (QKD) enables secure key exchanges between two remote users. The ultimate goal of secure communication is to establish a global quantum network. The existing field tests suggest that quantum networks are feasible. To achieve a practical quantum network, we need to overcome several challenges including realizing versatile topologies for large scales, simple network maintenance, extendable configuration and robustness to node failures. To this end, we present a field operation of a quantum metropolitan-area network with 46 nodes and show that all these challenges can be overcome with cutting-edge quantum technologies. In particular, we realize different topological structures and continuously run the network for 31 months, by employing standard equipment for network maintenance with an extendable configuration. We realize QKD pairing and key management with a sophisticated key control centre. In this implementation, the final keys have been used for secure communication such as real-time voice telephone, text messaging and file transmission with one-time pad encryption, which can support 11 pairs of users to make audio calls simultaneously. Combined with intercity quantum backbone and ground–satellite links, our metropolitan implementation paves the way toward a global quantum network.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, have achieved good efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients, but eventual drug resistance is inevitable. Thus, new TKI-based combination therapies should be urgently explored to extend the overall survival time of these patients. CD8 + CD56+ natural killer T (NKT) cells are a natural and unique subset of lymphocytes in humans that present characteristics of T and NK cells and exert cytotoxicity on tumour cells in a granzyme B-dependent manner. The aim of this trial was to explore the efficacy and safety of CD8 + CD56+ NKT cell immunotherapy combined with gefitinib in patients with advanced EGFR-mutated NSCLC. Methods The study was designed as a prospective, randomized, controlled, open-label, phase I/II trial that includes 30 patients with EGFR mutation-positive stage III/IV NSCLC. All patients will be randomized in blocks at a 1:1 ratio and treated with gefitinib 250 mg/day monotherapy or combination therapy with allogeneic CD8 + CD56+ NKT cell infusions twice per month for 12 cycles or until disease progression occurs. The effectiveness of this treatment will be evaluated based on by progression-free survival (PFS), the time to progression (TTP), overall response rate (ORR), disease control rate (DCR) and overall survival (OS). The safety of the trail is being assessed based on adverse events (AEs). Recruitment and data collection, which started in December 2017, are ongoing. Discussion Although immunotherapy, including programmed death-1/programmed death-1 ligand (PD-1/PD-L1) immunotherapy, has been used for NSCLC treatment with or without EGFR-TKIs, its clear efficacy still has not been shown. Assessing the safety and therapeutic potential of allogeneic CD8 + CD56+ NKT killer cells in combination with EGFR-TKIs in NSCLC will be of great interest. Trial registration This trial (Phase I/II Trails of NKT Cell in Combination With Gefitinib For Non Small Cell Lung Cancer) was registered on 21 November 2017 with www.chictr.org.cn , ChiCTR-IIR-17013471 .

Abstract Quantum memory—the capacity to faithfully preserve quantum coherence and correlations—is essential for quantum-enhanced technology. There is thus a pressing need for operationally meaningful means to benchmark candidate memories across diverse physical platforms. Here we introduce a universal benchmark distinguished by its relevance across multiple key operational settings, exactly quantifying (1) the memory’s robustness to noise, (2) the number of noiseless qubits needed for its synthesis, (3) its potential to speed up statistical sampling tasks, and (4) performance advantage in non-local games beyond classical limits. The measure is analytically computable for low-dimensional systems and can be efficiently bounded in the experiment without tomography. We thus illustrate quantum memory as a meaningful resource, with our benchmark reflecting both its cost of creation and what it can accomplish. We demonstrate the benchmark on the five-qubit IBM Q hardware, and apply it to witness the efficacy of error-suppression techniques and quantify non-Markovian noise. We thus present an experimentally accessible, practically meaningful, and universally relevant quantifier of a memory’s capability to preserve quantum advantage.