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Abstract Background Pilon fractures are challenging to treat and carry a risk of delayed healing. MicroRNA (miRNA) is closely associated with various diseases due to its ability to regulate gene expression. Consequently, this study aimed to examine the connection between miR-1271-5p expression levels and pilon fracture healing processes, while also exploring the underlying mechanisms. The objective of this research was to provide valuable insights for the future clinical treatment of pilon fractures. Materials Venous blood samples were obtained for RNA extraction from patients with normal healing (n = 107) or delayed healing (n = 45) of pilon fractures. The expression levels of miR-1271-5p were measured using qRT-PCR. MiR-1271-5p and ZBTB7A biological functions in MC3T3-E1 cells were examined using the Cell Counting Kit-8 (CCK-8), flow cytometry, and qRT-PCR. Finally, an investigation into the underlying mechanisms was carried out using a dual luciferase reporter assay. Results This study found that, compared to those who healed normally, patients who experienced delayed healing of pilon fractures had significantly higher expression of miR-1271-5p. This suggests that miR-1271-5p may be an indicator for delayed healing in pilon fractures. Moreover, the upregulation of miR-1271-5p may result in a reduction of ZBTB7A expression, which is thought to mediate the effects of miR-1271-5p on MC3T3-E1 cell activities. Conclusions MiR-1271-5p was involved in the healing processes of pilon fractures via targeting ZBTB7A. MiR-1271-5p was a possible target for the therapy of pilon fractures.

Abstract This study aimed to explore physicians’ and pharmacists’ knowledge, attitudes, and practice (KAP) regarding the prevention and treatment of cardiovascular toxicity associated with cancer treatment. A multicenter cross-sectional study included physicians and pharmacists between April 2023 and June 2023. The study included 918 participants (514 physicians and 404 pharmacists). The average scores of knowledge, attitudes, and practice were 11.6 ± 3.39, 24.7 ± 2.6, and 26.3 ± 6.8 points. Sufficient knowledge was significantly associated with age ≥ 41 years (odds ratio (OR) = 2.745, 95% confidence interval (CI) 1.086–6.941, P = 0.033), male (OR = 2.745, 95% CI 1.150–2.223, P = 0.005), bachelor’s degree (OR = 0.084, 95% CI 0.013–0.533, P = 0.009), master’s degree and above (OR = 0.096, 95% CI 0.015–0.609, P = 0.013), physician occupation (OR = 7.601, 95% CI 1.337–43.207, P = 0.022), pharmacy department (OR = 18.858, 95% CI 3.245–109.57, P = 0.001), oncology department (OR = 4.304, 95% CI 2.426–7.634, P

Abstract An essential problem in quantum machine learning is to find quantum-classical separations between learning models. However, rigorous and unconditional separations are lacking for supervised learning. Here we construct a classification problem defined by a noiseless constant depth (i.e., shallow) quantum circuit and rigorously prove that any classical neural network with bounded connectivity requires logarithmic depth to output correctly with a larger-than-exponentially-small probability. This unconditional near-optimal quantum-classical representation power separation originates from the quantum nonlocality property that distinguishes quantum circuits from their classical counterparts. We further characterize the noise regimes for demonstrating such a separation on near-term quantum devices under the depolarization noise model. In addition, for quantum devices with constant noise strength, we prove that no super-polynomial classical-quantum separation exists for any classification task defined by Clifford circuits, independent of the structures of the circuits that specify the learning models.

ABSTRACT Introduction Various bronchoscopic guidance techniques have emerged to improve the diagnostic yield of peripheral pulmonary lesions (PPLs), especially when combined with ultra‐thin bronchoscopy. However, uncertainties exists in the convenience, accuracy rate, and complications of these techniques. We compared the feasibility, accuracy rate, and complication rates of transbronchial biopsy of PPLs sampled by the standard thin‐layer CT navigation combined with ultrathin bronchoscopy (CTNUTB), the Lungpro virtual navigation combined with ultrathin bronchoscopy (VNUTB), and electromagnetic navigation combined with ultrathin bronchoscopy (ENUTB). Methods Retrospectively identified were 256 patients sampled with transbronchial biopsy of PPLs. Eligible patients referred for CTNUTB, VNUTB, and ENUTB from January 2017 to December 2021 were included. We comprehensively compared the accuracy rate, feasibility, and complication rates for each method. Results There was no significant difference in the accuracy rate of CTNUTB, VNUTB, and ENUTB (p = 0.293). The operation time via Lungpro navigation was the shortest (14.4 min, p

Abstract General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)−C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Abstract Background Multiple evanescent white dot syndrome (MEWDS)-like features is a rare condition triggered by a macular disease or iatrogenic injury, exhibiting MEWDS changes in the fundus. This study aims to describe the multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) lesions with MEWDS-like features. Methods Six cases were studied retrospectively. All cases were given regional and oral corticosteroids. Results All cases showed an isolated juxtafoveal yellowish-white MFC/PIC lesion with disruption of RPE-Bruch’s membrane-choriocapillaris complex (RPE-BM-CC), subretinal hyperreflective materials and choroidal thickening on optical coherence tomography. Two weeks after presentation, the grayish-white dots disappeared spontaneously and the corticosteroids were given. After four weeks, the ellipsoid zone (EZ) around the lesion and hyper-autofluorescence resolved. After 13 weeks, five cases showed shrinkage of the juxtafoveal lesion and restoration of foveal EZ. After six months, the juxtafoveal lesion became pigmented. Only one case developed type 2 choroidal neovascularization. Conclusions The clinical course of MEWDS-like manifestations is still evanescent in our cases. The yellowish-white juxtafoveal MFC/PIC lesions with disruption of RPE-BM-CC and choroidal thickening showed a well-controlled prognosis after corticosteroid treatment.

Abstract Background Theaceae, comprising 300 + species, holds significance in biodiversity, economics, and culture, notably including the globally consumed tea plant. Stewartia gemmata, a species of the earliest diverging tribe Stewartieae, is critical to offer insights into Theaceae's origin and evolutionary history. Result We sequenced the complete organelle genomes of Stewartia gemmata using short/long reads sequencing technologies. The chloroplast genome (158,406 bp) exhibited a quadripartite structure including the large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs); 114 genes encoded 80 proteins, 30 tRNAs, and four rRNAs. The mitochondrial genome (681,203 bp) exhibited alternative conformations alongside a monocyclic structure: 61 genes encoding 38 proteins, 20 tRNAs, three rRNAs, and RNA editing-impacting genes, including ATP6, RPL16, COX2, NAD4L, NAD5, NAD7, and RPS1. Comparative analyses revealed frequent recombination events and apparent rRNA gene gains and losses in the mitochondrial genome of Theaceae. In organelle genomes, the protein-coding genes exhibited a strong A/U bias at codon endings; ENC-GC3 analysis implies selection-driven codon bias. Transposable elements might facilitate interorganelle sequence transfer. Phylogenetic analysis confirmed Stewartieae's early divergence within Theaceae, shedding light on organelle genome characteristics and evolution in Theaceae. Conclusions We studied the detailed characterization of organelle genomes, including genome structure, composition, and repeated sequences, along with the identification of lateral gene transfer (LGT) events and complexities. The discovery of a large number of repetitive sequences and simple sequence repeats (SSRs) has led to new insights into molecular phylogenetic markers. Decoding the Stewartia gemmata organellar genome provides valuable genomic resources for further studies in tea plant phylogenomics and evolutionary biology.

To clarify the effects of newly developed controlled-release iodine fertilizer (CRIF) on enhancing lettuce (Lactuca sativa L.) iodine accumulation, improving the physiological traits, and reducing iodine leaching from soil, a greenhouse pot experiment was conducted. Polymer-coated iodate (PCIO), polymer-coated iodide (PCI), and two conventional iodine fertilizers—iodate (CIO) and iodide (CI)—were applied at a rate of 15 mg iodine per kg soil. The study found that the coating of iodine fertilizers had no significant effects on the biomass of lettuce. The iodine concentration in lettuce leaves subjected to PCIO treatment was elevated by 50.1% and 45.5%, respectively, in comparison to leaves treated with CIO and PCI. The soil-to-leaf transfer factor (TFleaf, dry weight basis) for plants treated with PCIO was significantly higher than that of PCI-treated plants. PCIO also significantly reduced iodine leaching by 46.3% compared to CIO. In lettuce leaves with PCIO treatment, the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT) significantly increased by 50.8% and 27.6%, respectively. Likewise, malo-naldehyde (MDA) levels decreased by 23.2% compared to the control samples. PCIO also demonstrated advantages in enhancing the quality of the lettuce. In conclusion, the application of controlled-release iodine fertilizer could be a highly effective and eco-friendly approach to cultivating iodine-rich vegetables.

The existing body of research underscores the critical impact of intratumoral microbiomes on the progression of pancreatic ductal adenocarcinoma (PDAC), particularly in reshaping the tumor microenvironment and influencing gemcitabine resistance. However, peritumoral tissues’ microbiome, distinct from PDAC tumors, remain understudied, and Western-centric analyses overlooking potential variations in dietary-influenced microbiomes. Our study addresses this gap by 16 S rRNA sequencing of PDAC tumors and matched peritumoral tissues from Chinese Mainland patients. Our research has uncovered that the microbiome composition within tumors and paired peritumoral tissues exhibits a high degree of similarity, albeit with certain discrepancies. Notably, Exiguobacterium is found to be more abundant within the tumor tissues. Further investigations have revealed that a lower Exiguobacterium/Bacillus ratio in both the tumor and peritumoral tissues of PDAC patients is indicative of a more favorable prognosis. Further exploration utilizing an orthotopic tumor model demonstrates that the probiotic Bacillus Coagulans impedes PDAC progression, accompanied by an increased infiltration of inflammatory neutrophils in tumors. Additionally, in the subgroup with a low Exiguobacterium/Bacillus ratio, whole-exome sequencing reveals elevated missense mutations in ABL2 and MSH2. The elevated expression of ABL2 and MSH2 has been correlated with poorer prognostic outcomes in PDAC patients. Together, these insights shed light on risk factors influencing PDAC progression and unveil potential therapeutic targets, alongside probiotic intervention strategies.

Abstract A multi-class classification model for acute coronary syndrome (ACS) remains to be constructed based on multi-fluid metabolomics. Major confounders may exert spurious effects on the relationship between metabolism and ACS. The study aims to identify an independent biomarker panel for the multiclassification of HC, UA, and AMI by integrating serum and urinary metabolomics. We performed a liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based metabolomics study on 300 serum and urine samples from 44 patients with unstable angina (UA), 77 with acute myocardial infarction (AMI), and 29 healthy controls (HC). Multinomial machine learning approaches, including multinomial adaptive least absolute shrinkage and selection operator (LASSO) regression and random forest (RF), and assessment of the confounders were applied to integrate a multi-class classification biomarker panel for HC, UA and AMI. Different metabolic landscapes were portrayed during the transition from HC to UA and then to AMI. Glycerophospholipid metabolism and arginine biosynthesis were predominant during the progression from HC to UA and then to AMI. The multiclass metabolic diagnostic model (MDM) dependent on ACS, including 2-ketobutyric acid, LysoPC(18:2(9Z,12Z)), argininosuccinic acid, and cyclic GMP, demarcated HC, UA, and AMI, providing a C-index of 0.84 (HC vs. UA), 0.98 (HC vs. AMI), and 0.89 (UA vs. AMI). The diagnostic value of MDM largely derives from the contribution of 2-ketobutyric acid, and LysoPC(18:2(9Z,12Z)) in serum. Higher 2-ketobutyric acid and cyclic GMP levels were positively correlated with ACS risk and atherosclerosis plaque burden, while LysoPC(18:2(9Z,12Z)) and argininosuccinic acid showed the reverse relationship. An independent multiclass biomarker panel for HC, UA, and AMI was constructed using the multinomial machine learning methods based on serum and urinary metabolite signatures.

Abstract Catalytic enantioselective introduction of a propargyl group constitutes one of the most important carbon–carbon forming reactions, as it is versatile to be transformed into diverse functional groups and frequently used in the synthesis of natural products and biologically active molecules. Stereoconvergent transformations of racemic propargyl precursors to a single enantiomer of products via propargyl radicals represent a powerful strategy and provide new reactivity. However, only few Cu- or Ni-catalyzed protocols have been developed with limited reaction modes. Herein, a photoredox/cobalt-catalyzed regio-, diastereo- and enantioselective propargyl addition to aldehydes via propargyl radicals is presented, enabling construction of a broad scope of homopropargyl alcohols that are otherwise difficult to access in high efficiency and stereoselectivity from racemic propargyl carbonates. Mechanistic studies and DFT calculations provided evidence for the involvement of propargyl radicals, the origin of the stereoconvergent process and the stereochemical models.

Abstract Catalytic dynamic kinetic asymmetric transformation (DyKAT) provides a powerful tool to access chiral stereoisomers from racemic substrates. Such transformation has been widely employed on the construction of central chirality, however, the application in axial chirality remains underexplored because its equilibrium of substrate enantiomers is limited to five-membered metalacyclic intermediate. Here we report a tetracoordinate boron-directed dynamic kinetic asymmetric cross-coupling of racemic, configurationally stable 3-bromo-2,1-azaborines with boronic acid derivatives. A series of challenging C-B axially chiral compounds were prepared with generally good to excellent enantioselectivities. Moreover, this transformation can also be extended to prepare atropisomers bearing adjacent C-B and C-C diaxes with excellent diastereo- and enantio-control. The key to the success relies on the rational design of a reversible tetracoordinate boron intermediate, which is supported by theoretical calculations that dramatically reduces the rotational barrier of the original C-B axis and achieves the goal of DyKAT.

Summary: Lead (Pb(II)) contamination is common in liquid foods and can result from Pb(II) being present in the raw materials or during handling processes. However, due to the complexity of food matrices, there is limited data available concerning Pb(II) ion removal from food sources. This study focused on fabricating a PVA/PAA/DMTD electrospun nanofibrous membrane (ENFM) to efficiently and selectively remove Pb(II) ions from liquid foods. The PVA/PAA/DMTD ENFM had a maximum adsorption capacity of 138.3 mg/g for Pb(II) ions and demonstrated high selectivity toward the removal of Pb(II) ions. Negative values of the Gibbs free energy (ΔG°) showed that the spontaneous nature of the adsorption process was feasible at different temperatures. Moreover, it successfully removed Pb(II) ions from selected samples of commercially available drinks. Therefore, this adsorbent exhibits significant potential for removing Pb(II) ions from liquid food products, thereby reducing daily dietary exposure to Pb(II).

The Internet of Vehicles (IoV) has witnessed a substantial surge in its expansion during recent years, with the integration of edge servers emerging as an increasingly prevalent practice to cater to content requests that demand a superior quality of service. Nonetheless, conventional cache policies often prove inadequate for IoV applications, primarily due to their incapacity to effectively handle a diverse array of content requests, the high-speed mobility of vehicles, and the inherent instability of network connections. Within the scope of this study, we commence by bifurcating various content requests into two distinct categories: latency-sensitive content request and bandwidth-sensitive content request. Subsequently, we establish a model to evaluate the service quality under the joint consideration of different types of content requests, the mobility of vehicles and storage capacity of edge nodes. Furthermore, we transform the quality-of-service (QoS) penalty function into a system reward function. This adaption enables us to propose an innovative edge cache scheme founded upon the Deep Deterministic Policy Gradient (DDPG) algorithm of Reinforcement Learning (RL) method, which empowers dynamic adjustments in response to the evolving IoV environment. To validate the effectiveness of our proposed approach, we harness the Simulation of Urban Mobility (SUMO) traffic simulation software and construct a traffic road scenario based on a specific part segment of Nanjing Beltway. A wide-ranging set of contrast experiments was performed to ensure the improved performance of the DDPG based deep reinforcement learning method. Simulation experimental results show that the proposed algorithm converges quickly and outperforms existing algorithms in terms of service quality-hit ratio for latency-sensitive content and transmission speed for bandwidth-sensitive content.

Abstract Currently, checkpoint inhibitor‐based immunotherapy has emerged as prevailing treatment modality for diverse cancers. However, immunotherapy as a first‐line therapy has not consistently yielded durable responses. Moreover, the risk of immune‐related adverse events increases with combination regimens. Thus, the development of predictive biomarkers is needed to optimize individuals benefit, minimize risk of toxicities, and guide combination approaches. The greatest focus has been on tumor programmed cell death‐ligand 1 (PD‐L1), microsatellite instability (MSI), and tumor mutational burden (TMB). However, there remains a subject of debate due to thresholds variability and significant heterogeneity. Major unmet challenges in immunotherapy are the discovery and validation of predictive biomarkers. Here, we show the status of tumor PD‐L1, MSI, TMB, and emerging data on novel biomarker strategies with oncogenic signaling and epigenetic regulation. Considering the exploration of peripheral and intestinal immunity has served as noninvasive alternative in predicting immunotherapy, this review also summarizes current data in systemic immunity, encompassing solute PD‐L1 and TMB, circulating tumor DNA and infiltrating lymphocytes, routine emerging inflammatory markers and cytokines, as well as gut microbiota. This review provides up‐to‐date information on the evolving field of currently available biomarkers in predicting immunotherapy. Future exploration of novel biomarkers is warranted.

Abstract Preretinal deposits (PDs) are a rare condition among fundus diseases. We found that preretinal deposits have some features in common that can provide clinical information. This review affords an overview of PDs in different but related ocular diseases and events, and summarizes the clinical features and possible origin of PDs in related conditions, providing diagnostic clues for ophthalmologists when facing PDs. A literature search was performed using three major electronic databases (PubMed, EMBASE, and Google Scholar) to identify potentially relevant articles published on or before June 4, 2022. Most of the cases in the enrolled articles had optical coherence tomography (OCT) images to confirm the preretinal location of the deposits. Thirty-two publications reported PD-related conditions, including ocular toxoplasmosis (OT), syphilitic uveitis, vitreoretinal lymphoma, human T-cell lymphotropic virus type 1 (HTLV-I) associated uveitis or HTLV-I carriers, acute retinal necrosis, endogenous fungal endophthalmitis, idiopathic uveitis, and exogenous materials. Based on our review, OT is the most frequent infectious disease to exhibit PDs, and silicone oil tamponade is the most common exogenous cause of preretinal deposits. PDs in inflammatory diseases are highly suggestive of active infectious disease and are preferentially accompanied by a retinitis area. However, PDs will largely resolve after etiological treatment in either inflammatory or exogenous conditions.

Abstract Background Immune checkpoint inhibitors (ICIs) are regarded as the most promising treatment for advanced-stage non-small cell lung cancer (aNSCLC). Unfortunately, there has been no unified accuracy biomarkers and systematic model specifically identified for prognostic and severe immune-related adverse events (irAEs). Our goal was to discover new biomarkers and develop a publicly accessible method of identifying patients who may maximize benefit from ICIs. Methods This retrospective study enrolled 138 aNSCLC patients receiving ICIs treatment. Progression-free survival (PFS) and severe irAEs were end-points. Data of demographic features, severe irAEs, and peripheral blood inflammatory-nutritional and immune indices before and after 1 or 2 cycles of ICIs were collected. Independent factors were selected by least absolute shrinkage and selection operator (LASSO) combined with multivariate analysis, and incorporated into nomogram construction. Internal validation was performed by applying area under curve (AUC), calibration plots, and decision curve. Results Three nomograms with great predictive accuracy and discriminatory power were constructed in this study. Among them, two nomograms based on combined inflammatory-nutritional biomarkers were constructed for PFS (1 year-PFS and 2 year-PFS) and severe irAEs respectively, and one nomogram was constructed for 1 year-PFS based on immune indices. ESCLL nomogram (based on ECOG PS, preSII, changeCAR, changeLYM and postLDH) was constructed to assess PFS (1-, 2-year-AUC = 0.893 [95% CI 0.837–0.950], 0.828 [95% CI 0.721–0.935]). AdNLA nomogram (based on age, change-dNLR, changeLMR and postALI) was constructed to predict the risk of severe irAEs (AUC = 0.762 [95% CI 0.670–0.854]). NKT-B nomogram (based on change-CD3+CD56+CD16+NKT-like cells and change-B cells) was constructed to assess PFS (1-year-AUC = 0.872 [95% CI 0.764–0.965]). Although immune indices could not be modeled for severe irAEs prediction due to limited data, we were the first to find CD3+CD56+CD16+NKT-like cells were not only correlated with PFS but also associated with severe irAEs, which have not been reported in the study of aNSCLC-ICIs. Furthermore, our study also discovered higher change-CD4+/CD8+ ratio was significantly associated with severe irAEs. Conclusions These three new nomograms proceeded from non-invasive and straightforward peripheral blood data may be useful for decisions-making. CD3+CD56+CD16+NKT-like cells were first discovered to be an important biomarker for treatment and severe irAEs, and play a vital role in distinguishing the therapy response and serious toxicity of ICIs.

In order to solve the problems of obstacle avoidance planning and trajectory optimization of unmanned platform in hilly orchards, this paper proposes a dynamic planning algorithm based on Gaussian probability model to predict dynamic obstacle behavior. The technical route and method of theoretical derivation-algorithm design-simulation analysis-real vehicle testing are both adopted. Firstly, the global reference path of orchard is optimized based on the quadratic programming. Secondly, the intentions of surrounding pedestrians and other dynamic obstacles are estimated based on the Gaussian probability model. Subsequently, a dynamic grid map is created based on the Frenet coordinate system. Then, the obstacles avoidance paths are dynamically planned to obtain discrete optimal paths. Finally, the quintic polynomial curve is utilized to connect the sampling points to generate the path with continuous curvature. The analysis by ROS/Rviz simulation indicates that the planning time decreases by 57.97%, the number of sampled nodes decreases by 79.57%, and the curvature is smoother and continuous compared with the RRT algorithm. A field test is conducted on a hilly orchard road. With the Gaussian model, the algorithm can effectively predict the behavioral state of dynamic obstacles. The platform can autonomously plan a continuous, smooth and safe driving route in a shorter period of time, effectively avoiding obstacles and reducing the impact of steering-in-place on operating efficiency. Through the research, a dynamic obstacle behavior prediction and obstacle avoidance algorithm is proposed for the crawler chassis in hilly orchards based on the Gaussian probability model and dynamic programming, and the obstacle avoidance curve obtained by the algorithm satisfies the kinematic constraints of the crawler chassis, and has good safety, better real-time and enforceability. Additionally, a comprehensive set of software and hardware solutions for spontaneous static obstacle avoidance planning in hilly orchards is presented.

Abstract Ischemia-reperfusion (I/R) induced acute kidney injury (AKI), characterized by excessive mitochondrial damage and cell apoptosis, remains a clinical challenge. Recent studies suggest that regulator of calcineurin 1 (RCAN1) regulates mitochondrial function in different cell types, but the underlying mechanisms require further investigation. Herein, we aim to explore whether RCAN1 involves in mitochondrial dysfunction in AKI and the exact mechanism. In present study, AKI was induced by I/R and cisplatin in RCAN1 flox/flox mice and mice with renal tubular epithelial cells (TECs)-specific deletion of RCAN1. The role of RCAN1 in hypoxia-reoxygenation (HR) and cisplatin-induced injury in human renal proximal tubule epithelial cell line HK-2 was also examined by overexpression and knockdown of RCAN1. Mitochondrial function was assessed by transmission electron microscopy, JC-1 staining, MitoSOX staining, ATP production, mitochondrial fission and mitophagy. Apoptosis was detected by TUNEL assay, Annexin V-FITC staining and Western blotting analysis of apoptosis-related proteins. It was found that protein expression of RCAN1 was markedly upregulated in I/R- or cisplatin-induced AKI mouse models, as well as in HR models in HK-2 cells. RCAN1 deficiency significantly reduced kidney damage, mitochondrial dysfunction, and cell apoptosis, whereas RCAN1 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration demonstrated that RCAN1 increases the phosphorylation of mitochondrial fission factor (Mff) by binding to downstream c-Jun N-terminal kinase (JNK), then promotes dynamin related protein 1 (Drp1) migration to mitochondria, ultimately leads to excessive mitochondrial fission of renal TECs. In conclusion, our study suggests that RCAN1 could induce mitochondrial dysfunction and apoptosis by activating the downstream JNK/Mff signaling pathway. RCAN1 may be a potential therapeutic target for conferring protection against I/R- or cisplatin-AKI.

Abstract Purpose To describe and analyze the clinical prognosis of infants diagnosed of familial exudative vitreoretinopathy (FEVR) with single gene mutation in long-term follow-up. Methods A retrospective case study was conducted on 355 FEVR infants with single positive gene. Result Of the 335 single-gene positive infant FEVR cases (under 3 years old), 20% (n = 67) was diagnosed of strabismus at first visit. Staging of various genotypes was different (P

Abstract Functioning and quality of life (QOL) are typical outcomes assessed in children and adolescents with major depressive disorder (MDD); however, meta-analytical evidence remains scarce. The aim of this meta-analysis was to assess functioning and QOL antidepressant outcomes in this population. Eight electronic databases (PubMed, Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LILACS, and ProQuest Dissertation Abstracts) were searched for double-blind randomized controlled trials (RCTs) up to July 31, 2020. RCTs that compared antidepressants with placebo for treating functioning and QOL in children and adolescents with MDD were included. Primary outcomes were mean change scores of functioning and QOL scales from baseline to post-treatment. Subgroup and sensitivity analyses were conducted to examine whether results were affected by moderator variables (e.g., medication type, age, sample size, and treatment duration). From 7284 publications, we included 17 RCTs (all 17 assessed functioning and 4 assessed QOL outcomes) including 2537 participants. Antidepressants showed significant positive effects on functioning (standardized mean difference [SMD] = 0.17, 95% confidence interval [CI] = 0.09–0.25, p

Enantioselective catalytic methods for the construction of boron-stereogenic compounds are elusive. In this article, the authors describe a route to these compounds via a copper-catalysed desymmetric B-H insertion on 2-arylpyridine-boranes with carbenes.

As one of the world’s top three popular non-alcoholic beverages, tea is economically and culturally valuable. Xinyang Maojian, this elegant green tea, is one of the top ten famous tea in China and has gained prominence for thousands of years. However, the cultivation history of Xinyang Maojian tea population and selection signals of differentiation from the other major variety Camellia sinensis var. assamica (CSA) remain unclear. We newly generated 94 Camellia sinensis (C. sinensis) transcriptomes including 59 samples in the Xinyang area and 35 samples collected from 13 other major tea planting provinces in China. Comparing the very low resolution of phylogeny inferred from 1785 low-copy nuclear genes with 94 C. sinensis samples, we successfully resolved the phylogeny of C. sinensis samples by 99,115 high-quality SNPs from the coding region. The sources of tea planted in the Xinyang area were extensive and complex. Specifically, Shihe District and Gushi County were the two earliest tea planting areas in Xinyang, reflecting a long history of tea planting. Furthermore, we identified numerous selection sweeps during the differentiation of CSA and CSS and these positive selection genes are involved in many aspects such as regulation of secondary metabolites synthesis, amino acid metabolism, photosynthesis, etc. Numerous specific selective sweeps of modern cultivars were annotated with functions in various different aspects, indicating the CSS and CSA populations possibly underwent independent specific domestication processes. Our study indicated that transcriptome-based SNP-calling is an efficient and cost-effective method in untangling intraspecific phylogenetic relationships. This study provides a significant understanding of the cultivation history of the famous Chinese tea Xinyang Maojian and unravels the genetic basis of physiological and ecological differences between the two major tea subspecies.

Boltzmann Machines offer the potential of more efficient solutions to combinatorial problems compared to von Neumann computing architectures. Here, Yan et al introduce a stochastic memristor with dynamically tunable properties, a vital feature for the efficient implementation of a Boltzmann Machine.

BackgroundMultiple sclerosis is a chronic demyelinating disease of uncertain etiology. Traditional treatment methods produce more adverse effects. Epidemiological and clinical treatment findings showed that unknown environmental factors contribute to the etiology of MS and that diet is a commonly assumed factor. Despite the huge interest in diet expressed by people with MS and the potential role diet plays in MS, very little data is available on the role of diet in MS pathogenesis and MS course, in particular, studies on fats and MS. The oil of Acer truncatum is potential as a resource to be exploited in the treatment of some neurodegenerative diseases.ObjectiveHere, we investigated the underlying influences of Acer truncatum oil on the stimulation of remyelination in a cuprizone mouse model of demyelination.MethodsCuprizone (0.2% in chow) was used to establish a mouse model of demyelination. Acer truncatum oil was administrated to mice during remyelination. Following techniques were used: behavioral test, histochemistry, fluorescent immunohistochemistry, transmission electron microscope.ResultsMice exposed to cuprizone for 6 weeks showed schizophrenia-like behavioral changes, the increased exploration of the center in the open field test (OFT), increased entries into the open arms of the elevated plus-maze, as well as demyelination in the corpus callosum. After cuprizone withdrawal, the diet therapy was initiated with supplementation of Acer truncatum oil for 2 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (CC1) and myelin basic protein (MBP). More importantly, the supplementation with Acer truncatum oil in the diet reduced the schizophrenia-like behavior in the open field test (OFT) and the elevated plus-maze compared to the cuprizone recovery group. The results revealed that the diet supplementation with Acer truncatum oil improved behavioral abnormalities, oligodendrocyte maturation, and remyelination in the cuprizone model during recovery.ConclusionDiet supplementation with Acer truncatum oil attenuates demyelination induced by cuprizone, indicating that Acer truncatum oil is a novel therapeutic diet in demyelinating diseases.

Endothelial dysfunction plays a pivotal role in the development and progression of diabetic vascular complications. Naringenin (Nar) is a flavanone bioactive isolated from citrus fruits known to have in vitro and in vivo antidiabetic properties. However, whether Nar affects endothelial function remains unclear in diabetes or under high-glucose (HG) condition. Using an in vitro model of hyperglycemia in human umbilical vein endothelial cells (HUVECs), we found that Nar administration markedly attenuated HG-induced alterations of endothelial function, evidenced by the mitigation of oxidative stress and inflammation, the reduction of cell adhesion molecular expressions, and the improvement of insulin resistance. We also found that HG exposure significantly reduced the levels of intracellular heat shock protein 70 (iHSP70 or iHSPA1A) and the release of HSP70 from HUVECs. HSP70 depletion mimicked and clearly diminished the protective effects of Nar on HG-induced alterations of endothelial function. In addition, Nar treatment significantly enhanced iHSP70 protein levels through a transcription-dependent manner. These results demonstrated that Nar could protect HUVECs against HG-induced alterations of endothelial function through upregulating iHSP70 protein levels. These findings are also helpful in providing new therapeutic strategies that are promising in the clinical use of Nar for the treatment of diabetes and diabetic complications.

To resolve the issues of a deep backbone network, a large model, slow reasoning speed on a mobile terminal, low detection accuracy for small targets and difficulties detecting and recognizing traffic lights in real time and accurately with YOLOv4, a traffic lights recognition method based on improved YOLOv4 is proposed. The lightweight ShuffleNetv2 network is utilized to replace the CSPDarkNet53 network of YOLOv4 to satisfy the requirements of a mobile terminal. The reformed k-means clustering algorithm is applied to generate anchor boxes for avoiding the sensitivity issue of outliers and initial values. A novel attention mechanism named CS2A is added to enhance the extraction capability of effective features. Multiple data augmentation methods are combined to improve the generalization ability of the model. Ultimately, the detection and recognition of traffic lights can be realized. The S2TLD dataset is selected for training and testing, and it can be proved that the recognition accuracy and model size are greatly optimized. Meanwhile, a self-made dataset is selected for training and testing. Compared with the conventional YOLOv4, the recognition accuracy of the proposed algorithm for traffic lights’ state information increases by 1.79%, and the model size decreases by 81.97%. Appropriate scenes are selected for real-vehicle testing and the results demonstrate that the detection speed of the presented algorithm increases by 16%, and the recognition effect for small targets increases by 37% in comparison with conventional YOLOv4.

This study is to evaluate the athermal forward osmosis (FO) concentration process of blueberry juice using food additives as a draw solution (DS). The effects of food additives, including citric acid, sodium benzoate, and potassium sorbate, on the concentration processes are studied, and their effects on the products and membranes are compared. Results show that all these three food additives can be alternative DSs in concentration, among which citric acid shows the best performance. The total anthocyanin content (TAC) of blueberry juice concentrated by citric acid, sodium benzoate, and potassium sorbate were 752.56 ± 29.04, 716.10 ± 30.80, and 735.31 ± 24.92 mg·L−1, respectively, increased by 25.5%, 17.8%, and 19.9%. Meanwhile, the total phenolic content (TPC) increased by 21.0%, 10.6%, and 16.6%, respectively. Citric acid, sodium benzoate, and potassium sorbate all might reverse into the concentrated juice in amounts of 3.083 ± 0.477, 1.497 ± 0.008, and 0.869 ± 0.003 g/kg, respectively. These reversed food additives can make the TPC and TAC in juice steadier during its concentration and storage. Accordingly, food additives can be an excellent choice for DSs in the FO concentration process of juices, not only improving the concentration efficiency but also increasing the stability of blueberry juice.

This paper proposes a novel gear-like disk resonator (GDR). The design, fabrication, and characterization of GDR are presented. In comparison with a ring-like disk resonator (RDR), a GDR replaces the circular rings with meander-shaped rings consisting of linear beams. The finite element method (FEM) is implemented, and the simulation results show that the GDR has a much lower frequency and effective stiffness, higher quality factor (Q), and better immunity to crystal orientation error. Affected by high Q and small frequency splits, the mechanical sensitivity (Smech) is shown to increase greatly. GDR and RDR with the same structure parameters are built side-by-side on the same wafer, and prototypes are fabricated through the SOI fabrication technique. The frequency response test and ring-down test are implemented using a readout circuit under a vacuum condition (5 Pa) at room temperature. The frequency split (9.1 Hz) of the GDR is about 2.8 times smaller than that (25.8 Hz) of the RDR without electrostatic tuning. Compared with the RDR, the Q (19.2 k) and decay time constant (0.59 s) of the GDR are improved by 145% and 236%, respectively. The experimental results show great promise for the GDR being used as a gear-like disk resonator gyroscope (GDRG).

The interface crack of a slab track is a fracture of mixed-mode that experiences a complex loading–unloading–reloading process. A reasonable simulation of the interaction between the layers of slab tracks is the key to studying the interface crack. However, the existing models of interface disease of slab track have problems, such as the stress oscillation of the crack tip and self-repairing, which do not simulate the mixed mode of interface cracks accurately. Aiming at these shortcomings, we propose an improved cohesive zone model combined with an unloading/reloading relationship based on the original Park–Paulino–Roesler (PPR) model in this paper. It is shown that the improved model guaranteed the consistency of the cohesive constitutive model and described the mixed-mode fracture better. This conclusion is based on the assessment of work-of-separation and the simulation of the mixed-mode bending test. Through the test of loading, unloading, and reloading, we observed that the improved unloading/reloading relationship effectively eliminated the issue of self-repairing and preserved all essential features. The proposed model provides a tool for the study of interface cracking mechanism of ballastless tracks and theoretical guidance for the monitoring, maintenance, and repair of layer defects, such as interfacial cracks and slab arches.

The heat generation, contact state, material flow and friction coefficient are all intertwined during friction stir welding (FSW) because of the fully thermomechanical coupling nature of FSW. The value of friction coefficient and the fraction of sliding will dominate heat generation which is the driving force to make the FSW process successful. This work detailedly clarified how to roughly estimate the fraction of sliding and friction coefficient at the tool/workpiece interface. Results showed that friction coefficients in FSW of various materials were in a range of 0.2-0.56. The fraction of sliding was significantly affected by friction coefficient. The fraction of sliding was in a range of about 73-88% for FSW of Al1100-H14 alloy and about 38-65% for FSW of Al7050-T7451 alloy. Moreover, the fraction of sliding increased with decreasing heat input.

Cytoglobosins H (1) and I (2), together with seven known cytochalasan alkaloids (3–9), were isolated from the deep-sea-derived fungus Chaetomium globosum. The structures of new compounds 1 and 2 were elucidated by extensive 1D and 2D NMR and mass spectroscopic data. All the compounds were evaluated for their antiproliferative activities against MDA-MB-231 human breast cancer cells, LNCaP human prostate cancer cells, and B16F10 mouse melanoma cells. Compound 6 showed significant antiproliferative activity against LNCaP and B16F10 cell lines with IC50 values of 0.62 and 2.78 μM, respectively. Further testing confirmed that compound 6 inhibited the growth of LNCaP cells by inducing apoptosis.