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Abstract Herein, we develop a straightforward, metal-free, and acid-/base-free electrochemical C4-selective C − H deuteration of pyridine derivatives with economic and convenient D2O at room temperature. This strategy features an efficient and environmentally friendly approach with high chemo- and regioselectivity, affording a wide range of D-compounds, such as pyridines, quinolones, N-ligands and biorelevant compounds. Notably, the mechanistic experiments and cyclic voltammetry (CV) studies demonstrate that N-butyl-2-phenylpyridinium iodide is a crucial intermediate during the electrochemical transformation, which provides a general and efficient way for deuteration of pyridine derivatives.

Abstract Iso-butene (iso-C4H8) is an important raw material in chemical industry, whereas its efficient separation remains challenging due to similar molecular properties of C4 olefins. The ideal adsorbent should possess simultaneous high uptakes for 1,3-butadiene (C4H6) and n-butene (n-C4H8) counterparts, endowing high efficiency for iso-C4H8 separation in adsorption columns. Herein, a sulfate-pillared adsorbent, SOFOUR-DPDS-Ni (DPDS = 4,4′-dipyridyldisulfide), is reported for the efficient iso-C4H8 separation from binary and ternary C4 olefin mixtures. The rigidity in pore sizes and shapes of SOFOUR-DPDS-Ni exerts the molecular sieving of iso-C4H8, while exhibiting high C4H6 and n-C4H8 uptakes. The benchmark Henry’s selectivity for C4H6/iso-C4H8 (2321.8) and n-C4H8/iso-C4H8 (233.5) outperforms most reported adsorbents. Computational simulations reveal the strong interactions for C4H6 and n-C4H8. Furthermore, dynamic breakthrough experiments demonstrate the direct production of high-purity iso-C4H8 (>99.9%) from C4H6/iso-C4H8 (50/50, v/v), n-C4H8/iso-C4H8 (50/50, v/v), and C4H6/n-C4H8/iso-C4H8 (50/15/35, v/v/v) gas-mixtures.

The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and schizophrenia patients (p = 0.006 to 0.07). In Study II with another 30 patient smokers, a proof-of-concept, patient- and rater-blind, randomized, sham-controlled rTMS design was used to test whether targeting the newly identified dmPFC location may causally enhance the rsFC and reduce nicotine addiction in schizophrenia. Although significant interactions were not observed, exploratory analyses showed that this dmPFC–extended amygdala rsFC was enhanced by 4-week active 10Hz rTMS (p = 0.05) compared to baseline; the severity of nicotine addiction showed trends of reduction after 3 and 4 weeks (p ≤ 0.05) of active rTMS compared to sham; Increased rsFC by active rTMS predicted reduction of cigarettes/day (R = −0.56, p = 0.025 uncorrected) and morning smoking severity (R = −0.59, p = 0.016 uncorrected). These results suggest that the dmPFC–extended amygdala circuit may be linked to nicotine addiction in schizophrenia and healthy individuals, and future efforts targeting its underlying pathophysiological mechanisms may yield more effective treatment for nicotine addiction.

Birds pose a serious threat to the safe operation of aircrafts. Existing object detection methods have achieved good results for big and medium instances; however, for small flying bird instances, drawbacks such as slow speed, low accuracy, and large model size are still present. Therefore, to overcome these shortcomings, we propose the SMB-YOLOv5 model to detect birds near airports. First, we introduce a self-supervised predictive convolution attention block to enable YOLOv5s6 to focus on critical information, thereby enhancing detection performance. Second, we introduce a multi-branch block (MBB) that enhances the expressive capability of the network by incorporating branches with different receptive fields. Third, to enhance the feature fusion capability of the model and detection mAP@50 for small-bird instances, drawing inspiration from the bidirectional feature pyramid network, we reutilize the shallow-level features of the feature extraction network. We also remove some modules to ensure an increased accuracy without excessively inflating the model size. Finally, to increase the convergence speed of the network, we modify its loss function by replacing complete IoU (CIoU) with efficient IoU (EIoU), which improves the detection mAP@50 of the network. Compared to the YOLOv5s6 model, the proposed SMB-YOLOv5 model achieves a 2.6% increase in mAP@50 on the test dataset. The detection speed has reached 24 fps. We find that the SMB-YOLOv5 has a higher mAP@50 than the other algorithms in the test dataset and the lowest number of parameters, and it can be applied in airport bird detection systems to provide more precise bird orientation information for airport bird detection tasks.

Abstract Olefin/paraffin separations are among the most energy-intensive processes in the petrochemical industry, with ethylene being the most widely consumed chemical feedstock. Adsorptive separation utilizing molecular sieving adsorbents can optimize energy efficiency, whereas the size-exclusive mechanism alone cannot achieve multiple olefin/paraffin sieving in a single adsorbent. Herein, an unprecedented sieving adsorbent, BFFOUR-Cu-dpds (BFFOUR = BF4 -, dpds = 4,4’-bipyridinedisulfide), is reported for simultaneous sieving of C2-C4 olefins from their corresponding paraffins. The interlayer spaces can be selectively opened through stronger guest-host interactions induced by unsaturated C = C bonds in olefins, as opposed to saturated paraffins. In equimolar six-component breakthrough experiments (C2H4/C2H6/C3H6/C3H8/n-C4H8/n-C4H10), BFFOUR-Cu-dpds can simultaneously divide olefins from paraffins in the first column, while high-purity ethylene ( > 99.99%) can be directly obtained through the subsequent column using granular porous carbons. Moreover, gas-loaded single-crystal analysis, in-situ infrared spectroscopy measurements, and computational simulations demonstrate the accommodation patterns, interaction bonds, and energy pathways for olefin/paraffin separations.

Abstract Epithelial ovarian cancer (EOC) is universally acknowledged as a terrifying women killer for its high mortality. Recent research advances support that ferroptosis, an emerging iron-dependent type of regulated cell death (RCD) triggered by the excessive accumulation of lipid peroxides probably possesses extraordinary therapeutic potential in EOC therapy. Herein, we firstly provide a very concise introduction of ferroptosis. Special emphasis will be put on the ferroptosis’s vital role in EOC, primarily covering its role in tumorigenesis and progression of EOC, the capability of reversing chemotherapy resistance, and the research and development of related therapeutic strategies. Furthermore, the construction of ferroptosis-related prognostic prediction systems, and mechanisms of ferroptosis resistance in EOC are also discussed. Finally, we propose and highlight several important yet unanswered problems and some future research directions in this field.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis.Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger’s test and represented with funnel plots. All statistical analyses were executed within the R statistical framework.Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6).Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Context: Sanchi promotes wound healing by repressing fibroblast proliferation. Objective: This study examined the effect of Sanchi on keratinocytes (KCs) and microvascular endothelial cells (MECs) and rats with skin injury. Materials & methods: Hydrogels containing different concentrations of Sanchi extract were prepared to observe wound closure over 10 days. SD rats were divided into the control, Hydrogel, 5% Hydrogel, 10% Hydrogel, 10% Hydrogel + Ad5-NC, and 10% Hydrogel + Ad5-IL1B groups. KCs and MECs were induced with H2O2 for 24 h. Cell viability, apoptosis, and the levels of inflammation- and oxidative stress-related factors were examined. The effect of IL1B on wound healing was also evaluated. Results: Compared to the Control group (83% ± 7.4%) or Hydrogel without Sanchi extract (84% ± 8.5%), Hydrogel with 5% (95% closure ± 4.0%) or 10% Sanchi extract (98% ± 1.7%) accelerated wound healing in rats and attenuated inflammation and oxidative stress. Hydrogels containing Sanchi extract increased collagen deposition and CD31 expression in tissues. H2O2 (100 μM) induced injury in KCs and MECs, whereas Sanchi rescued the viability of KCs and MECs. Sanchi inhibited cell inflammation and oxidative stress and decreased apoptosis. As Sanchi blocked the NFκB pathway via IL1B, IL1B mitigated the therapeutic effect of Sanchi. Discussion and conclusion: Sanchi demonstrated therapeutic effects on wound healing in rats by promoting KCs and MECs activity. These findings provide valuable information for the clinical application of Sanchi, which needs to be validated in future clinical trials.

Abstract Gastric cancer (GC) is a malignant tumor with high incidence rate and mortality. Due to the lack of effective diagnostic indicators, most patients are diagnosed in late stage and have a poor prognosis. An increasing number of studies have proved that Peptidylprolyl isomerase A (PPIA) can play an oncogene role in various cancer types. However, the precise mechanism of PPIA in GC is still unclear. Herein, we analyzed the mRNA levels of PPIA in pan-cancer. The prognostic value of PPIA on GC was also evaluated using multiple databases. Additionally, the relationship between PPIA expression and clinical factors in GC was also examined. We further confirmed that PPIA expression was not affected by genetic alteration and DNA methylation. Moreover, the upstream regulator miRNA and lncRNA of PPIA were identified, which suggested that LINC10232/miRNA-204-5p/PPIA axis might act as a potential biological pathway in GC. Finally, this study revealed that PPIA was negatively correlated with immune checkpoint expression, immune cell biomarkers, and immune cell infiltration in GC.

Abstract The equipment used in various fields contains an increasing number of parts with curved surfaces of increasing size. Five-axis computer numerical control (CNC) milling is the main parts machining method, while dynamics analysis has always been a research hotspot. The cutting conditions determined by the cutter axis, tool path, and workpiece geometry are complex and changeable, which has made dynamics research a major challenge. For this reason, this paper introduces the innovative idea of applying dimension reduction and mapping to the five-axis machining of curved surfaces, and proposes an efficient dynamics analysis model. To simplify the research object, the cutter position points along the tool path were discretized into inclined plane five-axis machining. The cutter dip angle and feed deflection angle were used to define the spatial position relationship in five-axis machining. These were then taken as the new base variables to construct an abstract two-dimensional space and establish the mapping relationship between the cutter position point and space point sets to further simplify the dimensions of the research object. Based on the in-cut cutting edge solved by the space limitation method, the dynamics of the inclined plane five-axis machining unit were studied, and the results were uniformly stored in the abstract space to produce a database. Finally, the prediction of the milling force and vibration state along the tool path became a data extraction process that significantly improved efficiency. Two experiments were also conducted which proved the accuracy and efficiency of the proposed dynamics analysis model. This study has great potential for the online synchronization of intelligent machining of large surfaces.

Obtaining cemented carbides with smaller WC grain size and better properties is key to their wider application. Ultrafine cemented carbides were prepared by using spark plasma sintering (SPS) with nano VC-Cr3C2 as nanocomposite grain growth inhibitors (NGGIs) and multi-walled carbon nanotubes (MWCNTs) as reinforcing materials. The effects of NGGIs and MWCNTs on the microstructure and mechanical properties of alloys were evaluated. The results indicated that the specimens (0.5 wt % NGGIs and 0.4 wt % MWCNTs) prepared at 1350 °C for 8 min under a pressure of 50 MPa have enhanced mechanical properties (HV 2520.85 kgf/mm2, KIC 13.26 MPa m1/2) and a homogeneous microstructure. The grain size of WC is suppressed (the average grain size is 200–400 nm). NGGIs can prevent the dissolution of W and C in liquid Co, thereby inhibiting the growth of WC grains. The uniform dispersion of MWCNTs in WC matrix mobilizes their fiber-reinforcement effect. The combination of NGGIs, MWCNTs, and SPS can improve the mechanical properties and optimize the microstructure of the alloy.

A seeding machine for planting potatoes in double rows on large ridges in the cold and arid regions of northwest China was designed and built at Gansu Agricultural University. The machine is capable to achieve the integrated operations of ridge formation, mulching, hole punching, and the precise covering of holes on the film. The key components were analyzed and designed, and the link lengths of the crank film-piercing and hole-punching mechanism were refined using MATLAB R2022a software. The structures and working parameters of the film-piercing and hole-punching mechanism, the dual-opening punching and seeding mechanism, the ridge-forming and soil-covering mechanism, and the seed-casting device were designed. The dynamics of the ridge-forming and soil-covering were simulated using the discrete element method to capture the effects of different machine parameters on the soil covering operation. Field tests showed that the full soil-covering rate of film holes, the qualified rate of hole spacing, the hole misalignment rate, the degree of damage to the light-receiving surface of the film, and the qualified rate of sowing depth under the film were 94.8%, 87.6%, 4.3%, 33.4%, and 95.6%, respectively. These indicators met the requirements of industry standards, and the test results met the design and actual operation requirements, enabling the integrated operations of ridge formation, mulching, hole punching, sowing on the film, and the accurate soil covering of the holes.

The study determined the impacts of dietary fermented residues’ (FBR) inclusion on growth, nutrient utilization, carcass characteristics, and meat properties in fattening pigs. Seventy-two robust pigs were randomly assigned to two experimental groups (Duroc × Landrace × Yorkshire, thirty-six pigs each). Each group was subjected to a 52-day trial, during which they received either a corn–soybean meal-based diet or diet enhanced with a 10% addition of FBR. Consequently, adding 10% FBR caused a significant decrease in the digestive utilization of crude dietary components in fattening pigs (p < 0.05) but showed no significant impact on the growth performance. Additionally, FBR inclusion increased the marbling scores (p < 0.05) and total antioxidant functions (p < 0.05) of muscle tissues, indicating improved meat quality. Gender affected backfat depth, with barrows showing thicker backfat depth. In conclusion, dietary supplementation with 10% FBR in finishing pigs influenced the meat quality by improving the marbling score and antioxidant performance while reducing digestibility without compromising growth performance.

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear.Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment.Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA’s roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP’s main bioactives, underscoring their therapeutic potential.Conclusion: This research delineates UR-AP’s pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP’s potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

Abstract Signal amplification is vitally important for sensing low‐dose X‐rays in medical diagnosis by amplifying the generated electric read‐out signal. However, the complexity of external amplification circuits hampers device miniaturization and portability, while integrating amplification functionality directly into sensors or detectors remains a significant and formidable challenge. In this work, a direct high‐gain X‐ray detector with facile electron drift speed manipulation is reported in perovskite single‐crystal film (SCF). By employing laser‐assisted nucleation, high‐quality MAPbBr3 SCF is fabricated with precise control of thickness from ≈20 to ≈500 µm and the area up to 3 by 2 cm, while the architecture of ITO/MAPbBr3/Au is constructed to form the Schottky junction in opposite polarity. With the assistance of applied bias, the space electric field over MAPbBr3 SCF can be tunable, which ensures the manipulation of charge carrier drift speed to form recirculation for internal gain. The resultant photodetector exhibits an ultrahigh sensitivity of 1.44 × 105 µC Gy−1 cm−2 with a gain of 5.14 × 105, an ultralow detection limit of 39.8 nGy s−1, and the X‐ray array imaging is achieved at a low dose rate of 5 µGy s−1. These results confirm the advance of high‐gain detectors in constructing sensing arrays for practical safe medical diagnosis.

Urban agglomerations are sophisticated territorial systems at the mature stage of city development that are concentrated areas of production and economic activity. Therefore, the study of vulnerability from the perspective of production-living-ecological space is crucial for the sustainable development of the Yellow River Basin and global urban agglomerations. The relationship between productivity, living conditions, and ecological spatial quality is fully considered in this research. By constructing a vulnerability evaluation index system based on the perspectives of production, ecology, and living space, and adopting the entropy value method, comprehensive vulnerability index model, and obstacle factor diagnostic model, the study comprehensively assesses the vulnerability of the urban agglomerations along the Yellow River from 2001 to 2020. The results reveal that the spatial differentiation characteristics of urban agglomeration vulnerability are significant. A clear three-level gradient distribution of high, medium, and low degrees is seen in the overall vulnerability; these correspond to the lower, middle, and upper reaches of the Yellow River Basin, respectively. The percentage of cities with higher and moderate levels of vulnerability did not vary from 2001 to 2020, while the percentage of cities with high levels of vulnerability did. The four dimensions of economic development, leisure and tourism, resource availability, and ecological pressure are the primary determinants of the urban agglomeration's vulnerability along the Yellow River. And the vulnerability factors of various urban agglomerations showed a significant evolutionary trend; the obstacle degree values have declined, and the importance of tourism and leisure functions has gradually increased. Based on the above conclusions, we propose several suggestions to enhance the quality of urban development along the Yellow River urban agglomeration. Including formulating a three-level development strategy, paying attention to ecological and environmental protection, developing domestic and foreign trade, and properly planning and managing the tourism industry.

Aprotic Li-CO2 batteries have attracted significant research interest over the past decade, notable for their energy storage capability and CO2 recyclability. However, the operational mechanism of Li-CO2 batteries remains incompletely understood, which has severely hindered their practical applications. In this comment, the current understandings and remaining uncertainties of the Li-CO2 electrochemistry are summarized, and the future perspectives for next steps are proposed.

Abstract Background Leishmaniasis is one of the most neglected tropical diseases and is spread mainly in impoverished regions of the world. Although many studies have focused on the host’s response to Leishmania invasion, relatively less is known about the complex processes at the metabolic level, especially the metabolic alterations in the infected hosts. Methods In this study, we conducted metabolomics analysis on the urine of golden hamsters in the presence or absence of visceral leishmaniasis (VL) using the ultra-performance liquid chromatography (UPLC) system tandem high-resolution mass spectrometer (HRMS). The metabolic characteristics of urine samples, along with the histopathological change and the parasite burden of liver and spleen tissues, were detected at 4 and 12 weeks post infection (WPI), respectively. Results Amino acid metabolism was extensively affected at both stages of VL progression. Meanwhile, there were also distinct metabolic features at different stages. At 4 WPI, the significantly affected metabolic pathways involved alanine, aspartate and glutamate metabolism, the pentose phosphate pathway (PPP), histidine metabolism, tryptophan metabolism and tyrosine metabolism. At 12 WPI, the markedly enriched metabolic pathways were almost concentrated on amino acid metabolism, including tyrosine metabolism, taurine and hypotaurine metabolism and tryptophan metabolism. The dysregulated metabolites and metabolic pathways at 12 WPI were obviously less than those at 4 WPI. In addition, seven metabolites that were dysregulated at both stages through partial least squares-discriminant analysis (PLS-DA) and receiver-operating characteristic (ROC) tests were screened to be of diagnostic potential. The combination of these metabolites as a potential biomarker panel showed satisfactory performance in distinguishing infection groups from control groups as well as among different stages of infection. Conclusion Our findings could provide valuable information for further understanding of the host response to Leishmania infection from the aspect of the urine metabolome. The proposed urine biomarker panel could help in the development of a novel approach for the diagnosis and prognosis of VL. Graphical Abstract

Abstract Background To explore the clinical and laboratory features, therapy and prognosis of Kikuchi–Fujimoto disease (KFD) in the cervical region. Methods We retrospectively reviewed the medical records of 134 patients who were diagnosed and treated with KFD from January 2000 to May 2022 in Fujian Medical University Union Hospital (Fujian, China). Their clinical characteristics, affected lymph node size, imaging examinations, and laboratory study results were analyzed. Results The mean patient age was 24.9 years, and the male–female ratio was 1:1.73. Fever (55.2%, n = 74) was the most common clinical manifestation. Leukopenia (49.3%) was the commonest reported laboratory abnormality. A majority (65.7%) of the 134 patients presented with bilateral nodal involvement. Conclusion KFD should be considered as a possible diagnosis in a female patient under the age of 30 presenting with cervical lymphadenopathy, fever, leukopenia, and elevated LDH. Level of Evidence 4.

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in broccoli, and transgenic transformation and CRISPR-Cas9 gene editing techniques have been applied to improve broccoli quality, postharvest shelf life, glucoraphanin accumulation, and disease and stress resistance, among other factors. The construction and application of genetic transformation technology systems have led to rapid development in broccoli worldwide, which is also good for functional gene identification of some potential traits in broccoli. This review comprehensively summarizes the progress in transgenic technology and CRISPR-Cas9 gene editing for broccoli over the past four decades. Moreover, it explores the potential for future integration of digital and smart technologies into genetic transformation processes, thus demonstrating the promise of even more sophisticated and targeted crop improvements. As the field continues to evolve, these innovations are expected to play a pivotal role in the sustainable production of broccoli and the enhancement of its nutritional and health benefits.

Due to the open underwater channels and untransparent network deployment environments, underwater acoustic networks (UANs) are more vulnerable to hostile environments. Security research is also being conducted in cryptography, including authentication based on asymmetric algorithms and key distribution based on symmetric algorithms. In recent years, the advancement of quantum computing has made anti-quantum attacks an important issue in the field of security. Algorithms such as lattice and SPHINCS+ have become a research topic of interest in the field of security. However, within the past five years, few papers have discussed security algorithms for UANs to resist quantum attacks, especially through classical algorithms. Some existing classical asymmetric and symmetric algorithms are considered to have no prospects. From the perspective of easy deployment in engineering and anti-quantum attacks, our research focuses on a comprehensive lightweight security framework for data protection, authentication, and malicious node detection through the Elliptic Curve and Hash algorithms. Our mechanism is suitable for ad hoc scenarios with limited underwater resources. Meanwhile, we have designed a multi-party bit commitment to build a security framework for the system. A management scheme is designed by combining self-certifying with the threshold sharing algorithm. All schemes are designed based on certificate-less and ad hoc features. The proposed scheme ensures that the confidentiality, integrity, and authentication of the system are well considered. Moreover, the scheme is proven to be of unconditional security and immune to channel eavesdropping. The resource and delay issues are also taken into consideration. The simulations considered multiple variables like number of nodes, attackers, and message length to calculate proper values that can increase the efficiency of this scheme. The results in terms of delay, delivery ratio, and consumption demonstrate the suitability of the proposal in terms of security, especially for malicious node detection. Meanwhile, the computational cost has also been controlled at the millisecond level.

To satisfy the needs of precision machining, ultrafine tungsten carbide (WC)-based cemented carbide with fine grain size and excellent mechanical properties was prepared. Ultrafine cemented carbide was prepared by spark plasma sintering (SPS) using WC, Co as raw materials and metal elements V, and Cr as additives, and the effects of metal elements on the microstructure and mechanical properties of cemented carbide were investigated. The results show that the specimen (91.6WC-1.2V-1.2Cr-6Co) prepared at 1350 °C, 6 min, 25 MPa has the best mechanical properties (HV 2322.9, KIC 8.7 MPa·m1/2) and homogeneous microstructure. The metal elements could react with WC to form a (W, V, Cr) Cx segregation layer, which effectively inhibits the growth of WC grains (300 nm). The combination of SPS and metal element additives provides a new approach for the preparation of ultrafine cemented carbides with excellent properties.

The application of Ti(C,N)-based cermets remains limited due to their low toughness. The fracture toughness of cermets can be significantly improved by using advanced sintering methods and appropriate additives. Here, cermets were prepared by spark plasma sintering (SPS) technology with graphene nanosheets (GNSs) and nano-scale tungsten carbide (WC) as additives. The effects of GNSs and sintering conditions on the microstructure, mechanical properties, and magnetic properties of Ti(C,N)-based cermets were studied. The results show that the sample with 0.6 wt% GNSs fabricated at 1450 °C, 8 min, and 35 MPa has a denser microstructure and better mechanical properties. The cermet has a Vickers hardness of HV 2415.40 and fracture toughness of 10.6 MPa·m1/2. Compared with the specimen without GNSs, the hardness and fracture toughness are significantly improved by 44.58% and 92.73%, respectively. A certain amount of GNSs can increase the movement of hard phases in the liquid phase, inhibiting their solubility and grain growth, and greatly improving the fracture toughness of cermets. The addition of nano-WC is conducive to promoting the formation of a (Ti,W) (C,N) rim phase and improving properties of cermets. SPS can activate particle surfaces and promote the densification of cermets.

The residual stress inside stock materials is a fundamental property related to the quality of manufactured parts in terms of geometric/dimensional stability and fatigue life. For large parts that must meet high-precision requirements, accurately measuring and predicting the residual stress field has been a major challenge. Existing technologies for measuring the residual stress field are either strain-based measurement methods or non-destructive methods with low efficiency and accuracy. This paper reports a new non-destructive method for inferencing the residual stress field based on deformation forces. In the proposed method, the residual stress field of a workpiece is inferred based on the characteristics of the deformation forces that reflect the overall effect of the unbalanced residual stress field after material removal operations. The relationship between deformation forces and the residual stress field is modeled based on the principle of virtual work, and the residual stress field inference problem is solved using an enforced regularization method. Theoretical verification is presented and actual experiment cases are tested, showing reliable accuracy and flexibility for large aviation structural parts. The underlying principle of the method provides an important reference for predicting and compensating workpiece deformation caused by residual stress using dynamic machining monitoring data in the context of digital and intelligent manufacturing.

Compared with the pure lead-based MAPbBr3 (MA = CH3NH3) perovskite single crystals (PSCs), tin–lead alloy (MAPbxSn1−xBr3) PSCs with higher carrier mobility and longer carrier lifetime are expected to perform as better-quality ionization radiation detectors. In this work, we design MAPbBr3–MAPb0.9Sn0.1Br3–MAPb0.8Sn0.2Br3 structure detectors by employing solution-process epitaxial growth. Because of the gradient change in tin element proportion, the relatively low mismatch rates between different PSC layers can effectively reduce defects generated at the interface, which improves charge collection efficiency. Moreover, band barriers between different PSC layers form depletion layers due to the differences in band structure, and the high resistivity and built-in electric field of depletion layers can suppress dark current under high voltages. The optimized detector exhibits a high x-ray detection sensitivity of 6.76 × 104 μC Gy−1 cm−2 and the lowest detectable dose rate of 7.4 nGy s−1 under 40 kVp x-ray radiation. Based on 241Am (5.95 MeV) α particle irradiation, tin–lead HD has lower detection noise and more obvious response compared to MAPbBr3 PSCs. The electron mobility was indicated as high as 612 cm2 s−1 V−1, and the mobility-lifetime (μτ) products were measured to be 3.5 × 10−3 cm2 V−1 using the Hecht equation, demonstrating superior transport properties.

Summary: The halide lead perovskite single crystals (HLPSCs) have great potential in gamma-ray detection with high attenuation coefficient, strong defects tolerance, and large mobility-lifetime product. However, mobile halide ions would migrate under high external bias, which would both weaken the gamma-ray response and cause additional noise. Here, we report the gamma-ray PIN photodiodes made of cascade HLPSCs including both ion-formed and electron-hole-formed electrical junctions that could suppress the ions migration and improve the charges collection. Our photodiodes based on cascade HLPSCs (MAPbBr3/MAPbBr2.5Cl0.5/MAPbCl3) show a wide halide-ion-formed depletion layer of ∼52 μm. The built-in potential along the wide ionic-formed junction ensures a high mobility-lifetime product of 1.1 × 10−2 cm2V−1. As a result, our gamma-ray PIN photodiodes exhibit compelling response to 241Am, 137Cs, and 60Co; the energy resolution can reach 9.4%@59.5keV and 5.9%@662keV, respectively. This work provides a new path toward constructing high-performance gamma-ray detectors based on HLPSCs.

BackgroundPerturbation of osmolality is associated with increased mortality in adults and children in critically ill conditions. However, it is still unclear whether osmolality imbalance impacts the prognosis of critically ill infants. This study aimed to investigate the relationship between plasma osmolality and prognosis in critically ill infants within 24 h of admission.MethodsThis retrospective study enrolled 1,042 infants who had plasma osmolality data from 2010 to 2018. The initial plasma osmolality (within 24 h after admission) was extracted from the pediatric intensive care database (PIC V1.1). The locally weighted scatter-plot smoothing (LOWESS) and restricted cubic splines (RCS) methods were used to explore the approximate relationship between plasma osmolality and in-hospital mortality. Univariate and multivariate logistic regression analyses were used to further analyse this relationship. Kaplan–Meier analysis was applied to estimate the probability of hospital mortality within 90 days of admission. Subgroup analysis was employed to assess the impact of potential confounders (including postnatal days, gender, and gestational age).ResultsAn approximately“U”-shaped relationship between plasma osmolality and mortality was detected. In the logistic regression model, plasma osmolality 300 mmol/L (high osmolality group) was also significantly associated with mortality (P

New fluorescent materials with a low cost, hypotoxicity, and concealment are desired for the application of anti-counterfeiting. Herein, we report a CsCu2I3@Cs3Cu2I5 composite with a triple-mode photoluminescence (PL) feature by simply adjusting the excitation wavelengths, which are ascribed to the multiple excited states of different phases in the CsCu2I3@Cs3Cu2I5 composite. The broadband emission and high quantum yield (∼51%) of the composite originate from the structure-oriented self-trapped excitons effect of Cs3Cu2I5 and CsCu2I3 phases. Moreover, the incorporation of polyethylene oxide (PEO) into this composite improves the stability of CsCu2I3@Cs3Cu2I5@PEO against harsh environments. The CsCu2I3@Cs3Cu2I5@PEO composite has a slight decay of ∼5% of its initial PL intensity and only a 3.5% shift of the corresponding color coordinate after 30 days of storage. More importantly, its initial PL intensity shows only 10.3% decay under ultraviolet exposure for 200 h. Our work provides a promising approach to design materials for advanced anti-counterfeiting applications.

In recent years, polymyxin has been used as a last-resort therapy for carbapenem-resistant bacterial infections. The emergence of heteroresistance (HR) to polymyxin hampers the efficacy of polymyxin treatment by amplifying resistant subpopulation. However, the mechanisms behind polymyxin HR remain unclear. Small noncoding RNAs (sRNAs) play an important role in regulating drug resistance. The purpose of this study was to investigate the effects and mechanisms of sRNA on polymyxin B (PB)-HR in carbapenem-resistant Klebsiella pneumoniae. In this study, a novel sRNA PhaS was identified by transcriptome sequencing. PhaS expression was elevated in the PB heteroresistant subpopulation. Overexpression and deletion of PhaS were constructed in three carbapenem-resistant K. pneumoniae strains. Population analysis profiling, growth curve, and time-killing curve analysis showed that PhaS enhanced PB-HR. In addition, we verified that PhaS directly targeted phoP through the green fluorescent protein reporter system. PhaS promoted the expression of phoP, thereby encouraging the expression of downstream genes pmrD and arnT. This upregulation of arnT promoted the 4-amino-4-deoxyL-arabinosaccharide (L-Ara4N) modification of lipid A in PhaS overexpressing strains, thus enhancing PB-HR. Further, within the promoter region of PhaS, specific PhoP recognition sites were identified. ONPG assays and RT-qPCR analysis confirmed that PhaS expression was positively modulated by PhoP and thus up-regulated by PB stimulation. To sum up, a novel sRNA enhancing PB-HR was identified and a positive feedback regulatory pathway of sRNA-PhoP/Q was demonstrated in the study. This helps to provide a more comprehensive and clear understanding of the underlying mechanisms behind polymyxin HR in carbapenem-resistant K. pneumoniae.

ABSTRACTThis study investigated resistance evolution mechanisms of conjugated plasmids and bacterial hosts under different concentrations of antibiotic pressure. Ancestral strain ECNX52 was constructed by introducing the blaNDM-5-carrying IncX3 plasmid into E. coli C600, and was subjected to laboratory evolution under different concentrations of meropenem pressure. Minimal inhibitory concentrations and conjugation frequency were determined. Fitness of these strains was assessed. Whole genome sequencing and transcriptional changes were performed. Ancestral host or plasmids were recombined with evolved hosts or plasmids to verify plasmid or host factors in resistance evolution. Role of the repA mutation on plasmid copy number was determined. Two out of the four clones (EM2N1 and EM2N3) exhibited four-fold increase in MIC when exposed to a continuous pressure of 2 μg/mL MEM (1/32 MIC), by down regulating expression of outer membrane protein ompF. Besides, all four clones displayed four-fold increase in MIC and higher conjugation frequency when subjected to a continuous pressure of 4 μg/mL MEM (1/16 MIC), attributing to increasing plasmid copy number generated by repA D140Y (GAT→TAT) mutation. Bacterial hosts and conjugative plasmids can undergo resistance evolution under certain concentrations of antimicrobial pressure by reducing the expression of outer membrane proteins or increasing plasmid copy numbers.

Abstract Precise control of machining deformation is crucial for improving the manufacturing quality of structural aerospace components. In the machining process, different batches of blanks have different residual stress distributions, which pose a significant challenge to machining deformation control. In this study, a reinforcement learning method for machining deformation control based on a meta-invariant feature space was developed. The proposed method uses a reinforcement-learning model to dynamically control the machining process by monitoring the deformation force. Moreover, combined with a meta-invariant feature space, the proposed method learns the internal relationship of the deformation control approaches under different stress distributions to achieve the machining deformation control of different batches of blanks. Finally, the experimental results show that the proposed method achieves better deformation control than the two existing benchmarking methods.

Abstract Background As a noninvasive tool, myocardial deformation imaging may facilitate the early detection of cardiac dysfunction. However, normal reference ranges of myocardial strain and strain rate (SR) based on large-scale East Asian populations are still lacking. This study aimed to provide reference values of left ventricular (LV) and right ventricular (RV) strain and SR based on a large cohort of healthy Chinese adults using cardiovascular magnetic resonance (CMR) feature tracking (FT). Methods Five hundred and sixty-six healthy Chinese adults (55.1% men) free of hypertension, diabetes, and obesity were included. On cine CMR, biventricular global radial, circumferential, and longitudinal strain (GRS, GCS, and GLS), and the peak radial, circumferential, and longitudinal systolic, and diastolic SRs (PSSRR, PSSRC, PSSRL, PDSRR, PDSRC, and PDSRL), and regional radial and circumferential strain at the basal, mid-cavity, and apical levels were measured. Associations of global and regional biventricular deformation indices with age and sex were investigated. Results Women demonstrated greater magnitudes of LV GRS (37.6 ± 6.1% vs. 32.1 ± 5.3%), GCS (− 20.7 ± 1.9% vs. − 18.8 ± 1.9%), GLS (− 17.8 ± 1.8% vs. − 15.6 ± 1.8%), RV GRS (25.1 ± 7.8% vs. 22.1 ± 6.7%), GCS (− 14.4 ± 3.6% vs. − 13.2 ± 3.2%), GLS (− 22.4 ± 5.2% vs. − 20.2 ± 4.6%), and biventricular peak systolic and diastolic SR in all three coordinate directions (all P

CRY2 mediates photoperiod-responsive floral initiation in Arabidopsis. Here the authors show that CRY2 also regulates temperature sensitive flowering and that CRY2 can interact with and regulate the splicing factor CIS1 to affect alternative splicing of transcripts that regulate flowering.

The SARS-CoV-2 Omicron variant has quickly become the predominant circulating variant, due to the high transmissibility and immune escape. Here, the authors develop a trimeric protein vaccine candidate and show a sustained humoral immune response, and protection from challenge (Omicron and Delta) in various animal models.

Abstract Initial residual stress is the main reason causing machining deformation of the workpiece, which has been deemed as one of the most important aspects of machining quality issues. The inference of the distribution of initial residual stress inside the blank has significant meaning for machining deformation control. Due to the principle error of existing residual stress detection methods, there are still challenges in practical applications. Aiming at the detection problem of the initial residual stress field, an initial residual stress inference method by incorporating monitoring data and mechanism model is proposed in this paper. Monitoring data during machining process is used to represent the macroscopic characterization of the unbalanced residual stress, and the finite element numerical model is used as the mechanism model so as to solve the problem that the analytic mechanism model is difficult to establish; the policy gradient approach is introduced to solve the gradient descent problem of the combination of learning model and mechanism model. Finally, the initial residual stress field is obtained through iterative calculation based on the fusing method of monitoring data and mechanism model. Verification results show that the proposed inference method of initial residual stress field can accurately and effectively reflect the machining deformation in the actual machining process.

Abstract BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the “priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.

Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient’s results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and −39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.

WC-based cemented carbides were prepared by spark plasma sintering (SPS) of WC-Co-Cr3C2-VC alloy powder by adding different contents of graphene. The phase composition, microstructure, mechanical properties, and magnetic properties of cemented carbide were investigated by means of XRD, SEM, Vickers hardness and fracture toughness tests, and magnetic properties tests. The results showed that the mechanical properties of the specimens show a trend of first increasing and then decreasing with the increase in graphene content. After adding 0.6 wt.% graphene, graphene is uniformly distributed on the substrate in the form of flakes, WC grain size decreases, the hardness of the specimen increases to 2009 HV, the relative density increases to 94.3%, the fracture toughness is 11.72 MPa·m1/2, and the coercivity of the sample is 437.55 Oe. Therefore, cemented carbide with a graphene content of 0.6 wt.% has excellent comprehensive performance (Vickers hardness and fracture toughness).

Abstract Background The blood–testis barrier (BTB) is essential to the microenvironment of spermatogenesis, and Sertoli cells provide the cellular basis for BTB construction. Numerous nuclear transcription factors have been identified to be vital for the proper functioning of Sertoli cells. PA1 has been reported to play important roles during diverse biological processes, yet its potential function in male reproduction is still unknown. Results Here, we show that PA1 was highly expressed in human and mouse testis and predominantly localized in the nuclei of Sertoli cells. Sertoli cell-specific Pa1 knockout resulted in an azoospermia-like phenotype in mice. The knockout of this gene led to multiple defects in spermatogenesis, such as the disorganization of the cytoskeleton during basal and apical ectoplasmic specialization and the disruption of the BTB. Further transcriptomic analysis, together with Cut-Tag results of PA1 in Sertoli cells, revealed that PA1 could affect the expression of a subset of genes that are essential for the normal function of Sertoli cells, including those genes associated with actin organization and cellular junctions such as Connexin43 (Cx43). We further demonstrated that the expression of Cx43 depended on the interaction between JUN, one of the AP-1 complex transcription factors, and PA1. Conclusion Overall, our findings reveal that PA1 is essential for the maintenance of BTB integrity in Sertoli cells and regulates BTB construction-related gene expression via transcription factors. Thus, this newly discovered mechanism in Sertoli cells provides a potential diagnostic or even therapeutic target for some individuals with azoospermia.

Abstract Background To investigate the value of endobronchial ultrasound (EBUS) and virtual bronchoscopic navigation (VBN) combined with rapid on-site evaluation (ROSE) in diagnosing peripheral pulmonary lesions (PPLs). Methods Between January 1st 2019 to September 1st 2021, EBUS and VBN examination were performed in expected consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, based on the calculation of expected diagnostic yield of R-EBUS biopsy and drop out, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). The diagnostic yield of brushing and biopsy, the complications, the procedure time, the diagnosis time and expense during diagnosis were analyzed. Results In the ROSE group, the positive rate of EBUS brushing and biopsy were 68%, 84%, respectively. The average procedure time and diagnosis time were 18.6 ± 6.8 min, 3.84 ± 4.28 days, respectively, and the average expense was 643.44 ± 706.56 US.$ (4093.15 ± 4494.67 yuan ¥). In the controls, the positive rate of brushing and biopsy were 44%, 74%, respectively. The average procedure time and diagnosis time were 15.4 ± 5.7 min, 6.46 ± 3.66 days, respectively. And the average expense during diagnosis was 1009.27 ± 713.89 US.$ (6420.28 ± 4541.33 yuan ¥). There was significant difference in the positive rate of EBUS brushing and biopsy, diagnosis time and expense during diagnosis between both groups. And no significant difference was observed in the complications and the procedure time. Additionally, the impact of ROSE on diagnostic yield in right upper lobe and the size of lesion ≤ 2 cm in diameter was significant. Conclusion In combination with ROSE, EBUS could significantly improve the positive rate of diagnosing PPLs, shorten diagnosis time and reduce expense during diagnosis. ROSE will be of great importance in the diagnosis of PPLs and medical resource.

IntroductionIn the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences.MethodsSingle-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing.ResultsThe up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging.ConclusionsTaken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.

Objectives. Management of chronic coronary syndrome (CCS) encompasses a broad spectrum of practices, posing considerable complexity and variability. While guidelines have been established to augment the management quality of CCS, notable disparities persist across their recommendations. This study strives to scrutinize, compare, and reconcile these guideline recommendations pertaining to the diagnosis, treatment, and management of CCS patients. Our goal is to align these recommendations with contemporary clinical practices, thus laying a robust foundation for their pragmatic application in clinical settings. Methods. A comprehensive systematic search was conducted across multiple databases, including PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, Chinese Biomedical Literature Service System, Chinese Science and Technology Periodical Database, and Chinese Biological Medicine Database. The timeframe for this search spanned from their inception up to May 30, 2022, aiming to collate all published guidelines relevant to CCS. Subsequently, two independent reviewers undertook the task of appraising the quality of these guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation II instrument. Results. The search yielded a total of 10,699 citations. Following a thorough evaluation, fourteen clinical practice guidelines and four consensus statements, each offering specific recommendations for CCS, were selected. The quality of these guidelines showcased a broad spectrum of variation. The domain of “presentation clarity” received the highest accolades, while “applicability” languished at the lower end of the scoring spectrum. On average, the guidelines attained a quality score denoting sufficiency. Furthermore, recommendations across different guidelines for the diagnosis, treatment, and management of CCS displayed a striking level of divergence. Conclusion. The landscape of published CCS guidelines is marked by extensive variations in scope, quality, and recommendations. Hence, there is a compelling need for collaborative efforts amongst multidisciplinary professionals to forge comprehensive, higher-quality evidence-based guidelines; such a concerted approach is paramount to enhance treatment efficacy and health outcomes for patients grappling with CCS.

Methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor and plays an important role in neuronal degradation of Alzheimer’s disease (AD). According to molecular modeling docking studies, we have designed the compound Arg-Glu-Arg-Met-Ser-(3,5)-dimethyladamantan-1-amine (RERMS-MEM), consisting of an AβPP 5-mer peptide (RERMS) and memantine (MEM). This compound could dock into the active sites of N-methyl-D-aspartate receptor type 2B (NMDAR2B) with a −64.14 kcal/mol CDOCKER interaction energy. The stability of RERMS-MEM was evaluated through a 50 ns molecular dynamics simulation. The results revealed that the docked ligand-receptor complex was stable. Furthermore, surface plasmon resonance (SPR) revealed that the RERMS-MEM binding affinity to the NMDAR2B fragment exhibited over 15-fold enhancement compared to MEM. The SH-SY5Y cell assays showed that RERMS-MEM or RERMS at concentrations of 0.1, 1, 10, or 50 μM could enhance the metabolic rate, and MEM showed no difference compared to the control and indicated cytotoxic effects at 50 μM. RERMS-MEM at concentrations of 0.01, 0.1, 1, 10, or 50 μM increased the number of viable cells and reduced the release of lactate dehydrogenase (LDH). RERMS at concentrations of 10 or 50 μM was similar to RERMS-MEM for increasing viable cells, and MEM showed no difference compared to the control and decreased the number of viable cells at 50 μM. RERMS-MEM or RERMS at concentrations of 10 or 50 μM could antagonize Aβ25-35-induced cytotoxicity, and MEM at 50 μM strengthened the cytotoxicity effects. The results revealed that RERMS-MEM showed a strong NMDAR-blocking activity as a potential NMDAR antagonist, enhancing the neurotrophic effect and cellular growth in SH-SY5Y cells.

Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.

BackgroundThe early diagnosis of autism in children is particularly important. However, there is no obvious objective indices for the diagnosis of autism spectrum disorder (ASD), especially in toddlers aged 1–3 years with language development delay (LDD). The early differential diagnosis of ASD is challenging.ObjectiveTo examine differences in the dynamic characteristics of regional neural activity in toddlers with ASD and LDD, and whether the differences can be used as an imaging biomarker for the early differential diagnosis of ASD and LDD.MethodsDynamic regional homogeneity (dReHo) and dynamic amplitude of low-frequency fluctuations (dALFF) in 55 children with ASD and 31 with LDD, aged 1–3 years, were compared. The correlations between ASD symptoms and the values of dReHo/dALFF within regions showing significant between-group differences were analyzed in ASD group. We further assessed the accuracy of dynamic regional neural activity alterations to distinguish ASD from LDD using receiver operating characteristic (ROC) analysis.ResultsCompared with the LDD group, the ASD group showed increased dReHo in the left cerebellum_8/Crust2 and right cerebellum_Crust2, and decreased dReHo in the right middle frontal gyrus (MFG) and post-central gyrus. Patients with ASD also exhibited decreased dALFF in the right middle temporal gyrus (MFG) and right precuneus. Moreover, the Childhood Autism Rating Scale score was negatively correlated with the dReHo of the left cerebellum_8/crust2 and right cerebellum_crust2. The dReHo value of the right MFG was negatively correlated with social self-help of the Autism Behavior Checklist score.ConclusionThe pattern of resting-state regional neural activity variability was different between toddlers with ASD and those with LDD. Dynamic regional indices might be novel neuroimaging biomarkers that allow differentiation of ASD from LDD in toddlers.

Endophytes are essential in plant succession and evolution, and essential for stress resistance. Coralloid root is a unique root structure found in cycads that has played a role in resisting adverse environments, yet the core taxa and microbial community of different Cycas species have not been thoroughly investigated. Using amplicon sequencing, we successfully elucidated the microbiomes present in coralloid roots of 10 Cycas species, representing all four sections of Cycas in China. We found that the endophytic bacteria in coralloid roots, i.e., Cyanobacteria, were mainly composed of Desmonostoc_PCC-7422, Nostoc_PCC-73102 and unclassified_f__Nostocaceae. Additionally, the Ascomycota fungi of Exophiala, Paraboeremia, Leptobacillium, Fusarium, Alternaria, and Diaporthe were identified as the core fungi taxa. The Ascomycota fungi of Nectriaceae, Herpotrichiellaceae, Cordycipitaceae, Helotiaceae, Diaporthaceae, Didymellaceae, Clavicipitaceae and Pleosporaceae were identified as the core family taxa in coralloid roots of four sections. High abundance but low diversity of bacterial community was detected in the coralloid roots, but no significant difference among species. The fungal community exhibited much higher complexity compared to bacteria, and diversity was noted among different species or sections. These core taxa, which were a subset of the microbiome that frequently occurred in all, or most, individuals of Cycas species, represent targets for the development of Cycas conservation.

Hyaloperonospora parasitica is a global pathogen that can cause leaf necrosis and seedling death, severely threatening the quality and yield of cabbage. However, the genome sequence and infection mechanisms of H. parasitica are still unclear. Here, we present the first whole-genome sequence of H. parasitica isolate BJ2020, which causes downy mildew in cabbage. The genome contains 4631 contigs and 9991 protein-coding genes, with a size of 37.10 Mb. The function of 6128 genes has been annotated. We annotated the genome of H. parasitica strain BJ2020 using databases, identifying 2249 PHI-associated genes, 1538 membrane transport proteins, and 126 CAZy-related genes. Comparative analyses between H. parasitica, H.arabidopsidis, and H. brassicae revealed dramatic differences among these three Brassicaceae downy mildew pathogenic fungi. Comprehensive genome-wide clustering analysis of 20 downy mildew-causing pathogens, which infect diverse crops, elucidates the closest phylogenetic affinity between H. parasitica and H. brassicae, the causative agent of downy mildew in Brassica napus. These findings provide important insights into the pathogenic mechanisms and a robust foundation for further investigations into the pathogenesis of H. parasitica BJ2020.

In nature, arbuscular mycorrhizal fungi (AMF) play a crucial role in the root systems of plants. They can help enhance the resistance of host plants by improving the compartmentalization of toxic metal contaminants in the cell walls (CWs). However, the functions and responses of various CW subfractions to mycorrhizal colonization under Cd exposure remain unknown. Here we conducted a study to investigate how Cd is stored in the cell walls of maize roots colonized by Funneliformis mosseae. Our findings indicate that inoculating the roots with AMF significantly lowers the amount of Cd in the maize shoots (63.6 ± 6.54 mg kg−1 vs. 45.3 ± 2.19 mg kg−1, p < 0.05) by retaining more Cd in the mycorrhized roots (224.0 ± 17.13 mg kg−1 vs. 289.5 ± 8.75 mg kg−1, p < 0.01). This reduces the adverse effects of excessive Cd on the maize plant. Additional research on the subcellular distribution of Cd showed that AMF colonization significantly improves the compartmentalization of 88.2% of Cd in the cell walls of maize roots, compared to the 80.8% of Cd associated with cell walls in the non-mycorrhizal controls. We observed that the presence of AMF did not increase the amount of Cd in pectin, a primary binding site for cell walls; however, it significantly enhanced the content of lignin and the proportion of Cd in the total root cell walls. This finding is consistent with the increased activity of lignin-related enzymes, such as PAL, 4CL, and laccase, which were also positively impacted by mycorrhizal colonization. Fourier transform infrared spectroscopy (FTIR) results revealed that AMF increased the number and types of functional groups, including −OH/−NH and carboxylate, which chelate Cd in the lignin. Our research shows that AMF can improve the ability of maize plants to tolerate Cd by reducing the amount of Cd transferred from the roots to the shoots. This is achieved by increasing the amount of lignin in the cell walls, which binds with Cd and prevents it from moving through the plant. This is accomplished by activating enzymes related to lignin synthesis and increasing the exposure of Cd-binding functional groups of lignin. However, more direct evidence on the immobilization of Cd in the mycorrhiza-altered cell wall subfractions is needed.

In response to the problem of no supporting equipment for the cultivation of Codonopsis in the hilly and mountainous areas of northwest China, a combined machine for transplanting outcrop of Codonopsis with micro ridges covered with film is designed. The key components of the prototype are analyzed and designed, and the structures and working parameters of the seedbed preparation device, seedling-casting device, rotary tillage soil-covering device, film-covering device, seedling head burial, and film edge soil-covering device are determined. The transmission system scheme is established, and the working mechanism of the core components is analyzed. Field experiments show that when the target seedling spacing is 4.4 cm and the machine moves forward at a speed of 0.1, 0.15, and 0.2 m/s, the variation coefficient of planting spacing and the qualification rate of planting depth meet the standard requirements. The qualified rate of planting posture and film side outcrop are greatly affected by the operating speed of the machine and decrease with the increase in operating speed. When the operating speed reaches 0.1 m/s, the average variation coefficient of planting spacing is 0.08% and the average qualified rate of planting depth, planting posture and film side outcrop is 95.83%, 94.17%, and 93.33%, respectively, which shows that the operating performance is better than that of the operating speeds of 0.15 m/s and 0.2 m/s. This study provides a new reference for the theoretical research and design of mechanized and automated transplanting machinery for Codonopsis seedlings.

The analysis of the dynamic process of winding destabilization under sudden short-circuit conditions is of great importance to accurately assess the short-circuit resistance of power transformers. Based on magneto-solid coupling, an axisymmetric model of the transformer and a 3D multilayer model of the transformer considering the support components are established, respectively, and the short-circuit electromagnetic force (EF) is simulated by using the finite element method. It is concluded that the middle layer of the winding is subjected to the larger radial EF, while the axial EF has a greater effect on the layers at both ends. Moreover, the impression of the preload force, aging temperatures, and the area share of spacers on the vibration and deformation of windings are studied under short-circuit conditions. The overall distribution of plastic strain and residual stress in the winding is symmetrical, and the maximum values occur in the lower region of the middle of the winding. Finally, considering the material properties of disks and insulating components, the cumulative effect of plastic deformation under multiple successive short-circuit shocks is calculated. Compared with the traditional axisymmetric model of transformer, the three-dimensional multilayer model of the transformer established in this paper is more suitable for the actual winding structure and the obtained results are more accurate.