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Abstract Background Cell wall integrity (CWI) is crucial for fungal growth, pathogenesis, and adaptation to extracellular environments. Calcofluor white (CFW) is a cell wall perturbant that inhibits fungal growth, yet little is known about how phytopathogenic fungi respond to the CFW-induced stress. Results In this study, we unveiled a significant discovery that CFW triggered the translocation of the transcription factor CgCrzA from the cytoplasm to the nucleus in Colletotrichum gloeosporioides. This translocation was regulated by an interacting protein, CgMkk1, a mitogen-activated protein kinase involved in the CWI pathway. Further analysis revealed that CgMkk1 facilitated nuclear translocation by phosphorylating CgCrzA at the Ser280 residue. Using chromatin immunoprecipitation sequencing, we identified two downstream targets of CgCrzA, namely CgCHS5 and CgCHS6, which are critical for growth, cell wall integrity, and pathogenicity as chitin synthase genes. Conclusions These findings provide a novel insight into the regulatory mechanism of CgMkk1-CgCrzA-CgChs5/6, which enables response of the cell wall inhibitor CFW and facilitates infectious growth for C. gloeosporioides.

Abstract Antiferromagnets are promising for nano-scale oscillator in a wide frequency range from gigahertz up to terahertz. Experimentally realizing antiferromagnetic moment oscillation via spin-orbit torque, however, remains elusive. Here, we demonstrate that the optical spin-orbit torque induced by circularly polarized laser can be used to drive free decaying oscillations with a frequency of 2 THz in metallic antiferromagnetic Mn2Au thin films. Due to the local inversion symmetry breaking of Mn2Au, ultrafast a.c. current is generated via spin-to-charge conversion, which can be detected through free-space terahertz emission. Both antiferromagnetic moments switching experiments and dynamics analyses unravel the antiferromagnetic moments, driven by optical spin-orbit torque, deviate from its equilibrium position, and oscillate back in 5 ps once optical spin-orbit torque is removed. Besides the fundamental significance, our finding opens a new route towards low-dissipation and controllable antiferromagnet-based spin-torque oscillators.

Abstract Chloroplasts are key players in photosynthesis and immunity against microbial pathogens. However, the precise and timely regulatory mechanisms governing the control of photosynthesis-associated nuclear genes (PhANGs) expression in plant immunity remain largely unknown. Here we report that TaPIR1, a Pst-induced RING-finger E3 ubiquitin ligase, negatively regulates Pst resistance by specifically interacting with TaHRP1, an atypical transcription factor histidine-rich protein. TaPIR1 ubiquitinates the lysine residues K131 and K136 in TaHRP1 to regulate its stability. TaHRP1 directly binds to the TaHRP1-binding site elements within the PhANGs promoter to activate their transcription via the histidine-rich domain of TaHRP1. PhANGs expression induces the production of chloroplast-derived ROS. Although knocking out TaHRP1 reduces Pst resistance, TaHRP1 overexpression contributes to photosynthesis, and chloroplast-derived ROS production, and improves disease resistance. TaPIR1 expression inhibits the downstream activation of TaHRP1 and TaHRP1-induced ROS accumulation in chloroplasts. Overall, we show that the TaPIR1-mediated ubiquitination and degradation of TaHRP1 alters PhANGs expression to disrupt chloroplast function, thereby increasing plant susceptibility to Pst.

Abstract Background We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). Methods The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 and 2001–2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. Results Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. Conclusions Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.

Introduction Recently, NLR family pyrin domain containing 3 (NLRP3) and pyroptosis have been reported to be involved in traumatic brain injury-induced acute lung injury (TBI-ALI). Studies have shown that triggering receptor expressed on myeloid cells-1 (TREM-1) may be one of the upstream molecules regulating NLRP3/pyroptosis, and 5-hydroxytryptamine type 3-receptor (5-HT3R) antagonists can inhibit NLRP3/pyroptosis. However, the role of TRME-1 in TBI- ALI, the therapeutic effect of 5-HT3R inhibition on TBI-ALI and its mechanism are still unclear. Therefore, this study aimed to evaluate the protective effect of ondansetron, a 5-HT3 inhibitor, on TBI-ALI, and to explore whether the underlying mechanism is related to the regulation of TREM-1. Material and methods A TBI-ALI rat model was constructed via lateral fluid percussion (LFP) brain injury, and either TREM-1 inhibitor (LP17) or ondansetron was administered as needed. Results TBI induced NLRP3 inflammasome, pyroptosis, and TREM-1 activation in rat lung tissues in a time-dependent manner. Inhibition of TREM-1 activity attenuated TBI-ALI; this is evident from reduced pathological scores, wet/dry ratios, and bronchoalveolar lavage fluid protein levels and alleviated NLRP3 inflammasome/pyroptosis. In addition, ondansetron reduced NLRP3 inflammasome/pyroptosis and alleviated TBI-ALI. Moreover, ondansetron reduced TREM-1 activation in macrophages and lung tissue. Conclusions Ondansetron alleviated TBI-ALI. In terms of mechanism, TREM-1 promotes TBI-ALI via the NLRP3-related pyroptosis pathway, and the protective effect of ondansetron on TBI-ALI may be related to the inhibition of TREM-1.

Abstract In this study, we investigate the tail dependency between bank stocks in China and 35 common risk factors. We measure univariate and multivariate conditional tail risk probabilities. The evidence indicates that tail events from risk factors in the banking, security trading, real estate, and energy industries have the largest effects on the realization of extreme returns from Chinese bank stocks. The univariate conditional tail risk is considerably higher than the unconditional tail risk. The impact of multiple tail events from several risk factors occurring simultaneously is much stronger than tail events from one single risk factor. In general, there is a stronger cross‐market tail linkage between emerging market risk factors and bank stocks in China when compared with developed market risk factors. However, the cross‐market tail linkage between developed market risk factors and bank stocks in China rose sharply during the 2008 financial crisis.

The accurate understanding of rockburst mechanism poses a global challenge in the field of rock mechanics. Particularly for strain rockburst, achieving self-initiated static-dynamic state transition is a crucial step in the formation of catastrophic events. However, the state transition behavior and its impact on rockburst have not received sufficient attention, and are still poorly understood. Therefore, this study specifically focuses on the state transition behavior, aiming to investigate its abrupt transition process and formation mechanism, and triggering effects on rockburst. To facilitate the study, a novel burst rock-surrounding rock combined laboratory test model is proposed and its effectiveness is validated through experiment verification. Subsequently, corresponding numerical models are established using the three-dimensional (3D) discrete element method (DEM), enabling successful simulation of static brittle failure and rockbursts of varying intensities under quasi-static displacement loading conditions. Moreover, through secondary development, comprehensive recording of the mechanical and energy information pertaining to the combined specimen system and its subsystems is achieved. As a result of numerical investigation studies, the elastic rebound dynamic behavior of the surrounding rock was discovered and identified as the key factor triggering rockburst and controlling its intensity. The impact loading on the burst rock, induced by elastic rebound, directly initiates the dynamic processes of rockburst, serving as the direct cause. Additionally, the transient work and energy convergence towards the burst rock resulting from elastic rebound are recognized as the inherent cause of rockburst. Moreover, it has been observed that a larger extent of surrounding rock leads to a stronger elastic rebound, thereby directly contributing to a more intense rockburst. The findings can provide novel theoretical insights for the exploring of rockburst mechanism and the development of monitoring and prevention techniques.

Abstract Background We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. Case presentation A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. Conclusions To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Abstract Background Trimethylamine-N-Oxide (TMAO) is believed to be linked to increased likelihood of cardiovascular disease. While probiotics have shown limited effectiveness in reducing TMAO levels, the potential of postbiotics remains underexplored. This study aimed to evaluate the impact of Akkermansia muciniphila (A. muciniphila) postbiotic administration on choline-induced TMAO production in mice by modifying the gut microbiota. Methods Female C57BL/6J mice were divided into six groups, including a control group, high-choline diet group, live A. muciniphila probiotic group, pasteurized A. muciniphila postbiotic group, sodium butyrate group, and sodium propionate group. Various measurements and analyses were conducted, including TMAO and TMA levels in serum, urine, and cecal contents, as well as the expression of FXR and FMO3 in liver tissues. Additionally, metabolic parameters, body weight, serum lipid profile, hepatic protein expression (FMO3, FXR, CutC, and CutD), and gut microbiota composition were assessed. Results Administration of A. muciniphila postbiotic significantly reduced choline-induced plasma TMAO levels in mice. Furthermore, improvements in serum lipid profiles and liver enzyme levels suggested potential enhancements in lipid metabolism and liver function. The study also observed modulation of specific proteins related to TMAO production and metabolism, including CutC and CutD. Conclusion The findings highlight the potential of A. muciniphila postbiotics as a dietary strategy for mitigating cardiovascular disease risk by modulating the gut-TMAO axis. Postbiotics, particularly A. muciniphila, offer advantages over probiotics and warrant further investigation for their therapeutic applications in gastrointestinal and metabolic disorders. Graphical Abstract

Abstract Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

Abstract Background Intervertebral disc degeneration (IDD) is an increasingly important cause of low back pain (LBP) that results in substantial health and economic burdens. Inflammatory pathway activation and the production of reactive oxygen species (ROS) play vital roles in the progression of IDD. Several studies have suggested that phillyrin has a protective role and inhibits inflammation and the production of ROS. However, the role of phillyrin in IDD has not been confirmed. Purpose The purpose of this study was to investigate the role of phillyrin in IDD and its mechanisms. Study design To establish IDD models in vivo, ex-vivo, and in vitro to verify the function of phillyrin in IDD. Method The effects of phillyrin on extracellular matrix (ECM) degeneration, inflammation, and oxidation in nucleus pulposus (NP) cells were assessed using immunoblotting and immunofluorescence analysis. Additionally, the impact of phillyrin administration on acupuncture-mediated intervertebral disc degeneration (IDD) in rats was evaluated using various techniques such as MRI, HE staining, S-O staining, and immunohistochemistry (IHC). Result Pretreatment with phillyrin significantly inhibited the IL-1β-mediated reduction in the degeneration of ECM and apoptosis by alleviating activation of the NF-κB inflammatory pathway and the generation of ROS. In addition, in vivo and ex-vivo experiments verified the protective effect of phillyrin against IDD. Conclusion Phillyrin can attenuate the progression of IDD by reducing ROS production and activating inflammatory pathways.

Abstract Background Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the “test and treat” era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. Methods Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants’ self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. Results A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01–3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09–4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27–4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03–3.19), no social participation (aOR = 5.65, 95%CI: 1.71–18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26–0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P

Abstract Background Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. Methods To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. Results We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. Conclusions Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

Abstract As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.

High-resolution observations of short-term changes in sea ice are critical to understanding ice dynamics and also provide important information used in advice to shipping, especially in the Arctic. Although individual satellite sensors provide periodic sea ice observations with spatial resolutions of tens of meters, information regarding changes that occur over short time intervals of minutes or hours is limited. In this study, a gridded ice–water classification dataset with a high temporal resolution was developed based on observations acquired by multiple satellite sensors in the Marginal Ice Zone (MIZ). This dataset – DynIceData – which combines Sentinel-1 Synthetic Aperture Radar (SAR) data with Gaofen-3 (GF-3) SAR and SDGSAT-1 thermal infrared imagery was used to obtain observations of the MIZ with a range of temporal resolutions ranging from minutes to tens of hours. The areas of the Arctic covered include the Kara Sea, Beaufort Sea, and Greenland Sea during the period from August 2021 to August 2022. Object-oriented segmentation and thresholding were used to obtain the ice–water classification map from Sentinel-1 and GF-3 SAR image pairs and Sentinel-1 SAR and SDGSAT-1 thermal image pairs. The time interval between the images in each pair ranged from 1 minute to 68 hours. Ten-kilometer grid sample granules with a spatial resolution of 25 m for the GF-3 SAR data and 30 m for the SDGSAT-1 thermal data were used. The classification was verified as having an overall accuracy of at least 95.58%. The DynIceData dataset consists of 7338 samples, which could be used as reference data for further research on rapid changes in sea ice patterns at different short time scales and provide support for research on thermodynamic and dynamic models of sea ice in combination with other environmental data, thus potentially improving the accuracy of sea ice forecasting using Artificial Intelligence. The dataset can be accessed at https://doi.org/10.57760/sciencedb.j00001.00784.

Global path planning is one of the key technologies in unmanned underwater vehicle (UUV) intelligent control. At present, research on UUV global path planning technology tends to choose long-distance and large-scale 3D space as the research environment, which leads to a sharp increase in the amount of data and search range for 3D spatial path planning. Therefore, an efficient and relatively small data volume 3D spatial path planning method is an urgent problem that needs to be solved for UUV engineering applications. To solve this problem, a new bilevel path planning algorithm for UUV is proposed. In the upper level of the algorithm, a Max Min Ant System-Elite Genetic (MMAS-EGA) algorithm is put forward, which is a hybrid ant colony optimization/genetic algorithm, in order to improve the convergence speed of the algorithm. In the lower level of the bilevel algorithm, a function optimization algorithm and the MMAS algorithm are used to minimize the number of variables to be optimized. To verify the effectiveness of the algorithm, we conducted simulation experiments in a three dimensional environment. The simulation results in the three-dimensional environment show that, compared with the existing bilevel algorithm, the time to search the global optimal solution is reduced by 9%, and the number of iterations is reduced by 4.4%. Furthermore, the new algorithm we proposed is more efficient and suitable for global path planning for different tasks.

ObjectiveThis study aimed to conduct a network meta-analysis to compare the diagnostic efficacy of diverse novel endoscopic techniques for detecting gastric Helicobacter pylori infection.MethodsFrom inception to August 2023, literature was systematically searched across Pubmed, Embase, and Web of Science databases. Cochrane’s risk of bias tool assessed the methodological quality of the included studies. Data analysis was conducted using the R software, employing a ranking chart to determine the most effective diagnostic method comprehensively. Convergence analysis was performed to assess the stability of the results.ResultsThe study encompassed 36 articles comprising 54 observational studies, investigating 14 novel endoscopic techniques and involving 7,230 patients diagnosed with gastric H. pylori infection. Compared with the gold standard, the comprehensive network meta-analysis revealed the superior diagnostic performance of two new endoscopic techniques, Magnifying blue laser imaging endoscopy (M-BLI) and high-definition magnifying endoscopy with i-scan (M-I-SCAN). Specifically, M-BLI demonstrated the highest ranking in both sensitivity (SE) and positive predictive value (PPV), ranking second in negative predictive value (NPV) and fourth in specificity (SP). M-I-SCAN secured the top position in NPV, third in SE and SP, and fifth in PPV.ConclusionAfter thoroughly analyzing the ranking chart, we conclude that M-BLI and M-I-SCAN stand out as the most suitable new endoscopic techniques for diagnosing gastric H. pylori infection.Systematic review registrationhttps://inplasy.com/inplasy-2023-11-0051/, identifier INPLASY2023110051.

Anthocyanins are plant secondary metabolites belonging to the polyphenol class of natural water-soluble phytopigments. The accumulation of anthocyanins in different plant tissues can improve plant survival under adverse conditions. In addition, plants with the resulting colorful morphology can be utilized as landscape plants. Triticum boeoticum (syn. Triticum monococcum ssp. aegilopoides, 2n=2x=14, AbAb) serves as a valuable genetic resource for the improvement of its close relative common wheat in terms of enhancing resilience to various biotic and abiotic stresses. In our previous study, the EMS-mutagenized mutant Z2921 with a red glume, stem, and rachis was generated from T. boeoticum G52, which has a green glume, stem, and rachis. In this study, the F1, F2, and F2:3 generations of a cross between mutant-type Z2921 and wild-type G52 were developed. A single recessive gene, tentatively designated RgM4G52, was identified in Z2921 via genetic analysis. Using bulked segregant exome capture sequencing (BSE-Seq) analysis, RgM4G52 was mapped to chromosome 6AL and was flanked by the markers KASP-58 and KASP-26 within a 3.40-cM genetic interval corresponding to 1.71-Mb and 1.61-Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Triticum boeoticum (TA299) reference genomes, respectively, in which seven and four genes related to anthocyanin synthesis development were annotated. Unlike previously reported color morphology-related genes, RgM4G52 is a recessive gene that can simultaneously control the color of glumes, stems, and rachis in wild einkorn. In addition, a synthetic Triticum dicoccum–T. boeoticum amphiploid Syn-ABAb-34, derived from the colchicine treatment of F1 hybrids between tetraploid wheat PI 352367 (T. dicoccum, AABB) and Z2921, expressed the red stems of Z2921. The flanking markers of RgM4G52 developed in this study could be useful for developing additional common wheat lines with red stems, laying the foundation for marker-assisted breeding and the fine mapping of RgM4G52.

Given that China's cross-border e-commerce (CBEC) industry has garnered significant attention from various overseas suppliers, this study aims to explore the CBEC shopping patterns of domestic Chinese consumers. The objective of the study is to integrate the theory of the e-commerce acceptance model (EAM) and multi-target trust to forecast the cross-border e-commerce shopping (CBECS) behavior of domestic Chinese consumers. PLS-based structural equation modeling analysis indicates that the CBECS intention is significantly influenced by perceived usefulness, perceived ease of use, and perceived risk. With regard to multi-target trust, seller trust impacts perceived risk and ease of use, whereas logistics trust influences perceived usefulness and perceived ease of use. Platform trust influences both seller trust and logistics trust. These results contribute to the advancement of CBEC literature and practices.

Microwave ablation (MWA) is a potent cancer treatment tool, but its effectiveness can be hindered by the lack of visual feedback. This paper validates the feasibility of using microwave-induced thermoacoustic imaging (TAI) technique to monitor the MWA process. A feasibility analysis was conducted at the principle level and a high-performance real-time TAI system was introduced. To address the interference caused by MWA, a robust principal component analysis (RPCA)-based method for TAI was proposed. This method leverages the correlation between multiple signal frames to eliminate interference. RPCA’s effectiveness in TAI was demonstrated through three sets of different experiments. Experiments demonstrated that TAI can effectively monitors the MWA process. This work represents the first application of RPCA-related matrix decomposition methods in TAI, paving the way for the application of TAI in more complex clinical scenarios. By providing rapid and accurate visual feedback, this research advances MWA technology.

IntroductionSome evidence suggests that fruit and alcohol consumption may be related to cognitive impairment.MethodsThis study conducted a cross-sectional study on the “correlation between eating habits and cognitive function of the middle-aged and elderly population in China.” The purpose of this study is to explore the relationship between fruit consumption, drinking habits and cognitive impairment in Chinese people over 50 years old.ResultsThe results show that the protective factors of cognitive impairment are the preference for berries and the daily intake of 100-200 grams grapes in Chinese middle-aged and elderly people with objective cognitive unimpaired. The habit of drinking red wine is a protective factor for cognitive impairment in Chinese middle-aged and elderly people with mild cognitive impairment (MCI). However, this study did not find the relationship between white wine, beer, yellow rice wine, liquor and cognitive impairment.DiscussionTherefore, we believe that berries, grapes and red wine consumption can protect the cognitive function of the middle-aged and elderly people in China, and the protective function is related to the basic cognitive state.

In Northeast (NE) China, the largest commodity grain base and natural forest area in China, both agricultural production and ecological protection require attention. In recent years, land degradation in NE China has increased, seriously affecting the production-ecology synergy. In this paper, four key ecosystem services (ESs) in NE China are quantified: provisioning, water conservation (WC), soil conservation (SC) and sand fixation (SF), and the spatiotemporal evolution characteristics and trade-offs and synergies (T&S) of ESs are analyzed. The driving factors of provisioning services and the characteristics of T&S are considered, and the county zoning scheme and the corresponding production-ecological function synergistic optimization paths are proposed. The results show that (1) the provisioning, WC and SF services in NE China have slightly increased in the past 20 years, and the provisioning in the Greater-Khingan-Mountains-Region (GKMR) and Lesser-Khingan-Mountains-Region (LKMR), the WC in the LKMR, and the SF in the Liao-River-Plain (LRP) have more obviously increased. The SC service has slightly decreased, especially in the Changbai-Mountains-Region (CBMR). (2) The provisioning service in NE China mainly shows a synergistic relationship with WC and SF, accounting for 79.1 % and 62.9 % of the area, respectively, and a trade-off relationship with SC, accounting for 52.54 % of the area. (3) Human activities (HA) are the dominant driving factor of the provisioning service change in NE China, with an impact degree of 62.65 %. The LKMR is an exception, as climate change (CC) dominates. The LRP, Songnen-Plain (SNP) and GKMR have high degrees of HA. (4) The number of synergistic optimized (SO), light optimized (LO) and trade-off limited (TL) counties accounted for 19.0 %, 61.7 % and 19.3 %, respectively. Among them, the SO type counties should prioritize improving provision and grain production capacity, the LO type counties should protect basic farmland and decrease trade-offs between ESs, and the TL type counties should improve ecological functions and strengthen ecological protection and restoration. This paper clarifies the main contradictions of ESs in NE China and provides an important scientific basis for ecological protection and restoration, which is important for ensuring food and ecological security and realizing the ecological and efficient sustainable utilization of black soil.

The research on complex workshop scheduling methods has important academic significance and has wide applications in industrial manufacturing. Aiming at the job shop scheduling problem, a hybrid algorithm based on comprehensive search mechanisms (HACSM) is proposed to optimize the maximum completion time. HACSM combines three search methods with different optimization scales, including fireworks algorithm (FW), extended Akers graphical method (LS1+_AKERS_EXT), and tabu search algorithm (TS). FW realizes global search through information interaction and resource allocation, ensuring the diversity of the population. LS1+_AKERS_EXT realizes compound movement with Akers graphical method, so it has advanced global and local search capabilities. In LS1+_AKERS_EXT, the shortest path is the core of the algorithm, which directly affects the encoding and decoding of scheduling. In order to find the shortest path, an effective node expansion method is designed to improve the node expansion efficiency. In the part of centralized search, TS based on the neighborhood structure is used. Finally, the effectiveness and superiority of HACSM are verified by testing the relevant instances in the literature.

Abstract Objective This meta-analysis aims to explore the potential link between vaccines and systemic lupus erythematosus (SLE). Methods We systematically searched PubMed, Cochrane Library, and Embase for observational studies from inception to September 3, 2023, using medical subject headings (MeSH) and keywords. Study quality was assessed using the NOS scale. Statistical analyses were conducted using STATA software (version 14.0). Publication bias was evaluated using funnel plots and Egger’s regression. Results The meta-analysis incorporated 17 studies, encompassing 45,067,349 individuals with follow-up periods ranging from 0.5 to 2 years. The pooled analysis revealed no significant association between vaccinations and an increased risk of SLE [OR = 1.14, 95% CI (0.86–1.52), I2 = 78.1%, P = 0.348]. Subgroup analyses indicated that HBV vaccination was significantly associated with an elevated risk of SLE [OR =2.11, 95% CI (1.11-4.00), I2 = 63.3%, P = 0.02], HPV vaccination was slightly associated with an increased risk of SLE [OR = 1.43, 95% CI (0.88–2.31), I2 = 72.4%, P = 0.148], influenza vaccination showed no association with an increased risk of SLE [OR = 0.96, 95% CI (0.82–1.12), I2 = 0.0%, P = 0.559], and COVID-19 vaccine was marginally associated with a decreased risk of SLE [OR = 0.44, 95% CI (0.18–1.21), I2 = 91.3%, P = 0.118]. Conclusions This study suggests that vaccinations are not linked to an increased risk of SLE. Our meta-analysis results provide valuable insights, alleviating concerns about SLE risk post-vaccination and supporting further vaccine development efforts.

Abstract Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.

Chinese fir (Cunninghamia lanceolata) is a special fast-growing commercial tree species in China and has significant ecological and economic value. However, it experienced damage from leaf blight caused by pathogenic fungi of the genus Alternaria. To determine the diversity of Alternaria species associated with leaf blight of Chinese fir in China, infected leaves were collected from five major cultivation provinces (Fujian, Henan, Hunan, Jiangsu and Shandong provinces). A total of 48 fungal strains of Alternaria were obtained. Comparison of morphology and phylogenetic analyses, based on nine loci (ITS, SSU, LSU, GAPDH, RPB2, TEF1, Alt a1, endoPG and OPA10-2) of the representative isolates as well as the pairwise homoplasy index tests, revealed that the fungal strains belonged to seven undescribed taxa of Alternaria, which are described here and named as Alternaria cunninghamiicola sp. nov., A. dongshanqiaoensis sp. nov., A. hunanensis sp. nov., A. kunyuensis sp. nov., А. longqiaoensis sp. nov., A. shandongensis sp. nov. and A. xinyangensis sp. nov. In order to prove Koch’s postulates, pathogenicity tests on detached Chinese fir leaves revealed significant pathogenicity amongst these species, of which A. hunanensis is the most pathogenic to Chinese fir. This study represents the first report of A. cunninghamiicola, A. dongshanqiaoensis, A. hunanensis, A. kunyuensis, A. longqiaoensis, A. shandongensis and A. xinyangensis causing leaf blight on Chinese fir. Knowledge obtained in this study enhanced our understanding of Alternaria species causing leaf blight on Chinese fir and was crucial for the disease management and the further studies in the future.

Chinese fir (Cunninghamia lanceolata) is a special fast-growing commercial tree species in China with high economic value. In recent years, leaf blight disease on C. lanceolata has been observed frequently. The diversity of Fusarium species associated with leaf blight on C. lanceolata in China (Fujian, Guangxi, Guizhou, and Hunan provinces) was evaluated using morphological study and molecular multi-locus analyses based on RNA polymerase second largest subunit (RPB2), translation elongation factor 1-alpha (TEF-1α), and RNA polymerase largest subunit (RPB1) genes/region as well as the pairwise homoplasy index tests. A total of five Fusarium species belonging to four Fusarium species complexes were recognized in this study. Two known species including Fusarium concentricum and F. fujikuroi belonged to the F. fujikuroi species complex, and three new Fusarium species were described, i.e., F. fujianense belonged to the F. lateritium species complex, F. guizhouense belonged to the F. sambucinum species complex, and F. hunanense belonged to the F. solani species complex. To prove Koch’s postulates, pathogenicity tests on C. lanceolata revealed a wide variation in pathogenicity and aggressiveness among the species, of which F. hunanense HN33-8-2 caused the most severe symptoms and F. fujianense LC14 led to the least severe symptoms. To our knowledge, this study also represented the first report of F. concentricum, F. fujianense, F. fujikuroi, F. guizhouense, and F. hunanense causing leaf blight on C. lanceolata in China.

Abstract Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m -/- Bim -/- lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.

Abstract Background Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer’s disease (AD). The study aims to investigate the association between mGluR5 availability and AD’s biomarkers and cognitive function. Methods We examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed. Results The mGluR5 availability was significantly reduced in AD patients’ hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance. Conclusions [18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.

Abstract With the development of the electric vehicle industry, the number of power batteries has increased dramatically. Establishing a recycling EOL (end-of-life) battery network for secondary use is an effective way to solve resource shortage and environmental pollution. However, existing networks are challenging due to the high uncertainty of EOL batteries, e.g., quantity and quality, resulting in a low recycling rate of the recovery network. To fill this gap, this paper proposes a stochastic programming approach for recovery network design under uncertain conditions of EOL batteries. Firstly, a multi-objective model for battery recovery network is established, considering carbon emissions and economic benefits. Secondly, a stochastic programming approach is proposed to clarify the model. Subsequently, the genetic algorithm is employed to solve the proposed model. Finally, a recovery network case of Region T is given to verify the credibility and superiority of the proposed method. The results demonstrate that the proposed model reduces carbon emissions by 20 metric tons and increases overall economic benefits by 10 million yuan in Region T compared to the deterministic model. Furthermore, the two portions affecting the optimization results are also discussed to provide a reference for reducing carbon emissions and improving economic efficiency in recycling networks.

In response to the poor positioning performance and errors of the wheeled robot under a single sensor, a combination of wheel odometry dead reckoning, Inertial Measurement Unit (IMU) heading angle information, and map environment information obtained from LiDAR is used for indoor positioning of the wheeled robot. By using data from multiple sensors, errors are reduced and positioning accuracy is improved. The results show that combining the Extended Kalman Filter (EKF), Gmapping algorithm, and Adaptive Monte Carlo Localization (AMCL) reduces the relative error by 8.35 % compared to the single wheel odometry heading calculation method. Compared with the EKF fusion method for dead reckoning and inertial measurement unit heading angle information, the relative error is reduced by 4 %, and there is no cumulative trend in angle error. This effectively addresses the challenge of cumulative errors in indoor positioning within environments that lack base stations, thereby enhancing accuracy and reliability in such specialized conditions.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Polyphenols with antioxidant properties are of significant interest in medical and pharmaceutical applications. Given the diverse range of activities of polyphenols in vivo, accurate detection of these compounds plays a crucial role in nutritional surveillance and pharmaceutical development. Yet, the efficient quantitation of polyphenol contents and qualification of monomer compositions present a notable challenge when studying polyphenol bioavailability. In this study, platinum-modified nickel-iron layered double hydroxide (Pt/NiFe-LDH hybrids) were designed to mimic peroxidases for colorimetric analysis and act as enhanced matrices for laser desorption/ionization mass spectrometry (LDI MS) to quantify and qualify polyphenols. The hybrids exhibited an enzymatic activity of 33.472 U/mg for colorimetric assays, facilitating the rapid and direct quantitation of total tea polyphenols within approximately 1 min. Additionally, the heterogeneous structure and exposed hydroxyl groups on the hybrid surface contributed to photoelectric enhancement and in-situ enrichment of polyphenols in LDI MS. This study introduces an innovative approach to detect polyphenols using advanced materials, potentially inspiring the future development and applications of other photoactive nanomaterials.

IntroductionEmbryo implantation requires synchronous communication between the embryo and maternal endometrium. Inadequate maternal endometrial receptivity is one of the principal causes for embryo implantation failure [especially repeated implantation failure (RIF)] when biopsied good-quality euploid embryos are transferred. An RNA-seq-based endometrial receptivity test (rsERT) was previously established to precisely guide successful embryo implantation. In this study, we aimed to evaluate the effect of personalized embryo transfer (pET) via rsERT on the clinical outcomes in patients with RIF.MethodsA total of 155 patients with RIF were included in the present retrospective study and were divided into two groups: 60 patients who underwent rsERT and pET (Group rsERT) and 95 patients who underwent standard frozen embryo transfer (FET) without rsERT (Group FET). Reproductive outcomes were compared for patients who underwent rsERT-guided pET and standard FET.ResultsForty percent (24/60) of the patients who underwent rsERT were receptive, and the remaining 60% (36/60) were non-receptive. The positive human chorionic gonadotropin (β-hCG) rate (56.3% vs. 30.5%, P = 0.003) and clinical pregnancy rate (43.8% vs. 24.2%, P = 0.017) were significantly higher in Group rsERT patients than in FET group patients. Additionally, Group rsERT patients also showed a higher implantation rate (32.1% vs. 22.1%, P = 0.104) and live birth rate (35.4% vs. 21.1%, P = 0.064) when compared with FET patients, although without significance. For subpopulation analysis, the positive β-hCG rate, clinical pregnancy rate, implantation rate, and live birth rate of receptive patients were not statistically significant different from those of non-receptive patients.ConclusionsThe rsERT can significantly improve the pregnancy outcomes of RIF patients, indicating the clinical potential of rsERT-guided pET.

Osteosarcoma (OS) is notorious for its high malignancy, and conventional chemotherapy drugs, while killing tumor cells, often inflict significant harm on the patient’s body. The tumor microenvironment of OS is characterized by high levels of hydrogen peroxide (H2O2). Leveraging this feature, we have developed Mg-ZIF nanoparticles, which incorporate magnesium (Mg) to confer robust peroxidase (POD)-like enzymatic activity. These Mg-ZIF nanozymes can generate highly lethal superoxide anions within tumor cells in a responsive manner, thereby achieving effective tumor destruction. Both in vitro and in situ OS models have corroborated the anti-tumor efficacy of Mg-ZIF nanozymes, while also validating their biosafety. The design of Mg-ZIF nanozymes opens a new avenue for the treatment of OS, offering a promising therapeutic strategy.

Abnormalities in pulmonary vasculature or technical issues during lung procurement can lead to an insufficient left atrial (LA) cuff in donors. However, surgeons frequently need to reconfigure these less-than-ideal lungs for transplantation. This case report introduces a novel technique for such reconstruction. The patient was a 35-year-old male diagnosed with pneumoconiosis for over a year. Due to progressive worsening dyspnoea leading to respiratory failure on multiple occasions, he was deemed a candidate for lung transplantation. While obtaining the donor's lung, an inadvertent short cut of the LA cuff around the left inferior pulmonary vein orifice resulted in the residual vein retracting into the pulmonary hilum. To overcome this, we employed the aortic arch for reconstruction, enabling the successful completion of the lung transplantation. On post-transplantation day 2, extracorporeal membrane oxygenation was no longer required. Mechanical ventilation ceased after 13 days, with the subsequent removal of a tracheostomy. The patient spent 35 days in the intensive care unit and 58 days in the hospital. Post-transplantation complications included primary graft dysfunction, acute kidney failure, pneumothorax in the transplanted lung, the clots in the inferior vena cava, and pneumonia. Remarkably, over a year of follow-up (19 months after lung transplantation), the patient reported no adverse events and had successfully returned to work. In this case, the aortic arch is an alternative for reconstructing an insufficient LA cuff.

Background Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy.Method 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS1 and p

Abstract Phenylketonuria (PKU) is the most common inherited metabolic disease in humans. Clinical screening of newborn heel blood samples for PKU is costly and time‐consuming because it requires multiple procedures, like isotope labeling and derivatization, and PKU subtype identification requires an additional urine sample. Delayed diagnosis of PKU, or subtype identification can result in mental disability. Here, plasmonic silver nanoshells are used for laser desorption/ionization mass spectrometry (MS) detection of PKU with label‐free assay by recognizing metabolic profile in dried blood spot (DBS) samples. A total of 1100 subjects are recruited and each DBS sample can be processed in seconds. This platform achieves PKU screening with a sensitivity of 0.985 and specificity of 0.995, which is comparable to existing clinical liquid chromatography MS (LC‐MS) methods. This method can process 360 samples per hour, compared with the LC‐MS method which processes only 30 samples per hour. Moreover, this assay enables precise identification of PKU subtypes without the need for a urine sample. It is demonstrated that this platform enables high‐performance and fast, low‐cost PKU screening and subtype identification. This approach might be suitable for the detection of other clinically relevant biomarkers in blood or other clinical samples.

Summary: Abnormal accumulation of hydrogen peroxide (H2O2) in the tumor microenvironment is associated with altered metabolism, abnormal proliferation of tumor cells, and changes in the tumor microenvironment. Based on this phenomenon, we have developed manganese-doped zeolitic imidazolate frameworks (Mn-ZIF) nanozymes, which exhibit superior peroxidase (POD)-like activity and enhanced cytotoxicity. Inside the tumor, the H2O2 is catalyzed by Mn-ZIF nanozymes through the Fenton reaction to generate more potent hydroxyl radicals (·OH), further increasing the local reactive oxygen species (ROS) levels in tumor cells and inducing tumor cell death. Meanwhile, the removal of H2O2 in the tumor microenvironment reduces tumor proliferation. We have confirmed the anti-tumor effect of these particles in an in situ osteosarcoma (OS) model, providing a direction for the future design of hybrid nanozyme drug delivery systems.

Pachychoroid spectrum diseases(PSD)have been defined as a group of diseases with similar choroidal features and pathological processes, such as central serous chorioretinopathy(CSC), polypoidal choroidal vasculopathy(PCV), etc. The main features are the changes in the thickness of vascular layers of the choroid and increasing vascular permeability. The development of modern ophthalmic imaging devices represented by optical coherence tomography angiography(OCTA)allowed intuitive investigation of the changes in the choroidal vascular layers, which gives a new insight into the pathogenesis of this spectrum diseases. This article summarizes the common clinical characteristics of healthy individuals and PSD and reviews the latest imaging findings. Whether each type of PSD is a phenotype of the same disease at different stages or other with similar characteristics was discussed from different perspectives, such as genetic background and anatomical structure, providing a reference for the study of pathogenesis, early clinical diagnosis, and prevention and treatment of this disease.

To avoid crowd evacuation simulations depending on 2D environments and real data, we propose a framework for crowd evacuation modeling and simulation by applying deep reinforcement learning (DRL) and 3D physical environments (3DPEs). In 3DPEs, we construct simulation scenarios from the aspects of geometry, semantics and physics, which include the environment, the agents and their interactions, and provide training samples for DRL. In DRL, we design a double branch feature extraction combined actor and critic network as the DRL policy and value function and use a clipped surrogate objective with polynomial decay to update the policy. With a unified configuration, we conduct evacuation simulations. In scenarios with one exit, we reproduce and verify the bottleneck effect of congested crowds and explore the impact of exit width and agent characteristics (number, mass and height) on evacuation. In scenarios with two exits and a uniform (nonuniform) distribution of agents, we explore the impact of exit characteristics (width and relative position) and agent characteristics (height, initial location and distribution) on agent exit selection and evacuation. Overall, interactive 3DPEs and unified DRL enable agents to adapt to different evacuation scenarios to simulate crowd evacuation and explore the laws of crowd evacuation.

ABSTRACTThe bacterial communities of Zaopocu (ZPC), a tropical specialty fermented food in Hainan Island, were characterized in this study using high-throughput sequencing. Firmicutes and Proteobacteria were the two dominant phyla. The primary genus in ZPC_A was Weissella, while ZPC_B and ZPC_C had Lactobacillus as the dominant genus. The biomarker lactic acid bacteria (LAB) in ZPC_A were Lactobacillus brevis, Weissella confusa, and Leuconostoc citreum, whereas Lactobacillus amylolyticus and Lactobacillus helveticus were significantly higher in ZPC_B. In contrast, Lactobacillus pontis and Lactobacillus fermentum were the core LAB in ZPC_C. ZPC_A has the highest value of titratable acid (TA), amino acid, and lactic acid. TA had the most powerful influence on the structure of the bacterial communities, whereas salinity had a negligible effect. It is worth noting that ZPC may also faces food safety issue because opportunistic pathogenic bacteria like Stenotrophomonas and genes closely associated with Staphylococcus aureus infection were highly detected.

Abstract Precise energy management in distribution power system requires high‐precision time synchronization among large‐scale deployed devices. Multiple clock sources‐based time synchronization possesses advantages of reliability, high precision, and robustness, but still faces several challenges such as coupling between time synchronization error and delay, as well as different timescales between clock source and clock weight optimization. In this paper, a multi‐clock source time synchronization model is constructed and a problem is formulated to minimize the synchronization error and delay through jointly optimizing large‐timescale clock source selection and small‐timescale weight selection. A reinforcement learning‐based multi‐timescale multi‐clock source time synchronization algorithm named RL‐M2 is proposed to solve the formulated problem from a learning perspective. Besides, a lossless switching method is proposed to address the switching problem for multiple clock sources. Simulation results demonstrate the superior performance of RL‐M2 and the lossless switching method in time synchronization delay and error.

Abstract Polyploidization is a major driver of genome diversification and environmental adaptation. However, the merger of different genomes may result in genomic conflicts, raising a major question regarding how genetic diversity is interpreted and regulated to enable environmental plasticity. By analyzing the genome-wide binding of 191 trans-factors in allopolyploid wheat, we identified like heterochromatin protein 1 (LHP1) as a master regulator of subgenome-diversified genes. Transcriptomic and epigenomic analyses of LHP1 mutants reveal its role in buffering the expression of subgenome-diversified defense genes by controlling H3K27me3 homeostasis. Stripe rust infection releases latent subgenomic variations by eliminating H3K27me3-related repression. The simultaneous inactivation of LHP1 homoeologs by CRISPR–Cas9 confers robust stripe rust resistance in wheat seedlings. The conditional repression of subgenome-diversified defenses ensures developmental plasticity to external changes, while also promoting neutral-to-non-neutral selection transitions and adaptive evolution. These findings establish an LHP1-mediated buffering system at the intersection of genotypes, environments, and phenotypes in polyploid wheat. Manipulating the epigenetic buffering capacity offers a tool to harness cryptic subgenomic variations for crop improvement.

Demand fluctuates in actual production. When manufacturers face demand under their maximum capacity, suspension shifts are crucial for cost reduction and on-time delivery. In this case, suspension shifts are needed to minimize idle time and prevent inventory buildup. Thus, it is essential to integrate suspension shifts with scheduling under an uncertain production environment. This paper addresses the two-stage hybrid flow shop scheduling problem (THFSP) with suspension shifts under uncertain processing times, aiming to minimize the weighted sum of earliness and tardiness. We develop a stochastic integer programming model and validate it using the Gurobi solver. Additionally, we propose a dual-space co-evolutionary biased random key genetic algorithm (DCE-BRKGA) with parallel evolution of solutions and scenarios. Considering decision-makers’ risk preferences, we use both average and pessimistic criteria for fitness evaluation, generating two types of solutions and scenario populations. Testing with 28 datasets, we use the value of the stochastic solution (VSS) and the expected value of perfect information (EVPI) to quantify benefits. Compared to the average scenario, the VSS shows that the proposed algorithm achieves additional value gains of 0.9% to 69.9%. Furthermore, the EVPI indicates that after eliminating uncertainty, the algorithm yields potential improvements of 2.4% to 20.3%. These findings indicate that DCE-BRKGA effectively supports varying decision-making risk preferences, providing robust solutions even without known processing time distributions.

The development of a piezoelectric linear motor is presented in this paper, based on the principle of alternating motion, to meet the acting stroke and accuracy requirements for the probe station’s motion servo system. By partitioning the stator into tangential and normal components, two tangential actuators are affixed to the base, while two normal actuators are fixed on the preloading mechanism, thereby proposing a novel approach for connecting the stator and base. First, the construction and the working principle of the motor were introduced. Subsequently, the motor’s major components were designed through finite element simulation, followed by modeling the motor dynamics and deriving its displacement transfer function. Finally, an experimental prototype was fabricated, and a prototype test system was constructed. The driving method can realize a large stroke operation at a low frequency. The minimum operating frequency of the motor is 1 Hz, the minimum step is 12.55 μm, and the stroke is 105 mm. The study results will promote the development of high-performance probe systems.

Tunable laser sources with a wide wavelength tuning range, mode-hop-free (MHF) operation, and high spectral purity are essential for applications such as high-resolution spectroscopy, coherent detection, and intelligent fiber sensing. In this paper, we present a wide-range tunable laser source that operates without mode hopping, based on external cavity feedback using a semiconductor gain chip as the laser gain medium. The wavelength, power, and spectral characteristics of the laser are experimentally measured. A wide MHF continuous wavelength tuning range from 1480 nm to 1620 nm with a side-mode suppression ratio of more than 61.65 dB is achieved. An output optical power of more than 11.14 dBm with good power stability can also be realized in the full C+L band. This proposed external-cavity tunable laser source features a narrow intrinsic linewidth and MHF tunable radiation with a maximum sweep speed of 200 nm/s, enabling practical applications such as high-resolution vector spectrum analysis.