Search

Zhen-Hong Jiang, Guo-Hu Zhang, Jin-Ming Xia, Shi-Jin Lv Emergency Department, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, People’s Republic of ChinaCorrespondence: Shi-Jin Lv, Email lvshijin706@163.comBackground: The number of patients with thrombocytopenia (TCP) is relatively high in intensive care units (ICUs). It is therefore necessary to evaluate the prognostic risk of such patients.Aim: This study investigated the risk factors affecting the survival of patients with TCP in the ICU. Using the findings of this investigation, we developed and validated a risk prediction model.Methods: We evaluated patients admitted to the ICU who presented with TCP. We used LASSO regression to identify important clinical indicators. Based on these indicators, we developed a prediction model complete with a nomogram for the development cohort set. We then evaluated the mode’s accuracy using a receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA) in a validation cohort.Results: A total of 141 cases of ICU TCP were included in the sample, of which 47 involved death of the patient. Clinical results were as follows: N (HR 0.91, 95% CI 0.86– 0.97, P=0.003); TBIL (HR 1.98, 95% CI 1.02– 1.99, P=0.048); APACHE II (HR 1.94, 95% CI 1.39, 2.48, P=0.045); WPRN (HR 6.22, 95% CI 2.86– 13.53, P< 0.001); WTOST (HR 0.56, 95% CI 0.21– 1.46, P< 0.001); and DMV [HR1.87, 95% CI 1.12– 2.33]. The prediction model yielded an area under the curve (AUC) of 0.918 (95% CI 0.863– 0.974) in the development cohort and 0.926 (95% CI 0.849– 0.994) in the validation cohort. Application of the nomogram in the validation cohort gave good discrimination (C-index 0.853, 95% CI 0.810– 0.922) and good calibration. DCA indicated that the nomogram was clinically useful.Conclusion: The individualized nomogram developed through our analysis demonstrated effective prognostic prediction for patients with TCP in ICUs. Use of this prediction metric may reduce TCP-related morbidity and mortality in ICUs.Keywords: thrombocytopenia, intensive care unit, nomogram, prediction model

Jing-Fang Shi,1,2 Ping Wu,2 Xiao-Li Cheng,2 Xiao-Yi Wei,2 Zi-Hua Jiang3 1Guangdong Provincial Key Laboratory for Crop Germplasm Resources Preservation and Utilization, Agro-Biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, People’s Republic of China; 2Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, People’s Republic of China; 3Department of Chemistry, Lakehead University, Thunder Bay, Ontario P7B 5E1, CanadaCorrespondence: Zi-Hua JiangDepartment of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1, CanadaTel +1-807-766-7171Email zjiang@lakeheadu.caXiao-Yi WeiKey Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Xingke Road 723, Tianhe District, Guangzhou 510650, People’s Republic of ChinaTel +86-20-37252538Email wxy@scbg.ac.cnBackground: Annonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated.Methods: In order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay.Results: Nine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS).Conclusion: The conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.Keywords: annonaceous acetogenins, squamocin, bullatacin, glycosylated, cytotoxicity, anticancer, solubility

Cheng-Ting Zi,1,2,* Liu Yang,2,* Qing-Hua Kong,2 Hong-Mei Li,2 Xing-Zhi Yang,2 Zhong-Tao Ding,3 Zi-Hua Jiang,4 Jiang-Miao Hu,2 Jun Zhou2 1Key Laboratory of Pu-Er Tea Science, Ministry of Education, College of Science, Yunnan Agricultural University, Kunming, 650201, People’s Republic of China; 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China; 3Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China; 4Department of Chemistry, Lakehead University, Thunder Bay ON P7B 5E1, Canada*These authors contributed equally to this workCorrespondence: Zi-Hua JiangDepartment of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay ON P7B 5EI, CanadaTel +1 807 766 7171Fax +1 807 346 7775Email zjiang@lakeheadu.caJiang-Miao HuState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, No. 132, Lanhei Road, Kunming 650201, People’s Republic of ChinaTel +86 871 6522 3264Fax +86 871 6522 3261Email hujiangmiao@mail.kib.ac.cnBackground: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4β-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied.Methods: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure–activity relationship and the physicochemical property–anticancer activity relationship of these compounds.Results: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 μM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10.Conclusion: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.Keywords: podophyllotoxin, glucoside, synthesis, cytotoxicity, physicochemical properties

Diabetic retinopathy (DR), a common microvascular complication, is the leading cause of visual impairment among the working-age population. Late-stage DR can lead to irreversible vision loss, whereas vision impairment can be prevented by controlling blood sugar in a normal level in the early stage of DR. Notably, as early-stage DR is typically asymptomatic, the majority of DR patients are diagnosed at an advanced stage, which causes a great burden to the patients. Therefore, the development of accurate and efficient biomarkers for the early diagnosis of DR is essential for the prevention of DR. In recent decades, a large number of studies have found that serum complement C3 is closely associated with the development of DR. In this study, a method for the detection of complement C3 by mass spectrometry was established by optimizing the enrichment conditions of glycopeptides using C18 materials. It was found that among volunteers with different stages of DR, the level of complement C3 galactose modification showed a tendency to rise first and then go down with the development of DR. The difference in complement C3 glycosylation was used for the diagnosis of different stages of DR, yielding an area under curve (AUC) of up to 0.761.

Abstract Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F2-F1 linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development.

The genus Karstsinnectes of blind fishes known as karst loaches from China was established in 2023 during a revision of the genus Oreonectes (Nemacheilidae). Six species are recorded in this study and some taxonomic progress has been made; however, the lack of genetic data for some species (e.g., K. anophthalmus) may have weakened our current understanding of Karstsinnectes. This study reassessed the phylogeny and evolutionary history of Karstsinnectes by integrating a combination of previously published and newly sequenced mitochondrial genomic data. A phylogenetic tree was developed that was able to divide Karstsinnectes into two clades corresponding to drainages and clarify the phylogenetic position of K. anophthalmus. Divergence times show that Karstsinnectes originated at the Oligocene/Miocene boundary (~22.37 Mya), with the most recent common ancestor occurring in the early Miocene (~18.87 Mya) and interspecific divergence occurring in the late Miocene. Ancestral area reconstruction suggests that the most recent common ancestor of Karstsinnectes most likely inhabited the Hongshui River basin and dispersed into the Zuojiang-Yujiang, Beipanjiang, and Youjiang river basins during the early Miocene (~18.87 Mya), middle Miocene (~12.78 Mya), and late Miocene (~6.71 Mya), respectively. The dispersal under the influence of orogenesis and a monsoon climate drove the speciation and diverse distribution of Karstsinnectes. Such findings are important for conservation considering that Karstsinnectes strictly inhabits deep caves. Additionally, the taxonomic status of the distributed Karstsinnectes population in Leiping Town, Daxin County, Guangxi, China was revised by combining genetic and morphological differences to describe this population as a new species, Karstsinnectes daxinensis Luo, Zhou & Zhou, sp. nov. The definition of the phylogenetic position of K. anophthalmus emphasizes the importance of using type locality material for the identification of cryptic species.

AIM: To systematically evaluate the efficacy and safety of low-concentrations atropine eye drops in controlling adolescent myopia.METHODS:A computer search was conducted on Wanfang Data, CNKI, VIP, PubMed, Cochrane Library, and Embase databases from January 2010 to March 2024 on clinical studies on low-concentration atropine eye drops for controlling adolescent myopia. Two researchers independently screened trials, extracted data, evaluated risk of bias and quality, and used Review Manager5.4 software to perform Meta-analysis.RESULTS:A total of 17 articles, involving 3 764 cases and 3 952 eyes, were included. The Meta-analysis showed that compared with the control group, low concentrations of atropine could effectively slow down the growth of axial length [MD=-0.15, 95% CI(-0.20, -0.10), P

Abstract The non-vanishing neutrino mass strongly hints the existence of right-handed neutrinos (RHNs), singlets of the standard model (SM). However, they are highly decoupled from the SM and difficult to probe. In this work, we consider the Majorana RHNs from the type-I seesaw mechanism may well mix with the heavy neutral lepton dwelling in certain vector-like lepton (VLL), thus acquiring a sizable electroweak charge. Such a simple scenario yields many interesting consequences, and the imprint on oblique corrections, well expected from the mass splitting between components of VLL by virtue of VLL-RHN mixing, is our focus here. We analytically calculate the Peskin-Takeuchi parameters S, T and U with full details, carefully treating the Majorana loop to obtain the self consistent expressions free of divergence. Then, we constrain on the VLL-RHN system which only gives a sizable T parameter using the PDG-2021 data and CDF-II data, separately, by imposing T ≲ O $$ \mathcal{O} $$ (0.1). It is found that for the RHN and VLL below the TeV scale, with a properly large mixing, stands in the frontier of the electroweak precision test such as W-boson mass.

Abstract Objectives Repeatability is crucial for ensuring the generalizability and clinical utility of radiomics-based prognostic models. This study aims to investigate the repeatability of radiomic feature (RF) and its impact on the cross-institutional generalizability of the prognostic model for predicting local recurrence-free survival (LRFS) and overall survival (OS) in esophageal squamous cell cancer (ESCC) receiving definitive (chemo) radiotherapy (dCRT). Methods Nine hundred and twelve patients from two hospitals were included as training and external validation sets, respectively. Image perturbations were applied to contrast-enhanced computed tomography to generate perturbed images. Six thousand five hundred ten RFs from different feature types, bin widths, and filters were extracted from the original and perturbed images separately to evaluate RF repeatability by intraclass correlation coefficient (ICC). The high-repeatable and low-repeatable RF groups grouped by the median ICC were further analyzed separately by feature selection and multivariate Cox proportional hazards regression model for predicting LRFS and OS. Results First-order statistical features were more repeatable than texture features (median ICC: 0.70 vs 0.42–0.62). RFs from LoG had better repeatability than that of wavelet (median ICC: 0.70–0.84 vs 0.14–0.64). Features with smaller bin widths had higher repeatability (median ICC of 8–128: 0.65–0.47). For both LRFS and OS, the performance of the models based on high- and low-repeatable RFs remained stable in the training set with similar C-index (LRFS: 0.65 vs 0.67, p = 0.958; OS: 0.64 vs 0.65, p = 0.651), while the performance of the model based on the low-repeatable group was significantly lower than that based on the high-repeatable group in the external validation set (LRFS: 0.61 vs 0.67, p = 0.013; OS: 0.56 vs 0.63, p = 0.013). Conclusions Applying high-repeatable RFs in modeling could safeguard the cross-institutional generalizability of the prognostic model in ESCC. Critical relevance statement The exploration of repeatable RFs in different diseases and different types of imaging is conducive to promoting the proper use of radiomics in clinical research. Key Points The repeatability of RFs impacts the generalizability of the radiomic model. The high-repeatable RFs safeguard the cross-institutional generalizability of the model. Smaller bin width helps improve the repeatability of RFs. Graphical Abstract

Two new species of the genus Triplophysa from southwestern Guizhou Province, China, are described. These are Triplophysa ziyunensis Wu, Luo, Xiao & Zhou, sp. nov. and Triplophysa yaluwang Lan, Liu, Zhou & Zhou, sp. nov. from Maoying Town, Ziyun County, Guizhou Province, China. Triplophysa ziyunensis Wu, Luo, Xiao & Zhou, sp. nov. is distinguished from other hypogean species of the genus Triplophysa by having a combination of the following characteristics: body naked, scaleless, pigmented markings on surface of body, except ventral; eyes reduced, diameter 2.4–4.9% of head length; pelvic-fin tip extending to anus; tip of pectoral fin not reaching pelvic fin origin; anterior and posterior nostrils closely set, with anterior nostril elongated to a barbel-like tip; tip of outrostral barbel extending backward, not reaching anterior margin of the eye; lateral line complete; posterior chamber of air bladder degenerated; and fin differences. Triplophysa yaluwang Lan, Liu, Zhou & Zhou, sp. nov. is distinguished from other hypogean species of the genus Triplophysa by having a combination of the following characteristics: body naked, scaleless, with irregular pale and dark brownish brown markings, except ventrally; eyes reduced, diameter 4.6–6.1% of head length; pelvic-fin tip reaching anus; tip of pectoral fin not reaching to pelvic fin origin; anterior and posterior nostrils closely set, with anterior nostril elongated to a barbel-like tip; tip of outrostral barbel extending backward, not reaching to anterior margin of the eye; lateral line complete; posterior chamber of air bladder degenerated; and fin differences. Mitochondrial Cyt b revealed relatively small genetic differences, 1.4–2.0%, between the two new species and close relatives. Nuclear gene RAG1 indicated that the two new species possessed unique haplotypes with multiple linking mutations. This study emphasizes the importance of utilizing nuclear genes to identify new species in rapidly speciation cave species, with small genetic differences due to mitochondrial introgression occurring interspecies.

This study describes a new species, Sinocyclocheilus xiejiahuai sp. nov., discovered within a cave located in Hongguo Town, Panzhou City, Guizhou Province, southwestern China, with the type locality in the Nanpanjiang River basin. Phylogenetic trees reconstructed based on mitochondrial genes show that the new species represents an independent evolutionary lineage with large genetic differences, 1.9%–13.8% in mitochondrial Cyt b, from congeners. Morphologically, this species can be differentiated from the 79 species currently classified under the genus Sinocyclocheilus by several characteristics: absence of horn-like structures and indistinct elevation at the head-dorsal junction, absence of irregular black markings on the body lateral and scaleless, eyes large, eye diameter 13% of head length, dorsal-fin rays, iii, 6½, last unbranched ray strong, with serrations along posterior margin, pectoral-fin rays, i, 13, anal-fin rays, iii, 5, pelvic-fin rays, i, 7, lateral line pores 74, gill rakers well developed, nine on first gill arch, pectoral fins short, tip not reaching to pelvic-fin origin. The number of Sinocyclocheilus species has been increased from 79 to 80 since the description of this new species.

Metasurfaces, composed of planar arrays of intricately designed meta-atom structures, possess remarkable capabilities in controlling electromagnetic waves in various ways. A critical aspect of metasurface design involves selecting suitable meta-atoms to achieve target functionalities such as phase retardation, amplitude modulation, and polarization conversion. Conventional design processes often involve extensive parameter sweeping, a laborious and computationally intensive task heavily reliant on designer expertise and judgement. Here, we present an efficient genetic algorithm assisted meta-atom optimization method for high-performance metasurface optics, which is compatible to both single- and multi-objective device design tasks. We first employ the method for a single-objective design task and implement a high-efficiency Pancharatnam-Berry phase based metalens with an average focusing efficiency exceeding 80% in the visible spectrum. We then employ the method for a dual-objective metasurface design task and construct an efficient spin-multiplexed structural beam generator. The device is capable of generating zeroth-order and first-order Bessel beams respectively under right-handed and left-handed circular polarized illumination, with associated generation efficiencies surpassing 88%. Finally, we implement a wavelength and spin co-multiplexed four-channel metahologram capable of projecting two spin-multiplexed holographic images under each operational wavelength, with efficiencies over 50%. Our work offers a streamlined and easy-to-implement approach to meta-atom design and optimization, empowering designers to create diverse high-performance and multifunctional metasurface optics.

Abstract Interannual global mean surface temperature (GMST) forecast provides critical insights into the economic and societal implications of climate variability. The pronounced GMST elevation in 2023–2024 indicates that the Earth may have accumulated enough heat to cause widespread disasters, underscoring the necessity for establishing accurate short-term GMST predictions to offer timely and sustainable public service. However, capturing high-frequency annual variability (ANV) component of GMST poses challenges due to its susceptibility to intraseasonal-to-interannual (ISI) noises, particularly across the Northern Hemisphere’s mid-to-high latitudes. Averaging these ISI variations in November and December effectively enhances signal clarity, especially over oceans, and masks unpredictable noises on land. By forecasting the average GMST for November and December to extract ANV predictability, a strategy for annual GMST prediction was established. This approach successfully advanced precise GMST hindcasts by up to 2-months during 1980–2022, exceeding performance of existing climate models and boosting early warning for interannual GMST shifts.

Abstract Implementing the strongly coupled data assimilation (SCDA) in coupled earth system models remains big challenging, primarily due to accurately estimating the coupled cross background-error covariance. In this work, through simplified two-variable one-dimensional assimilation experiments focusing on the air–sea interactions over the tropical pacific, we aim to clarify that SCDA based on the variance–covariance correlation, such as the ensemble-based SCDA, is limited in handling the inherent nonlinear relations between cross-sphere variables and provides a background matrix containing linear information only. These limitations also lead to the analysis distributions deviating from the truth and miscalculating the strength of rare extreme events. However, free from linear or Gaussian assumptions, the application of the data-driven machine learning (ML) method, such as multilayer perceptron, on SCDA circumvents the expensive matrix operations by avoiding the explicit calculation of background matrix. This strategy presents comprehensively superior performance than the conventional ensemble-based assimilation strategy, particularly in representing the strongly nonlinear relationships between cross-sphere variables and reproducing long-tailed distributions, which help capture the occurrence of small probability events. It is also demonstrated to be cost-effective and has great potential to generate a more accurate initial condition for coupled models, especially in facilitating prediction tasks of the extreme events.

Abstract Two-dimensional (2D) materials, as adsorbents, have garnered great attention in removing heavy metal ions (HMIs) from drinking water due to their extensive exposed adsorption sites. Nevertheless, there remains a paucity of experimental research to remarkably unlock their adsorption capabilities and fully elucidate their adsorption mechanisms. In this work, exceptional lead ion (Pb2+) (a common HMI) removal capacity (up to 758 mg g−1) is achieved using our synthesized metallic 1T/1T′ phase 2D transition metal dichalcogenide (TMD, including MoS2, WS2, TaS2, and TiS2) nanosheets, which hold tremendous activated S chemisorption sites. The residual Pb2+ concentration can be reduced from 2 mg L−1 to 2 μg L−1 within 0.5 min, meeting the drinking water standards following World Health Organization guideline (Pb2+ concentrations

Abstract Background Plant traits and plant adaptive strategies have been affected by the increasing intensity and severity of environmental changes. Given the uncertainty surrounding future environmental conditions, investigating plant trait variations under various stresses is crucial for unraveling plant survival strategies. Leaf anatomical traits are closely responsible for plants’ photosynthesis, respiration and transpiration. However, knowledge of how the multi-species leaf anatomical traits varied in extremely and moderately stressful environments is limited. Our objective was to compare the variation of leaf anatomic traits and adaptation strategies in two different stressful regions of the Qinghai-Tibet Plateau (TP) and Mongolian Plateau (MP) of China. Methods We sampled ten sites in each of the two regions (MP and TP) along an environmental gradient. Seven leaf anatomical traits and two leaf economic traits were measured for all leaf samples. Leaf anatomical traits include the traits related to leaf physiological processes (mesophyll thickness (MT), palisade tissue thickness (PT), spongy tissue thickness (ST), palisade-spongy tissue thickness ratio (PST) and epidermal thickness (ET)) and the traits related to trait construction investment (epiderm-leaf thickness ratio (ET/LT) and mesophyll-leaf thickness ratio (MT/LT)). Leaf economic traits include specific leaf area (SLA) and leaf nitrogen content (LN). Results The results revealed that leaf anatomical traits in the TP exhibited greater phylogenetic conservation with thicker structures, being less susceptible to environmental impacts than those in the MP. Additionally, the leaf anatomical and economic traits decoupled both in the MP and TP. Conclusion These findings highlight that plants adopt diverse strategies to cope with extremely and moderately environmental stresses, but multidimensional trait patterns are generally favored in stressful environments.

Objective To investigate the electrophysiological characteristics and clinical significance of unilateral tinnitus with normal hearing threshold. Methods A total of 34 patients with normal hearing but unilateral tinnitus admitted to our department from May 2022 to February 2023 were recruited as the study subjects. Pure tone hearing threshold detection, distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR) detection and extended high-frequency pure tone audiometry were performed on both ears (affected side and healthy side) of every patient. The data of the affected side group and those of healthy side group were compared. Results The Ⅰ-wave latency of ABR was significantly shorter (1.60 vs 1.73 ms, P=0.018), and its amplitude was obviously decreased (0.19 vs 0.23 μV, P=0.003) in the affected side group when compared with the healthy side group. In the affected group (34 ears), there were 18 ears (52.94%) having amplitude of wave Ⅲ greater than that of wave Ⅴ, while in the healthy group, no such difference in the amplitude between wave Ⅲ and wave Ⅴ was observed. There was statistical significance between the 2 groups (Chi-square=24.480, P < 0.001). In the 12.5, 14.0, 16.0, 18.0 and 20.0 kHz conditions, the average hearing threshold of extended high-frequency audiometry was all significantly higher in the affected side group than the healthy group (P < 0.05). Conclusion For subjective tinnitus patients with normal hearing threshold, ABR examination is helpful in preliminarily determining whether there are hidden functional changes in the auditory pathway. Decreased Ⅰ-wave amplitude, shortened Ⅰ-wave latency, and wave Ⅲ amplitude greater than wave Ⅴ amplitude can be used as objective reference indicators.

Abstract Background Plants have evolved various defense mechanisms against insect herbivores, including the formation of physical barriers, the synthesis of toxic metabolites, and the activation of phytohormone responses. Although plant-associated microbiota influence plant growth and health, whether they play a role in plant defense against insect pests in natural ecosystems is unknown. Results Here, we show that leaves of beetle-damaged weeping willow (Salix babylonica) trees are more resistant to the leaf beetle Plagiodera versicolora (Coleoptera) than those of undamaged leaves. Bacterial community transplantation experiments demonstrated that plant-associated microbiota from the beetle-damaged willow contribute to the resistance of the beetle-damaged willow to P. versicolora. Analysis of the composition and abundance of the microbiome revealed that Pseudomonas spp. is significantly enriched in the phyllosphere, roots, and rhizosphere soil of beetle-damaged willows relative to undamaged willows. From a total of 49 Pseudomonas strains isolated from willows and rhizosphere soil, we identified seven novel Pseudomonas strains that are toxic to P. versicolora. Moreover, re-inoculation of a synthetic microbial community (SynCom) with these Pseudomonas strains enhances willow resistance to P. versicolora. Conclusions Collectively, our data reveal that willows can exploit specific entomopathogenic bacteria to enhance defense against P. versicolora, suggesting that there is a complex interplay among plants, insects, and plant-associated microbiota in natural ecosystems. Graphical Abstract Video Abstract

In this paper, we utilize the Littlewood–Paley decomposition theory to establish two regularity criteria for the 3D magneto-micropolar equations in Vishik spaces, specifically focusing on the gradient of the velocity field.

Abstract Paleoclimate model simulations provide reference data to help interpret the geological record and offer a unique opportunity to evaluate the performance of current models under diverse boundary conditions. Here, we present a dataset of 35 climate model simulations of the warm early Eocene Climatic Optimum (EECO; ~ 50 million years ago) and corresponding preindustrial reference experiments. To streamline the use of the data, we apply standardised naming conventions and quality checks across eight modelling groups that have carried out coordinated simulations as part of the Deep-Time Model Intercomparison Project (DeepMIP). Gridded model fields can be downloaded from an online repository or accessed through a new web application that provides interactive data exploration. Local model data can be extracted in CSV format or visualised online for streamlined model-data comparisons. Additionally, processing and visualisation code templates may serve as a starting point for advanced analysis. The dataset and online platform aim to simplify accessing and handling complex data, prevent common processing issues, and facilitate the sharing of climate model data across disciplines.

Objective Making a reasonable train delay adjustment plan is one of the key tasks to ensure the safe and reliable operation of urban rail transit lines. For those lines with express and local trains running on, it is necessary to study the passengers′ train selection behavior during train delays, and analyze the influence of express and local trains overtaking on their choices as well. Method An analysis is conducted on passenger retention and their train selection behavior during express and local train operation on the line. A simulation algorithm that conforms to the rules of passenger boarding/alighting and their train selection behavior is designed, and a simulation and evaluation model for the operation plan adjustment due to express and local train delay is established. In consideration of the departure time and sequence of the express and local trains, and the overtaking trains and stations, different train delay adjustment plans are developed. The passenger′s travel process under the original operation plan and four delay adjustment plans on Shanghai Metro Line 16 is simulated, and the four delay adjustment plans are comprehensively evaluated. Result & Conclusion The simulation and evaluation model is effective and reliable, which can provide simulation means for urban rail transit operators to evaluate train operation plans, and also provide the basis for improving passenger service level, train capacity utilization rate and train operation plans.

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

Abstract Background Schistosomiasis is still one of the most serious parasitic diseases. Evidence showed that the metabolite profile in serum can potentially act as a marker for parasitic disease diagnosis and evaluate disease progression and prognosis. However, the serum metabolome in patients with Schistosoma japonicum infection is not well defined. In this study, we investigated the metabolite profiles of patients with chronic and with advanced S. japonicum infection. Methods The sera of 33 chronic S. japonicum patients, 15 patients with advanced schistosomiasis and 17 healthy volunteers were collected. Samples were extracted for metabolites and analyzed with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Results We observed significant differences in metabolite profiles in positive and negative ion modes between patients with advanced and chronic S. japonicum infection. In patients with chronic S. japonicum infection, 199 metabolites were significantly upregulated while 207 metabolites were downregulated in advanced infection. These differential metabolites were mainly concentrated in steroid hormone biosynthesis, cholesterol metabolism and bile secretion pathways. We also found that certain bile acid levels were significantly upregulated in the progression from chronic to advanced S. japonicum infection. In receiver operator characteristic (ROC) analysis, we identified three metabolites with area under the curve (AUC) > 0.8, including glycocholic (GCA), glycochenodeoxycholate (GCDCA) and taurochenodeoxycholic acid (TCDCA) concentrated in cholesterol metabolism, biliary secretion and primary bile acid biosynthesis. Conclusions This study provides evidence that GCA, GCDCA and TCDCA can potentially act as novel metabolite biomarkers to distinguish patients in different stages of S. japonicum infection. This study will contribute to the understanding of the metabolite mechanisms of the transition from chronic to advanced S. japonicum infection, although more studies are needed to validate this potential role and explore the underlying mechanisms. Graphical Abstract

Mitogenome data of Odonata is accumulating and widely used in phylogenetic analysis. However, noncoding regions, especially control region, were usually omitted from the phylogenetic reconstruction. In an effort to uncover the phylogenetic insights offered by the control region, we have amassed 65 Odonata mitogenomes and conducted an examination of their control regions. Our analysis discovered that species belonging to Anisoptera and Anisozygoptera exhibited a stem-loop structure, which was formed by a conserved polyC-polyG stretch located near the rrns gene (encoding 12S rRNA). Conversely, the polyC-polyG region was not a conserved fragment in Zygoptera. The length and number of repetitions within the control region were identified as the primary determinants of its overall length. Further, sibling species within Odonata, particularly those in the genus Euphaea, displayed similar patterns of repetition in their control region. Collectively, our research delineates the structural variations within the control region of Odonata and suggests the potential utility of this region in elucidating phylogenetic relationships among closely related species.

Highlights Negative charged acidic polarity (NCAP) has been unveiled as the guideline for selecting additives to regulate electric double layer (EDL) for Zn-ion batteries. NCAP glutamate has been verified to regulate EDL structure with synergetic effects, including preferential adsorption on Zn anode and reconstruction of hydrated Zn-ion clusters. Adding NCAP additives, Zn|Cu half-cell achieves a high Coulombic efficiency of 99.83% for 2000 cycles, and NH4V4O10|Zn full cell realizes a high-capacity retention of 82.1% for 3000 cycles.

Abstract The paleoclimate record provides a test-bed in which climate models can be evaluated under conditions of substantial CO2 change; however, these data are typically under-used in the process of model development and evaluation. Here, we use a set of metrics based on paleoclimate proxy observations to evaluate climate models under three past time periods. We find that the latest CMIP6/PMIP4 ensemble mean does a remarkably good job of simulating the global mean surface air temperatures of these past periods, and is improved on CMIP5/PMIP3, implying that the modern climate sensitivity of the CMIP6/PMIP4 model ensemble mean is consistent with the paleoclimate record. However, some models, in particular those with very high or very low climate sensitivity, simulate paleo temperatures that are outside the uncertainty range of the paleo proxy temperature data; in this regard, the paleo data can provide a more stringent constraint than data from the historical record. There is also consistency between models and data in terms of polar amplification, with amplification increasing with increasing global mean temperature across all three time periods. The work highlights the benefits of using the paleoclimate record in the model development and evaluation cycle, in particular for screening models with too-high or too-low climate sensitivity across a range of CO2 concentrations.

The construction of ultra-wide working face is helpful to promote the safe and efficient mining of coal resources. However, due to the limitation of roadway space and construction conditions, the detection depth of conventional mine geophysics is limited, and the geological information inside the ultra-wide working face and within a certain range of roof and floor cannot be accurately obtained. In order to improve the detection accuracy of the water rich area on the bottom plate of the ultrawide working face and provide a basis for the processing and interpretation of measured data, based on the summary and analysis of current mine geophysical detection technology, the three-dimensional(3D) DC resistivity method that can be applied to the detection of the ultrawide working face, combined with the occurrence characteristics of limestone water on the bottom plate of the working face 21106 in a coal mine in Yongcheng, Henan, was systematically studied using a combination of theoretical analysis, numerical simulation, and measured data to study the data characteristics and resolution ability of 3D observation and 2D observation modes. The research results show that: Compared with the traditional two-dimensional observation mode of the same side transmitter-receiver, the three-dimensional observation mode of the opposite side transmitter-receiver is more sensitive to the low resistance body on the floor of the mining face. The data obtained by the three-dimensional observation mode of the opposite side transmitter-receiver are calculated by the conventional apparent resistivity formula, the obtained apparent resistivity is sometimes opposite to the actual electrical property, so it is necessary to use the three-dimensional inversion method for data processing. Finally, the 3D model data observed during the 21106 work in a coal mine in Yongcheng, Henan Province was subjected to 3D inversion processing, and the reliability of the 3D inversion results was verified through underground drilling data. The research results provide a theoretical basis for the two-dimensional observation and three-dimensional observation data interpretation of the pole-pole device conditions.

Network assisted with reconfigurable intelligent surface is a kind of low-cost and low-power solution which can provide stable, continuous and ubiquitous connection to satisfy deep coverage requirements in 5G-Advanced (5G-A) and 6G era. A kind of reconfigurable intelligent surface assisted high and low frequency collaborative network architecture based on the positioning analysis of reconfigurable intelligent surface technology was proposed. The proportion of base station and reconfigurable intelligent surface collaborative deployment was analyzed. Furthermore, a interference reduction based on bandwidth design scheme was proposed to reduce adjacent frequency interference. System level performance simulation of network assisted with reconfigurable intelligent surface was verified to analyze the impact of reconfigurable intelligent surface deployment location and number of array elements under different UE distribution conditions. The simulation results show that the RIS-assisted network can significantly improve the edge and weak coverage area, so as to improve the network performance of the whole communication system.

At present, the combination of edge computing and machine vision has a good application prospect for coal mine safety monitoring. But the storage space and computing resources at the edge are limited, and high-precision complex visual models are difficult to deploy on it. In order to solve the above problems, a YOLOv5s pruning method based on indirect and direct evaluation space fusion (IDESF) is proposed for the edge end of coal mine safety monitoring, aiming to achieve lightweight YOLOv5s network. Firstly, a structural analysis is conducted on the convolutional layers of each module in the YOLOv5s network to determine the free pruning layer and conditional pruning layer. It lays the foundation for subsequent allocation of pruning rates and calculation of the number of pruning kernels. Secondly, the pruning rate is assigned to the prunable layers according to the convolutional kernel weight importance score based on the convolutional kernel weight magnitude and the relative computational complexity of the layers, which effectively reduces the computational complexity of the network after pruning. Thirdly, based on the direct importance evaluation criterion of convolutional kernels, the indirect output importance of convolutional layers is introduced into the direct importance space in the form of scaling factors. The position distribution of convolutional kernels is updated to construct a fused importance evaluation space that includes the output information and amplitude information of convolutional kernels. It thereby improves the comprehensiveness of convolutional kernel importance evaluation. Finally, drawing on the idea of topk voting, the process of median filtering for screening redundant convolution kernels is optimized. The method quantifies the degree of redundancy of a convolutional kernel in terms of the incidence of nodes in the adjacency matrix of a directed graph, which improves the interpretability and generality of the redundant convolutional kernel screening process. The experimental results show the following points. ① From the perspective of balancing model precision and lightweighting, YOLOV5s_IDESF with a pruning rate of 50% is the optimal lightweight YOLOv5s. On the VOC dataset, YOLOv5s_IDESF mAP@.5 and mAP@0.5 is the highest, reaching 0.72 and 0.44 respectively. The parameter count is reduced to a minimum of 2.65×106, the computational complexity is reduced to 1.16×109, and the overall complexity is also reduced to the lowest. The image processing frame rate reaches 31.15 frames per second. ② On the coal mine dataset, YOLOv5s_IDESF mAP@.5 and mAP@0.5∶0.95 achieve the highest values of 0.94 and 0.52, respectively. The parameter count is reduced to a minimum of 3.12×106, the computational complexity is reduced to 1.24×109, and the overall complexity is also minimized. The image processing frame rate reaches 31.55 frames per second.

The high-end equipment industries in the fields of aerospace， energy， petrochemical， shipbuilding， rail transportation， new energy vehicles， energy conservation and environmental protection， and electronic information have developed strongly， putting forward higher requirements for the quality and performance of special steel and special alloy materials， and the demand has surged. Therefore， in recent ten years， China's special metallurgy industry has been rapidly development. This paper first analyzes and summarizes the new requirements of ultra-high strength steel， supper alloy， corrosion resistant alloy， heat resistant steel， special stainless steel， high performance bearing steel， tool and die steel and precision alloy for the above-mentioned high-end equipment manufacturing. Secondly， the development status and trend of traditional special metallurgical processes and several new special metallurgical processes are analyzed. It is emphasized that the combination with basic oxygen furnace/electric arc furnace steelmaking process can provide high clean consumable electrode for electroslag remelting and vacuum arc remelting， and can also provide pure raw material for vacuum induction furnace. The short process of the electroslag remelting with continuous casting billet as the consumable electrode can significantly improve the production efficiency and reduce the production cost. At the same time， the duplex process of high nitrogen stainless steel smelting and the process flow of powder metallurgy and spray forming of tool and die steel are also briefly introduced. Third， China's special metallurgical industry development status， as well as the progress of new technology and new equipment have been summarized. Finally， suggestions and prospects for the technical development of special metallurgy in China in the next ten years are put forward.

Distributed computing systems based on cloud-edge-device have been successfully serving thousands of applications and have become mainstream, characterized by a wide audience, high user experience requirements, and high security expectations. However, in recent years, frequent attacks on cloud-edge-device systems have resulted in serious security risks and significant economic losses for users. The defense mechanisms of cloud-edge-device systems have been found to operate independently, leading to major differences in the ability to resist risks, which makes it difficult to eliminate global security risks. Security measures of the pre-configuration and post-event remedy type have been found to hardly meet the security needs of high-load and high real-time in cloud-edge-device collaborative networks. The root cause has been identified as the hierarchical architecture of cloud-edge-device systems being separate, and no effective collaborative defense system has been formed, leading to problems such as difficult cross-domain security governance, poor real-time performance, and difficult collaborative consistency evaluation. Firstly, a cloud-edge-device collaborative security architecture that integrates real-time perception, dynamic decision, and proactive defense was proposed. The cloud-edge-device security collaboration capability was established through rigorous theoretical consistency proofs. Secondly, a collaborative security assessment model based on the order parameter was put forward to achieve consistency of risk perception, decision, and defense. In this way, the efficient and low-cost collaborative protection of security risks could be realized to maximize systemic security benefits. Finally, the consistency theory and assessment method were verified through simulations. The results show that the proposed collaborative security system and consistency evaluation model are correct and effective.

ObjectiveTo establish a rapid， accurate， and sensitive multiplex PCR detection method for the simultaneous identification of the six common edible meats （beef， lamp， chicken， pork， goose， duck）， and to evaluate its application value in meat adulteration identification.MethodsBased on complete mitochondrial genomic sequences of six species in the GenBank database， DNA sequences （cattle： 16S rRNA; sheep： COX-1; chickens： Cytb; pig： COX-1; goose： NADH2; duck： 16S rRNA） with intra-species conservation and inter-species specificity were screened， and species-specific primers were designed to construct a multiplex PCR detection system that can simultaneously detect the meat of six common species. The species specificity， sensitivity and reproducibility of the system were studied, and the simulated mixture sample detection was performed.ResultsThis study successfully constructed a multiplex PCR detection system that can detect the meats of six common species simultaneously. The system was not effective in DNA amplification of non-target species. When the DNA template sizes were 0.062 5-2 ng/μL， the amplified products of all six species could be detected. The duck component was still detected when the mixing ratio of duck and beef was as low as 0.5%.ConclusionThis study constructs and establishes a multiplex PCR detection system with strong specificity， high sensitivity， and good reproducibility. It can accurately identify the components of animal origin in common edible meats and provide a simple and practical method for identifying adulteration of common edible meats and meat products in China.

Manganese is an indispensable trace element in the human body, pivotal in development, reproduction, metabolism, neurological functions, and antioxidative processes. Recently, the important role of manganese in host immunity has been increasingly recognized and valued. Serving as a damage-associated molecular pattern, manganese exhibits robust immune activation capabilities. Manganese ions stimulate cells to generate numerous cytokines, including type Ⅰ interferons, regulating both innate and adaptive immune responses, thus showing great potential in adjuvant and tumor immunotherapy. In this review, the homeostatic regulation of Manganese and its role in the immune response are summarized. Subsequently, it extensively explores diverse applications of manganese and its derivatives in immune adjuvants and tumor immunotherapy, and looks ahead to their future prospects.

Abstract [Objective] The Northern Hengduan Mountains are rich in biodiversity. Over the last 10 years, there have been many reports of the biodiversity of the region. The team conducted a survey of plant diversity and vegetation structure in Northern Hengduan Mountains from June to August 2023. [Methods] Through field investigation and collection and photograph of plants, as well as preparing, classifying, and identifying specimens. [Results] Eight newly recorded species were reported from Chaya of Changdu in the Northern Hengduan Mountains in Xizang. They were Ephedra minuta Florin (Ephedraceae), Caragana korshinskii Kom. (Fabaceae), Rhododendron luhuoense H. P. Yang (Ericaceae), R. orthocladum var. longistylum Philipson et M. N. Philipson (Ericaceae), R. thymifolium Maxim. (Ericaceae), R. nivale Hook. f. subsp. australe Philipson et M. N. Philipson (Ericaceae), Artemisia capillaris Thunb. (Asteraceae), and Chenopodiastrum gracilispicum (H.W.Kung) Uotila (Amaranthaceae) [Conclusion] The discovery of the newly distributed plants is an important supplement for the flora of the Hengduan Mountains in Xizang. The voucher specimens are stored in the herbarium of Yibin University

The development of advanced nuclear energy systems imposes stringent requirements on the service stability of nuclear materials under extreme environments characterized by multiple stressors. Continuous silicon-carbide-fiber-reinforced silicon carbide (SiCf/SiC) ceramic matrix composites possess advantages such as low density, excellent high-temperature mechanical properties,corrosion resistance, and irradiation tolerance. Furthermore, SiCf/SiC composites demonstrate a pseudo-ductile fracture behavior under external forces, positioning them as highly promising structural materials for advanced nuclear energy systems. This study systematically summarizes the fundamental research framework on nuclear-grade SiCf/SiC composites at the material, component,and service performance levels. It also analyzes the developmental trends in this field among traditional nuclear powerhouses such as the United States, France, and Japan, as well as in other emerging nuclear energy countries and China. Furthermore, the study identifies existing issues and challenges faced by China’s nuclear-grade SiCf/SiC sector in terms of raw materials, data accumulation,and patent standards, and proposes targeted measures and suggestions: (1) strengthening the research and development of material preparation technologies, (2) developing a new paradigm of research and development, (3) reinforcing the industry-universityresearch-application cooperation, and (4) enhancing international exchanges on the basis of maintaining independence. The aim of the study is to provide guidance and reference for the research directions and policy-making in China’s nuclear-grade SiCf/SiC sector.

Abstract As a typical failure phenomenon in transformers, sulfur corrosion has garnered significant attention in the field of high‐voltage engineering. Grain boundary character distribution (GBCD) copper windings have been introduced to enhance sulfur corrosion resistance by slowing down intergranular corrosion. In this study, the sulfur corrosion behaviour and mechanisms of the GBCD copper windings under various temperatures were experimentally and theoretically studied. Results show that GBCD can enhance the corrosion resistance of copper in liquid environments. With the increase in temperatures, the insulating properties of oil and papers in traditional copper windings experience notable degradation, while GBCD copper windings show more stable insulating behaviours. In addition, modelling of grain boundary energy indicates that the grain boundary structure of GBCD copper windings has a lower average interface energy of 0.170 eV/Å2. Calculations of reaction thermodynamics show that GBCD copper windings possess a higher failure temperature (135.2°C) and inhibition degree (activation energy) of the sulfur corrosion (32,557.62 J/mol), revealing the stability and enhanced sulfur corrosion resistance at elevated temperatures.

Abstract High-quality ocean in situ profile observations are fundamental for ocean and climate research and operational oceanographic applications. Here we describe a new global ocean subsurface temperature profile database named the Chinese Academy of Science (CAS) Oceanography Data Center version 1 (CODC-v1). This database contains over 17 million temperature profiles between 1940–2023 from all available instruments. The major data source is the World Ocean Database (WOD), but CODC-v1 also includes some data from some Chinese institutes which are not available in WOD. The data are quality-controlled (QC-ed) by a new QC system that considers the skewness of local temperature distributions, topographic barriers, and the shift of temperature distributions due to climate change. Biases in Mechanical Bathythermographs (MBTs), eXpendable Bathythermographs (XBTs), and Bottle data (OSD) are all corrected using recently proposed correction schemes, which makes CODC-v1 a bias-corrected dataset. These aspects ensure the data quality of the CODC-v1 database, making it suitable for a wide spectrum of ocean and climate research and applications.

Objective The large section tunnel, due to flat shape and large span, usually adopts multiple steps and staged excavation. In the process of construction, the surrounding rock and the temporary support are repeatedly disturbed, affecting the stability of surrounding rock and supporting structure. Therefore, the deformation characteristics of the surrounding rock should be studied and the construction scheme should be optimized. Method Taking the mined tunnel of Qingdao Metro Line 4 in turn-back section as the example, based on the on-site monitoring data and using finite element simulation, the deformation characteristics of the surrounding rock in the excavation process of the large-section metro tunnel with three-step and nine-stage method are analyzed, and then compared with the optimized three-step and five-stage method. Result & Conclusion The simulation results show that the ground settlement is relatively large caused by the current construction scheme within the horizontal distance of 26m from the tunnel center line, accounting for 89.77% of the total settlement. The arch and the spandrel deform are large after excavation, and the maximum settlement reaches 102 mm. The stress of the surrounding rock of the arch increases rapidly with excavation. As the excavation advances, the local principal stress concentration appears in the upper part of the haunch and the corner. The optimized three-step and five-stage excavation method can realize rapid excavation and support, and simplify the construction process by 40%, while reducing disturbance to the surrounding rock and controlling its deformation within a reasonable range of 10 mm. Thus, the stress redistribution of the arch and the stress concentration in the corner are improved.

Objective The health of metro communication system has a direct bearing on the efficiency and safety of metro operation. In view of the problems such as one-sided evaluation results and subjective evaluation criteria in current health evaluation method for metro communication systems, it is necessary to construct a method that can scientifically and accurately evaluate the operation status and health of the metro communication system. Method A dynamic health evaluation method based on random forests algorithm is proposed, and a communication health inspection is conducted in combination with deep learning. The evaluation index system is designed to collect the corresponding data. The mixed label method is used to determine the label and calculate the importance of each index when the label (true health degree) is not clear. The health degree of each subsystem of communication system is calculated according to the index weight and the index self scoring standards established by experts, which properly incorporates the influence of experts' knowledge. Based on the maintenance data of Chengdu Metro, the method is tested and verified. Result & Conclusion The test verification results show that with the above method, effective index importance can be obtained and the health of metro communication system can be reasonably evaluated.

With the increasing integration of renewable energy sources and the presence of numerous controllable loads such as electric vehicles and energy storage in the modern power system, higher nonlinearities and uncertainty both sources and loads are introduced. These factors pose challenges in achieving fast and accurate emergency frequency control. Therefore, this paper addresses the issue of dual source-load uncertainties in power system and presents an optimization strategy based on the Soft Actor Critic (SAC) algorithm that involves the participation of controllable loads in emergency frequency control. Firstly, the spatio-temporal uncertainties of wind farm power output on power supply side and power demand on the load side are described using Weibull and normal probability distributions, respectively. Secondly, an improved Markov Decision Process (MDP) model for emergency frequency control is established, which considers the characteristics of the dual source-load uncertainties. Finally, an optimization of the SAC algorithm is conducted based on Deep Reinforcement Learning (DRL), aiming to achieve rapid system frequency recovery and minimize the cost of removing controllable loads. The presented approach in the paper enhances the emergency frequency control strategy for uncertain power systems and effectively addresses the issue of source-load uncertainty compounded by fault power shortages.

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) has a dismal prognosis owing to its high aggressiveness, rapid drug resistance, and early metastasis. ES-SCLC responds well to first-line chemotherapy, and chemotherapy coupled with immunotherapy can further improve overall survival. However, the long-term survival of patients remains unsatisfactory because of its high recurrence rate and the poor efficacy of second-line treatment. Although local radiotherapy is an important component of the overall treatment for ES-SCLC, its value in the age of immunotherapy remains controversial.Case descriptionA 54-year-old male with ES-SCLC achieved a complete response (CR), as determined using enhanced computed tomography (CT) after four cycles of immunochemotherapy (serplulimab, carboplatin, and etoposide). Whole-body positron emission tomography-CT was performed during maintenance treatment with serplulimab, which showed primary lung, liver, and bone metastatic lesions with CR. However, several mediastinal lymph nodes exhibited glucose metabolism uptake, and new lesions appeared on the head. The patient underwent palliative radiotherapy of the head and consolidative thoracic radiotherapy of the chest and continued maintenance treatment with serplulimab. Subsequent magnetic resonance imaging of the head suggested good control of metastatic lesions (CR). The patient received first-line immunotherapy for approximately 20 months.ConclusionsThis report presents a patient with ES-SCLC who underwent local radiotherapy in addition to serplulimab as maintenance therapy. Although the programmed death-ligand 1 (PD-L1) expression level was negative and a PD-1 inhibitor instead of a PD-L1 inhibitor was used, the patient did not experience significant pneumonia during treatment, and the efficacy of the current treatment was evident. This treatment model warrants further clinical investigation.

BackgroundCystic Echinococcosis (CE) is a zoonotic disease causing fibrosis and necrosis of diseased livers caused by infection with Echinococcus granulosus (E.g). There is evidence that E.g is susceptible to immune escape and tolerance when host expression of immunoinflammation and fibrosis is suppressed, accelerating the progression of CE. Ghrelin has the effect of suppressing immunoinflammation and fibrosis, and whether it is involved in regulating the progression of E.g-infected liver lesions is not clear.MethodsSerum and hepatic Ghrelin levels were observed in E.g-infected mice (4, 12 and 36 weeks) and compared with healthy control groups. Co-localization analysis is performed between protein expression of Ghrelin in and around the hepatic lesions of E.g-infected 12-week mice and protein expression of different hepatic histiocytes by mIHC. HepG2 cells and protoscoleces (PSCs) protein were co-cultured in vitro, as well as PSCs were alone in vitro, followed by exogenously administered of Ghrelin and its receptor blocker, [D-Lys3]-GHRP-6, to assess their regulatory effects on immunoinflammation, fibrosis and survival rate of PSCs.ResultsSerum Ghrelin levels were increased in E.g-infected 4- and 12-week mice, and reduced in 36-week mice. E.g-infected mice consistently recruited Ghrelin in and around the hepatic lesions, which was extremely strongly co-localized with the protein expression of hepatic stellate cells (HSCs), T cells and the TGF-β1/Smad3 pathway. The secretion of Ghrelin was increased with increasing concentrations of PSCs protein in HepG2 cells culture medium. Moreover, Ghrelin could significantly inhibit the secretion of IL-2, INF-γ and TNF-α, as well as the expression of Myd88/NF-κB and TGF-β1/Smad3 pathway protein, and promoted the secretion of IL-4 and IL-10. Blocking Ghrelin receptor could significantly inhibit PSCs growth in in vitro experiment.ConclusionGhrelin is highly expressed in the early stages of hepatic E.g infection and may be involved in regulating the progression of liver lesions by suppression immunoinflammation and fibrosis.

Adenomatoid tumors are rare, specific, benign tumors of the reproductive tract that originate from mesenchymal tissue. A patient was diagnosed with uterine fibroids 1 year previously when a mass of approximately 30 mm was found in the left adnexal region during a physical examination. At 1 year of follow-up, ultrasound showed that the mass in the left adnexal area had greatly increased to 61 × 45 × 50 mm. Contrast-enhanced pelvic magnetic resonance imaging (MRI) was performed before surgery and suggested a borderline tumor. Histopathology suggested signet ring cell carcinoma, and an immunohistochemical examination suggested a uterine adenomatoid tumor. Our suspicion of a borderline tumor was based mainly on the following features: the mass had increased in size within 1 year, the cancer antigen 125 concentration had increased, and several lymph nodes in the pelvic and groin regions showed positive signals on MRI enhancement. Uterine adenomatoid tumors are challenging to diagnose, especially adenomatosis with signet ring cells. However, the accuracy of diagnosing this disease can be greatly improved by combining ultrasound and MRI. This article describes the most comprehensive and reliable imaging features of ultrasound and MRI, which play an important role in diagnosing uterine adenomatoid tumors and provide useful information for clinicians.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, affecting millions of people worldwide. Due to the complexity and variability of the disease, there are major challenges in the treatment of HCC in its intermediate and advanced stages; despite advances in various treatment modalities, there are still gaps in our understanding of effective therapeutic strategies. Key findings from several studies have shown that the combination of immunotherapy and targeted therapy has a synergistic anti-tumor effect, which can significantly enhance efficacy with a favorable safety profile. In addition, other studies have identified potential biomarkers of therapeutic response, such as tumor protein 53 (TP53) and CTNNB1 (encoding β-conjugated proteins), thus providing personalized treatment options for patients with intermediate and advanced hepatocellular carcinoma. The aim of this article is to review the recent advances in the treatment of intermediate and advanced HCC, especially targeted immune-combination therapy, chimeric antigen receptor T cell therapy (CAR-T cell therapy), and gene therapy for these therapeutic options that fill in the gaps in our knowledge of effective treatment strategies, providing important insights for further research and clinical practice.

Abstract The link between mantle plumes and the formation of large igneous provinces (LIPs) is well established although the anatomy of these remains equivocal. Recent experimental studies and geophysical data suggest that the mantle plume head is more likely to be irregular and asymmetric, rather than an axisymmetric flattened disk. The Emeishan large igneous province (ELIP) provides a unique opportunity to test this hypothesis. According to robust petrographic, geochronologic, and geochemical evidence from the late Permian basalts in the Sichuan Basin, and in conjunction with a comprehensive compilation of geologic maps and published geochemical data from the ELIP, we identified several giant radial “fingering” structures. Based on the shallow mantle source from the center to margin in the ELIP and relief of the lithosphere‐asthenosphere boundary, we propose a new mantle plume model to explain the evolution of the Emeishan plume periphery, where narrow finger‐like protrusions and plumelets developed outwards from the main body of the plume to the edges of the flattened plume head. Dragged fingers might have been torn apart into some plumelets, which dispersed and were trapped beneath the thinnest lithosphere relief, and eventually erupted to form small‐scale flood basalt in the Outer Zone of the ELIP.

Abstrat: The nuclear factor-κB (NF-κB) signalling pathway exists in a variety of cells and is involved in the gene regulation of various physiological and pathological processes such as inflammation, immunity, cell proliferation and apoptosis. It has been shown that this signaling pathway is also involved in numerous events associated with osteoarthritis, including chondrocyte catabolism, chondrocyte survival, and synovial inflammation. SRY-related high mobility group-box 9(SOX9) is the “master regulator” of chondrocytes and one of the key transcription factors that maintain chondrocyte phenotype and cartilage homeostasis. NF-κB can positively regulate the expression of SOX9 by directly binding to its promoter region, and play a role in the formation and development of chondrocytes. This article reviews the regulatory effect of the NF-κB-SOX9 signaling axis on osteoarthritis.