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Abstract This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

The increasing frequency of cervical and lumbar spine disorders, driven by aging and evolving lifestyles, has led to a rise in spinal surgeries using pedicle screws. Robotic spinal surgery systems have emerged as a promising innovation, offering enhanced accuracy in screw placement and improved surgical outcomes. We focused on literature of this field from the past 5 years, and a comprehensive literature search was performed using PubMed and Google Scholar. Robotic spinal surgery systems have significantly impacted spinal procedures by improving pedicle screw placement accuracy and supporting various techniques. These systems facilitate personalized, minimally invasive, and low‐radiation interventions, leading to greater precision, reduced patient risk, and decreased radiation exposure. Despite advantages, challenges such as high costs and a steep learning curve remain. Ongoing advancements are expected to further enhance these systems' role in spinal surgery.

Abstract The basic idea of modulating the immune system to better recognize and fight tumor cells has led to the successful introduction of adoptive cellular immunotherapy (ACT). ACT-based treatment regimens, in which the patient's own immune cells are isolated and subsequently expanded (ex vivo) and reinfused, have also contributed significantly to the development of a personalized treatment strategy. Complementing this, the unprecedented advances in ACTs as chimeric antigen receptor (CAR)-T cell therapies and their derivatives such as CAR-NK, CAR-macrophages, CAR-γδT and CAR-NKT have further maximized the therapeutic outcomes. Herein, we provide a comprehensive overview of the development of ACTs in multiple myeloma (MM) and outline how they have evolved from an experimental form to a mainstay of standard clinical settings. Besides, we provide insights into cytokine-induced killer cell (CIK) therapy, an alternative form of ACT that (as CIK or CAR-CIK) has enormous potential in the clinical spectrum of MM. We also summarize the results of the major preclinical and clinical studies of adoptive cell therapy in MM and address the current challenges (such as cytokine release syndrome (CRS) and neurotoxicity) that limit its complete success in the cancer landscape.

Abstract Study design Retrospective cohort study. Purpose To explore the complications and risk factors for total resection (TR) of primary thoracic and lumbar spinal tumors over the past decade at our institution. Methods Patients meeting inclusion criteria (primary spinal tumors, thoracic or lumbar location, TR at our center) were included. Demographic characteristics, surgical data, perioperative complications and management results were reviewed. Patients were stratified by tumor site, the number of excised segments, and recurrence status to elucidate distinctive characteristics. Results The cohort comprised 103 patients, with a mean age of 35.8 years. On average, 1.83 vertebral segments were resected per patient. Perioperative complications were substantial, totaling 166 events, with 71 classified as major and 95 as minor, yielding an average of 1.61 complications per patient. No perioperative deaths occurred, but 79 patients (76.7%) experienced at least one complication. Multiple vertebral sections correlated with a higher complication rate (P = 0.031), and lumbar surgeries exhibited elevated risks of large vascular injury (P = 0.001), neurological deterioration, and cerebrospinal fluid leakage compared to thoracic cases. Conversely, thoracic spinal procedures showed a higher rate of pleural effusion (P = 0.004). Binary logistics stepwise regression identified multi-segmental resection as the independent risk factor for major perioperative complications. Conclusions TR of primary spinal tumors is associated with a high perioperative complication rate, although most events have a favorable prognosis. Complication characteristics vary based on the surgical site, number of excised segments, and surgical history. A nuanced preoperative evaluating approach considering patient age, surgical segments, and extent of resection is crucial.

Abstract The epidermal infiltration of neutrophils is a hallmark of psoriasis (PSO) and its activation leads to the release of neutrophil extracellular traps (NETs). However, the molecular mechanism of NETs-related genes (NETRGs) has not been extensively studied in PSO. To define NETs-related-biomarkers for PSO. The GSE13355 and GSE78097 datasets, and NETRGs gene set were included in this study. The datasets used in this study were all microarray data. The weighted gene co-expression network analysis (WGCNA) and machine learning algorithms were used to mine key genes. Later on, single-gene gene set enrichment analysis (GSEA) and immune infiltration analysis were implemented. Finally, the expression of key genes was verified using quantitative real-time fluorescence PCR (qRT-PCR). A total of 3 key genes (S100A9, CLEC7A, and CXCR4) were derived, and they all had excellent diagnostic performance. The single-gene GSEA enrichment results indicated that the key genes were mainly enriched in the chemokine signaling pathway and humoral immune response in the high-expression group, while focal adhesion was enriched in the low-expression group. The correlation analysis indicated that all key genes were strongly negatively correlated with resting mast cells and TGF-β family member receptor, while they were strongly positively correlated with activated CD4 memory T cells and antigen processing and presentation. Lastly, the experimental results showed that the expression trends of key genes were consistent with public database. In this study, we successfully screened three potential PSO diagnostic genes (S100A9, CLEC7A and CXCR4) that were closely related to NETs, and these findings not only provided new molecular marker candidates for the precise diagnosis of PSO patients, but also revealed possible future therapeutic targets. However, further in-depth research and validation were necessary.

To reveal the effects of milling methods on the physicochemical properties of rice flour and the qualities of fresh rice noodles, the rice was treated by dry, semi-dry, and wet milling methods and the resultant products were utilized to produce fresh rice noodles. The basic chemical components, the damaged starch rate, the size distribution, the morphology, the solubility and swelling power, and the pasting properties of the rice flour, as well as the texture, cooking, and sensory qualities of fresh rice noodles, were investigated. The obtained results suggested that the rice flour produced by drying methods with a 300 mesh had the highest damaged starch rate (17.55%) and solubility, smallest particle size, peak viscosity, final viscosity, and setback viscosity. By contrast, the rice flour produced from wet milling methods showed the lowest damaged starch rate (2.87%) and solubility, and the highest peak viscosity, final viscosity, and setback viscosity. Increasing the moisture content during the semi-dry milling treatment, the damaged starch rate of the rice flour decreased from 4.49% to 3.55%, and similar trend was observed for particle size distribution and solubility. Scanning electron microscopy suggested that the lower damaged starch rate, the more intact structure of the rice flour. The fresh rice noodles made from wet milling flour showed the best cooking qualities, and the cooking qualities of semi-dry milled flour-made and semi-soaking milled flour-made fresh noodles were close to those of wet milled flour-made fresh rice noodles while the rice flour produced from dry milled method was not suitable for making fresh rice noodles. The semi-dry and semi-soaking milled rice flour can replace the wet milled rice flour for the preparation of rice noodles during the practical production process. The findings in this study may assist the revolution for the traditional production of rice noodles.

Context The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer’s disease (AD) remains unknown.Objective This study investigates the effects and mechanism of RSSW for ameliorating AD.Materials and methods Ten SAMR1 mice and 40 SAMP8 mice were divided into five groups: control (SAMR1), model (SAMP8), positive drug (Donepezil, 1.3 mg/kg/d), and RSSW (Low-dose, 117 mg/kg/d; High-dose, 234 mg/kg/d). Starting from 6 months of age, the medications were administered intragastrically for a total of 60 days. Subsequently, memory improvement in rapidly aging mice was assessed using the novel object recognition test and Morris water maze test. Through the identification of absorbed blood components and analysis of network pharmacology, active ingredients and potential targets involved in the treatment of AD were identified. Finally, AD-related biological indicators were detected using western blotting and ELISA.Result Our results demonstrated that RSSW effectively ameliorated memory impairments, inhibited tau hyperphosphorylation, and reduced β-amyloid plaque deposition in SAMP8 mice. Thirty absorbed blood components in RSSW were identified, revealing identified 96 major targets that play a key role in alleviating AD. Notably, the obtained main targets were highly enriched in SIRT1-mediated signaling pathways. Subsequent experimental validation confirmed that RSSW activated the SIRT1/NF-κB, SIRT1/AMPK, and SIRT1/p53 signaling cascades. Nine potential active ingredients were predicted through molecular docking.Discussion and conclusions Our research findings suggest the mechanism of RSSW treatment for AD, which ameliorates memory impairments by reducing cortical tissue inflammation and apoptosis.

Abstract The primary aim of this investigation was to leverage radiomics features derived from contrast-enhanced abdominal computed tomography (CT) scans to devise a predictive model to discern the benign and malignant nature of intraductal papillary mucinous neoplasms (IPMNs). Radiomic signatures were meticulously crafted to delineate benign from malignant IPMNs by extracting pertinent features from contrast-enhanced CT images within a designated training cohort (n = 84). Subsequent validation was conducted with data from an independent test cohort (n = 37). The discriminative ability of the model was quantitatively evaluated through receiver operating characteristic (ROC) curve analysis, with the integration of carefully selected clinical features to improve the comparative analysis. Arterial-phase images were utilized to construct a model comprising 8 features for distinguishing between benign and malignant cases. The model achieved an accuracy of 0.891 [95% confidence interval (95% CI), 0.816–0.996] in the cross-validation set and 0.553 (95% CI 0.360–0.745) in the test set. Conversely, employing 9 features from the venous-phase resulted in a model with a cross-validation accuracy of 0.862 (95%CI 0.777–0.946) and a test set accuracy of 0.801 (95% CI 0.653–0.950).Integrating the identified clinical features with imaging features yielded a model with a cross-validation accuracy of 0.934 (95% CI 0.879–0.990) and a test set accuracy of 0.904 (95% CI 0.808–0.999), thereby further improving its discriminatory ability. Our findings distinctly illustrate that venous-phase radiomics features eclipse arterial-phase radiomic features in terms of predictive accuracy regarding the nature of IPMNs. Furthermore, the synthesis and meticulous screening of clinical features with radiomic data significantly increased the diagnostic efficacy of our model, underscoring the pivotal importance of a comprehensive and integrated approach for accurate risk stratification in IPMN management.

IntroductionUnder the background of digitalization of traditional Chinese medicine (TCM), this study aimed to realize the digital identification and adulteration analysis of Codonopsis Radix (CR) and Stellariae Radix (SR) based on chemical analysis.MethodsThis study combined digitalization concepts and chemical analysis and conducted a chemical analysis of CR and SR from different batches based on UHPLC-QTOF-MSE. Furthermore, the shared ions were extracted from different batches of CR and SR as their “ion characterization” after digital quantization. Then, the data matrices of unique ions of CR relative to SR and SR relative to CR were screened out, and the top-N ions were outputted as the “digital identities” of CR and SR, sorted by ionic strength. Finally, the above “digital identities” of CR and SR were used as benchmarks for matching positive samples and market samples to provide feedback on the matching credibility (MC) for identification and adulteration analysis.ResultsThe results showed that based on the “digital identities” of CR and SR, the digital identification of CR, SR, and positive samples can be realized at the individual level of TCM efficiently and accurately, even if 3% of SR in the mixed samples can still be identified efficiently and accurately. Moreover, 1 of the 12 batches of market samples was identified as an adulterated sample.ConclusionIt proved that the identification and adulteration analysis of two herbs can be realized efficiently and quickly through the “digital identities” of chemical compositions. It has important reference significance for developing the digital identification of CR and SR at the individual level of Chinese medicine based on the “digital identity” of chemical compositions, which was beneficial to the construction of digital quality control of CR and SR.

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.

ABSTRACT: Based on the data of China’s overseas arable land investment in 47 countries along the “Belt and Road”, the Tobit model is used to analyze the effects of cultural distance and friendship cities on the production rates of contracted arable land in China’s overseas arable land investment. This study provided theoretical basis and empirical support for promoting China’s agricultural “going abroad” and improving the production rates of contracted arable land in China’s overseas arable land investment. The results show that differences in cultural distance, power distance and the degree of uncertainty avoidance have significant positive effects on the production rates of contracted arable land in China’s overseas arable land investment, and differences in individualism have a significant negative effect on the production rates. Friendship city has a positive but insignificant effect on the production rates, meanwhile, it also weaken the positive impact of cultural distance on production rates of contracted arable land in China’s overseas arable land investment. The proportion of joint ventures with host country, the economic level and institutional environment of the host country will all have an impact on the production rates. Finally, recommendations are proposed to promote the production rates of contracted arable land, such as focusing on the positive role of cultural distance, establishing friendship cities, and investing host countries with high potential precisely.

ObjectivePolyenylphosphatidylcholine (PPC), a significant therapeutic agent for liver repair, exhibits potent antioxidant and anti-inflammatory properties. Nonetheless, its impact on hypertension and hypertensive vascular diseases requires clarification. Our objective was to elucidate the protective role and mechanism of PPC in a spontaneously hypertensive rat model.Materials and methodsMale WKY and SHRs were randomly assigned to four groups: WKY control, SHRs control, SHRs treated with Telmisartan (SHR-TS), and SHRs treated with PPC (SHR-PPC). Blood pressure was monitored biweekly during the treatment. Histological analyses assessed aortic vascular remodeling and cardiac and renal injuries. RNA-seq was performed on vascular smooth muscle cells (VSMCs) isolated from WKY or SHRs, and protein levels of target genes were quantified using Western blotting.ResultsIn a dose-dependent screening test, we confirmed that PPC (200 mg/kg/day) effectively reduced blood pressure in SHRs. Treatment with PPC also mitigated cardiac and renal injury in SHRs by attenuating hypertrophy and fibrosis. Compared to WKY rats, SHRs exhibited increased intima thickness, reduced vascular tone, and heightened aortic fibrosis; however, PPC treatment significantly reversed vascular remodeling. Analysis of RNA-seq data revealed that downregulated genes were enriched in inflammation and oxidative stress pathways based on GO and KEGG enrichment analyses. PPC markedly inhibited genes such as Rela, Relb, Nfkb2, and others involved in the NF-κB pathway. Given PPC's influence on glycerophospholipid synthesis and metabolism, and its role in NF-κB-mediated transcription affecting oxidative stress and inflammation, changes in the PLAs, PLPs, and PLPPs families were analyzed in PPC-treated VSMCs. Among these, PPC notably inhibited Plpp3. Importantly, overexpression of Plpp3 significantly reversed the protective effects of PPC on hypertension-related cardiac and renal injuries, vascular fibrosis, remodeling, and tension.ConclusionWe identified a new protective role for PPC in mitigating cardiac and renal injuries associated with hypertension, as well as in preventing aortic fibrosis and remodeling. Targeting the NF-κB/Plpp3 pathway may offer a promising therapeutic strategy for treating vascular diseases related to hypertension.

ABSTRACT: In the spring of 2023, 10 to 21-day-old chicks in a broiler duck farm in Shandong Province, China, developed swelling of the head and neck, moist eyes with mucous discharge, difficulty in walking, shrinking of the neck, and loose and disorganized coat. Anatomical observation revealed hemorrhages in the esophageal mucosa, myocardium, and liver, and severe hemorrhages in the trachea with copious inflammatory secretions. Soon after, similar symptoms appeared in a large number of ducks in the flock, which eventually led to the elimination of all the 20,000-odd newly introduced ducklings on the farm, resulting in huge economic losses. We detected duck plague virus in the tissues of liver, spleen and lungs of diseased and dead ducks, and successfully isolated the pathogenic strain, named SD423, by inoculating duck embryos and inoculating duck embryo fibroblasts. We successfully conducted animal regression experiments with the isolated strain, and the experimental animals in the 1 d of age group showed symptoms of swollen eyes and tearing, shrinking of the neck, crouching, and hemorrhage in organs such as the liver and intestines successively from the 3rd d. We sequenced the whole genome of the isolated duck plague strain, and by comparing the homology with the published duck plague virus whole sequences in Genbank, the virus strain obtained in this study had the highest homology with the Chinese virulent strain SD (MN518864.1), with nucleotide (nt) homology of about 99.90% and amino acid (aa) homology of about 99.75%, which indicated that the isolate is a virulent strain. Previously, it was reported that the natural infection of duck plague virus mainly occurs above 30 d of age, but the duck plague virus found in this study can naturally infect ducklings up to 20 d of age, and the mortality rate is as high as 100%. In this study, the pathogenicity test and whole genome sequence analysis of this isolate provided data support and theoretical basis for further research on pathogenicity and virulence-related gene analysis of duck plague virus.

ObjectiveThe traditional predictive control approach usually employs a fixed time horizon and often overlooks the impact of changes in curvature and road bends. This oversight leads to subpar tracking performance and inadequate adaptability of robots for navigating curves and paths. Although extending the time horizon of the standard fixed time horizon model predictive control (MPC) can improve curve path tracking accuracy, it comes with high computational costs, making it impractical in situations with restricted computing resources. Consequently, an adaptive time horizon MPC controller was developed to meet the requirements of complex tasks such as autonomous mowing.MethodsInitially, it was crucial to establish a kinematic model for the mowing robot, which required employing Taylor linearization and Euler method discretization techniques to ensure accurate path tracking. The prediction equation for the error model was derived after conducting a comprehensive analysis of the robot's kinematics model employed in mowing. Second, the size of the previewing area was determined by utilizing the speed data and reference path information gathered from the mowing robot. The region located a certain distance ahead of the robot's current position, was identified to as the preview region, enabling a more accurate prediction of the robot's future traveling conditions. Calculations for both the curve factor and curve change factor were carried out within this preview region. The curvature factor represented the initial curvature of the path, while the curvature change factor indicated the extent of curvature variation in this region. These two variables were then fed into a fuzzy controller, which adjusted the prediction time horizon of the MPC. The integration enabled the mowing robot to promptly adjust to changes in the path's curvature, thereby improving its accuracy in tracking the desired trajectory. Additionally, a novel technique for triggering MPC execution was developed to reduce computational load and improve real-time performance. This approach ensured that MPC activation occurred only when needed, rather than at every time step, resulting in reduced computational expenses especially during periods of smooth robot motion where unnecessary computation overhead could be minimized. By meeting kinematic and dynamic constraints, the optimization algorithm successfully identified an optimal control sequence, ultimately enhancing stability and reliability of the control system. Consequently, these set of control algorithms facilitated precise path tracking while considering both kinematic and dynamic limitations in complex environments.Results and DiscussionThe adaptive time-horizon MPC controller effectively limited the maximum absolute heading error and maximum absolute lateral error to within 0.13 rad and 11 cm, respectively, surpassing the performance of the MPC controller in the control group. Moreover, compared to both the first and fourth groups, the adaptive time-horizon MPC controller achieved a remarkable reduction of 75.39% and 57.83% in mean values for lateral error and heading error, respectively (38.38% and 31.84%, respectively). Additionally, it demonstrated superior tracking accuracy as evidenced by its significantly smaller absolute standard deviation of lateral error (0.025 6 m) and course error (0.025 5 rad), outperforming all four fixed time-horizon MPC controllers tested in the study. Furthermore, this adaptive approach ensured precise tracking and control capabilities for the mowing robot while maintaining a remarkably low average solution time of only 0.004 9 s, notably faster than that observed with other control data sets-reducing computational load by approximately 10.9 ms compared to maximum time-horizon MPC.ConclusionsThe experimental results demonstrated that the adaptive time-horizon MPC tracking approach effectively addressed the trade-off between control accuracy and computational complexity encountered in fixed time-horizon MPC. By dynamically adjusting the time horizon length the and performing MPC calculations based on individual events, this approach can more effectively handle scenarios with restricted computational resources, ensuring superior control precision and stability. Furthermore, it achieves a balance between control precision and real-time performance in curve route tracking for mowing robots, offering a more practical and reliable solution for their practical application.

Abstract Purpose To evaluate the perioperative clinical outcomes of en bloc resection and anterior column reconstruction for thoracolumbar spinal tumors. Methods This study conducted a retrospective analysis of prospective data collection of 86 consecutive patients, including 40 males and 46 females, with an average age of 39 years (ranged from 10 to 71 years). There were 35 cases of a malignant primary tumor,42 cases of an aggressive benign tumor, and nine cases of metastases. The main lesions were located in 65 cases of thoracic spine, 17 cases of lumbar spine, and 4 cases of thoracolumbar spine. Tumors involved one level in 45 patients, two levels in 12 patients, three levels in 21 patients, four levels in five patients, five levels in two patients, and six levels in one patient. Results According to the Weinstein-Boriani-Biagini surgical staging system, all patients achieved en bloc resections, including 74 cases of total en bloc spondylectomy and 12 cases of sagittal resections. The mean surgical time was 559 min (210–1208 min), and the mean total blood loss was 1528 ml (260–5500 ml). A total of 122 complications were observed in 62(72.1%) patients, of which 18(20.9%) patients had 25 major complications and one patient (1.2%) died of complications. The combined approach (P = 0.002), total blood loss (P = 0.003), staged surgery (P = 0.004), previous surgical history (P = 0.045), the number of involved vertebrae (P = 0.021) and lumbar location (P = 0.012) were statistically significant risk factors for major complication. When all above risk factors were incorporated in multivariate analysis, only the combined approach (P = 0.052) still remained significant. Conclusions En bloc resection and anterior column reconstruction is accompanied by a high incidence of complications, especially when a combined approach is necessary.

Abstract Background En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. Methods Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. Results Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). Conclusions The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Objective Re‐resection of spinal giant cell tumors is an exceedingly difficult procedure. Moreover, the prognosis of patients with en bloc resection or intralesional excision for re‐resection has rarely been reported. This study aimed to compare the prognostic value of en bloc resection with that of intralesional excision in patients undergoing re‐resection for giant cell tumors of the spine. Methods This retrospective analysis evaluated patients who underwent revision surgeries for relapse of giant cell tumors of the spine at our center between January 2005 and January 2021. Local progression‐free survival represents the duration between en bloc resection or intralesional excision and tumor recurrence. Neurological recovery, survival rates, local control, and complications were evaluated. The Kaplan–Meier estimator was used for survival analysis. Results A total of 22 patients (nine men and 13 women) with a mean age of 34.1 (range 19–63) years were included. Significant statistical differences were found in the local tumor recurrence rate between patients treated with en bloc resection and those treated with intralesional excision (p

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%–77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

IntroductionVerticillium dahliae, a soil-borne fungal pathogen, can cause cotton Verticillium wilt. In this study, VdP5CDH, the member of the ALDH_F4-17 family of carboxylate dehydrogenases, was identified in the genome of V. dahliae and investigated function in regulating virulence by generating gene deletion mutants and complementary mutants.MethodsHomologous recombination method was used to construct mutants, transcriptome sequencing revealed gene-related metabolic pathways, and disease degree of cotton was observed through pathogen infection experiments.ResultsThe conidial surface of VdP5CDH deletion strains was dented and shriveled, and the number of conidial spores increased. Compared with the wild-type (WT), the mycelial diameter of deletion mutants increased by 10.59%-11.16%, the mycelial growth showed irregular branching patterns, and misaligned arrangement. Although capable of penetrating cellophane, deletion mutants were unable to produce melanin. VdP5CDH was mainly associated with glucose metabolism, nitrogen metabolism, ABC transporter activity as well as various amino acid metabolic processes. After gene knockout, raffinose and pectin were used as the main carbon sources to promote the growth of strains and the growth rate of deletion strains in the medium containing raffinose was higher than that of WT. Consequently, the deletion mutant strains decreased utilization efficiency with which they utilized various nitrogen sources. The deletion mutants maintain responsiveness to osmotic stress and oxidative stress stimuli. Additionally, compared to WT strains, the deletion mutant strains exhibited differences in culture temperature tolerance, UV exposure response, and fungicide sensitivity. After cotton was infected with deletion strains conidial suspension, its disease index increased dramatically, while it gradually decreased after spraying with 2 mM glutamate in batches. With the increase of spraying times, the effect was more significant, and the disease index decreased by 18.95%-19.66% at 26 dpi.DiscussionThese results indicated that VdP5CDH regulates the pathogenicity of fungi and controls mycelia growth, melanin formation, conidia morphology, abiotic stress resistance, and the expression of infecting structure-related genes.

Introduction: Early risk assessment studies usually based on total heavy metal (loid) contents, inevitably leading to an overestimation of the health risks. In addition, inputs are represented as single-point estimates in deterministic models, leading to underestimation or overestimation of the health risks.Methods: To overcome these barriers, a novel probabilistic risk assessment strategy based on the combinational use of bioaccessibility and Monte Carlo simulation was developed to assess heavy metal (loid) associated health risks of earthworms in this study. To obtain a realistic and robust probabilistic risk assessment, heavy metal (loid) exposure duration and frequency were determined using our questionnaire data.Results: As a result, the mean gastrointestinal bioaccessibility was in the order: Cd > As > Cu > Hg. The mean hazard index (HI) values for investigated metal (loid)s were 0.65 and 0.59 for male and female, respectively, demonstrating an acceptable health risk in an average community. However, the 90th percentile of HI values was 1.87 and 1.65 for male and female, respectively. And the total non-cancer risks of heavy metal (loid) exposure exceeded the acceptable threshold for 19.9% and 17.8% of male and female, respectively. In addition, the total cancer risk (TCR) value through co-exposure to As and Cd suggested that the carcinogenic risks may be of concern for average exposure population. Sensitivity analyses revealed that the exposure frequency and bioaccessible As concentration were the dominant contributors to the total risk variance, which provided meaningful implications for environmental management.Conclusion: Altogether, the refined strategy based on bioaccessibility and Monte Carlo simulation is the first of its kind, such effort attempts to scientifically guide the rational clinic use of TCM and the improvement of population-health.

Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC. Neoadjuvant treatment for HCC has become a possibility—findings from the IMbrave 050 trial indicated that ICIs offer the benefit of recurrence-free survival for high-risk HCC patients post-resection or local ablation. However, only a small fraction of individuals benefit from systemic therapy. Consequently, there is an urgent need to identify predictive biomarkers for treatment response and outcome assessment. This study reviewed the historical progression of systemic therapy for HCC, highlighting notable therapeutic advancements. This study examined the development of systemic therapies involving conventional drugs and clinical trials utilized in HCC treatment, as well as potential predictive biomarkers for advanced and/or locally advanced HCC. Various studies have revealed potential biomarkers in the context of HCC treatment. These include the association of dendritic cells (DCs) with a favorable response to neoadjuvant therapy, the presence of enriched T effector cells and tertiary lymphoid structures, the identification of CD138+ plasma cells, and distinct spatial arrangements of B cells in close proximity to T cells among responders with locally advanced HCC receiving neoadjuvant cabozantinib and nivolumab treatment. Furthermore, pathological response has been associated with intratumoral cellular triads consisting of progenitor CD8+ T cells and CXCL13+ CD4+ T helper cells surrounding mature DCs in patients receiving neoadjuvant cemiplimab for resectable HCC. Despite no widely recognized predictive biomarkers for HCC individualized treatment, we believe neoadjuvant trials hold the most promise in identifying and validating them. This is because they can collect multiple samples from resectable HCC patients across stages, especially with multi-omics, bridging preclinical and clinical gaps.

Abstract In order to clarify the impact mechanism of shallow buried soft rock tunnel excavation on the upper existing highway, as well as the mechanism of pipe shed reinforcement, a combination of theoretical analysis and on-site monitoring was used to conduct in-depth research on the Diantou Tunnel Crossing the existing highway project of Dayong Expressway. The impact of shallow buried soft rock tunnel crossing construction on the existing highway and safety control issues were studied, a new deformation control index, namely deformation difference rate, was introduced. The results show that the main lateral area of influence of rock deformation is within a distance of one diameter, and the overall area of influence is within a distance of twice the diameter. From the perspective of axial tunnel deformation, the deformation of surrounding rock tends to be stable when the excavation face passes through the monitoring section about twice the tunnel diameter. Effectively controlling rock deformation depends on the total amount of settlement deformation, the change rate of deformation, and the difference rate of deformation. For V-class shallow buried tunnel surrounding rock, in order to prevent cracks on the surface, the cumulative deformation of the surrounding rock needs to be less than 50 mm, the change rate needs to be less than 3 mm/day, and the difference rate needs to be less than 5 mm/m. Finally, the proposed control standard for surface subsidence is given for similar engineering reference.

Objective To investigate the relationship between the development of terminal rectal ganglion and spinal cord/sacral abnormalities in boys with complex anorectal malformations (ARMs) in order to improve the understanding of rectal ganglion development abnormalities in ARMs patients. Methods A retrospective trial was conducted on the male patients with complex ARMs admitted to our hospital from 2015 to 2021. The terminal rectal specimens were taken from them during anoplasty. According to the findings on development of terminal rectal ganglion after HE staining, the patients were classified into G1 group (ganglion cells observed) and G2 group (no ganglion cells observed). Imaging techniques were used to evaluate whether there were abnormalities in the spinal cord and sacrum, and their correlation with the terminal rectal ganglion development was analyzed. Results A total of 139 patients were enrolled, and their median age at anoplasty was 5.77(4.57, 6.97) months. There were no significant differences between the G1 (n=80, 57.6%) and G2 (n=59, 42.4%) groups in ARMs pathological type (P=0.706) and age at surgery (P=0.140). Radiological findings showed there were 48 cases (34.5%) of spinal cord anomalies (SCA), 25 cases (18.0%) of sacral abnormalities and 18 cases (12.9%) of coccyx abnormalities. No significant differences were observed in the incidences of SCA and sacral abnormalities between the G1 and G2 groups (P

Abstract Previous studies on the molecular classification of cholangiocarcinoma (CCA) focused on certain anatomical sites, and disregarded tissue contamination biases in transcriptomic profiles. We aim to provide universal molecular classification scheme and prognostic biomarker of CCAs across anatomical locations. Comprehensive bioinformatics analysis is performed on transcriptomic data from 438 CCA cases across various anatomical locations. After excluding CCA tumors showing normal tissue expression patterns, we identify two universal molecular subtypes across anatomical subtypes, explore the molecular, clinical, and microenvironmental features of each class. Subsequently, a 30-gene classifier and a biomarker (called “CORE-37”) are developed to predict the molecular subtype of CCA and prognosis, respectively. Two subtypes display distinct molecular characteristics and survival outcomes. Key findings are validated in external cohorts regardless of the stage and anatomical location. Our study provides a CCA classification scheme that complements the conventional anatomy-based classification and presents a promising prognostic biomarker for clinical application.

The atomization mechanism of lubrication fluid in rolling bearings under high-speed airflow between the rings was investigated. A simulation model of gas–liquid two-phase flow in angular contact ball bearings was developed, and the jet lubrication process between the bearing rings was simulated using FLUENT computational fluid dynamics software (Ansys 19.2). The complex motion boundary conditions of the rolling elements were addressed through a layered approach. We can obtain more accurate boundary layer flow field changes and statistics of the diameter of oil particles in lubricating oil atomization, which lays the foundation for analyzing the law of influence on lubricating oil atomization. The results show that as the number of boundary layer layers increases, the influence of the boundary layer flow field on the lubricating oil is more obvious. The oil particle size is excessively flat, and the concentration of large particles of oil appears to decrease. As the speed increases, the amount of oil in the cavity decreases, but the oil droplets are also fragmented, which intensifies the atomization and reduces the particle diameter. This reduces the Sauter Mean Diameter (SMD), which is not conducive to the lubrication of the bearing. Under different injection pressures, when the injection pressure is large, it is beneficial to the lubrication of the bearing.

Situated in central China, the region surrounding Mount Song is a pivotal area within the Central Plains, renowned for its extensive and high-grade cultural heritage. This study aims to analyze the spatiotemporal distribution of this heritage using advanced spatial pattern analysis methods, including the Average Nearest Neighbor Ratio and Kernel Density Estimation within ArcGIS. Our findings reveal a distinct continuity in temporal distribution and a pronounced clustering in spatial terms. By investigating the underlying factors such as the geographical setting, historical political capitals, cultural and religious influences, water transportation systems, and traditional Fengshan ceremonies, this research elucidates the dynamics shaping this distribution. This study’s outcomes provide essential insights for policymakers and stakeholders involved in the protection and revitalization of cultural heritage, ensuring informed decision making for sustainable cultural conservation.

China’s agricultural green development exhibits spatial imbalances. To promote the coordinated green development of agriculture across various regions, this paper explores the evolution of spatial association networks and driving factors of agricultural green development from a bidirectional correlation perspective, using social network analysis and spatial econometric methods. This research indicates that China’s agricultural green efficiency has steadily improved, with a complex multi-threaded network structure. Although the spatial interaction and spillover effects of the overall network structure have increased, they remain relatively weak. The individual network structure shows significant regional imbalances. The spatial association network of agricultural green efficiency forms four major blocks, with sparse connections within the blocks but close connections between blocks, demonstrating strong spillover effects. Regarding the driving factors, the proportion of the primary industry, labor level, and R&D investment have significant spatial impacts, while the spatial impacts of human capital level, degree of openness, economic development level, and new quality productivity level are not significant. Therefore, we believe that it is necessary to establish the concept of coordinated green development in agriculture, fully leverage regional associations and spillover effects, and formulate differentiated policies to improve agricultural green efficiency.

This study aimed to analyze the structure of polysaccharides from eight different Dendrobium species and their protective effects on gastric mucosa. Ultraviolet (UV) analysis showed that the contents of eight polysaccharides ranged from 51.89 ± 6.91% to 80.57 ± 11.63%; the degree of acetylation ranged from 0.17 ± 0.03 to 0.48 ± 0.03. High-performance liquid chromatography (HPLC) results showed that these polysaccharides were mainly composed of mannose (Man) and glucose (Glc) with a small amount of galactose (Gal) and arabinose (Ara), and the monosaccharide ratios of different Dendrobium species were different. High-performance size exclusion chromatography—multi angle light scattering—refractive index detector (HPSEC-MALS-RID) showed that the molecular weight (Mw) of all Dendrobium polysaccharides was >1 × 105 Da; D. huoshanense had the lowest molecular weight. Subsequently, an ethanol injured GES-1 cell model was constructed to evaluate the gastric mucosal protective potential of polysaccharides from eight different Dendrobium species. The results showed that the protective effect of the low concentration 50 μg/mL DHP treatment group was similar to that of the control group (p > 0.05), and the cell viability could reach 97.32% of that of the control group. Based on the polysaccharide composition, different kinds of Dendrobium have different degrees of migration and repair effects on GES-1 damaged cells, and the effect of DHP is slightly better than that of other varieties (83.13 ± 1.05%). Additionally, Dendrobium polysaccharides alleviated ethanol-induced oxidative stress and inflammatory response in gastric mucosal cells by enhancing the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) and reducing the levels of malondialdehyde and reactive oxygen species. Overall, DHP can most effectively protect gastric mucosa. These findings enhance our understanding of the relationship between the structure and biological activity of Dendrobium polysaccharides, providing a foundation for the quality control of Dendrobium. Furthermore, these findings offer theoretical support for the development of Dendrobium polysaccharides as nutraceuticals to treat digestive system diseases.

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate, and the survival rate of HCC patients remains low. Animal medicines have been used as potential therapeutic tools throughout the long history due to their different structures of biologically active substances with high affinity to the human body. Here, we focus on the effects and the mechanism of action of animal-derived natural products against HCC, which were searched in databases encompassing Web of Science, PubMed, Embase, Science Direct, Springer Link, and EBSCO. A total of 24 natural products from 12 animals were summarized. Our study found that these natural products have potent anti-hepatocellular carcinoma effects. The mechanism of action involving apoptosis induction, autophagy induction, anti-proliferation, anti-migration, and anti-drug resistance via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Ras/extracellular signal regulated kinases (ERK)/mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Huachansu injection and sodium cantharidate have been used in clinical applications with good efficacy. We review the potential of animal-derived natural products and their derivatives in the treatment of HCC to date and summarize their application prospect and toxic side effects, hoping to provide a reference for drug development for HCC.

Sti1/Hop, a stress-induced co-chaperone protein, serves as a crucial link between Hsp70 and Hsp90 during cellular stress responses. Despite its importance in stress defense mechanisms, the biological role of Sti1 in Verticillium dahliae, a destructive fungal pathogen, remains largely unexplored. This study focused on identifying and characterizing Sti1 homologues in V. dahliae by comparing them to those found in Saccharomyces cerevisiae. The results indicated that the VdSti1-deficient mutant displayed increased sensitivity to drugs targeting the ergosterol synthesis pathway, leading to a notable inhibition of ergosterol biosynthesis. Moreover, the mutant exhibited reduced production of microsclerotia and melanin, accompanied by decreased expression of microsclerotia and melanin-related genes VDH1, Vayg1, and VaflM. Additionally, the mutant’s conidia showed more severe damage under heat shock conditions and displayed growth defects under various stressors such as temperature, SDS, and CR stress, as well as increased sensitivity to H2O2, while osmotic stress did not impact its growth. Importantly, the VdSti1-deficient mutant demonstrated significantly diminished pathogenicity compared to the wild-type strain. This study sheds light on the functional conservation and divergence of Sti1 homologues in fungal biology and underscores the critical role of VdSti1 in microsclerotia development, stress response, and pathogenicity of V. dahliae.

BackgroundImmune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC).MethodsFifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively.ResultsA comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival.ConclusionsThese results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

To examine the association between prediabetes/type 2 diabetes mellitus (T2DM) and hippocampal subfields and to investigate the effects of glycemic control (HbA1c and FBG)/diabetes duration on the volume of hippocampal subfields in T2DM patients. This cross-sectional study included 268 participants from Tianjin Union Medical Center between August 2019 and July 2022. The participants were divided into three groups: T2DM, prediabetes and no diabetes. All participants underwent brain MRI examination on a 3T MRI scanner. FreeSurfer was performed to segment hippocampus automatically based on T1 MPRAGE images. The relationships between glycemic status/glycemic control/diabetes duration and hippocampal subfield volumes were estimated by multiple linear regression analysis/generalized additive modeling (GAM). Among all participants, 76 (28.36%) had prediabetes, and 96 (35.82%) had T2DM. In multi-adjusted linear regression models, those with prediabetes had a significantly lower volume of bilateral parasubiculum (βright = –5.540; βleft = –6.497). Those with diabetes had lower volume of parasubiculum (βleft = –7.868), presubiculum-head (βleft = –6.244) and fimbria (βleft = –7.187). We did not find relationship between diabetes duration and hippocampal subfield volumes. In stratified analysis, long duration with high FBG related with lower volume of right fimbria (βright = –15.583). Long duration with high HbA1c related with lower volume of presubiculum-head (βright = –19.693), subiculum-head (βright = –28.303), subiculum-body (βleft = –38.599), CA1-head (βright = –62.300, βleft = –47.922), CA1-body (βright = –19.043), CA4-body (βright = –14.392), GC-ML-DG-head (βright = –20.521), GC-ML-DG-body (βright = –16.293, βleft = –12.799), molecular_layer_HP-head (βright = –44.202, βleft = –26.071) and molecular_layer_HP-body, (βright = –31.368), hippocampal_tail (βleft = –80.073). Prediabetes related with lower bilateral parasubiculum volume, and T2DM related with lower left parasubiculum, presubiculum-head and fimbria. T2DM with chronic poor glycemic control had lower volume in multiple hippocampal subregions.

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.

Aircraft tire hydroplaning can cause a sharp decrease in friction between it and the ground, increasing the takeoff and landing distance of the aircraft, and thus affecting flight safety. Therefore, it is necessary to carry out research on airplane tire hydroplaning. Aiming at the tire hydroplaning problem of aircraft tires, a simplified tire model was established by FEM method and verified by experiments. A water model was established by SPH method,and finally a tire hydroplaning model with the interaction of tire, water and pavement was established. The influence of different influencing factors and different tire configurations on tire hydroplaning was analyzed. The results show that, the greater the water depth, the more likely occur the tire hydroplaning, but after the water depth is greater than 6 mm, the water depth on the tire hydroplaning effect is small; The greater the tire speed, tire pressure and wheel load, the more likely the tire hydroplaning; With the increase of groove width, the tire hydroplaning speed increases, but the stability decreases. The more severe the tire abrasion, the more likely it is to tire hydroplaning; The greater the number of grooves, the greater the critical water skiing speed.

ObjectiveTo understand the epidemic characteristics of notifiable infectious diseases （NIDs） other than coronavirus disease 2019 （COVID-19） in Shanghai in 2020， and to provide evidence for formulating infectious disease prevention and control strategies.MethodsData of NIDs reported in Shanghai from 2015 to 2020 were collected through the National Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the incidence and prevalence characteristics of NIDs in Shanghai in 2020， and compared them with the average values of 2015 to 2019.ResultsA total of 45 574 cases of 23 kinds of NIDs were reported in Shanghai in 2020， except for COVID-19， with an incidence of 187.69/105， and a decrease rate of 50.58% compared with the average value of 2015 to 2019. The incidence of category B and C infectious diseases decreased by 38.07% and 57.47%， respectively （All P

Abstract Gradient porous structures enable the fast capillary-directed mass transport and enhance the chemical reaction rate with optimal efficiency and minimal energy consumption. Rational design and facile synthesis of functional mesoporous materials with sheet structure and gradient mesopores still face challenges of stacked structures and unadjustable pore sizes. Herein, an interfacial co-assembly strategy for gradient mesoporous hollow silica sheets is reported. The modulated oil-water interface allows the assembly of gradient mesoporous silica layers on the water-removable ammonium sulfate crystals. The obtained mesoporous silica layers possess narrow pore size distributions (~2.2 nm and ~6.6 nm). Owing to the good mono-dispersity, sheet structure and proper pore size, the designed gradient mesoporous hollow silica sheets can serve as flexible building blocks for fabricating nanoscale molecule filtration device. Experiments reveal that the obtained nanofiltration device shows remarkable gradient rejection rates (range from 23.5 to 99.9%) for molecules with different sizes (range from 1.2 to 4.4 nm).

Abstract Goose astrovirus 2 (GAstV-2) causes visceral gout in goslings and has resulted in significant economic losses in the goose industry of China since its outbreak in 2017. To further investigate the distribution and localization of GAstV-2 in different tissues at different times, a monoclonal antibody (mAb)-based immunohistochemical (IHC) assay was developed to detect GAstV-2. A total of 80 1-day-old healthy goslings were inoculated with GAstV-2 via the oral (n = 40) and intramuscular routes (n = 40). GAstV-2 in the tissues of interest was detected using the established IHC assay. The results showed that positive signals were detected in most tissues at 1 day post-infection (dpi). Viral antigens were mainly distributed in the cytoplasm, and the staining intensity was higher in the renal tubular epithelial cells than in other cells. Taken together, our data demonstrated that GAstV-2 has a broad tissue tropism and primarily targets the kidneys. These results are likely to provide a scientific basis for further elucidation of the pathogenesis of GAstV-2.

Background: Periplocae Cortex (PC), Acanthopanacis Cortex (AC), and Lycii Cortex (LC), as traditional Chinese medicines, are all dried root bark, presented in a roll, light and brittle, easy to break, have a fragrant scent, etc. Due to their similar appearances, it is tough to distinguish them, and they are often confused and adulterated in markets and clinical applications. To realize the identification and quality control of three herbs, in this paper, Ultra Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry Expression (UHPLC-QTOF-MSE) combined with chemometric analysis was used to explore the different chemical compositions. Methods: LC, AC, and PC were analyzed by UHPLC-QTOF-MSE, and the quantized MS data combined with Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) were used to explore the different chemical compositions with Variable Importance Projection (VIP) > 1.0. Further, the different chemical compositions were identified according to the chemical standard substances, related literature, and databases. Results: AC, PC, and LC can be obviously distinguished in PCA and PLS-DA analysis with the VIP of 2661 ions > 1.0. We preliminarily identified 17 differential chemical constituents in AC, PC, and LC with significant differences (p < 0.01) and VIP > 1.0; for example, Lycium B and Periploside H2 are LC and PC’s proprietary ingredients, respectively, and 2-Hydroxy-4-methoxybenzaldehyde, Periplocoside C, and 3,5-Di-O-caffeoylquinic acid are the shared components of the three herbs. Conclusions: UHPLC-QTOF-MSE combined with chemometric analysis is conducive to exploring the differential chemical compositions of three herbs. Moreover, the proprietary ingredients, Lycium B (LC) and Periploside H2 (PC), are beneficial in strengthening the quality control of AC, PC, and LC. In addition, limits on the content of shared components can be set to enhance the quality control of LC, PC, and AC.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32–72.49% and 4.98–51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were

Background: As one of the four most valuable animal medicines, Fel Ursi, named Xiong Dan (XD) in China, has the effect of clearing heat, calming the liver, and brightening the eyes. However, due to the special source of XD and its high price, other animals’ bile is often sold as XD or mixed with XD on the market, seriously affecting its clinical efficacy and consumers’ rights and interests. In order to realize identification and adulteration analysis of XD, UHPLC-QTOF-MSE and multivariate statistical analysis were used to explore the differences in XD and six other animals’ bile. Methods: XD, pig gall (Zhu Dan, ZD), cow gall (Niu Dan, ND), rabbit gallbladder (Tu Dan, TD), duck gall (Yan Dan, YD), sheep gall (Yang Dan, YND), and chicken gall (Ji Dan, JD) were analyzed by UHPLC-QTOF-MSE, and the MS data, combined with multivariate analysis methods, were used to distinguish between them. Meanwhile, the potential chemical composition markers that contribute to their differences were further explored. Results: The results showed that XD and six other animals’ bile can be distinguished from each other obviously, with 27 ions with VIP > 1.0. We preliminarily identified 10 different bile acid-like components in XD and the other animals’ bile with significant differences (p < 0.01) and VIP > 1.0, such as tauroursodeoxycholic acid, Glycohyodeoxycholic acid, and Glycodeoxycholic acid. Conclusions: The developed method was efficient and rapid in accurately distinguishing between XD and six other animals’ bile. Based on the obtained chemical composition markers, it is beneficial to strengthen quality control for bile medicines.

Increasing concerns about air quality due to fossil fuel combustion, especially nitrogen oxides (NOx) from marine and diesel engines, necessitate advanced monitoring systems due to the significant health and environmental impacts of nitrogen dioxide (NO2). In this study, a gas detection system based on the principle of the non-dispersive infrared (NDIR) technique is proposed. Firstly, the pyroelectric detector was developed by employing an ultra-thin LiTaO3 (LT) layer as the sensitive element, integrated with nanoscale carbon material prepared by wafer-level graphics technology as the infrared absorption layer. Then, the sensor was hermetically sealed using inert gas through energy storage welding technology, exhibiting a high detectivity (D*) value of 4.19 × 108 cm·√Hz/W. Subsequently, a NO2 gas sensor was engineered based on the NDIR principle employing a Micro Electro Mechanical System (MEMS) infrared (IR) emitter, featuring a light path chamber length of 1.5 m, along with integrated signal processing and software calibration algorithms. This gas sensor was capable of detecting NO2 concentrations within the range of 0–500 ppm. Initial tests indicated that the gas sensor exhibited a full-scale relative error of less than 0.46%, a limit of 2.8 ppm, a linearity of −1.09%, a repeatability of 0.47% at a concentration of 500 ppm, and a stability of 2% at a concentration of 500 ppm. The developed gas sensor demonstrated significant potential for application in areas such as industrial monitoring and analytical instrumentation.

Abstract Background Evaluating traditional Chinese medicine (TCM) quality is a powerful method to ensure TCM safety. TCM quality evaluation methods primarily include characterization evaluations and separate physical, chemical, and biological evaluations; however, these approaches have limitations. Nevertheless, researchers have recently integrated evaluation methods, advancing the emergence of frontier research tools, such as TCM quality markers (Q-markers). These studies are largely based on biological activity, with weak correlations between the quality indices and quality. However, these TCM quality indices focus on the individual efficacies of single bioactive components and, therefore, do not accurately represent the TCM quality. Conventionally, provenance, place of origin, preparation, and processing are the key attributes influencing TCM quality. In this study, we identified TCM-attribute-based quality indices and developed a comprehensive multiweighted multi-index-based TCM quality composite evaluation index (QCEI) for grading TCM quality. Methods The area of origin, number of growth years, and harvest season are considered key TCM quality attributes. In this study, licorice was the model TCM to investigate the quality indicators associated with key factors that are considered to influence TCM quality using multivariate statistical analysis, identify biological-evaluation-based pharmacological activity indicators by network pharmacology, establish real quality indicators, and develop a QCEI-based model for grading TCM quality using a machine learning model. Finally, to determine whether different licorice quality grades differently reduced the inflammatory response, TNF-α and IL-1β levels were measured in RAW 264.7 cells using ELISA analysis. Results The 21 quality indices are suitable candidates for establishing a method for grading licorice quality. A computer model was established using SVM analysis to predict the TCM quality composite evaluation index (TCM QCEI). The tenfold cross validation accuracy was 90.26%. Licorice diameter; total flavonoid content; similarities of HPLC chromatogram fingerprints recorded at 250 and 330 nm; contents of liquiritin apioside, liquiritin, glycyrrhizic acid, and liquiritigenin; and pharmacological activity quality index were identified as the key indices for constructing the model for evaluating licorice quality and determining which model contribution rates were proportionally weighted in the model. The ELISA analysis results preliminarily suggest that the inflammatory responses were likely better reduced by premium-grade than by first-class licorice. Conclusions In the present study, traditional sensory characterization and modern standardized processes based on production process and pharmacological efficacy evaluation were integrated for use in the assessment of TCM quality. Multidimensional quality evaluation indices were integrated with a machine learning model to identify key quality indices and their corresponding weight coefficients, to establish a multiweighted multi-index and comprehensive quality index, and to construct a QCEI-based model for grading TCM quality. Our results could facilitate and guide the development of TCM quality control research.

Abstract Background The incidence and mortality of gastric cancer (GC) are high worldwide. Tumor stemness is a major contributor to tumorigenesis and development of GC, in which long non-coding RNAs (lncRNAs) are deeply involved. The purpose of this study was to investigate the influences and mechanisms of LINC00853 in the progression and stemness of GC. Methods The level of LINC00853 was assessed based on The Cancer Genome Atlas (TCGA) database and GC cell lines by RT-PCR and in situ hybridization. An evaluation of biological functions of LINC00853 including cell proliferation, migration, and tumor stemness was conducted via gain-and loss-of-function experiments. Furthermore, RNA pull-down and RNA immunoprecipitation (RIP) assay were utilized to validate the connection between LINC00853 and the transcription factor Forkhead Box P3 (FOXP3). Nude mouse xenograft model was used to identify the impacts of LINC00853 on tumor development. Results We identified the up-regulated levels of lncRNA-LINC00853 in GC, and its overexpression correlates with poor prognosis in GC patients. Further study indicated that LINC00853 promoted cell proliferation, migration and cancer stemness while suppressed cell apoptosis. Mechanistically, LINC00853 directly bind to FOXP3 and promoted FOXP3-mediated transcription of PDZK1 interacting protein 1(PDZK1IP1). Alterations of FOXP3 or PDZK1IP1 reversed the LINC00853-induced biological effects on cell proliferation, migration and stemness. Moreover, xenograft tumor assay was used to investigate the function of LINC00853 in vivo. Conclusions Taken together, these findings revealed the tumor-promoting activity of LINC00853 in GC, expanding our understanding of lncRNAs regulation on GC pathogenesis.

Maritime unmanned system are crucial for future intelligent and unmanned warfare. They have become a new height of competition in the maritime domain and will play an increasingly important role in national defense security. Considering the development demand for national intelligence and unmanned strategies, the study analyzes the development status of maritime unmanned systems and corresponding technologies in China and abroad from the aspects of strategic planning and conceptual guidance, technological research and equipment development, and system demonstration and capability verification. The challenges and trends for the development of maritime unmanned systems are summarized and key technical challenges are proposed. Moreover, development pathways of maritime unmanned systems in key directions are explored and countermeasures to promote the sustained, steady, and rapid development of maritime unmanned systems are recommended from the perspectives of overall thinking, system composition, equipment development, and technology breakthroughs.

ObjectiveTo quickly and accurately assess the situation of crop lodging disasters, it is necessary to promptly obtain information such as the location and area of the lodging occurrences. Currently, there are no corresponding technical standards for identifying crop lodging based on UAV remote sensing, which is not conducive to standardizing the process of obtaining UAV data and proposing solutions to problems. This study aims to explore the impact of different spatial resolution remote sensing images and feature optimization methods on the accuracy of identifying wheat lodging areas.MethodsDigital orthophoto images (DOM) and digital surface models (DSM) were collected by UAVs with high-resolution sensors at different flight altitudes after wheat lodging. The spatial resolutions of these image data were 1.05, 2.09, and 3.26 cm. A full feature set was constructed by extracting 5 spectral features, 2 height features, 5 vegetation indices, and 40 texture features from the pre-processed data. Then three feature selection methods, ReliefF algorithm, RF-RFE algorithm, and Boruta-Shap algorithm, were used to construct an optimized subset of features at different flight altitudes to select the best feature selection method. The ReliefF algorithm retains features with weights greater than 0.2 by setting a threshold of 0.2; the RF-RFE algorithm quantitatively evaluated the importance of each feature and introduces variables in descending order of importance to determine classification accuracy; the Boruta-Shap algorithm performed feature subset screening on the full feature set and labels a feature as green when its importance score was higher than that of the shaded feature, defining it as an important variable for model construction. Based on the above-mentioned feature subset, an object-oriented classification model on remote sensing images was conducted using eCognition9.0 software. Firstly, after several experiments, the feature parameters for multi-scale segmentation in the object-oriented classification were determined, namely a segmentation scale of 1, a shape factor of 0.1, and a tightness of 0.5. Three object-oriented supervised classification algorithms, support vector machine (SVM), random forest (RF), and K nearest neighbor (KNN), were selected to construct wheat lodging classification models. The Overall classification accuracy and Kappa coefficient were used to evaluate the accuracy of wheat lodging identification. By constructing a wheat lodging classification model, the appropriate classification strategy was clarified and a technical path for lodging classification was established. This technical path can be used for wheat lodging monitoring, providing a scientific basis for agricultural production and improving agricultural production efficiency.Results and DiscussionsThe results showed that increasing the altitude of the UAV to 90 m significantly improved flight efficiency of wheat lodging areas. In comparison to flying at 30 m for the same monitoring range, data acquisition time was reduced to approximately 1/6th, and the number of photos needed decreased from 62 to 6. In terms of classification accuracy, the overall classification effect of SVM is better than that of RF and KNN. Additionally, when the image spatial resolution varied from 1.05 to 3.26 cm, the full feature set and all three optimized feature subsets had the highest classification accuracy at a resolution of 1.05 cm, which was better than at resolutions of 2.09 and 3.26 cm. As the image spatial resolution decreased, the overall classification effect gradually deteriorated and the positioning accuracy decreased, resulting in poor spatial consistency of the classification results. Further research has found that the Boruta-Shap feature selection method can reduce data dimensionality and improve computational speed while maintaining high classification accuracy. Among the three tested spatial resolution conditions (1.05, 2.09, and 3.26 cm), the combination of SVM and Boruta-Shap algorithms demonstrated the highest overall classification accuracy. Specifically, the accuracy rates were 95.6%, 94.6%, and 93.9% for the respective spatial resolutions. These results highlighted the superior performance of this combination in accurately classifying the data and adapt to changes in spatial resolution. When the image resolution was 3.26 cm, the overall classification accuracy decreased by 1.81% and 0.75% compared to 1.05 and 2.09 cm; when the image resolution was 2.09 cm, the overall classification accuracy decreased by 1.06% compared to 1.05 cm, showing a relatively small difference in classification accuracy under different flight altitudes. The overall classification accuracy at an altitude of 90 m reached 95.6%, with Kappa coefficient of 0.914, meeting the requirements for classification accuracy.ConclusionsThe study shows that the object-oriented SVM classifier and the Boruta-Shap feature optimization algorithm have strong application extension advantages in identifying lodging areas in remote sensing images at multiple flight altitudes. These methods can achieve high-precision crop lodging area identification and reduce the influence of image spatial resolution on model stability. This helps to increase flight altitude, expand the monitoring range, improve UAV operation efficiency, and reduce flight costs. In practical applications, it is possible to strike a balance between classification accuracy and efficiency based on specific requirements and the actual scenario, thus providing guidance and support for the development of strategies for acquiring crop lodging information and evaluating wheat disasters.

Abstract Marine traditional Chinese medicines (MTCMs) hold a significant place in the rich cultural heritage in China. It plays an irreplaceable role in addressing human diseases and serves as a crucial pillar for the development of China's marine economy. However, the rapid pace of industrialization has raised concerns about the safety of MTCM, particularly in relation to heavy metal pollution. Heavy metal pollution poses a significant threat to the development of MTCM and human health, necessitating the need for detection analysis and risk assessment of heavy metals in MTCM. In this paper, the current research status, pollution situation, detection and analysis technology, removal technology and risk assessment of heavy metals in MTCM are discussed, and the establishment of a pollution detection database and a comprehensive quality and safety supervision system for MTCM is proposed. These measures aim to enhance understanding of heavy metals and harmful elements in MTCM. It is expected to provide a valuable reference for the control of heavy metals and harmful elements in MTCM, as well as the sustainable development and application of MTCM.

Abstract Background Heavy metals are considered a global concern because they can deteriorate human health. This guideline aims to scientifically evaluate health risk of heavy metals in TCM and to propose a reference for decision making in developing TCM-related health policies. Methods Using a multidisciplinary approach, a steering committee oversaw the development of the guideline. To obtain a reasonable and accurate risk assessment, key exposure assessment parameters for TCM, e.g., exposure frequency (EF), exposure duration (ED), and daily ingestion rate (IR) were obtained from surveys. In addition, transfer rates for heavy metals from Chinese medicinal materials (CMM) to decoctions or preparations were examined. Results Based on the scientific theory of risk control, the guideline was designed systematically, and principles and procedures for the risk assessment of heavy metals in TCM were identified. The guideline can be utilized to assess the risk of heavy metals in CMM and Chinese patent medicines (CPM). Conclusion This guideline may help standardize the risk assessment of heavy metals in TCM, advance regulatory standards for heavy metals in TCM, and ultimately improve human health through scientific TCM usage in clinic.