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INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to

Abstract Background Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. Methods This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. Results Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P

The phases, microstructure, and mechanical properties of Si-alloyed (Ti28Zr40Al20Nb12)100-xSix (x = 1, 3, 5, 10) high entropy alloys are studied. Although silicides were not detected in the as-cast 1 at. % Si-alloyed sample, after annealing all the four alloys have the same phase composition: the Zr5Al3-type phase, Zr5Si3-type silicides, and the BCC/B2 dual-phase matrix, indicating that 1 at. % Si addition is adequate for the formation of silicides in equilibrium. The phase morphologies show a dependence on the Si content and the cooling rate, which changed from the occurrence of columnar grain zones together with coarse dendrites of the as-cast 1 at. % Si-alloyed alloy to four different cooling-rate-related morphologies in the other three as-cast alloys. After heat treatment, differently shaped precipitates tend to aggregate and spherize, and a three-step-shaped phase morphology is observed when the Si content is above 5 at. %. All precipitates are rich in Zr due to either the strong Si–Zr pair or Al–Zr pair, but heterogeneous distributions of Si and Al exist. An increase of the Si content led to a gradual decrease of the compressive strength in both as-cast and annealed samples, yet the total fracture strain does not show monotonously decrease trend. 5 at. % Si-alloyed samples possessed a higher total fracture strain than the 3 at. % Si-alloyed samples.

Abstract Objectives Newly detected hepatic nodules during follow-up of cancer survivors receiving chemotherapy may pose a diagnostic dilemma. We investigated a series of hepatic focal nodular hyperplasia (FNH) diagnosed by either typical MRI features and follow-up or pathology in cancer survivors. Methods This retrospective study evaluated 38 patients with tumours who developed new hepatic FNH after cyclophosphamide-based (n = 19) and oxaliplatin-based (n = 19) chemotherapies. The main tumour types were breast cancer (n = 18) and colorectal cancer (n = 17). MRI findings, clinical features, and temporal evolution of all target hepatic lesions (n = 63) were reported. In addition, the two chemotherapy drug groups were compared. Results The median interval between chemotherapy completion and FNH detection was 30.4 months (12.9, 49.4). Six patients underwent biopsy or surgery, while the remaining patients were diagnosed based on typical MRI features and long-term follow-up. Among the patients, 60.5% (23/38) presented with multiple nodules and 63 target lesions were detected. The median size of target lesions was 11.5 mm (8.4, 15.1). The median follow-up time was 32.5 months (21.2, 48.6), and 15 patients experienced changes in their lesions during the follow-up period (11 increased and 4 decreased). The cyclophosphamide-based treatment group had a younger population, a greater proportion of females, and a shorter time to discovery than the oxaliplatin-based chemotherapy group (all p ≤ 0.016). Conclusions FNH may occur in cancer survivors after cyclophosphamide- or oxaliplatin-based chemotherapy. Considering a patient’s treatment history and typical MRI findings can help avoid misdiagnosis and unnecessary invasive treatment. Clinical relevance statement When cancer survivors develop new hepatic nodules during follow-up, clinicians should think of the possibility of focal nodular hyperplasia in addition to liver metastasis, especially if the cancer survivors were previously treated with cyclophosphamide or oxaliplatin. Key Points Cancer survivors, after chemotherapy, can develop hepatic focal nodular hyperplasia. Cyclophosphamide and oxaliplatin are two chemotherapeutic agents that predispose to focal nodular hyperplasia development. Focal nodular hyperplasia occurs at shorter intervals in patients treated with cyclophosphamide. Graphical Abstract

Abstract Background The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®. Methods CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system. Results The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1–55 CTCs, median = 6),

Abstract Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78–0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73–0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74–0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87–1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78–0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88–1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61–0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

The effect of initial grain size prior to cold rolling on the microstructure, texture evolution, and magnetic properties of Fe-3.5 wt% Si non-oriented electrical steel (NOES) was investigated through the introduction of normalization. There were massive intragranular shear bands in {111} and {111} deformed grains in the cold-rolled sheet with large initial grain size, providing nucleation sites for new recrystallized grains with Goss ({110}), λ-fiber, γ-fiber, and {113} components. Subsequent annealing resulted in weaker γ-fiber ({111}−{111}), stronger α*-fiber concentrated at {113}, along with Goss and λ-fiber ({100}−{100}) textures. In addition, appropriate final annealing temperature effectively reduced iron loss. The simultaneous optimization of texture and grain size by normalization and annealing treatments led to improved magnetic properties, with the superior magnetic induction (B50 = 1.719) T, and the lowest core loss (P15/50 = 2.69 W/kg, P10/400 = 16.337 W/kg).

AIM: To determine the factors related to preoperative ocular characters that are predictive of insufficient vault (

ABSTRACTThe digital twin city technique maps the massive city environmental and social data on a three-dimensional virtual model. It presents the operational status of physical world and supports intelligent city governance. However, the inefficient utilization of distributed data resources, and the lack of sharing and collaboration among multiple departments restrict the data formulation of digital twin city construction. This research proposes a new cross-domain spatio-temporal data fusion framework for supporting complex urban governance. It integrates the heterogeneous urban information generated and stored by different government departments using multiple-information techniques. A specified geographic base reflecting the real city status is established, using geographical entities with unified address as identifiers to encapsulate the urban elements information. We introduce a comprehensive urban spatio-temporal data center construction process, which has already supported multiple urban governance projects. The two distinct advantages in using this data fusion system are: 1) The proposed Bert+PtrNet+ESIM-based address mapping method associates the urban elements information to their corresponding geographic entities with 99.3% F1-Score on real-world dataset. 2) The Wuhan spatio-temporal data center operation illustrates the capability of our framework for complex urban governance, which significantly improves the efficiency of urban management and services. This integrated system engineering provides reference and inspiration for further spatio-temporal data management, which contributes to the future social governance in digital twin city platform.

Abstract We use elastic and inelastic neutron scattering (INS) to study the antiferromagnetic (AF) phase transitions and spin excitations in the two-dimensional (2D) zig-zag antiferromagnet FePSe3. By determining the magnetic order parameter across the AF phase transition, we conclude that the AF phase transition in FePSe3 is first-order in nature. In addition, our INS measurements reveal that the spin waves in the AF ordered state have a large easy-axis magnetic anisotropy gap, consistent with an Ising Hamiltonian, and possible biquadratic magnetic exchange interactions. On warming across T N, we find that dispersive spin excitations associated with three-fold rotational symmetric AF fluctuations change into FM spin fluctuations above T N. These results suggest that the first-order AF phase transition in FePSe3 may arise from the competition between C 3 symmetric AF and C 1 symmetric FM spin fluctuations around T N, in place of a conventional second-order AF phase transition.

Abstract Background There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. Methods Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. Results Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). Conclusions High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

Abstract Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD+, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.

ABSTRACT Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens.IMPORTANCEOur study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Abstract Aggressive triple‐negative breast cancer (TNBC) still lacks approved targeted therapies, requiring more exploration of its underlying mechanisms. Previous studies have suggested a potential role of SAT1 (Spermidine/Spermine N1‐acetyltransferase 1) in cancer, which needs to be further elucidated in breast cancer. In this study, highly expressed SAT1 in TNBC signified worse patient prognoses. And SAT1 knockdown effectively inhibited the proliferation and migration abilities of TNBC cells in vitro and in vivo. In terms of mechanism, the transcription factor JUN enhanced SAT1 transcriptional activity by binding to its promoter region. Then, SAT1 protein in the cytoplasm engaged in directly binding with YBX1 for sustaining YBX1 protein stability via deubiquitylation mediated by the E3 ligase HERC5. Further, SAT1 was found to suppress autophagy remarkably via stabilization of mTOR mRNA with the accumulation of YBX1‐mediated methyl‐5‐cytosine (m5C) modification. These findings proved that SAT1 drives TNBC progression through the SAT1/YBX1/mTOR axis, which may provide a potential candidate for targeted therapy in advanced TNBC.

Nitrogen mustard (NM) is a chemotherapeutic agent capable of alkylating nucleophilic proteins and DNA, causing severe cell damage. However, no reports have been on the dynamic changes in proteomics induced by NM. In this study, we established a model of acute exposure to NM for 1 h and a continuous cultured model for 24 h after NM removal (repair stage) using 16HBE cells. The nuclear protein spectrum and nuclear proteins crosslinked with DNA were analyzed, and the function of p97 during NM damage was examined. An hour of NM exposure resulted in severe changes in the nuclear protein spectrum and protein into the cell nucleus, which is mainly involved in nuclear acid-related issues. After 24 h, the return to normal process of the types and amounts of differentially expressed proteins was inhibited by si-p97. The main processes involved in si-p97 intervention were nucleocytoplasmic transport, processing in the endoplasmic reticulum, metabolic abnormalities, and DNA-response; however. An hour of exposure to NM increased DNA-protein crosslinking (DPC), total-H2AX, and p-H2AX. In contrast, si-p97 only further increased or maintained their levels at 24 h yet not at 1 h. The effect of the proteasome inhibitor, MG132, was similar to that of si-p97. The siRNA of DVC1, a partner of p97, also increased the DPC content. Both si-p97 and si-DVC1 increased the cytoplasmic levels of the proteasome (PSMD2). These results suggest acute NM exposure induces severe nuclear protein spectral changes, rapid protein influx into the nucleus, DPC formation, and DNA double-strand breaks. Furthermore, our data indicated that p97 is involved in normal protein spectrum maintenance and DPC removal after NM withdrawal, requiring the participation of DVC1 and the proteasome.

Kitchen cooking particles can severely deteriorate indoor environment, aggravating the risk of cardiovascular and cerebrovascular diseases, as well as respiratory diseases. In view of the severe hazard of cooking particles to human health, this paper numerically studies the trajectory and deposition of the cooking particles in the kitchen environment based on a numerical model. Also, quantitative evaluations for the air quality and thermal comfort are performed, hoping to provide a useful reference for the control of kitchen air pollution. Firstly, a kitchen environment simulation model is established based on Fluent. A post-processing UDF program for evaluating the effectiveness of fume absorption is developed. The reliability of the numerical model is verified by comparing the results of the fume concentration with those by the cooking experiments. Using this numerical model, the fume extraction effectiveness of the range hood under different velocities of the fresh air is analyzed comprehensively, including particle trajectory, air age, temperature, PMV (Predicted Mean Vote), and PPD (Predicted Percentage of Dissatisfied) indicators. Results have shown that high speed of the fresh air can cause a strong blowing sensation, deteriorating indoor air quality. The PMV and PPD values around the human body show a parabolic trend. Generally, the relatively low fresh air speed can achieve satisfactory air quality and thermal comfort while saving energy consumption.

Microplastics (MPs) (64.12 %) of detected MPs were

BackgroundNirmatrelvir-ritonavir (Paxlovid) has received emergency use authorization from the US Food and Drug Administration owing to its effectiveness and safety. However, data on the effectiveness and safety of Paxlovid use in COVID-19 patients with onset of more than 5 days are lacking.MethodsA real-world retrospective study was performed during the outbreak involving the SARS-CoV-2 BA.5.2 subvariant. Hospitalized COVID-19 patients (including mild, moderate, severe and critical cases) were divided into three groups: Paxlovid treatment within (Group A) or more than (Group B) 5 days of COVID-19 onset and no Paxlovid treatment during more than 5 days of COVID-19 onset with only basic symptomatic treatment (Group C). Endpoints were all-cause 28-day mortality, improvement in clinical classification, and a composite endpoint of disease progression, viral load and virus elimination time. Safety was assessed by comparing adverse events reported during treatment in each group.ResultsDuring the period, 248 hospitalized COVID-19 patients, including 55 in Group A, 170 in Group B, and 23 in Group C, were enrolled. There were no significant differences in the clinical classification improvement rate [80.0% (16/20) vs. 81.3% (52/64), p = 1.000; 60.0% (21/35) vs. 55.7% (59/106), p = 0.653, respectively] or all-cause 28-day mortality [0% (0/20) vs. 1.6% (1/64), p = 1.000; 11.4% (4/35) vs. 6.6% (7/106), p = 0.576, respectively] between Groups A and B for nonsevere and severe cases. However, the clinical classification improvement rate in Group B was markedly higher than that in Group C [81.3% (52/64) vs. 50.0% (6/12), p = 0.049] among nonsevere cases. Cycle threshold values of the N and ORF genes in Group B were significantly increased after Paxlovid treatment [31.14 (IQR 26.81–33.93) vs. 38.14 (IQR 36.92–40.00), p < 0.001; 31.33 (IQR 26.00–33.47) vs. 38.62 (IQR 35.62–40.00), p < 0.001, respectively]. No significant differences in reported adverse events of neurological disease (p = 0.571), liver injury (p = 0.960) or kidney injury (p = 0.193) between Group A and Group B were found.ConclusionPaxlovid treatment within 10 days of onset can shorten the disease course of COVID-19 by reducing the viral load. Paxlovid is effective and safe in treating COVID-19 with onset of more than five or even 10 days when patients have a high viral load.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

IntroductionThe rapid aging of the labor force has serious implications for socioeconomic development and poses challenges to food sustainability. Existing studies have focused on the impact of labor force aging on land productivity, but little attention has been paid to the comprehensive capacity of agricultural production, namely the total factor productivity of agriculture.MethodsWe estimate the impact of labor force aging on total factor productivity in agriculture using data from 170,506 sample farm households from the National Fixed Point Survey data from 2003 to 2020. We estimate the results using a panel fixed effects approach and mitigate the endogeneity problem using an instrumental variables approach to ensure the robustness of the estimates.Results and discussionThe results show that labor force aging has an adverse effect on the agricultural total factor productivity of farm households and remains robust after addressing endogeneity and substituting explanatory variables. The aging effect shows significant heterogeneity across different food functional areas with different types of farm households. The negative impact of labor force aging on total factor productivity in agriculture is mainly concentrated in the main grain-production and grain-producing and marketing-balanced areas. We also find that the negative impact of labor force aging is more significant among large-scale farmers. The mechanism analysis finds that the aging of the labor force adversely affects the agricultural total factor productivity by inhibiting technological progress and reducing the efficiency of agricultural resource allocation. These insights, when considered in the light of global trends towards agricultural labor aging, suggest that policy interventions aimed at promoting technological adoption, enhancing resource allocation efficiency, and supporting the transitioning of older farmers may hold promise for maintaining food sustainability and addressing the challenges posed by an aging agricultural workforce in numerous developing nations.

Abstract Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Abstract Heat shock protein 90 (HSP90) is overexpressed in numerous cancers, promotes the maturation of numerous oncoproteins and facilitates cancer cell growth. Certain HSP90 inhibitors have entered clinical trials. Although less than satisfactory clinical effects or insurmountable toxicity have compelled these trials to be terminated or postponed, these results of preclinical and clinical studies demonstrated that the prospects of targeting therapeutic strategies involving HSP90 inhibitors deserve enough attention. Nanoparticulate-based drug delivery systems have been generally supposed as one of the most promising formulations especially for targeting strategies. However, so far, no active targeting nano-formulations have succeeded in clinical translation, mainly due to complicated preparation, complex formulations leading to difficult industrialization, incomplete biocompatibility or nontoxicity. In this study, HSP90 and CD44-targeted A6 peptide functionalized biomimetic nanoparticles (A6-NP) was designed and various degrees of A6-modification on nanoparticles were fabricated to evaluate targeting ability and anticancer efficiency. With no excipients, the hydrophobic HSP90 inhibitor G2111 and A6-conjugated human serum albumin could self-assemble into nanoparticles with a uniform particle size of approximately 200 nm, easy fabrication, well biocompatibility and avoidance of hepatotoxicity. Besides, G2111 encapsulated in A6-NP was only released less than 5% in 12 h, which may avoid off-target cell toxicity before entering into cancer cells. A6 peptide modification could significantly enhance uptake within a short time. Moreover, A6-NP continues to exert the broad anticancer spectrum of Hsp90 inhibitors and displays remarkable targeting ability and anticancer efficacy both in hematological malignancies and solid tumors (with colon tumors as the model cancer) both in vitro and in vivo. Overall, A6-NP, as a simple, biomimetic and active dual-targeting (CD44 and HSP90) nanomedicine, displays high potential for clinical translation.

Objective During the train debugging process, significant vibrations may occur in the steel rail beams of high-speed maglev maintenance bases due to their unique structural characteristics, potentially leading to bolt loosening issues. This phenomenon could alter the vibration characteristics of the rail beams, and changes in the parameters of the vehicle-track coupling system might induce vehicle-track resonance, posing potential harm to rail structure. Therefore, it is essential to investigate the impact of bolt loosening on the vibration of rail structures. Method After expounding the experimental design scheme and principles, the impact of bolt loosening on the modal and dynamic response characteristics of the rail beam and structure are investigated. For structural modal analysis, pulse and ambient excitations are employed to test the track modal properties under both unloaded (the rail is unoccupied) and loaded (the rail is occupied by a train) conditions. Modal identification is carried out using the method of Stochastic Subspace Identification (SSI). Finally, the impact of loose bolt on rail modal properties under both conditions are analyzed through stability diagrams. In terms of dynamic response characteristics, levitation excitation is applied to the rail, and the bolt is gradually loosened during multiple times of static levitation process. Acceleration response signals of the steel beams are collected and a detailed analysis is conducted in both time and frequency domains. Result & Conclusion Bolt loosening, under both loaded and unloaded conditions, caused a decrease in modal frequencies and a change in mode shapes. But under the loaded condition, a considerable increase in the damping ratio is observed after bolt loosening. In the static levitation process, resonance occurred between the rail beam and the train, where bolt loosening not only affected the amplitude of the rail beam vibrations but also altered the symmetry of rail beam vibrations.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract Background Cuproptosis induces proteotoxic stress and eventually leads to cell death. However, the relationship between cuproptosis and lncRNAs in cervical cancer has not been fully elucidated. Therefore, we aim to explore the association among lncRNAs, cuproptosis and clinical features in cervical cancer. Methods RNA sequencing, genetic mutations, and clinical data of CESC patients were obtained from TCGA. Cuproptosis-associated genes were gathered. WGCNA was used to cluster important modules, and KEGG, GO, GSEA and GSVA were used to explore functional and pathway enrichment. The association between immune microenvironment and cuproptosis-related lncRNAs was performed by using cibersort algorithm and other platforms, including XCELL, TIMER, QUANTISEQ, MCPCOUNTER and EPIC. Fluorescence quantitative PCR was employed to detect the expression of LINC01833 and LINC02321, and CCK-8 and cell scratch assays were used to assess cell proliferation and migration capabilities after LINCRNA interference. Results 202 upregulated and 45 downregulated lncRNAs were selected. The survival analysis showed that there was a statistically significant difference in survival rates between the high-risk and low-risk groups. The prognosis of tumour mutation burden and the degree of immune infiltration were differed noticeably between the high-risk and low-risk groups. BHG712, TL-2-105, FR-180204, Masitinib, TAK-715, ODI-027, JW-7-24-2, and OSI-930 had substantially higher IC50 values in the high-risk group. Notably, we found AL360178.1 was associated with RNF44 E3 ubiquitin ligase expression. In cervical cancer cell lines, LINC01833 and LINC02321 displayed significant upregulation. Efficient siRNA transfection led to a decreased expression of LINC01833 and LINC02321. This knockdown significantly hindered both cell proliferation and migration capabilities in cervical cancer cells compared to the negative control. Conclusion In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer.

Abstract Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications. Graphical Abstract

Abstract The prediction of hydrological time series is of great significance for developing flood and drought prevention approaches and is an important component in research on smart water resources. The nonlinear characteristics of hydrological time series are important factors affecting the accuracy of predictions. To enhance the prediction of the nonlinear component in hydrological time series, we employed an improved whale optimisation algorithm (IWOA) to optimise an attention-based long short-term memory (ALSTM) network. The proposed model is termed IWOA-ALSTM. Specifically, we introduced an attention mechanism between two LSTM layers, enabling adaptive focus on distinct features within each time unit to gather information pertaining to a hydrological time series. Furthermore, given the critical impact of the model hyperparameter configuration on the prediction accuracy and operational efficiency, the proposed improved whale optimisation algorithm facilitates the discovery of optimal hyperparameters for the ALSTM model. In this work, we used nonlinear water level information obtained from Hankou station as experimental data. The results of this model were compared with those of genetic algorithms, particle swarm optimisation algorithms and whale optimisation algorithms. The experiments were conducted using five evaluation metrics, namely, the RMSE, MAE, NSE, SI and DR. The results show that the IWOA is effective at optimising the ALSTM and significantly improves the prediction accuracy of nonlinear hydrological time series.

Abstract The combination of a geometrically frustrated lattice, and similar energy scales between degrees of freedom endows two-dimensional Kagome metals with a rich array of quantum phases and renders them ideal for studying strong electron correlations and band topology. The Kagome metal, FeGe is a noted example of this, exhibiting A-type collinear antiferromagnetic (AFM) order at T N ≈ 400 K, then establishes a charge density wave (CDW) phase coupled with AFM ordered moment below T CDW ≈ 110 K, and finally forms a c-axis double cone AFM structure around T Canting ≈ 60 K. Here we use neutron scattering to demonstrate the presence of gapless incommensurate spin excitations associated with the double cone AFM structure of FeGe at temperatures well above T Canting and T CDW that merge into gapped commensurate spin waves from the A-type AFM order. Commensurate spin waves follow the Bose factor and fit the Heisenberg Hamiltonian, while the incommensurate spin excitations, emerging below T N where AFM order is commensurate, start to deviate from the Bose factor around T CDW, and peaks at T Canting. This is consistent with a critical scattering of a second order magnetic phase transition with decreasing temperature. By comparing these results with density functional theory calculations, we conclude that the incommensurate magnetic structure arises from the nested Fermi surfaces of itinerant electrons and the formation of a spin density wave order.

Objective To explore the differences in prognosis of young hypertensive intracerebral hemorrhage (HIH) patients with different age, gender, and bleeding sites. Methods A retrospective analysis of 111 young HIH patients admitted to Shandong Second Provincal General Hospital from October 2016 to October 2021 was conducted. The patients were divided into 24-34 age group (47 cases) and 35-45 age group (64 cases) according to age. The patients were divided into male group (60 cases) and female group (51 cases) according to gender. After excluding the compound hemorrhage (18 cases), patients were divided into basal ganglia hemorrhage group (39 cases), brainstem hemorrhage group (26 cases), and intraventricular hemorrhage group (28 cases) according to the location of bleeding. Glasgow Outcome Scale (GOS), National Institutes of Health Neurological Deficit Scale (NIHSS), and long-term Karnofsky Performance Status (KPS) were compared among patients in different age groups, gender groups, and bleeding site groups at 1, 3, and 12 months after treatment. Results There was no significant difference in scores of GOS, NIHSS and KPS at 1 and 3 months between 24-34 age group and 35-45 age group (P＞0.05). The 12-month GOS, NIHSS and KPS scores of the 24-34 age group were significantly higher than those of the 35-45 age group (P＜0.05). There was no significant difference in GOS, NIHSS and KPS scores between male group and female group at 1, 3 and 12 months (P＞0.05). The scores of GOS, NIHSS and KPS in basal ganglia hemorrhage group were better than those in brainstem hemorrhage group and intraventricular hemorrhage group at 1 and 3 months, and the scores of GOS, NIHSS and KPS in brainstem hemorrhage group were better than those in basal ganglia hemorrhage group and intraventricular hemorrhage group at 12 months (P＜0.05). Conclusion The short-term prognosis of young patients with HIH is not directly related to age. But for the long-term prognosis, the younger the better. There is no correlation between the prognosis and gender in HIH in young people. The short-term prognosis of basal ganglia cerebral hemorrhage is better than brainstem hemorrhage and intraventricular hemorrhage. The long-term prognosis of brain stem hemorrhage is better than basal ganglia hemorrhage and intraventricular hemorrhage.

The application of deep neural networks in target detection has been widely adopted in various fields.However, the introduction of adversarial patch attacks, which add local perturbations to images to mislead deep neural networks, poses a significant threat to target detection systems based on vision techniques.To tackle this issue, an adversarial patch defense algorithm based on PatchTracker was proposed, leveraging the semantic differences between adversarial patches and image backgrounds.This algorithm comprised an upstream patch detector and a downstream data enhancement module.The upstream patch detector employed a YOLOV5 (you only look once-v5) model with attention mechanism to determine the locations of adversarial patches, thereby improving the detection accuracy of small-scale adversarial patches.Subsequently, the detected regions were covered with appropriate pixel values to remove the adversarial patches.This module effectively reduced the impact of adversarial examples without relying on extensive training data.The downstream data enhancement module enhanced the robustness of the target detector by modifying the model training paradigm.Finally, the image with removed patches was input into the downstream YOLOV5 target detection model, which had been enhanced through data augmentation.Cross-validation was performed on the public TT100K traffic sign dataset.Experimental results demonstrated that the proposed algorithm effectively defended against various types of generic adversarial patch attacks when compared to situations without defense measures.The algorithm improves the mean average precision (mAP) by approximately 65% when detecting adversarial patch images, effectively reducing the false negative rate of small-scale adversarial patches.Moreover, compared to existing algorithms, this approach significantly enhances the accuracy of neural networks in detecting adversarial samples.Additionally, the method exhibited excellent compatibility as it does not require modification of the downstream model structure.

Abstract Accurate building extraction is crucial for urban understanding, but it often requires a substantial number of building samples. While some building datasets are available for model training, there remains a lack of high-quality building datasets covering urban and rural areas in China. To fill this gap, this study creates a high-resolution GaoFen-7 (GF-7) Building dataset utilizing the Chinese GF-7 imagery from six Chinese cities. The dataset comprises 5,175 pairs of 512 × 512 image tiles, covering 573.17 km2. It contains 170,015 buildings, with 84.8% of the buildings in urban areas and 15.2% in rural areas. The usability of the GF-7 Building dataset has been proved with seven convolutional neural networks, all achieving an overall accuracy (OA) exceeding 93%. Experiments have shown that the GF-7 building dataset can be used for building extraction in urban and rural scenarios. The proposed dataset boasts high quality and high diversity. It supplements existing building datasets and will contribute to promoting new algorithms for building extraction, as well as facilitating intelligent building interpretation in China.

Abstract This multicenter, phase II study (NCT03872791) aims to evaluate the efficacy and safety of the anti-PD-L1/CTLA-4 bispecific antibody KN046 combined with nab-paclitaxel in the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC). The primary endpoints included objective response rate (ORR) and duration of response (DoR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) rate, safety, and the correlation of PD-L1 status with clinical efficacy. This trial met pre-specified endpoints. 27 female patients were enrolled sequentially to receive KN046 in two dose levels (3 mg/kg or 5 mg/kg). Among the 25 evaluable patients, the ORR achieved 44.0% (95% CI, 24.4% − 65.1%), and the median DoR was not mature. The median PFS reached 7.33 months (95%CI, 3.68 − 11.07 months), and the median OS was 30.92 months (95%CI, 14.75 - NE months). In PD-L1 positive patients, PFS was 8.61 months (versus 4.73 months) and the 2-year OS rate was 62.5% (versus 57.1%) compared to PD-L1 negative patients. Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.