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Abstract In recent years, with advancements in medicine, the survival period of patients with tumours has significantly increased. The adverse effects of tumour treatment on patients, especially cardiac toxicity, have become increasingly prominent. In elderly patients with breast cancer, treatment-related cardiovascular toxicity has surpassed cancer itself as the leading cause of death. Moreover, in recent years, an increasing number of novel antitumour drugs, such as multitargeted agents, antibody‒drug conjugates (ADCs), and immunotherapies, have been applied in clinical practice. The cardiotoxicity induced by these drugs has become more pronounced, leading to a complex and diverse mechanism of cardiac damage. The risks of unintended cardiovascular toxicity are increased by high-dose anthracyclines, immunotherapies, and concurrent radiation, in addition to traditional cardiovascular risk factors such as smoking, hypertension, diabetes, hyperlipidaemia, and obesity. However, these factors do not fully explain why only a subset of individuals experience treatment-related cardiac toxicity, whereas others with similar clinical features do not. Recent studies indicate that genetics play a significant role in susceptibility to the development of cardiovascular toxicity from cancer therapies. These genes are involved in drug metabolism, oxidative damage, cardiac dysfunction, and other processes. Moreover, emerging evidence suggests that epigenetics also plays a role in drug-induced cardiovascular toxicity. We conducted a review focusing on breast cancer as an example to help oncologists and cardiologists better understand the mechanisms and effects of genetic factors on cardiac toxicity. In this review, we specifically address the relationship between genetic alterations and cardiac toxicity, including chemotherapy-related genetic changes, targeted therapy-related genetic changes, and immune therapy-related genetic changes. We also discuss the role of epigenetic factors in cardiac toxicity. We hope that this review will improve the risk stratification of patients and enable therapeutic interventions that mitigate these unintended adverse consequences of life-saving cancer treatments.

Abstract Background Inetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated. Methods This prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. Results Forty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. Conclusion Neoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment. Trial registration NCT05749016 (registration date: Nov 01, 2021).

Abstract Edible oil adulteration is a mostly practiced phenomenon. However, the traditional discriminant methods fail to detect oil adulteration involving more than one adulterant. Recently, one‐class classifiers were built for food or oil authentication. Unfortunately, as it is hard to determine the application domain of the one‐class classifier, high prediction error was obtained for real samples in market surveillance. In this study, a new method was developed based on one‐class classification and outlier detection for edible oil adulteration detection in market surveillance. The model population was constructed using Monte Carlo sampling of unidentified inspected samples to select the plateau region exhibiting the highest accumulated absolute centered residual (ACR) values. Subsequently, the number of models in the plateau region was validated by the theoretical ones calculated by the classical probability model. The models in the plateau region with the highest cumulative accumulated ACR values were used to identify adulterated oils. Furthermore, the cross‐validation was conducted by comparing identification results from two different Monte Carlo sampling ratios to ensure the accuracy of our method. Both single adulteration and multiple adulteration of peanut oils were prepared to validate our method. Moreover, this method was used to detect adulteration of sesame oils, which have already been identified by the markers in our previous study. The validation results of three datasets indicated that this method could effectively identify adulterated samples and therefore provide a novel solution for inspecting potential adulteration in practice.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

Abstract Hematoma expansion (HE) is a high risky symptom with high rate of occurrence for patients who have undergone spontaneous intracerebral hemorrhage (ICH) after a major accident or illness. Correct prediction of the occurrence of HE in advance is critical to help the doctors to determine the next step medical treatment. Most existing studies focus only on the occurrence of HE within 6 h after the occurrence of ICH, while in reality a considerable number of patients have HE after the first 6 h but within 24 h. In this study, based on the medical doctors recommendation, we focus on prediction of the occurrence of HE within 24 h, as well as the occurrence of HE every 6 h within 24 h. Based on the demographics and computer tomography (CT) image extraction information, we used the XGBoost method to predict the occurrence of HE within 24 h. In this study, to solve the issue of highly imbalanced data set, which is a frequent case in medical data analysis, we used the SMOTE algorithm for data augmentation. To evaluate our method, we used a data set consisting of 582 patients records, and compared the results of proposed method as well as few machine learning methods. Our experiments show that XGBoost achieved the best prediction performance on the balanced dataset processed by the SMOTE algorithm with an accuracy of 0.82 and F1-score of 0.82. Moreover, our proposed method predicts the occurrence of HE within 6, 12, 18 and 24 h at the accuracy of 0.89, 0.82, 0.87 and 0.94, indicating that the HE occurrence within 24 h can be predicted accurately by the proposed method.

Objective: To analyze the impact of global population aging on cancer epidemiology, with a focus on the incidence and mortality rates among individuals aged 60 years and above. Methods: We utilized open-source data, retrieving population age estimates from the United Nations Population Division website. The GLOBOCAN 2020 database provided estimates for cancer cases and deaths in 2020 and 2040, while the Global Burden of Disease 2019 database supplied estimates of new cancer cases worldwide from 2000 to 2019. Inclusion criteria considered individuals aged 60 years and over, focusing on the top five deadliest cancers. The cohort-component method was employed for population prediction, with age-specific incidence and mortality rates estimated for 2020 used to forecast the cancer burden. Results: In 2021, the global population aged over 60 years accounted for 13.7%, with Europe/North America and Australia/New Zealand having the highest proportions. The older population is predicted to reach 19.2% by 2040. In 2020, of the 19.3 million new cancer cases worldwide, 64% occurred in individuals aged 60 and above, contributing to 71.3% of cancer-related deaths. The five most common cancer sites were the lung, colorectum, prostate, breast, and stomach. Cancer incidence and deaths are projected to rise significantly among older individuals, reaching 20.7 million new cases and 12.7 million deaths by 2040. Older age, tobacco use, dietary factors, alcohol consumption, and high body mass index (BMI) were identified as major risk factors for various cancers in this demographic. Conclusions: This study reveals a significant rise in cancer incidence and mortality among the elderly due to global population aging. The urgency for targeted interventions in cancer prevention, screening, and treatment for older individuals is emphasized. Despite acknowledged limitations, these findings contribute valuable insights to inform strategies for managing cancer in the elderly amidst evolving demographic trends.

BackgroundThe serious air pollution of highway toll booths poses a high occupational exposure risk to toll collectors. It is urgent to develop purification methods suitable for airborne particles and microbial pathogens in highway toll booths. ObjectiveTo verify the purification effect of low temperature plasma air purifiers on airborne particles and microbes in highway toll booths. MethodsBased on controlled-intervention design, we selected three toll booths in an expressway toll station as on-site experimental locations for 6 d (no-intervention period: the low-temperature plasma purifier was turned off in the first three days; intervention period: the purifier was turned on from 9:00 to 17:00 in the following three days). The indoor and outdoor PM2.5 and PM10 concentrations were continuously monitored during the study. At 9:00, 12:00, and 17:00 of every day during the experiment, indoor and outdoor air samples were collected to analyze the concentration of airborne culturable colonies with a plankton sampler. Airborne particle samples were collected in the outermost exit continuously from 9:00 to 17:00 every day during the experiment using a medium flow particulate sampler, and the species and relative abundance of fungi and bacteria contained in the samples were analyzed by gene sequencing. Independent-sample t test was used to compare the concentration of indoor PM2.5, PM10, and culturable colonies between the intervention period and the non-intervention period. α diversity analysis, β diversity analysis, and t test were used to compare the diversity and relative abundance of specific species of bacteria and fungi, as well as typical pathogenic bacteria and fungi in the samples between the non-intervention period and the intervention period to reflect the purification effect of low temperature plasma air purifier on airborne PM2.5, PM10, and microorganisms. ResultsDuring the intervention period, the mean indoor concentrations of PM2.5, PM10, and culturable colonies were lower than those of the no-intervention period (P

Abstract Background Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment. Materials and methods Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein–protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations. Results A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations. Conclusion Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA.

Abstract Climate change increases the risk of illness through rising temperature, severe precipitation and worst air pollution. This paper investigates how monthly excess mortality rate is associated with the increasing frequency and severity of extreme temperature in Canada during 2000-2020. The extreme associations were compared among four age groups across five sub-blocks of Canada based on the datasets of monthly T90 and T10, the two most representative indices of severe weather monitoring measures developed by the actuarial associations in Canada and US. We utilize a combined seasonal Auto-regressive Integrated Moving Average (ARIMA) and bivariate Peaks-Over-Threshold (POT) method to investigate the extreme association via the extreme tail index $$\chi$$ χ and Pickands dependence function plots. It turns out that it is likely (more than 10%) to occur with excess mortality if there are unusual low temperature with extreme intensity (all $$\chi >0.1$$ χ > 0.1 except Northeast Atlantic (NEA), Northern Plains (NPL) and Northwest Pacific (NWP) for age group 0-44), while extreme frequent high temperature seems not to affect health significantly (all $$\chi \le 0.001$$ χ ≤ 0.001 except NWP). Particular attention should be paid to NWP and Central Arctic (CAR) since population health therein is highly associated with both extreme frequent high and low temperatures (both $$\chi =0.3182$$ χ = 0.3182 for all age groups). The revealed extreme dependence is expected to help stakeholders avoid significant ramifications with targeted health protection strategies from unexpected consequences of extreme weather events. The novel extremal dependence methodology is promisingly applied in further studies of the interplay between extreme meteorological exposures, social-economic factors and health outcomes.

Abstract A fast, simple, and sensitive analytic method was proposed for the simultaneous quantification of aflatoxins (AFTs) and capsaicinoids in vegetable oils by immunomagnetic sorbent coupled with ultra‐performance liquid chromatography coupled with tandem mass spectrometry. The immunomagnetic solid phase extraction (IMSPE) sorbents were synthesized with the monoclonal antibodies via cyanogen bromide magnetic sorbents, which could modify the surface magnetic sorbents under mild synthetic condition. The IMSPE procedure had the following aspects such as ease manipulation, easy disperse, quick isolation, eco‐friendly, and cost‐effective. The major conditions of IMSPE procedure were systemically studied, and the optimized pretreatment was accomplished in 15 min avoding complicated condition or sophisticated equipment. Excellent linearities were achieved by the correlation (R2) more than 0.9983. The limits of quantifications of all analytes ranged from 0.03 to 0.20 µg kg−1, and the recoveries were satisfactory ranging from 75.7% to 124.0% with the intra‐day and inter‐day precisions less than 10.1%. Additionally, the proposed method was used to analyze AFTs and capsaicinoids in retail oil samples. Overall, 25% of soybean and peanut oils and 12.5% of corn and blended oil were detected with AFTs, and no capsaicinoid was found. The content of AFTs was under the MRLs set by EU and China regulation for food quality and safety. The validated results indicated that this method could be utilized for a rapid, efficient, and accurate quantification of AFTs and capsaicinoids in complex lipid‐based matrix.

With advances in satellite technology, Polarimetric Synthetic Aperture Radar (PolSAR) now have higher resolution and better data quality, providing excellent data conditions for the refined visual interpretation of artificial targets. The primary method currently used is a multicomponent decomposition, but this method can result in pixel misdivision problems. Thus, we propose a non-fixed threshold division method for achieving advanced feature ship structure characterization in full-polarimetric SAR images. Yamaguchi decomposition can effectively identify the primary scattering mechanism and characterize artificial targets. Its modified volume scattering model is more consistent with actual data. The polarization entropy can serve as the target scattering mechanism at a specified equivalent point in the weakly depolarized state, which can effectively highlight the ship structure. This paper combines the three components of the Yamaguchi decomposition algorithm with the entropy, and divides it into a nine-classification plane with a non-fixed threshold. This method reduces category randomness generated by noise at the threshold boundary for complicated threshold treatments. Furthermore, the Mixed Scattering Mechanism (MSM) which is the region where both secondary scattering and single scattering are significant, was proposed to better match the scattering types of typical structures of vessels in the experiment. The Generalized Similarity Parameter (GSP) was used to further shorten the intra-class distance and perform iterative clustering using a modified GSP-Wishart classifier. This method improves the vessel distinguishability by enhancing the secondary and mixed scattering mechanisms. Finally, this paper uses full-polarimetric SAR data from a port in Shanghai, China, for the experiment. We collected and filtered ship information and optical data from this port through the Automatic Identification System (AIS) and matched them with the ships in full-polarimetric SAR images to verify the correct characterization of each vessel’s features. The experimental results show that the proposed method can effectively distinguish three types of vessels: bulk carriers, container ships and tankers.

Abstract Background CDK4/6 inhibitors in combination with traditional endocrine therapy (ET) have become the recommended first‐line therapy for HR‐positive/HER2‐negative metastatic breast cancer (MBC). The aim of this prospective study was to evaluate the relationship between HER2‐low expression and clinical outcomes in HR‐positive/HER2‐negative MBC patients receiving ET with or without CDK4/6 inhibitors. Methods Between April 2016 and November 2019, 233 women with HR‐positive/HER2‐negative MBC who received ET with or without CDK4/6 inhibitors were enrolled into the study. The primary endpoint was progression‐free survival (PFS). Statistical analysis included descriptive statistics, Kaplan–Meier curves, and Cox proportional hazards models. Results HER2‐low and HER2‐zero subgroups in the CDK4/6 inhibitor plus ET cohort showed no significant difference in the median PFS (10.9 vs. 8.0 months; hazard ratio: 0.92; 95% confidence interval [CI]: 0.64–1. 30; p = 0.65), while HER2‐low subgroup showed a significantly shorter median PFS compared to the HER2‐zero subgroup in the ET alone cohort (5.6 vs. 17.0 months; hazard ratio: 2.82; 95% CI: 1.34–5.93; p = 0.0044). Moreover, the objective response rate was significantly lower in the HER2‐low subgroup than the HER2‐zero subgroup in the ET alone cohort (10.5% vs. 40.0%, p = 0.047). Lastly, no significant difference was observed in the overall survival between the HER2‐low and HER2‐zero subgroups in both cohorts. Conclusion This study suggested that HER2‐low expression may predict the efficacy of ET but not that of CDK4/6 inhibitor plus ET in HR‐positive/HER2‐negative MBC patients. The results of this study highlight the importance of integrating HER2 status in tailoring personalized treatment strategies for HR‐positive MBC.

Abstract Stable isotopes, multi‐elements, metabolic profiles, and integrated spectroscopic fingerprints are priority options for food geographical origin traceability. However, til now, it is still hard to detect adteration with the same one from other geographic origins, which is harder than geographical origin traceability. In this study, partial least square discriminant analysis was employed to build a classification model to discriminate the domestic and imported soybeans after variable selection by uninformative variable elimination using near infrared hyperspectral imaging. As a result, this model could completely discriminate domestic and imported soybeans. Moreover, the developed model was used to detect the adulterated domestic soybean was adulterated with 13.3%, 20.0%, 26.7%, and 33.3% of imported soybean. When the skewness value was less than 0.76 and kurtosis value was less than 1.57 of a sample, the sample was considered as the adulterated. The results indicated that the domestic soybeans adulterated with 20.0%, 26.7%, and 33.3% of imported soybeans were successfully identified. This method could not only identify origin traceability but also detect adulteration of soybeans, which will be beneficial to guarantee the quality and safety of soybean.

Background: Traumatic injuries to the lower extremities are frequently accompanied by extensive soft tissue loss, combined with vascular damage or exposure of bony tissues, making it difficult to reconstruct; consequently, patients are commonly at risk of amputation. Due to its superior anatomical and biochemical properties, the omental flap has been used to reconstruct soft tissue defects for decades. However, few studies have reported the omental flap's effectiveness in treating severe and complex lower extremity deformities. We attempted to use a laparoscopically harvested omental flap in conjunction with a second-stage skin graft to reduce infections during limb preservation, increase flap survival probability, and restore the aesthetic and functional integrity of the affected extremity. Methods: Seventeen patients with severe lower extremity wounds underwent omental flap transplantation and were followed up for 6 to 12 months to check for surgical complications, evaluate cosmetic results, and ensure proper limb function. Results: There were no complications, such as intestinal adhesion, intestinal volvulus, and peritonitis, with any of the omental grafts. The affected extremities were well-functioning and aesthetically pleasing. Conclusion: Laparoscopically harvested omental flap transplantation with skin grafting is an alternative reconstruction technique for severe lower extremity injuries with massive soft tissue loss and exposed bones and tendons.

Summary: The rearrangement and expression of the immunoglobulin μ heavy chain (Igh) gene require communication of the intragenic Eμ and 3′ regulatory region (RR) enhancers with the variable (VH) gene promoter. Eμ binding of the transcription factor YY1 has been implicated in enhancer-promoter communication, but the YY1 protein network remains obscure. By analyzing the comprehensive proteome of the 1-kb Eμ wild-type enhancer and that of Eμ lacking the YY1 binding site, we identified the male-specific lethal (MSL)/MOF complex as a component of the YY1 protein network. We found that MSL2 recruitment depends on YY1 and that gene knockout of Msl2 in primary pre-B cells reduces μ gene expression and chromatin looping of Eμ to the 3′ RR enhancer and VH promoter. Moreover, Mof heterozygosity in mice impaired μ expression and early B cell differentiation. Together, these data suggest that the MSL/MOF complex regulates Igh gene expression by augmenting YY1-mediated enhancer-promoter communication.

Summary: Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC. Methods: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan–Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135. Findings: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48–1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41–0.66, p

This study was based on QuEChERS cleanup coupled with UHPLC-MS/MS for the determination of γ-oryzanol compounds in vegetable oils. Several parameters of QuEChERS and UHPLC-MS/MS were studied for purification and detection of γ-oryzanol compounds in oil samples. Under the optimized conditions, the whole pretreatment procedure could be accomplished within 10 min without tedious procedure, larger volume of organic solvent and complicated apparatus. The limit of detections and the limit of quantifications for γ-oryzanol compounds were ranging from 0.1-0.3 µg kg−1 and 0.4–1.0 µg kg−1, respectively. Satisfactory recoveries of all analyts were ranging from 72.2 % to 101.3 %, and the intra-day and inter-day precision were less than 10.6 %. The validation indicated that rice band oil and corn oil were rich in 24-mCAF, CAF, β-SIF, CMF and STF. The QuEChERS-UHPLC-MS/MS simultaneously quantified five γ-oryzanol compounds in lipid matrices and assessed the nutritional and functional substances of vegetable oils.

The unique advantage of optical-resolution photoacoustic microscopy (OR-PAM) is its ability to achieve high-resolution microvascular imaging without exogenous agents. This ability has excellent potential in the study of tissue microcirculation. However, tracing and monitoring microvascular morphology and hemodynamics in tissues is challenging because the segmentation of microvascular in OR-PAM images is complex due to the high density, structure complexity, and low contrast of vascular structures. Various microvasculature extraction techniques have been developed over the years but have many limitations: they cannot consider both thick and thin blood vessel segmentation simultaneously, they cannot address incompleteness and discontinuity in microvasculature, there is a lack of open-access datasets for DL-based algorithms. We have developed a novel segmentation approach to extract vascularity in OR-PAM images using a deep learning network incorporating a weak signal attention mechanism and multi-scale perception (WSA-MP-Net) model. The proposed WSA network focuses on weak and tiny vessels, while the MP module extracts features from different vessel sizes. In addition, Hessian-matrix enhancement is incorporated into the pre-and post-processing of the input and output data of the network to enhance vessel continuity. We constructed normal vessel (NV-ORPAM, 660 data pairs) and tumor vessel (TV-ORPAM, 1168 data pairs) datasets to verify the performance of the proposed method. We developed a semi-automatic annotation algorithm to obtain the ground truth for our network optimization. We applied our optimized model successfully to monitor glioma angiogenesis in mouse brains, thus demonstrating the feasibility and excellent generalization ability of our model. Compared to previous works, our proposed WSA-MP-Net extracts a significant number of microvascular while maintaining vessel continuity and signal fidelity. In quantitative analysis, the indicator values of our method improved by about 1.3% to 25.9%. We believe our proposed approach provides a promising way to extract a complete and continuous microvascular network of OR-PAM and enables its use in many microvascular-related biological studies and medical diagnoses.

Grain boundaries (GBs) play a crucial role on the structural stability and mechanical properties of Cu and its alloys. In this work, molecular dynamics (MD) simulations are employed to study the effects of Fe solutes on the formation energy, excess volume, dislocations and melting behaviors of GBs in CuFe alloys. It is illustrated that Fe solute affects the structural stability of Cu GBs substantially, the formation energy of GBs is reduced, but the thickness and melting point of GBs are increased, that is, the structural stability of Cu GBs is significantly improved owing to the Fe solutes. A strong scaling law exists between the formation energy, excess volume, thickness and melting point of GBs. Therefore, Fe solid solute plays an important role in the characteristics of GBs in bi-crystal Cu.

[Objective] Conventional positioning stiffness of rail transit vehicle bogies results in significant lateral forces between wheels and rails, leading to substantial wear and reduced operational efficiency when navigating curves with small to medium radii. To enhance the operational stability and curve negotiation performance of rail transit vehicles, an active radial system for bogies is proposed. [Method] The active radial system and the control principles are introduced. The software and hardware design process of the radial controller is outlined. A vehicle dynamics model is established, integrating with other system components. The functionality and performance of the radial controller are verified through semi-physical simulation experiments and circular track tests. [Result & Conclusion] Whether adopting a guided active detection mode or a precise beacon detection mode, the radial controller can effectively detect curve segments, aligning the bogie wheelsets toward radial positions during curve negotiation in accordance with the actual track information. When entering or exiting curves, the radial controller can drive the radial actuator to act immediately or in advance, effectively reducing the lag time. Simulation and circular track test results demonstrate that trains equipped with bogies featuring the active radial system exhibit a consistent and significantly lower variation in wheel-rail lateral force compared to conventional passive curve negotiation states. The performance of the guiding wheelsets is particularly outstanding. The proposed active radial controller improves the curve negotiation performance of trains and reduces wheel-rail wear.

Deep learning has shown remarkable proficiency in tasks related to synthetic aperture radar (SAR) interpretation. However, several studies have highlighted the inherent vulnerability of deep neural networks when faced with deliberately constructed adversarial examples (AEs). Current SAR adversarial attack research only focuses on generating AEs in the image domain, without considering SAR imaging systems. This approach can lead to two issues. First, the generated SAR AEs lack visual coherence. Second, they cannot be obtained as corresponding attack images through real SAR imaging systems. In this article, we propose a physically realizable SAR adversarial attack method, which includes two submodules based on optimization methods: Target perturbation generation and background perturbation generation. The former module utilizes attention mechanisms to extract the target regions from SAR images, followed by selecting the optimal small regions for perturbation placement. The latter module, on the other hand, utilizes scattering models to generate realistic scatterer images as perturbations, which are then optimized to identify the optimal position in the background regions. The individual attack performance of these two attack modules on five well-established SAR automatic target recognition models is demonstrated to be highly effective. Moreover, the combination of these attack modules achieves a fooling rate of approximately 90% and demonstrates superior adversarial transferability. The experimental results of this study provide an effective foundation for physical realization of SAR AEs.

Chromosome karyotyping is an important yet labor-intensive procedure for diagnosing genetic diseases. Automating such a procedure drastically reduces the manual work of cytologists and increases congenital disease diagnosing precision. Researchers have contributed to chromosome segmentation and classification for decades. However, very few studies integrate the two tasks as a unified, fully automatic procedure or achieved a promising performance. This paper addresses the gap by presenting: 1) A novel chromosome segmentation module named ChrRender, with the idea of rendering the chromosome instances by combining rich global features from the backbone and coarse mask prediction from Mask R-CNN; 2) A devised chromosome classification module named ChrNet4 that pays more attention to channel-wise dependencies from aggregated informative features and calibrating the channel interdependence; 3) An integrated Render-Attention-Architecture to accomplish fully automatic karyotyping with segmentation and classification modules; 4) A strategy for eliminating differences between training data and segmentation output data to be classified. These proposed methods are implemented in three ways on the public Q-band BioImLab dataset and a G-band private dataset. The results indicate promising performance: 1) on the joint karyotyping task, which predicts a karyotype image by first segmenting an original microscopical image, then classifying each segmentation output with a precision of 89.75% and 94.22% on the BioImLab and private dataset, respectively; 2) On the separate task with two datasets, ChrRender obtained AP50 of 96.652% and 96.809% for segmentation, ChrNet4 achieved 95.24% and 94.07% for classification, respectively. The COCO format annotation files of BioImLab used in this paper are available at https://github.com/Alex17swim/BioImLab The study introduces an integrated workflow to predict a karyotyping image from a Microscopical Chromosome Image. With state-of-the-art performance on a public dataset, the proposed Render-Attention-Architecture has accomplished fully automatic chromosome karyotyping.

Abstract Background Triple‐positive breast cancer (TPBC) is highly invasive and lacks well‐established treatment strategies, especially in patients with advanced stage disease. This study aimed to explore the efficacy of everolimus in patients with metastatic TPBC (mTPBC) in a multicenter real‐world setting. Methods A total of 2518 cancer patients who received everolimus‐based therapy were enrolled from three cancer institutes in China from 2014 to 2022. Their clinicopathological characteristics were collected from medical records. The indicators for the efficacy of everolimus were progression‐free survival (PFS), objective response rate (ORR) and clinical benefit rate (CBR). Results We collected 79 HER2‐enriched patients that were treated with everolimus‐based therapy, 43 of whom were mTPBC. The most commonly used therapeutic combinations was everolimus plus endocrine therapy (18/43, 41.9%). Among all combinations, everolimus plus chemotherapy plus trastuzumab developed the longest PFS of 10.9 months (95% CI: 1.5–20.3). Seventeen patients (32.6%) with mTPBC received everolimus as frontline treatment (1 L/2 L/3 L, FL), and 26 patients (67.4%) as backline treatment (>3 L, BL). Among all the population, the median PFS for everolimus was 4.5 months (range: 3.0–6.0), ORR was 30.2%, and CBR was 48.8%. PFSFL of 10.9 months was significantly longer than 4.0 months for PFSBL (p = 0.003, HR = 0.31, 95% CI: 0.14–0.67). ORRFL was 41.2%, showing no significance compared to ORRBL of 23.1% (one‐sided p = 0.11). CBRFL was observed better of 76.5% versus CBRBL of 46.2% (one‐sided p = 0.026). Conclusion Everolimus as frontline treatment achieves clinical benefits for Chinese patients with mTPBC, which may provide some references for the management of Chinese mTPBC patients.

Background: Clinical research competence determines the quality of clinical research and the reliability of research findings. We aimed to explore the clinical research implementation capabilities of breast cancer treatment departments in China. Methods: This was a department-based cross-sectional study conducted in the form of electronic questionnaires on the Wenjuanxing platform from 7th August to 31st August 2023 among hospitals from the first batch of breast cancer standardized diagnosis and treatment quality control pilot centers in China. Results: A total of 127 questionnaires from 122 hospitals were ultimately included in the analysis. Medical personnel involved in the clinical research of 118 (92.9 %) departments received good clinical practice (GCP) training. The steps of the approval process from research initiation to completion lasted 2–4 weeks or longer. The majority of departments initiated or participated in 2 or fewer clinical research projects over the past year. Among the differences between different departments, the Department of Medical Oncology had a better qualification profile and process and greater number of initiated and participated clinical studies than did the Department of Surgical Oncology. For needs and problems, most of the departments were strongly willing to undertake clinical research and receive professional training; the most common problem in the process of conducting studies was patient recruitment. Conclusions: Most departments generally exhibited complete capabilities for implementing clinical research. Improvements in implementation efficiency, quality of research and patient recruitment are still needed. Professional training and communication, as well as the recommendation of clinical research, are required in future development.

Background: The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues，contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. Methods: To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. Results: The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. Conclusion: In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.

ABSTRACT: Meat qualities of free-range chicken (Xuan-Zhou) (XZ-FRC) are closely associated with slaughter age and directly influence the economic benefits of supplier and consumer's preference. Understanding of the relationship between meat qualities and ages will be of prime important to explore a better slaughter age of XZ-FRC. In this study, the quality traits of breast and thigh muscles from XZ-FRCs at 9 to 14 wk were analyzed to establish a relatively reliable method for selecting a better slaughter age. The results showed that the effects of slaughter ages on color (CIE L*, a* and b* values), shear force, centrifugal loss, and flavor of XZ-FRCs were significant (P < 0.05). There were greater differences in meat qualities, whatever breast or thigh muscles, between same or different ages. Eleven feature indexes used for colligation evaluation of slaughter age were selected by combining the quality characteristics and data analysis. The score of colligation evaluation for XZ-FRCs at 12 wk was higher than that at 9 and 14 wk, suggesting that the 12 wk was an optimal slaughter age. This work would provide a reference method that helps the producers of livestock and poultry to select a better slaughter age.

When constructing a multiple automated guided vehicle (multi-AGV) system, it is essential to calculate the potential values of the system’s feature parameters. This article presents two time-cost calculators and an improved simulation platform for scientifically estimating the cost of constructing a multi-AGV system. By inputting the parameters of the number of automated guided vehicles (AGVs), the velocity of the AGV, the number of tasks, scheduling interval and path length, the designed calculator can output the system’s time expense when all tasks are completed. The designed simulation platform can display a specific multi-AGV system’s time cost and how the entire progress works in a visual interface. An advanced scheduling method based on handover mode and A* algorithm is used to solve task scheduling problems in a multi-AGV system. The overall performance of the newly integrated scheduling system is compared with other scheduling systems to validate its superiority and shortcomings in different corresponding work scenarios. The final results present a robust solution to improve a multi-AGV system’s effectiveness.

IntroductionThis study aimed to explore the transcriptomic profile of premature ovarian insufficiency (POI) by investigating alterations in gene expression.MethodsA total of sixty-one women, comprising 31 individuals with POI in the POI group and 30 healthy women in the control group (HC group), aged between 24 and 40 years, were recruited for this study. The transcriptomic profiles of peripheral blood samples from all study subjects were analyzed using RNA-sequencing.ResultsThe results revealed 39 differentially expressed genes in individuals with POI compared to healthy controls, with 10 upregulated and 29 downregulated genes. Correlation analysis highlighted the relationship between the expression of SLC25A39, CNIH3, and PDZK1IP1 and hormone levels. Additionally, an effective classification model was developed using SLC25A39, CNIH3, PDZK1IP1, SHISA4, and LOC389834. Functional enrichment analysis demonstrated the involvement of these differentially expressed genes in the “haptoglobin-hemoglobin complex,” while KEGG pathway analysis indicated their participation in the “Proteoglycans in cancer” pathway.ConclusionThe identified genes could play a crucial role in characterizing the genetic foundation of POI, potentially serving as valuable biomarkers for enhancing disease classification accuracy.

Introduction Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found.Methods/design The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35–45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases.Ethics and dissemination The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2300072472).

PurposeThis study was based on the Global Burden of Disease (GBD) database and aimed to analyze the trend of disease burden for complete edentulism in Chinese adults between 1990 and 2030, and to provide valuable information for the development of more effective management and preventive measures.MethodsData on Chinese adults with complete edentulism from 1990 to 2019 was analyzed using GHDx data. Descriptive analyses were used to analyze changes in the prevalence and burden of complete edentulism, gender and age distribution between 1990 and 2019. In addition, we used an autoregressive integrated moving average (ARIMA) model to predict the trend of disease burden for Chinese adults with complete edentulism between 2020 and 2030.ResultsThe incidence, prevalence, and rate of YLDs in adults with complete edentulism in China showed an increasing trend from 1990 to 2019. In 2019, the incidence was 251.20 per 100,000, the prevalence was 4512.78 per 100,000, and the YLDs were 123.44 per 100,000, marking increases of 20.58, 94.18, and 93.12% from 1990. Males experienced a higher increase than females. However, the standardized rates decreased over the same period. The ARIMA model predicts a subsequent upward and then downward trend for all indicators between 2019 and 2030, except for the standardized incidence rate which remained essentially unchanged. Specifically, the incidence is predicted to decrease from 388.93 to 314.40 per 100,000, prevalence from 4512.78 to 3049.70 per 100,000, and YLDs from 123.44 to 103.44 per 100,000. The standardized prevalence and YLDs rates are also expected to decrease.ConclusionThe burden of complete edentulism in China is projected to show an increasing trend from 2020 to 2022 and a decreasing trend from 2023 to 2030. Despite the decline in the burden of disease associated with complete edentulism in China, many problems remain to be solved.

Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 μM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development.

Breast cancer has become the most prevalent malignancy worldwide; however, therapeutic efficacy is far from satisfactory. To alleviate the burden of this disease, it is imperative to discover novel mechanisms and treatment strategies. Protein phosphatase 2 A (PP2A) comprises a family of mammalian serine/threonine phosphatases that regulate many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathologies, and plays a pivotal role in the initiation and progression of tumours. The role of PP2A as a tumour suppressor has been extensively studied, and its regulation can serve as a target for anticancer therapy. Recent studies have shown that PP2A is a tumour promotor. PP2A-mediated anticancer therapy may involve two opposing mechanisms: activation and inhibition. In general, the contradictory roles of PP2A should not be overlooked, and more work is needed to determine the molecular mechanism by which PP2A affects in tumours. In this review, the literature on the role of PP2A in tumours, especially in breast cancer, was analysed. This review describes relevant targets of breast cancer, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may lead to effective therapeutic strategies or influence drug development in breast cancer.

Multimodal emotion recognition techniques are increasingly essential for assessing mental states. Image-based methods, however, tend to focus predominantly on overt visual cues and often overlook subtler mental state changes. Psychophysiological research has demonstrated that heart rate (HR) and skin temperature are effective in detecting autonomic nervous system (ANS) activities, thereby revealing these subtle changes. However, traditional HR tools are generally more costly and less portable, while skin temperature analysis usually necessitates extensive manual processing. Advances in remote photoplethysmography (r-PPG) and automatic thermal region of interest (ROI) detection algorithms have been developed to address these issues, yet their accuracy in practical applications remains limited. This study aims to bridge this gap by integrating r-PPG with thermal imaging to enhance prediction performance. Ninety participants completed a 20-min questionnaire to induce cognitive stress, followed by watching a film aimed at eliciting moral elevation. The results demonstrate that the combination of r-PPG and thermal imaging effectively detects emotional shifts. Using r-PPG alone, the prediction accuracy was 77% for cognitive stress and 61% for moral elevation, as determined by a support vector machine (SVM). Thermal imaging alone achieved 79% accuracy for cognitive stress and 78% for moral elevation, utilizing a random forest (RF) algorithm. An early fusion strategy of these modalities significantly improved accuracies, achieving 87% for cognitive stress and 83% for moral elevation using RF. Further analysis, which utilized statistical metrics and explainable machine learning methods including SHapley Additive exPlanations (SHAP), highlighted key features and clarified the relationship between cardiac responses and facial temperature variations. Notably, it was observed that cardiovascular features derived from r-PPG models had a more pronounced influence in data fusion, despite thermal imaging’s higher predictive accuracy in unimodal analysis.

Abstract Background The wide use of antibody‐drug conjugates (ADCs) is transforming the cancer‐treatment landscape. Understanding the treatment‐related adverse events (AEs) of ADCs is crucial for their clinical application. We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies. Methods We searched the PubMed, Embase, and Cochrane Library databases for articles published from January 2001 to October 2022. The overall profile and incidence of all‐grade and grade ≥ 3 treatment‐related AEs were the primary outcomes of the analysis. Results A total of 138 trials involving 15,473 patients were included in this study. The overall incidence of any‐grade treatment‐related AEs was 100.0% (95% confidence interval [CI]: 99.9%–100.0%; I2 = 89%) and the incidence of grade ≥ 3 treatment‐related AEs was 6.2% (95% CI: 3.0%–12.4%; I² = 99%). Conclusions This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment. ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade ≥ 3 AEs. The AE profiles and incidence differed according to cancer type, ADC type, and ADC components.

Abstract Background and purpose To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value

This paper proposes an enhanced multi-strategy sparrow search algorithm to optimize the trajectory of a six-axis industrial robot, addressing issues of low efficiency and high vibration impact on joints during operation. Initially, the improved D-H parametric method is employed to establish both forward and inverse kinematic models of the robot. Subsequently, a 3-5-3 mixed polynomial interpolation trajectory planning approach is applied to the robot. Building upon the conventional sparrow algorithm, a two-dimensional Logistic chaotic system initializes the population. Additionally, a Levy flight strategy and nonlinear adaptive weighting are introduced to refine the discoverer position update operator, while an inverse learning strategy enhances the vigilante position update operator. These modifications boost both the local and global search capabilities of the algorithm. The improved sparrow algorithm, based on 3-5-3 hybrid polynomial trajectory planning, is then used for the time-optimal trajectory planning of the robot. This is compared with traditional sparrow search algorithm and particle swarm algorithm optimization results. The findings indicate that the proposed enhanced sparrow search algorithm outperforms both the standard sparrow algorithm and the particle swarm algorithm in terms of convergence speed and accuracy for robot trajectory optimization. This can lead to the increased work efficiency and performance of the robot.

The world’s transportation system is overburdened by ever-growing travel demand, which brings mobility, safety, and pollution problems. To combat these issues and make better use of existing road capacity on urban arterials, public transit buses are designed to carry more people in fewer vehicles. However, transit buses travel slowly and make frequent intermittent stops, resulting in unreliable travel times and inconvenient riding experiences; this hinders people from choosing to travel on public transit buses. However, a research gap exists in using connected and automated vehicle (CAV) technologies specifically for transit bus operation optimization. To bridge this gap, the present study extended CAV applications to transit bus operation and developed a transit bus control method based on cooperative adaptive cruise control (CACC). The proposed model first optimized bus segment speeds to minimize schedule deviations and fuel consumption. Then, a CACC algorithm was integrated with optimal segment speed. The proposed control method was implemented through micro-simulations of an actual corridor in Jinan, Shandong, China. The evaluation results indicate that the proposed control method reduced the total arrival deviation up to 65.1% and total fuel consumption up to 6.8%. The study adapts CAV technologies to transit bus operation. The findings in this study validate CAV applications in transit bus operation.

Low back pain caused by disc herniation and spinal stenosis imposes an enormous medical burden on society due to its high prevalence and refractory nature. This is mainly due to the long-term inflammation and degradation of the extracellular matrix in the process of intervertebral disc degeneration (IVDD), which manifests as loss of water in the nucleus pulposus (NP) and the formation of fibrous disc fissures. Biomaterial repair strategies involving hydrogels play an important role in the treatment of intervertebral disc degeneration. Excellent biocompatibility, tunable mechanical properties, easy modification, injectability, and the ability to encapsulate drugs, cells, genes, etc. make hydrogels good candidates as scaffolds and cell/drug carriers for treating NP degeneration and other aspects of IVDD. This review first briefly describes the anatomy, pathology, and current treatments of IVDD, and then introduces different types of hydrogels and addresses “smart hydrogels”. Finally, we discuss the feasibility and prospects of using hydrogels to treat IVDD.

ABSTRACTBackground Despite poor oral hygiene, the Baiku Yao (BKY) ethnic group in China presents a low prevalence of dental caries, which may be related to genetic susceptibility. Due to strict intra-ethnic marriage rule, this ethnic has an advantage in studying the interaction between genetic factors and other regulatory factors related to dental caries.Methods Peripheral blood from a caries-free adult male was used for whole genome sequencing, and the BKY assembled genome was compared to the Han Chinese genome. Oral saliva samples were collected from 51 subjects for metabolomic and metagenomic analysis. Multiomics data were integrated for combined analysis using bioinformatics approaches.Results Comparative genomic analysis revealed the presence of structural variations in several genes associated with dental caries. Metabolomic and metagenomic sequencing demonstrated the caries-free group had significantly higher concentration of antimicrobials and higher abundance of core oral health-related microbiota. The functional analysis indicated that cationic antimicrobial peptide resistance and the lipopolysaccharide biosynthesis pathway were enriched in the caries-free group.Conclusions Our study provided new insights into the specific regulatory mechanisms that contribute to the low prevalence of dental caries in the specific population and may provide new evidence for the genetic diagnosis and control of dental caries.

Purpose: To analyze the safety and efficacy of orally administered metronomic capecitabine plus pyrotinib in HER2 positive metastatic breast cancer (MBC) patients, we conducted a prospective phase II study with a single-arm design. Methods: HER2 positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety. Results: The study included 50 patients with MBC that was HER2-positive, while 1 patient was excluded due to nonstandard medication. The median PFS and OS was 11.9 months (95%CI 8.8–14.6) and 29.3 months (95%CI 24.4–34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse events included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15(30.6%) patients, including hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). 1 grade 4 adverse event of diarrhea (2.0%) was observed. Conclusion: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2 positive metastatic breast cancer patients.

Abstract Background This study sought to compare the benefits and safety of agents including Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors as second-line treatments for these patients by conducting a comprehensive systematic review and network meta-analysis. Methods The Medline, Embase and Cochrane Library databases were searched for randomized trials comparing CDK4/6 inhibitors, PI3K/mTOR inhibitors, or HDAC inhibitors vs. placebo with the addition of exemestane or fulvestrant as second-line treatments in patients with HR + advanced breast cancer up to December 16, 2021. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), clinical benefit rate (CBR), and grade 3–4 adverse drug events (ADEs). The present study was conducted according to the Cochrane Collaboration and PRISMA statements. The overall effect was pooled using the random effects model. Results Seventeen studies with a total of 9,100 participants were included in the current study. Compared with placebo plus fulvestrant, PFS was significantly improved by CDK4/6 inhibitor plus fulvestrant, mTOR inhibitor plus fulvestrant, mTOR inhibitor plus exemestane, and PI3K inhibitor plus fulvestrant, but not HDAC inhibitor plus exemestane. While mTOR inhibitor plus exemestane was the best regimen (SUCRA value 89.5%), the mTOR inhibitor plus exemestane regimen induced more severe adverse events (SAEs) than the HDAC inhibitor plus exemestane regimen [OR, 95% CI: 2.40 (1.40–4.10)]. Conclusion mTOR inhibitor and CDK4/6 inhibitor-based regimens demonstrated superior clinical efficacy and comparable safety profiles as second-line treatment in patients with HR-positive, HER2-negative advanced breast cancer.

Abstract Background This single‐arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in women with HER2‐negative metastatic breast cancer (MBC) in China. Methods The mNC regimen was administered to the enrolled cases, including oral vinorelbine (VNR) 40 mg three times weekly (on days 1, 3 and 5 every week) and capecitabine (CAP) 500 mg three times a day, until disease progression or intolerable toxicity. The primary endpoint was the 1‐year progression‐free survival (PFS) rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and treatment‐related adverse events (TRAEs). Stratified factors included treatment lines and hormone receptor (HR) status. Results Between June 2018 and March 2023, 29 patients were enrolled into the study. The median follow‐up time was 25.4 months (range, 2.0–53.8). In the entire group, the 1‐year PFS rate was 54.1%. ORR, DCR and CBR were 31.0%, 96.6% and 62.1%, respectively. The mPFS was 12.5 months (range, 1.1–28.1). Subgroup analysis revealed that ORRs were 29.4% and 33.3% in first‐ and ≥second‐line chemotherapy, respectively. ORRs were 29.2% (7/24) and 40.0% (2/5) for HR‐positive MBC and metastatic triple‐negative breast cancer (mTNBC), respectively. Grade 3/4 TRAEs were neutropenia (10.3%) and nausea/vomiting (6.9%). Conclusions The dual oral mNC regimen showed very good safety features and improved compliance without loss of efficacy in both first‐ and second‐line treatments. The regimen also reached an excellent ORR in the mTNBC subgroup.

In this note we proved that each nonlinear generalized semi-Jordan triple derivable mapping on completely distributive commutative subspace lattice algebras is an additive derivation.

Abstract Thanks to the significantly higher energy density compared with universal commercialized Li‐ion batteries, lithium–sulfur (Li–S) batteries are being investigated for use in prospective energy storage devices. However, the inadequate electrochemical kinetics of reactants and intermediates hinder commercial utilization. This limitation results in substantial capacity degradation and short battery lifespans, thereby impeding the battery's power export. Meanwhile, the capacity attenuation induced by the undesirable shuttle effect further hinders their industrialization. Considerable effort has been invested in developing electrocatalysts to fix lithium polysulfides and boost their conversion effectively. In the conventional process, the planar electrodes are prepared by slurry‐casting, which limits the electron and ion transfer paths, especially when the thickness of the electrodes is relatively large. Compared with traditional manufacturing methods, direct ink writing (DIW) technology offers unique advantages in both geometry shaping and rapid prototyping, and even complex three‐dimensional structures with high sulfur loading. Hence, this review presents a detailed description of the current developments in terms of Li–S batteries in DIW of metal‐based electrocatalysts. A thorough exploration of the behavior chemistry of electrocatalysis is provided, and the adhibition of metal‐based catalysts used for Li–S batteries is summarized from the aspect of material usage and performance enhancement. Then, the working principle of DIW technology and the requirements of used inks are presented, with a detailed focus on the latest advancements in DIW of metal‐based catalysts in Li–S battery systems. Their challenges and prospects are discussed to guide their future development.

Abstract Background Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastasis (BrM) and a poor prognosis. As the most lethal form of breast cancer, BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis (BCBrM), but the underlying mechanisms are far from being fully elucidated. Methods Through analysis of BCBrM transcriptome data from mice and patients, and immunohistochemical validation on patient tissues, we identified and verified the specific down-regulation of retinoic acid receptor responder 2 (RARRES2), a multifunctional adipokine and chemokine, in BrM of TNBC. We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies. Key signaling pathway components were evaluated using multi-omics approaches. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2. Results We found that down-regulation of RARRES2 is specifically associated with BCBrM, and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue (PTEN)-mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment. Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM. RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Abstract Purpose To establish an early clinical diagnosis model based on the retinal vascular features associated with POI, supplying a non-invasive way for accurately and early predicted the risk of POI. Methods A total of 78 women with spontaneous POI and 48 healthy women were recruited from the Affiliated Shenzhen Maternity & Child Healthcare Hospital in the study. Retinal characteristics were analyzed using an automated retinal image analysis system. Binary logistic regression was used to identify POI cases and develop predictive models. Results Compared to the normal group, the POI group had larger central retinal artery equivalent (CRAE) (P = 0.006), central retinal vein equivalent (CRVE) (P = 0.001), index of venules asymmetry (Vasym) (P = 0.000); larger bifurcation angles of arterioles (Aangle) (P = 0.001), bifurcation coefficient of venule (BCV) (P = 0.001) and more obvious arteriovenous nipping (Nipping) (P = 0.005), but lower arteriole-to-venule ratio (AVR) (P = 0.012). In the POI group, the odds ratio (OR) of Vasym was 6.72e-32 (95% C.I. 4.62e-49–9.79e-15, P = 0.000), the OR of BCV was 5.66e-20 (95% C.I. 1.93e-34–.0000, P = 5.66e-20) and the OR of Nipping was 6.65e-06 (95% C.I. 6.33e-10–.0698, P = 0.012). Moreover, the area under the ROC curve for the binary logistic regression with retinal characteristics was 0.8582, and the fitting degree of regression models was 60.48% (Prob > chi-square = 0.6048). Conclusion This study demonstrated that retinal image analysis can provide useful information for POI identification and certain characteristics may help with early clinical diagnosis of POI.