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Abstract Background Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure–function relationship, and is also of great interest in protein engineering and pharmaceutical design. Results Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes. mutDDG-SSM consists of two parts: a graph attention network-based protein structural feature extractor that is trained with a self-supervised learning scheme using large-scale high-resolution protein structures, and an eXtreme Gradient Boosting model-based stability change predictor with an advantage of alleviating overfitting problem. The performance of mutDDG-SSM was tested on several widely-used independent datasets. Then, myoglobin and p53 were used as case studies to illustrate the effectiveness of the model in predicting protein stability changes upon mutations. Our results show that mutDDG-SSM achieved high performance in estimating the effects of mutations on protein stability. In addition, mutDDG-SSM exhibited good unbiasedness, where the prediction accuracy on the inverse mutations is as well as that on the direct mutations. Conclusion Meaningful features can be extracted from our pre-trained model to build downstream tasks and our model may serve as a valuable tool for protein engineering and drug design.

Zhaohua Xiao,1,* Jiangfeng Zhao,1,* Guanhong Ji,1 Xiangqing Song,1 Xia Xue,2 Wenhao Zhang,1 Guomeng Sha,1 Yongjia Zhou,1 Jie Zhou,1 Zhongxian Tian,1,3 Xiaogang Zhao,1,3 Ning Jiang1 1Department of Thoracic Surgery, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 2Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Key Laboratory of Chest Cancer, Shandong University, the Second Hospital of Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Jiang, Department of Thoracic Surgery, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China, Tel +86-17660081908, Email sdujiangning@163.comBackground: Exosomal microRNAs (miRNAs) in the tumor microenvironment play crucial roles in tumorigenesis and tumor progression by participating in intercellular cross-talk. However, the functions of exosomal miRNAs and the mechanisms by which they regulate esophageal squamous cell carcinoma (ESCC) progression are unclear.Methods: RNA sequencing and GEO analysis were conducted to identify candidate exosomal miRNAs involved in ESCC development. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of plasma exosomal miR-493-5p. EdU, tube formation and Transwell assays were used to investigate the effects of exosomal miR-493-5p on human umbilical vein endothelial cells (HUVECs). A subcutaneous xenograft model was used to evaluate the antitumor effects of miR-493-5p and decitabine (a DNA methyltransferase inhibitor). The relationship between miR-493-5p and SP1/SP3 was revealed via a dual-luciferase reporter assay. A series of rescue assays were subsequently performed to investigate whether SP1/SP3 participate in exosomal miR-493-5p-mediated ESCC angiogenesis.Results: We found that miR-493-5p expression was notably reduced in the plasma exosomes of ESCC patients, which showed the high potential value in early ESCC diagnosis. Additionally, miR-493-5p, as a candidate tumor suppressor, inhibited the proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGFA and exerted its angiostatic effect via exosomes. Moreover, we found that SP1/SP3 are direct targets of miR-493-5p and that re-expression of SP1/SP3 could reverse the inhibitory effects of miR-493-5p. Further investigation revealed that miR-493-5p expression could be regulated by DNA methyltransferase 3A (DNMT3A) and DNMT3B, and either miR-493-5p overexpression or restoration of miR-493-5p expression with decitabine increased the antitumor effects of bevacizumab.Conclusion: Exosomal miR-493-5p is a highly valuable ESCC diagnosis marker and inhibits ESCC-associated angiogenesis. miR-493-5p can be silenced via DNA methylation, and restoration of miR-493-5p expression with decitabine increases the antitumor effects of bevacizumab, suggesting its potential as a therapeutic target for ESCC treatment.Keywords: esophageal squamous cell carcinoma, exosomes, miR-493-5p, VEGFA, angiogenesis

Accurate population mapping is crucial for disaster management, urban planning, etc. However, current methods using nighttime light (NTL) and gridded population datasets are limited by low spatial resolution and insufficient training data for complex models such as deep learning. These models do not adequately utilize spatial information in population mapping. To address these limitations, this study proposes a high-resolution population mapping method using the Sustainable Development Goals Science Satellite 1 (SDGSAT-1) glimmer imager data and deep learning. The method includes a sample generation strategy with multiple regression and multilevel screening to provide sufficient, high-quality samples for deep learning. A Fine Population mapping network (FinePop-net) is also developed to train regression models using image samples, capturing multi-scale features for model training. When applied to the Guangdong-Hong Kong-Macao Greater Bay Area with 40-meter resolution SDGSAT 1 glimmer imagery, the method significantly reduced the average absolute error and root-mean-square error by 9.35% and 11.44%, respectively, compared with those of the pixel-level learning methods. It also outperformed other population spatialization datasets and NTL data by over 30% and 10%, respectively, in terms of error reduction. The results highlight the method’s effectiveness and the value of SDGSAT-1 glimmer imagery for fine population spatialization.

Extraction of built-up areas from polarimetric synthetic aperture radar (PolSAR) images plays a crucial role in disaster management. The polarimetric orientation angles (POAs) of built-up areas exhibit diversity, and built-up areas with POA close to 45° are often misclassified as vegetation. To address this problem, a polarimetric feature suitable for the extraction of built-up areas with large POAs is first designed, and a mixed real-complex-valued polarimetric feature combination is constructed. Then, a real-complex and spatial feature fusion classification network (RCSFFCNet) is designed. In which the proposed mixed real-complex-valued residual structure can efficiently extract mixed numerical features. Additionally, a multi-local spatial convolutional attention module is designed and embedded to efficiently fuse mixed numerical features, as well as superpixel multi-local spatial features. Experiments were conducted using PolSAR images from Gaofen-3, Radarsat-2, and ALOS-2/PALSAR-2. The experimental results show that the feature combination proposed in this paper increases the F1 score of built-up areas by approximately 2%-3%, and the F1 score of built-up areas extracted using the RCSFFCNet also improves by about 2%-3%, with F1 scores exceeding 95%. On all three datasets, the proposed method achieves the best performance in extracting built-up areas with various POAs, indicating overall superiority from feature selection to model implementation.

Abstract Objective To investigate whether simethicone expediates the remission of abdominal distension after laparoscopic cholecystectomy (LC). Methods This retrospective study involved LC patients who either received perioperative simethicone treatment or not. Propensity score matching (PSM) was employed to minimize bias. The primary endpoint was the remission rate of abdominal distension within 24 h after LC. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors affecting the early remission of abdominal distension after LC. Subsequently, a prediction model was established and validated. Results A total of 1,286 patients were divided into simethicone (n = 811) and non-simethicone groups (n = 475) as 2:1 PSM. The patients receiving simethicone had better remission rates of abdominal distension at both 24 h and 48 h after LC (49.2% vs. 34.7%, 83.9% vs. 74.8%, respectively), along with shorter time to the first flatus (14.6 ± 11.1 h vs. 17.2 ± 9.1 h, P

Pelvic exenteration is often required for primary rectal cancer beyond total mesorectal excision (PRC-bTME) and locally recurrent rectal cancer (LRRC). Some patients with radical resection can achieve long-term survival, but they need to face risks, such as huge surgical trauma, serious perioperative complications, permanent loss of organ function and decline in quality of life. Preoperative evaluation of PRC-bTME and LRRC should emphasize multidisciplinary collaboration and develop individualized diagnosis and treatment strategies. The principles of function preservation and risk-benefit balance in surgery oncology should be followed, and R0 resection should be emphasized. Perioperative complications, surgical trauma and organ function loss should be minimized to achieve the best quality control and balance point. This consensus was formulated by the Colorectal Cancer Committee of the Chinese Medical Doctor Association and the Gastrointestinal Surgery Committee of China International Exchange and Promotive Association for Medical and Health Care. The draft was formed based on the summary of domestic and foreign research progress and expert experience. After discussion, review and modification by experts, an anonymous voting was conducted for each major opinion, and in-depth verification was carried out according to the principles of evidence-based medicine. Finally, the Chinese expert consensus on the pelvic exenteration with primary rectal cancer beyond total mesorectal excision planes and locally recurrent rectal cancer (2023 edition) was formed. This consensus mainly summarizes the indications and contraindications of pelvic exenteration (PE) for PRC-bTME and LRRC, preoperative diagnosis and evaluation, perioperative treatment, as well as the resection scope, surgical methods, reconstruction of related organs, safety and complications of PE, postoperative follow-up and other issues, in order to provide guidance for PE in patients with PRC-bTME and LRRC.

Abstract Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an “epitope-focused” vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.

Intermediate temperature embrittlement (ITE) is very common in Ni and Ni–Co based superalloys, which seriously restricts the application of these alloys. In this work, we developed a new Ni–Co based superalloy by increasing the content of Cr to eliminate ITE. The superalloy has a yield strength of ∼950 MPa in the intermediate temperature range (600–780 °C), while also maintain a tensile elongation of ∼15 %. Microstructural investigations showed that in the temperature range of 600–780 °C, the microstructure of the alloy consists of nano-sized L12 phase (γ′) distributing inside the γ matrix, and the deformation is dominated by anti-phase boundary (APB) shearing γ′ precipitates, which makes the yield strength of the alloy decrease only slightly at 600–780 °C (compared to that tested at room temperature). More importantly, the element Cr is enriched along the grain boundaries (GBs) to form a protective layer without the formation of brittle topologically close-packed (TCP) phases due to the inverse two-stage aging design. In addition, the formation of a discontinuous precipitation (DP) zone at the GBs can act as a stress buffer and introduce GB serrations to withstand intergranular cracking.

Abstract Waste biorefining processes face significant challenges related to the variability of feedstocks. The supply and composition of multiple feedstocks in these processes can be uncertain, making it difficult to achieve economically feasible and sustainable waste valorization for large-scale production. Here, we introduce a reinforcement learning-based framework that aims to control these uncertainties and improve the efficiency of the process. The framework is tested on an anaerobic digestion process and is found to perform better than traditional control strategies. In the short term, it achieves faster target tracking with increased precision and accuracy, while in the long term, it shows adaptive and robust behavior even under additional seasonal supply variability, meeting downstream demand with high probability. This reinforcement learning-based framework offers a promising and scalable solution to address uncertainty issues in real-world biorefining processes. If implemented, this framework could contribute to sustainable waste management practices globally, making waste biorefining processes more economically viable and environmentally friendly.

Abstract Purpose This study aimed to explore novel tumor immune microenvironment (TIME)-associated biomarkers in prostate adenocarcinoma (PRAD). Methods PRAD RNA-sequencing data were obtained from UCSC Xena database as the training dataset. The ESTIMATE package was used to evaluate stromal, immune, and tumor purity scores. Differentially expressed genes (DEGs) related to TIME were screened using the immune and stromal scores. Gene functions were analyzed using DAVID. The LASSO method was performed to screen prognostic TIME-related genes. Kaplan–Meier curves were used to evaluate the prognosis of samples. The correlation between the screened genes and immune cell infiltration was explored using Tumor IMmune Estimation Resource. The GSE70768 dataset from the Gene Expression Omnibus was used to validate the expression of the screened genes. Results The ESTIMATE results revealed that high immune, stromal, and ESTIMATE scores and low tumor purity had better prognoses. Function analysis indicated that DEGs are involved in the cytokine–cytokine receptor interaction signaling pathway. In TIME-related DEGs, METTL7B, HOXB8, and TREM1 were closely related to the prognosis. Samples with low expression levels of METTL7B, HOXB8, and TREM1 had better survival times. Similarly, both the validation dataset and qRT-PCR suggested that METTL7B, HOXB8, and TREM1 were significantly decreased. The three genes showed a positive correlation with immune infiltration. Conclusions This study identified three TIME-related genes, namely, METTL7B, HOXB8, and TREM1, which correlated with the prognosis of patients with PRAD. Targeting the TIME-related genes might have important clinical implications when making decisions for immunotherapy in PRAD.

Abstract Translational control exerts immediate effect on the composition, abundance, and integrity of the proteome. Ribosome-associated quality control (RQC) handles ribosomes stalled at the elongation and termination steps of translation, with ZNF598 in mammals and Hel2 in yeast serving as key sensors of translation stalling and coordinators of downstream resolution of collided ribosomes, termination of stalled translation, and removal of faulty translation products. The physiological regulation of RQC in general and ZNF598 in particular in multicellular settings is underexplored. Here we show that ZNF598 undergoes regulatory K63-linked ubiquitination in a CNOT4-dependent manner and is upregulated upon mitochondrial stresses in mammalian cells and Drosophila. ZNF598 promotes resolution of stalled ribosomes and protects against mitochondrial stress in a ubiquitination-dependent fashion. In Drosophila models of neurodegenerative diseases and patient cells, ZNF598 overexpression aborts stalled translation of mitochondrial outer membrane-associated mRNAs, removes faulty translation products causal of disease, and improves mitochondrial and tissue health. These results shed lights on the regulation of ZNF598 and its functional role in mitochondrial and tissue homeostasis.

Jian-Jun Wu,1 Ping-An Zhang,1 Ming-Zhe Chen,2 Yi Zhang,1 Wei-Sha Du,1 Xiao-Ning Li,1 Guo-Chao Ji,1 Liang-Duo Jiang,3 Yang Jiao,4,* Xin Li5,* 1Respiratory Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Infectious Disease Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 3Respiratory Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Respiratory Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Glaucoma Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Li, Glaucoma Department, Eye Hospital, China academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email doudou8295@163.comBackground: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear.Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained.Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated.Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated.Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.Keywords: COPD, GC, GEO database, miRNA-mRNA, DEMs, DEGs

Abstract Background Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. Methods Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. Results Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. Conclusions Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

To address the inefficiencies and time-consuming nature of traditional hot-air anti-icing system designs, reduced-order models (ROMs) and machine learning techniques are introduced to predict anti-icing surface temperature distributions. Two models, AlexNet combined with Proper Orthogonal Decomposition (POD-AlexNet) and multi-CNNs with GRU (MCG), are proposed by comparing several classic neural networks. Design variables of the hot-air anti-icing cavity are used as inputs of the two models, and the corresponding surface temperature distribution data serve as outputs, and then the performance of these models is evaluated on the test set. The POD-AlexNet model achieves a mean prediction accuracy of over 95%, while the MCG model reaches 96.97%. Furthermore, the proposed model demonstrates a prediction time of no more than 5.5 ms for individual temperature samples. The proposed models not only provide faster predictions of anti-icing surface temperature distributions than traditional numerical simulation methods but also ensure acceptable accuracy, which supports the design of aircraft hot-air anti-icing systems based on optimization methods such as genetic algorithms.

Ship engine misfire faults not only pose a serious threat to the safe operation of ships but may also cause major safety accidents or even lead to ship paralysis, which brings huge economic losses. Most traditional fault diagnosis methods rely on manual experience, with limited feature extraction capability, low diagnostic accuracy, and poor adaptability, which make it difficult to meet the demand for high-precision diagnosis. To this end, a fusion intelligent diagnostic model—ResNet–BiLSTM—is proposed based on a residual neural network (ResNet) and a bidirectional long short-term memory network (BiLSTM). Firstly, a multi-scale decomposition of the instantaneous rotational speed signal of a ship’s engine is carried out by using the continuous wavelet transform (CWT), and features containing misfire fault information are extracted. Subsequently, the extracted features are fed into the ResNet–BiLSTM model for learning. Finally, the intelligent diagnosis of ship dual-fuel engine misfire faults is realized by the classifier. The model combines the advantages of ResNet18 in image feature extraction and the capability of BiLSTM in temporal information processing, which can efficiently capture the time-frequency features and dynamic changes in the fault signal. Through comparison experiments with fusion models AlexNet–BiLSTM, VGG–BiLSTM, and the existing AlexNet–LSTM and VGG–LSTM models, the results show that the ResNet–BiLSTM model outperforms the other models in terms of diagnostic accuracy, robustness, and generalization ability. This model provides an effective new method for intelligent diagnosis of ship dual-fuel engine misfire faults to solve the traditional diagnostic methods’ limitations.

ABSTRACT: Seed vigor of tobacco (Nicotiana tabacum L.) is established during seed development stage, while its regulators remain largely unknown. Here, a comparative peptidomics analysis of the developing seeds was conducted to reveal the regulators involving the establishment of tobacco seed vigor. The most significant difference of seed vigor was observed between seeds harvested at 20 and 30 days after pollination (DAP), and then the corresponding seeds were collected separately for peptidomics analysis. A total of 2932 and 2812 nonredundant peptides were identified in seeds harvested at 20 and 30 DAP, respectively. In which, 349 differentially expressed peptides (DEPs) were characterized. To explore the potential functions of these DEPs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were further analyzed according to their precursor proteins. Most DEP precursor proteins were involved in response to abiotic stimulus, response to water, and protein processing in endoplasmic reticulum. Further, the peptides derived from the precursor proteins, such as late embryogenesis abundant (LEA) protein, heat shock protein, peroxiredoxin, and globulin proteins, may regulates the establishment of seed vigor by influencing reactive oxygen species. The results provide a foundation for further exploration of the peptides functions on the establishment of seed vigor in tobacco.

Abstract Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field. Graphical abstract

Abstract Objective To identify the risk factors for failure of first‐line poly (ADP‐ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer. Method Patients with stage III‐IV epithelial ovarian cancer who received first‐line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups—recur/progression of disease (PD) and non‐recur/PD. Results In total, 191 patients were included. Median follow‐up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non‐high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre‐PARPi serum CA‐125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox‐regression analysis revealed pre‐PARPi serum CA‐125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03–4.57; p = 0.042), non‐HGSC (3.28; 1.20–8.97; p = 0.021), NAC (2.11; 1.04–4.26; p = 0.037), and no BRCA mutation (2.23; 1.12–4.44; p = 0.023) as independent risk factors associated with poor progression‐free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre‐PARPi serum CA‐125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03–7.39; p = 0.044). Non‐HGSC (5.05; 1.80–14.18; p = 0.002) and NAC (3.36; 1.25–9.04; p = 0.016) were independent risk factors in women without BRCA mutations. Conclusion High pre‐PARPi serum CA‐125 levels, non‐HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first‐line PARPi maintenance therapy. In women with BRCA mutations, high pre‐PARPi serum CA‐125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.

Abstract Inability to meet nutrition needs resulting from multiple diseases‐related, and individual factors contribute significantly to malnutrition and poor disease outcome among cancer patients. Strategies capable of delivering metabolically efficient nutrients with less digestive and metabolic stress without adding bulk to the diet of patients may be suitable for dealing with cancer‐related malnutrition and quality of life (QoL). We sought to test the hypothesis that peptide supplementation could attenuate weight loss and improve QoL among brain cancer patients compared to conventionally treated controls. In a non‐blind pilot study, brain cancer patients received 9 g soybean peptide supplementation twice per day (peptide group, n = 9) and compared with conventional treatment (control group, n = 10) over two chemotherapy cycles of 42 days. Compared to the controls, soypeptide supplementation attenuated weight loss with 5.4% increase in weight. Moreover, QoL, assessed using the European Organization for Research and Treatment of Cancer QLQ‐C30, revealed that physical (8.1 ± 15.6, p

In this study, hot rolling treatment followed by water quenching was conducted on a TC18 titanium alloy in β single-phase region with varying reductions. Experimental evidences from X-ray diffraction and transmission electron microscopy indicate the formation of α phase, induced by sufficient stress and assisted by ω phase. In addition, the existence of α'' phase and diffuse streaks were also observed during the hot working processing. Furthermore, dynamic recrystallization (DRX) including continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX) was proved to exist in the hot rolling process. During the whole DRX process, with increasing the deformation degree, recrystallized grains nucleated preferentially at high-energy areas such as grain boundaries and shear bands, then accumulated and grew until achieving a complete recrystallization state. It should be noted that DDRX mainly occurred at the grain boundaries, while CDRX grains nucleated within the shear bands. The elongation gradually decreased and tensile strength gradually increased with the increment of the deformation degree.

Qiuling Tong,1,2 Yu Yao,3 Yanhuo Xia,4 Zhibo Chen,2 Gangze Ji,2 Liuzhu Chen,2 Rujun Jin,2 Wanli Dong1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Neurology, Ningbo First Hospital, Ningbo, People’s Republic of China; 4Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Wanli Dong, Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +8651265223637, Fax +8657755579318, Email wanlidong23@163.comObjective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA).Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann–Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test.Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores.Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.Keywords: migraine without aura, patent foramen ovale, clinical features, closure treatment

Abstract The RNA 5-methylcytosine (m5C) modification has been demonstrated to be an important epigenetic regulator and to impact colorectal cancer (CRC) progression. However, the potential roles of m5C modification in immune cell infiltration in the CRC tumor microenvironment (TME) remain unknown. The m5C modification phenotypes were comprehensively evaluated based on 14 m5C regulators in a meta-CRC cohort of 1792 patients and systematically correlated with the m5C modification phenotypes, immune cell infiltration characteristics and known biological processes. The m5Cscore model was constructed by principal component analysis (PCA) algorithms to quantify the m5C modification phenotypes of individual CRC samples and was used to predict the immunotherapy response. We identified three m5C modification phenotypes associated with distinct clinical outcomes and biological processes among the 1792 meta-CRC patients. Three phenotypes with a highly consistent TME landscape and characteristics were revealed: immune excluded, immune desert and immune inflammation. The meta-CRC patients were divided into high and low m5Cscore subgroups based on the m5Cscore. The m5Cscore was confirmed to have a negative correlation with infiltrating immune cells and PD-L1 expression and a positive correlation with tumor mutation burden (TMB), mutation rate and microsatellite instability (MSI) score. Moreover, patients in the low m5Cscore group had better immunotherapy responses and significant durable survival benefits in independent anti-PD-1/L1 immunotherapy cohorts for the immune checkpoint inhibitor (ICI) therapeutic strategy. This study revealed that m5C modification plays a crucial role in TME composition and complexity. Comprehensive evaluation of the m5C modification phenotypes of individual patients will enhance our understanding of TME characteristics and promote the application of more appropriate and personalized treatment strategies.

Iron is one of the most important basic materials in infrastructure development, spatial and temporal variation characteristics analysis of infrastructure iron stocks is conducive to revealing its distribution and change patterns from different scales, which can provide a scientific basis for sustainable urban development and iron resource management in China. In this article, we first calculated provincial infrastructure iron stock data from 2000 to 2020. Then, fitting equations between nighttime lighting data and infrastructure iron stock are constructed to simulate the spatial distribution of China’s infrastructure iron stock at 500 m resolution from 2000 to 2020. Finally, the spatial and temporal dynamics of China’s infrastructure iron stock is analyzed from four scales: national, regional, provincial, and urban agglomeration. The results show as follows: (1) China’s infrastructure iron stock grew at an average annual rate of 26.42% from 2000 to 2020, with China’s infrastructure iron stock increasing 6.28 times over the 21 years. Construction facilities are the most important part of the infrastructure iron stock, and its share is still increasing. (2) On a regional scale, the high-growth type of infrastructure iron stock is mainly distributed in the eastern region, while the no-obvious-growth type is mainly distributed in the western region. The high grade of infrastructure iron stock is mainly distributed in the eastern region, while the low grade is mainly distributed in the western region. (3) On a provincial scale, the highest share of no-obvious-growth type of infrastructure iron stock is in Xinjiang. The highest proportion of infrastructure iron stock of high-growth type is in Jiangsu. The highest proportion of low-grade infrastructure iron stock is in Xinjiang. The highest proportion of infrastructure iron stock of high grade is in Beijing. (4) In terms of urban agglomerations, the high-growth type of infrastructure iron stock is mainly located in Shanghai–Nanjing–Hangzhou, while the no-obvious-growth type is mainly located in the Middle south of Liaoning. The high-grade infrastructure iron stock is mainly distributed in Shanghai–Nanjing–Hangzhou, while the low grade is mainly distributed in Sichuan–Chongqing.

The support vector machine (SVM) is a classical machine learning method. Both the hinge loss and least absolute shrinkage and selection operator (LASSO) penalty are usually used in traditional SVMs. However, the hinge loss is not differentiable, and the LASSO penalty does not have the Oracle property. In this paper, the huberized loss is combined with non-convex penalties to obtain a model that has the advantages of both the computational simplicity and the Oracle property, contributing to higher accuracy than traditional SVMs. It is experimentally demonstrated that the two non-convex huberized-SVM methods, smoothly clipped absolute deviation huberized-SVM (SCAD-HSVM) and minimax concave penalty huberized-SVM (MCP-HSVM), outperform the traditional SVM method in terms of the prediction accuracy and classifier performance. They are also superior in terms of variable selection, especially when there is a high linear correlation between the variables. When they are applied to the prediction of listed companies, the variables that can affect and predict financial distress are accurately filtered out. Among all the indicators, the indicators per share have the greatest influence while those of solvency have the weakest influence. Listed companies can assess the financial situation with the indicators screened by our algorithm and make an early warning of their possible financial distress in advance with higher precision.

The malfunction of SEC61A1 has been linked to several types of cancers, but its role in acute myeloid leukemia (AML) remains poorly understood. In this study, we used a series of bioinformatics analysis techniques, including gene expression profiling and proteomic analysis. Our findings were subsequently validated through a series of in vitro experiments, such as SEC61A1 knockdown in cell lines and RT-qPCR. We discovered a significant up-regulation of SEC61A1 in AML patients compared to healthy controls. AML patients with elevated SEC61A1 expression exhibited reduced overall survival compared to those with lower expression. Moreover, SEC61A1 expression emerged as an independent risk factor for predicting the survival of AML patients undergoing allo-HSCT. Our analysis also revealed an association between high SEC61A1 expression and increased signaling pathways related to cell growth. Our study underscores the importance of SEC61A1 expression as a novel prognostic indicator for predicting survival among AML patients, while also identifying it as a promising therapeutic target.

Objective: To explore whether Bushen Huoxue Formula (BSHXF) improves the angiogenesis ability of transplanted endothelial progenitor cells (EPCs) in endplate and its potential mechanism in delaying intervertebral disc degeneration (IDD). Methods: BSHXF was analyzed via Ultra-High Performance Liquid Chromatography (UPLC). Rabbit axial compression lumbar IDD models were constructed and the effects of BSHXF, EPCs, and their combination in IDD were determined by MRI, histological evaluation, TUNEL, and immunofluorescence assays. Additionally, CCK-8 assay, flow cytometry, and tube formation assay were used to evaluate EPCs viability, proliferation, cell cycle and the angiogenesis ability of EPCs between groups. Results: BSHXF and transplanted EPCs both attenuate the process of IDD in the rabbit model assessed by MRI, HE staining and Masson staining. TUNEL-positive NP cells were significantly reduced in the BSHXF group, EPCs group, and EPC + BSHXF group compared to the model group (P

Introduction Mild cognitive impairment (MCI) is an important intervenable stage for the prevention of dementia. Hypertension is associated with impaired cognition, and when combined with MCI, it may lead to a poor prognosis. Digital computerised cognitive training (CCT) has recently become a potential instrument for improving cognition, but evidence for its efficacy remains limited. This study aims to evaluate the efficacy of a digital adaptive CCT intervention in older patients with hypertension and MCI.Methods and analysis The multicentre, double-blinded, randomised, actively -controlled clinical trial will recruit 200 older (≥60 years) patients with hypertension and MCI from 11 hospitals across China. Participants will be randomly assigned in a 1:1 ratio to the intervention group (multidomain adaptative CCT) and active control group (non-adaptive cognitive training) for 12-week cognitive training for 30 min/day and 5 days/week. Those who have completed their 12-week training in the intervention group will be rerandomised into the continuation and discontinuation training groups. All participants will be followed up to 24 weeks. Neuropsychological assessments and structural and functional 7.0 T MRI will be obtained at baseline and at 12-week and 24-week follow-up. The primary outcome is the possible improvement of global cognitive function at 12 weeks, as measured by the Basic Cognitive Aptitude Tests. Secondary and exploratory endpoints include the major cognitive domain function improvement, self-efficacy, mental health, quality of life and MRI measurements of the brain.Ethics and dissemination The trial has been approved by the institutional review board of Beijing Anzhen Hospital and thereafter by all other participating centres. Trial findings will be disseminated in peer-reviewed journals and conference presentations.Trial registration number NCT05704270.

This study aimed to identify the factor structure of the Korean version of the Short Grit Scale (Grit-S) and examine its cross-sectional and longitudinal measurement invariance (MI). Data from the Korean Children and Youth Panel Survey 2018 were analyzed, which included two cohorts, comprising 2,327 and 2,325 fourth-year elementary and first-year middle school students, respectively. It was found that the two-factor model fit the data well for the elementary and middle school samples. The results of the cross-sectional MI tests across genders indicated that the full threshold and loading invariance were also supported for the elementary school sample, and the partial threshold and loading invariance were supported for the middle school sample. The analyses of the longitudinal MI revealed that the partial threshold and loading invariance were supported for both samples. The reliability analysis revealed satisfactory McDonald's Omega values for both samples at each time point and moderate stability coefficients over time. Based on these findings, it was concluded that the Korean version of the Grit-S demonstrated satisfactory psychometric properties and exhibited MI across gender and time in Korean adolescents.

Abstract Background Acceptance-based pain management interventions have been receiving growing attention in cancer pain care. This study aimed to develop a cancer pain management program based on belief modification to improve the cancer pain experience of Chinese oral cancer survivors and to explore the acceptability and preliminary outcomes of the Cancer Pain Belief Modification Program (CPBMP). Methods A mixed-methods approach was applied to develop and revise the program. The CPBMP was developed and revised using the Delphi technique, and its further improvement was explored with a one-group pre- and post-trial designed with a sample of 16 Chinese oral cancer survivors, and semi-structured interviews. Research instruments included Numeric Rating Scale (NRS), Chinese version of Illness Perception Questionnaire-Revised for Cancer Pain (IPQ-CaCP), and the University of Washington Quality of Life assessment scale (UW-QOL). Descriptive statistics, t-test, and Mann–Whitney U test were used to analyse the data. The semi-structured questions were analysed using content analysis. Results The six-module CPBMP was endorsed by most experts and patients. The expert authority coefficient value was 0.75 in the first round of the Delphi survey and 0.78 in the second round. The “pain intense”, “negative pain beliefs” scores of pre- and post-testing decreased from 5.63 ± 0.48 to 0.81 ± 0.54 (t = -3.746, p

Sheng Liu,1,&ast; Guanyun Shi,1 Zhengbo Pan,1 Weisong Cheng,1 Linfei Xu,1 Xingzhang Lin,1 Yongfeng Lin,1 Liming Zhang,1 Guanghua Ji,1 Xin Lv,1 Dongguo Wang2,&ast; 1Department of Urinary Surgery, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang Province, People’s Republic of China; 2Department of Central Laboratory, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongguo Wang, Department of Central Laboratory, Taizhou Municipal Hospital Affiliated with Taizhou University, 381-1 Eastern Road of Zhongshan, Taizhou, Zhejiang Province, 318000, People’s Republic of China, Tel +86-13566871738, Email wdgtzs@163.comPurpose: The overall survival of clear cell renal cell carcinoma (ccRCC) is poor. Markers for early detection and progression could improve disease outcomes. This study aims to reveal the potential pathogenesis of ccRCC by integrative bioinformatics analysis and to further develop new therapeutic strategies.Patients and Methods: RNA-seq data of 530 ccRCC cases in TCGA were downloaded, and a comprehensive analysis was carried out using bioinformatics tools. Another 14 tissue samples were included to verify the expression of selected lncRNAs by qRT-PCR. DGIdb database was used to screen out potential drugs, and molecular docking was used to explore the interaction and mechanism between candidate drugs and targets.Results: A total of 58 differentially expressed lncRNAs (DElncRNAs) and 660 differentially expressed mRNAs (DEmRNAs) were identified in ccRCC. LINC02038, FAM242C, LINC01762, and PVT1 were identified as the optimal diagnostic lncRNAs, of which PVT1 was significantly correlated with the survival rate of ccRCC. GO analysis of cell components showed that DEmRNAs co-expressed with 4 DElncRNAs were mainly distributed in the extracellular area and the plasma membrane, involved in the transport of metal ions, the transport of proteins across membranes, and the binding of immunoglobulins. Immune infiltration analysis showed that MDSC was the most correlated immune cells with PVT1 and key mRNA SIGLEC8. Validation analysis showed that GABRD, SIGLEC8 and CDKN2A were significantly overexpressed, while ESRRB, ELF5 and UMOD were significantly down-regulated, which was consistent with the expression in our analysis. Furthermore, 84 potential drugs were screened by 6 key mRNAs, of which ABEMACICLIB and RIBOCICLIB were selected for molecular docking with CDKN2A, with stable binding affinity.Conclusion: In summary, 4 key lncRNAs and key mRNAs of ccRCC were identified by integrative bioinformatics analysis. Potential drugs were screened for the treatment of ccRCC, providing a new perspective for disease diagnosis and treatment.Keywords: clear cell renal cell carcinoma, bioinformatics analysis, lncRNA, mRNA, drugs prediction, molecular docking

ABSTRACTIn this work, by using multi-scale characterizations from electron channeling contrast imaging (ECCI) to atom probe tomography (APT), we directly evidenced that the massive cracking events in the selective-laser-melted (SLMed) Haynes 230 superalloy are due to the continuous decoration of an M23C6-type thin film at grain boundaries. The high-melting-point nature of the carbide rules out the possibility of liquidation cracking, while the long and straight film surface facilitates stress-induced solid-state cracking. Impurities, Si, Mn and Fe, greatly enhance the cracking susceptibility despite the interesting fact that they are strongly depleted from the carbide.

This study was carried out to determine the effect of autophagy modulation in radiation treatment of cervical cancer cells. HeLa and CaSki cells were irradiated with γ-rays (2 Gy/min) after treatment with an autophagy inducer (rapamycin) and inhibitor (3-MA). Expression of LC3 and cell death in two cell preparations were examined. In addition, expression of Caspase-3 and PARP were examined after radiation alone and with autophagy inhibitor treatment. A notable increment of LC3 expression was detected after radiation in both cell lines. Cell viability was observed to decrease in 3-MA-treated cells compared to radiation alone, and even further in rapamycin-treated cells. Apoptosis was confirmed to occur later than autophagy in radiation treatment, and inhibition of autophagy derived a decrease in apoptosis. In conclusion, radiation-induced autophagy may be regulated by modulators, and autophagy augmentation yields an increase in cervical cancer cell death under radiation.Impact statement What is already known on this subject? Autophagy is known to contribute both to tumour cell survival and death against radiation therapy. The effect of induction or inhibition of radiation-induced autophagy on cervical cancer cell death is not clear. What the results of this study add? Cell viability was observed to decrease in 3-MA-treated cells compared to radiation alone, and even further in rapamycin-treated cells. Apoptosis occurred later than autophagy in radiation treatment, and inhibition of autophagy derived a decrease in apoptosis. What the implications are of these findings for clinical practice and/or further research? Our results suggest that radiation-induced autophagy may be regulated by modulators, and autophagy augmentation yields an increase in cervical cancer cell death under radiation.

Objective: We aimed to evaluate associations between abdominal fat distribution (AFD) parameters and incisional hernia (IH) in patients who underwent transumbilical single-port laparoscopic surgery (SPLS) for gynecological disease. Methods: Medical records of 2116 patients who underwent SPLS for gynecological disease at Daejeon St. Mary's Hospital between March 2014 and February 2021 were reviewed. Among 21 (1.0%) patients who developed IH requiring surgical treatment after SPLS, 18 had preoperative abdominopelvic computed tomography (CT) images. As a control group, we randomly selected 72 patients who did not develop IH and who had undergone preoperative abdominopelvic CT scan, matched to test patients by type of surgery. Total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), visceral-to-subcutaneous fat ratio (VSR), and waist circumference (WC) were measured at the level of the third lumbar vertebral body on the preoperative abdominopelvic CT images, using National Institutes of Health (NIH) ImageJ version 1.53 k. Results: Receiver operating curve analysis showed that VFA has the highest predictive value for IH among AFD parameters (AUC = 0.749, 95% CI 0.630–0.869, p

We demonstrated an ultra-sensitive terahertz virus detection method combined with virus-sized gold nanogaps filled with Al2O3. Large-area high-density 20 nm-gap rectangular loop structures, containing a resonant frequency in the terahertz range, were fabricated on a 4-inch wafer using atomic layer lithography. When target viruses with a 60 nm diameter were located on the nanogaps, we observed a significant redshift of the resonant peak already with an average number of about 100 viruses per unit loop due to the strong field confinement and enhancement near the gap. Furthermore, when the virus was tightly attached to an etched gap like a bridge connecting metals, its sensitivity is doubled compared to the unetched gap, which resulted in 400% more resonance frequency shift per single virus particle than our previous work. Full-wave simulations and theoretical calculations based on modal expansions were in good agreement with the experiments, revealing that the resonant transmission spectrum was mostly determined by the change in refractive index in a two-dimensional-like optical hotspot near the nanogap. A further step could be taken to increase sensitivity by tuning nanogap-loops to the absorption frequencies associated with the intermolecular vibrational modes of the viruses and fingerprinting them as well.

Abstract An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

As an important tributary of the Yangtze River basin, the Jialing River Basin (JRB) has a variable topography and fragile ecological environment. Under the influence of climate warming and human activities, the runoff and vegetation cover of the area are undergoing significant changes. For evaluating the impact of different factors on vegetation and streamflow variation in the JRB, the univariate linear regression method was employed to analyze the variation trend of streamflow and vegetation, and a heuristic segmentation algorithm was applied for identifying the mutation year of streamflow and NDVI time-series data in the JRB. Then, the influence degree of different factors on streamflow variation in the JRB was calculated by the Budyko equation and elastic coefficient method. Finally, the contribution rates of different factors to vegetation variation in the JRB were calculated by the multiple linear regression method. The results indicated that the mutation year of streamflow and NDVI time series data were 1985 and 2006, respectively. The contribution rates of climate factors and human activities to streamflow change in the JRB were 42.7 and 57.3%, respectively. The contribution rates to vegetation change were 28.89 and 71.11%, respectively. In general, human activities are the main driving force leading to runoff and vegetation changes in the JRB. This study can provide a theoretical basis for the ecological environment protection and water resources management of the JRB.

Wenkai Chen,1,2,&ast; Wenping Lin,3,&ast; Naichun Yu,1,2,&ast; Linlin Zhang,1,2,&ast; Zuoxing Wu,2 Yongjie Chen,1,2 Zongguang Li,1,2 Fengqing Gong,1,2 Na Li,2 Xiaohui Chen,4 Xu He,3 Yue Wu,5 Xiangchen Zeng,1,2 Yuting Yueh,1,2 Ren Xu,2,4,6,&ast; Guangrong Ji1,2,&ast; 1Department of Orthopedic Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Department of Spine Surgery, Shenzhen Pingle Orthopedic Hospital, Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Shenzhen, People’s Republic of China; 4Department of Orthopedic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 5Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, People’s Republic of China; 6Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed by the Province and Ministry, Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangrong Ji; Ren Xu, Department of Orthopedic Surgery, Xiang’an Hospital of Xiamen University, No. 2000, Xiang’an East Road, Xiang’an District, Xiamen, 361000, People’s Republic of China, Tel +86-15710667257, Fax +86592-2889000, Email jiguangrong@xmu.edu.cn; xuren526@xmu.edu.cnPurpose: To investigate induction of cell death in Osteosarcoma (OS) using the anti-tuberculosis drug, rifampicin, loaded into exosomes.Patients and Methods: BMSC-exosomes were isolated by ultracentrifugation and loaded ultrasonically with rifampicin. Nanoparticle exosome-rifampicin (EXO-RIF) was added to the OS cell-lines, 143B and MG63, in vitro, to observe the growth inhibitory effect. In vivo experiments were conducted by injecting fluorescently labeled EXO-RIF through the tail vein of 143B cell xenograft nude mice and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically.Results: Sonication resulted in encapsulation of rifampicin into exosomes. Exosome treatment accelerated the entry of rifampicin into OS cells and enhanced the actions of rifampicin in inhibiting OS proliferation, migration and invasion. Cell cycle arrest at the G2/M phase was observed. Dynamin-related protein 1 (Drp1) was activated by EXO-RIF and caused mitochondrial lysis and apoptosis. Exosome treatment targeted rifampicin to the site of OS, causing OS apoptosis and improving mouse survival in vivo.Conclusion: The potent Drp1 agonist, rifampicin, induced OS apoptosis and exosome loading, improving OS targeting and mouse survival rates. EXO-RIF is a promising strategy for the treatment of diverse malignancies.Graphical Abstract: Keywords: bone tumor, drug delivery, exosomes, mesenchymal stem cells, survival

Abstract Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR‐absorbing small molecule named TBT‐2(TP‐DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE‐PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR‐responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications.

This study focuses on China's electricity productivity post-pandemic, employing the Logarithmic Mean Divisia Index (LMDI) method and the Kaya identity. Despite the clarity of the electricity productivity indicator, factors like industrial structure, energy efficiency, and electrification rates contribute to fluctuations. Quantitative analysis reveals a decisive role of the terminal electrification rate in declining electricity productivity. The proposed analytical method provides a more accurate assessment of electricity's contribution to economic growth, aiding informed policy decisions for sustainable energy development in China.

BackgroundThe Coronavirus (COVID-19) pandemic resulted in a dramatic increase in the prevalence of anxiety and depression globally. Although the impact on the mental health of young adults was especially strong, its underlying mechanisms remain elusive.Materials and methodsUsing a network approach, the present study investigated the putative pathways between pandemic-related factors and anxiety and depressive symptoms among young adults in South Korea and the U.S. Network analyses were conducted on cross-country data collected during the COVID-19 lockdown period (n = 1,036). Our model included depression symptoms (PHQ-9), generalized anxiety symptoms (GAD-7), and COVID-19-related factors (e.g., COVID-19-related traumatic stress, pandemic concerns, access to medical/mental health services).ResultsThe overall structure of pandemic-to-symptom networks of South Korea and the U.S. were found to be similar. In both countries, COVID-related stress and negative future anticipation (an anxiety symptom) were identified as bridging nodes between pandemic-related factors and psychological distress. In addition, worry-related symptoms (e.g., excessive worry, uncontrollable worry) were identified as key contributors in maintaining the overall pandemic-to-symptom network in both countries.ConclusionThe similar network structures and patterns observed in both countries imply that there may exist a stable relationship between the pandemic and internalizing symptoms above and beyond the sociocultural differences. The current findings provide new insights into the common potential pathway between the pandemic and internalizing symptoms in South Korea and in the U.S. and inform policymakers and mental health professionals of potential intervention targets to alleviate internalizing symptoms.

Objective: To establish a new animal model of intervertebral disc degeneration (IDD) by axial compression on lumbar spine of rabbits and to investigate the changes of microcirculation in bony endplates during the progress of IDD. Methods: 32 New Zealand white rabbits were equally divided into 4 groups as follows: Control group with no operation and compression, Sham operation group with apparatus placement only, 2-week compression group and 4-week compression group with the devices installed and compressed for their preset duration. All groups of rabbits underwent MRI, histological evaluation, disc height index measurement and Microfil contrast agent perfusions to examine the ratio of endplate microvascular channels. Results: The new animal model of IDD was successfully established after axial compression for 4 weeks. The MRI grades for the 4-week compression group was 4.63 ± 0.52 and significantly different to the sham operation group (P

SARS-CoV-2 variants with immune escape capability highlight the need for the development of cross-neutralising vaccines and regimens. Here, the authors assess the immunogenicity and safety of NVSI-06-08, that integrates antigens from multiple SARS-CoV-2 strains into a single immunogen, as a heterologous booster in adults previously vaccinated with the inactivated vaccine.

Abstract The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1–3 months, 4–6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination, whereas only 4.20–16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.

Objective: This study was aimed to compare the oncologic outcomes of patients with non-endometrioid endometrial cancer who underwent minimally invasive surgery with the outcomes of patients who underwent open surgery. Method: This is a retrospective, multi-institutional study of patients with non-endometrioid endometrial cancer who were surgically staged by either minimally invasive surgery or open surgery. Oncologic outcomes of the patients were compared according to surgical approach. Results: 113 patients met the inclusion and exclusion criteria. 57 underwent minimally invasive surgery and 56 underwent open surgery. Patients who underwent minimally invasive surgery had smaller tumors (median size, 3.3 vs. 5.2%, p = 0.0001) and a lower lymphovascular space invasion rate (29.8% vs. 48.2%, p = 0.045). In the overall population, the numbers and rate of recurrence were significantly higher in the open surgery group (p = 0.016). In multivariate analysis, disease stage and tumor size were associated with DFS in contrast to surgical procedure. Conclusion: Minimally invasive surgery showed similar survival outcomes when compared to open surgery in non-endometrioid endometrial cancer patients, irrespective of disease stage. When minimally invasive surgery is managed by expert surgeons, non-endometrioid histological subtypes should not be considered a contraindication for minimally invasive surgery.

Food safety has become a topic of global concern in the recent decades. The significant food safety incidents occur from time to time around the world, seriously threatening the public health and causing extensive economic losses. In particular, the occurrence of COVID-19 highlights the importance of the food safety for the public health. Therefore, there is an urgent need to establish a fast, simple, sensitive, and efficient method for the detection of food safety. In recent years, the upconversion (UC) nanotechnology has been widely used in the field of food detection. The UC fluorescence analysis technology possesses the advantages of ultra-sensitivity detection, non-invasiveness, light stability, etc., and has broad application prospects in the field of food safety. After cladding and surface modification, it can be combined with other substances through a variety of mechanisms, such as electrostatic interaction, thereby expanding its application in the food safety detection. Thus, overall, there is a vital need to evaluate and utilize the potential of UC nanoparticles in the field of rapid detection of food safety.

Abstract Nowadays, the increasingly complex and changeable marine environment makes the signals received by the underwater sensing equipment not only contain the weak signals radiated by underwater targets but also accompanied by marine solid background noise, which leads to the degradation and distortion of underwater acoustic signals and the decline of underwater communication quality. Under the severe influence of ocean noise, the underwater acoustic sensing and acquisition system will have the problems of high SNR ratio threshold, minimal sensing bandwidth, and unable to sense the signal with unknown frequency effectively. The Lévy noise model has been selected to describe the marine noise environment and explain its scientificity in this paper. A parameter estimation method for Lévy noise is proposed. Under the condition of characteristic index $$\alpha =1.5$$ α = 1.5 and noise intensity $$D=0.1$$ D = 0.1 of the Lévy noise model, the estimated mean values of parameters are 1.5026 and 1.1664. The estimated variances are 0.0034 and 0.0046, which proves the effectiveness and applicability of the estimation method. Then, an improved dual-coupled Duffing oscillator sensing system is proposed to sense the weak signals with unknown frequency under Lévy noise. Under the background of Lévy with characteristic index $$\alpha =1.5$$ α = 1.5 , deflection parameter $$\beta =0$$ β = 0 and noise intensity $$D=0.1$$ D = 0.1 , the sensing error rate of our system with unknown frequency is $$0.054\%$$ 0.054 % , the lowest sensing signal amplitude is $$A=0.010$$ A = 0.010 , the lowest sensing SNR ratio is − 23.9254 dB, and the frequency of multi-frequency weak signals to be measured can be obtained. The estimation error of frequency sensing is $$0.33\%$$ 0.33 % .

Ting Zhang,1– 3,&ast; Xiaohui Xie,2– 4,&ast; Qianqian Li,1– 3,&ast; Lei Zhang,2,3,5,6 Yue Chen,2,4 Gong-Jun Ji,2,3,5 Qiangqiang Hou,2– 4 Tianxia Li,7 Chunyan Zhu,2,3,5,6 Yanghua Tian,4,8,9 Kai Wang2– 5,9 1Department of Psychiatry, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, Anhui Province, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 5School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 6Department of Psychiatry, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 7Anhui Mental Health Center, Hefei, Anhui Province, People’s Republic of China; 8Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 9Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyan Zhu; Yanghua Tian, Email ayswallow@126.com; ayfytyh@126.comPurpose: Insomnia is a recognized feature of generalized anxiety disorder (GAD). The underlying neural substrate of insomnia in GAD is still unclear. Cortical folding is a reliable index and possibly an endophenotype of psychiatric disease. The aim of this study was to explore whether the aberrant cortical morphology was associated with insomnia in GAD.Patients and Methods: We enrolled 73 patients with GAD and 74 matched healthy controls (HCs) to undergo neuropsychiatric assessment and 3.0 T magnetic resonance imaging scanning. Neuropsychiatric batteries included the 14-item Hamilton Anxiety Rating Scale (HAMA) and the Insomnia Severity Index (ISI). Using FreeSurfer7.1.1, we calculated local gyrification index, cortical thickness and surface area and identified group differences in these parameters. Then, we calculated the functional connectivity of these identified regions and determined functional alterations. The relationship between these neuroimaging indicators and clinical measurement was explored.Results: Compared with HCs, the LGI in the bilateral orbitofrontal cortex (OFC), bilateral insula, left middle frontal gyrus, left temporal pole, and left fusiform area was significantly decreased in GAD. GAD patients had concurrent decreased surface area in the left OFC and thicker right OFC. GAD patients also exhibited increased functional connectivity between the left insula and frontoparietal control network. In addition, a negative relationship was observed between decreased LGI in these limbic regions and ISI score.Conclusion: GAD patients presented aberrant cortical folding in limbic network. Cortical morphology is a potential endophenotype in GAD, corresponding to an insomnia phenotype.Keywords: generalized anxiety disorder, cortical morphology, insomnia, limbic network, frontoparietal control network

In the period of “13th Five-Year Plan”, domestic deep and ultra-deep oil/gas well drilling technologies were developed quickly and a great number of technological achievements were obtained by means of continuous researches, including: (1) high-end devices, such as automatic drilling rig, managed pressure drilling, logging, cementing and completion technology, high-torque top drive system, and deep-well coiled tubing operation unit; (2) advanced tools, such as vertical drilling tool, non-planar tooth bit, high-strength expandable tubular, high-temperature, high-torque and long-life screw rod, torsion impact tool, synergistic damping based rock breaking tool, measurement while drilling tool, and safety monitoring tool; (3) core additives, such as temperature-resistance high-density oil based drilling fluid, high-performance water based drilling fluid, ductile cement slurry, and self-healing cement slurry; (4) life-cycle wellbore integrity technology system. Nevertheless, oil and gas well drilling and completion still faces severe challenges, including deep (great burial depth), steep (large formation dip), narrow (narrow pressure window), thick (thick gravel layer, salt bed and other complex intervals), difficult (complex multi-pressure system, abundant complex accidents and poor drillability) and high (high temperature, high pressure and high acid). Facing these challenges, the following suggestions are proposed. The key to the oil and gas reserve and production increase during the 14th Five-Year Plan and afterwards is till deep and ultra-deep layers. And it is necessary to focus on above mentioned geological difficulties to research key core technologies, such as automatic and intelligent drilling equipment, ultra-high temperature wellbore working fluid, pre-exploration while drilling and digital twin well construction, so as to realize the iterative upgrading of traditional superior technologies and improve the ability to drill deep and ultra-deep wells safely, quickly and optimally. In conclusion, during the 13th Five-Year Plan, China exceeded America in the number of ultra-deep wells for the first time and its well depth stepped up to a new stage of 8000 m, which plays an important role in supporting the development of deep oil and gas exploration and development and improving the market competitiveness of drilling and completion.

Recently, Synthetic Aperture Radar (SAR) data, especially Sentinel-1 data, have been increasingly used in rice mapping research. However, current studies usually use long time series data as the data source to represent the differences between rice and other ground objects, especially other crops, which results in complex models and large computational complexity during classification. To address this problem, a novel method for single season rice mapping is proposed, based on the principle that the scattering mechanism of rice paddies in the early flooding period is strongly influenced by water bodies, causing the volume scattering to be lower than that of other crops. Thus, a feature combination that can effectively and stably extract rice planting areas was constructed by combining multi-temporal volume scattering in the early flooding period of rice using dual-polarization SAR data, so that a simple semantic segmentation model could realize high-precision rice mapping tasks. A two-stage segmentation structure was introduced to further improve the mapping result with the Omni-dimensional Dynamic Convolution Residual Segmentation model (ODCRS model) as the bone model. In the experiment, Suihua City, Heilongjiang Province was selected as the study site, and the VH/VV polarized data of Sentinel-1 satellite in 2022 was used as the data source. The mapping accuracy of the ODCRS model was 88.70%, and the user accuracy was 84.19% on the field survey data. Furthermore, experiments with different years and regions also proved the effectiveness and stability of the proposed method.