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Abstract Drawing inspiration from the state‐of‐the‐art object detection framework YOLOv8, a new model termed adverse weather net (ADWNet) is proposed. To enhance the model's feature extraction capabilities, the efficient multi‐scale attention (EMA) module has been integrated into the backbone. To address the problem of information loss in fused features, Neck has been replaced with RepGDNeck. Simultaneously, to expedite the model's convergence, the bounding box's loss function has been optimized to SIoU loss. To elucidate the advantages of ADWNet in the context of adverse weather conditions, ablation studies and comparative experiments were conducted. The results indicate that although the model's parameter count increased by 18.4%, the accuracy for detecting rain, snow, and fog in adverse weather conditions improved by 22%, while the FLOPs (floating point operations) decreased by 5%. The results of the comparison experiments conducted on the WEDGE dataset show that ADWNet outperforms other object detection models in adverse weather in terms of accuracy, model parameters and FLOPs. To validate ADWNet's real‐world efficacy, data was extracted from a car recorder under adverse conditions on highways, visual inference was conducted, and its accuracy was demonstrated in interpreting real‐world scenarios. The config files are available at https://github.com/Xinyun‐Feng/ADWNet.

Abstract Diabetic encephalopathy (DE) is a severe complication of diabetes, but its pathogenesis remains unclear. This study aimed to investigate the roles and underlying mechanisms of high glucose (HG)- and advanced glycosylation end product (AGE)-induced oxidative stress (OS) in the cognitive decline in DE. The DE mouse model was established using a high-fat diet and streptozotocin, and its cognitive functions were evaluated using the Morris Water Maze, novel object recognition, and Y-maze test. The results revealed increased reactive oxygen species (ROS) generation, mitophagy inhibition, and decreased prohibitin 2 (PHB2) expression in the hippocampal neurons of DE mice and HG- or AGE-treated HT-22 cells. However, overexpression of PHB2 reduced ROS generation, reversed mitophagy inhibition, and improved mitochondrial function in the HG- or AGE-treated HT-22 cells and ameliorated cognitive decline, improved mitochondrial structural damage, and reversed mitophagy inhibition of hippocampal neurons in DE mice. Further analysis revealed that the Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was involved in the HG- or AGE-mediated downregulation of PHB2 in HT-22 cells. These results demonstrate that HG- or AGE-induced OS inhibits the mitophagy of hippocampal neurons via the Keap1–Nrf2–PHB2 pathway, thereby contributing to the cognitive decline in DE.

Abstract The RAB interacting factor (RABIF) is a putative guanine nucleotide exchange factor that also functions as a RAB-stabilizing holdase chaperone. It has been implicated in pathogenesis of several cancers. However, the functional role and molecular mechanism of RABIF in hepatocellular carcinoma (HCC) are not entirely known. Here, we demonstrate an upregulation of RABIF in patients with HCC, correlating with a poor prognosis. RABIF inhibition results in decreased HCC cell growth both in vitro and in vivo. Our study reveals that depleting RABIF attenuates the STOML2-PARL-PGAM5 axis-mediated mitophagy. Consequently, this reduction in mitophagy results in diminished mitochondrial reactive oxygen species (mitoROS) production, thereby alleviating the HIF1α-mediated downregulation of glycolytic genes HK1, HKDC1, and LDHB. Additionally, we illustrate that RABIF regulates glucose uptake by controlling RAB10 expression. Importantly, the knockout of RABIF or blockade of mitophagy sensitizes HCC cells to sorafenib. This study uncovers a previously unrecognized role of RABIF crucial for HCC growth and identifies it as a potential therapeutic target.

Abstract Background Endocrine function in patients with type 2 diabetes (T2DM) typically differs from those with normal glucose tolerance (NGT). However, few epidemiologic studies have explored how these differences impact the association between exposure to polychlorinated biphenyls (PCBs) and vitamin D levels. Methods This study included 1,705 subjects aged 18–79 years from the Henan Rural Cohort [887 NGT and 818 T2DM]. Linear regression was applied to evaluate the associations between PCB exposure and vitamin D levels. Quantile g-computation regression (QG) and Bayesian kernel machine regression (BKMR) were applied to evaluate the impact of PCB mixtures on vitamin D levels. Interaction effects of ΣPCBs with HOMA2-%β and HOMA2-IR on vitamin D levels were assessed. Results Plasma ΣPCBs was positively associated with 25(OH)D2 in the NGT group (β = 0.060, 95% CI: 0.028, 0.092). Conversely, in T2DM group, ΣPCBs was negatively associated with 25(OH)D3 and 25(OH)D (β = -0.049, 95% CI: -0.072, -0.026; β = -0.043, 95% CI: -0.063, -0.023). Similarly, both QG and BKMR analysis revealed a negative association between PCB mixture exposure and vitamin D levels in the T2DM group, contrary to the results observed in the NGT groups. Furthermore, the negative association of ΣPCBs with 25(OH)D2 and 25(OH)D disappeared or changed to a positive association with the increase of HOMA2-%β levels. Conclusions These findings suggest that decreased β cell function may exacerbate the negative effects of PCB exposure on vitamin D levels. Recognizing T2DM patients’ sensitivity to PCBs is vital for protecting chronic disease health.

Objective To explore the relationship between monocyte/high-density lipoprotein cholesterol ratio （MHR） and the progression and prognosis of type 2 diabetic kidney disease （DKD）. Methods From January 1， 2017 to December 31， 2022， 269 type 2 DKD patients were selected as DKD group while 269 healthy medical check-ups during the same period as healthy group. And the differences in MHR levels of two groups were compared. According to median MHR， DKD group were assigned into low-level MHR and high-level MHR sub-groups. General profiles， clinical data， the incidence rate of endpoint events and cumulative renal survival were compared two groups. Cox regression analysis was performed for exploring the independent risk factors for poor renal prognosis in DKD patients and drawing receiver operator characteristic curve （ROC） for exploring the diagnostic efficacy of MHR for poor prognosis of DKD. Results MHR level was higher in DKD group than that in healthy group [0.4918（0.3788，0.6818）×109/mmol vs 0.2984（0.1867，0.4112）×109/mmol] （P＜0.05）； high-level MHR group had higher levels of white blood cells （WBC） [7.70（6.40， 8.70）×109/L vs 6.50（5.40， 8.00）×109/L]， neutrophils （Ne） [4.60（3.60， 5.53）×109/L vs 3.99（3.18， 5.19）×109/L] and monocyte （Mono） [0.69（0.60， 0.70）×109/L vs 0.50（0.40， 0.60）×109/L]， urinary albumin to creatinine ratio （UACR） [1214.59（373.48， 3410.02）mg/g vs 1050.96（180.26， 3341.06） mg/g]， 24 h urine protein （24 hUP） [3.21（1.42， 5.51）g vs 2.66 （0.58， 4.56） g]， low-density lipoprotein cholesterol （LDL-C） [2.72（2.06， 3.40）mmol/L vs 2.23（1.63， 2.80）mmol/L]， serum creatinine （Scr） [152.10（95.20， 221.60）μmol/L vs 126.00（92.48， 186.55）μmol/L] than those in low-level MHR group； lymphocyte （Lym） [1.60（1.27， 2.20）×109/L vs 1.82（1.30， 2.40）×109/L]， high-density lipoprotein cholesterol （HDL-C） [0.94（0.83， 1.07）mmol/L vs 1.39（1.15， 1.65）mmol/L] and estimated glomerular filtration rate （eGFR） [39.69（25.19， 65.10）mL·min−1·（1.73 m²）−1 vs 47.12（28.86， 73.60）mL·min−1·（1.73 m²）−1] were lower than those in low-level MHR group； high-level MHR group had a cumulative kidney survival time and it was shorter than that in low level MHR group [63（39， 72）month vs 72（46， 72）month] （P＜0.05）； MHR was correlated positively with WBC， Ne， Mono， UACR， 24h UP， Scr and LDL-C （P＜0.05） and negatively with Lym， HDL-C， eGFR and cumulative renal survival time （P＜0.05）； the incidence of endpoint events was higher in high-level MHR group than that in low-level MHR group （52.59% vs 38.06%）（P＜0.05）； baseline MHR [0.5492（0.4030， 0.7235）×109/mmol vs 0.4255（0.3117， 0.5134）×109/mmol]， UACR [2062.65（752.80， 4234.80）mg/g vs 608.56（88.63. 1912.44）mg/g]， 24 hUP [3.79（2.54， 5.53）g vs 1.58（0.39， 4.85）g] and Scr [178.40（134.00， 234.23）μmol/L vs 100.95（74.25， 152.10）μmol/L] were higher than those in DKD patients without endpoint events； eGFR was lower than that in DKD patients without endpoint events [33.45（23.33， 46.41）mL·min−1·（1.73 m²）−1 vs 61.59（38.57， 95.98）mL·min−1·（1.73 m²）−1]（P＜0.05）. The results of Cox regression analysis indicated that MHR was an independent risk factor for a poor prognosis of DKD； The results of ROC curve showed that the area under the curve of MHR was 0.747 with a sensitivity of 0.820 and a specificity of 0.605. Conclusion DKD patients tend to have higher levels of MHR as compared with healthy individuals. As an independent risk for the progression of renal function in DKD patients， MHR has some diagnostic value for a poor prognosis of DKD. However， its specificity is not high.

Abstract Background Gliomas are the highly aggressive brain tumor and also the most devastating human tumors. The latent TGF binding proteins (LTBP) had been found to be involved in malignant biological process and could be used as potent biomarkers in several solid tumors. While the role of LTBP family in human glioma remain to be elucidated. Methods Normalized gene expression and corresponding clinical data of 2407 gliomas samples in public datasets were downloaded from Gliovis. Kaplan–Meier methods and Cox regression analysis was used for survival analyses.Western blot (WB) and Immunohistochemical (IHC) testing were employed to test LTBPs protein level in 154 gliomas samples. Correlation between LTBP2 expression and immune infiltration was evaluated by immunofluorescence (IF) and IHC in glioma tissues. CCK8 and flow cytometric analysis were used to detect the effect of LTBP2 on glioma cells. Orthotopic glioma- mouse models were utilized to evaluate effects in vivo. Results LTBP2 mRNA level was dramatically higher in glioma samples compared with non-tumor brain tissues in XENA-TCGA_GTEx, Gill and Gravendeel datasets (all P

Abstract Background Accurately classifying primary bone tumors is crucial for guiding therapeutic decisions. The National Comprehensive Cancer Network guidelines recommend multimodal images to provide different perspectives for the comprehensive evaluation of primary bone tumors. However, in clinical practice, most patients’ medical multimodal images are often incomplete. This study aimed to build a deep learning model using patients’ incomplete multimodal images from X-ray, CT, and MRI alongside clinical characteristics to classify primary bone tumors as benign, intermediate, or malignant. Methods In this retrospective study, a total of 1305 patients with histopathologically confirmed primary bone tumors (internal dataset, n = 1043; external dataset, n = 262) were included from two centers between January 2010 and December 2022. We proposed a Primary Bone Tumor Classification Transformer Network (PBTC-TransNet) fusion model to classify primary bone tumors. Areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the model’s classification performance. Results The PBTC-TransNet fusion model achieved satisfactory micro-average AUCs of 0.847 (95% CI: 0.832, 0.862) and 0.782 (95% CI: 0.749, 0.817) on the internal and external test sets. For the classification of benign, intermediate, and malignant primary bone tumors, the model respectively achieved AUCs of 0.827/0.727, 0.740/0.662, and 0.815/0.745 on the internal/external test sets. Furthermore, across all patient subgroups stratified by the distribution of imaging modalities, the PBTC-TransNet fusion model gained micro-average AUCs ranging from 0.700 to 0.909 and 0.640 to 0.847 on the internal and external test sets, respectively. The model showed the highest micro-average AUC of 0.909, accuracy of 84.3%, micro-average sensitivity of 84.3%, and micro-average specificity of 92.1% in those with only X-rays on the internal test set. On the external test set, the PBTC-TransNet fusion model gained the highest micro-average AUC of 0.847 for patients with X-ray + CT. Conclusions We successfully developed and externally validated the transformer-based PBTC-Transnet fusion model for the effective classification of primary bone tumors. This model, rooted in incomplete multimodal images and clinical characteristics, effectively mirrors real-life clinical scenarios, thus enhancing its strong clinical practicability.

Abstract Chemotherapeutic drugs, such as cisplatin (cis-dichlorodiamineplatinum [II], cDDP) and 5-fluorouracil (5Fu), are widely used in transarterial chemoembolization (TACE), which is a standard therapy for patients with hepatocellular carcinoma (HCC). Chemoresistance is a major cause of TACE treatment failure in HCC patients. Our previous studies have identified the expression levels of miR-101 responsive genes, such as EED, EZH2, STMN1 and JUNB, exhibit significant correlation with the occurrence and progression of HCC, while the role of miR-101 responsive gene signatures in the chemoresistance of HCC treatment remains unclear. In this study, we identified ubiquitin-coupled enzyme E2D1 (UBE2D1) as a crucial regulatory factor in the chemoresistance of HCC, which is a direct target of miR-101 and exhibits significant correlation with miR-101-responsive gene signatures. The bioinformatics analysis showed the expression of UBE2D1 was significantly increased in HCC tissues and was closely correlated with the poor prognosis. In addition, we analyzed the role of miR-101/UBE2D1 axis in regulating chemo-sensitive of HCC cells. Our results showed that miR-101 increases the DNA damage and apoptosis of HCC cells by inhibiting the expression of UBE2D1, which in turn increases the sensitivity of HCC cells to cDDP and 5Fu both in vitro and in vivo. Therefore, simultaneous assessment of miR-101 and UBE2D1 expression levels might provide an effective approach in preselecting HCC patients with survival benefit from TACE treatment. Moreover, further elucidation of the underlying molecular mechanisms of the miR-101/UBE2D1 axis could provide novel insight for targeted therapy of HCC.

Abstract Honey vaults are useful tools for password management. A vault usually contains usernames for each domain, and the corresponding passwords, encrypted with a master password chosen by the owner. By generating decoy vaults for incorrect master password attempts, honey vaults force attackers with the vault’s storage file to engage in online verification to distinguish the real vaults, thus thwarting offline guessing attacks. However, sophisticated attackers can acquire additional information, such as personally identifiable information (PII) and partial passwords contained within the vault from various data breaches. Since many users tend to incorporate PII in their passwords, attackers may utilize PII to distinguish the real vault. Furthermore, if attackers may learn partial passwords included in the real vault, it can exclude numerous decoy vaults without the need for online verification. Indeed, both leakages pose serious threats to the security of the existing honey vault schemes. In this paper, we explore two attack variants of the inspired attack scenario, where the attacker gains access to the vault’s storage file along with acquiring PII and partial passwords contained within the real vault, and design a new honey vault scheme. For security assurance, we prove that our scheme is secure against one of the aforementioned attack variants. Moreover, our experimental findings suggest enhancements in security against the other attack. In particular, to evaluate the security in multiple leakage cases where both the vault’s storage file and PII are leaked, we propose several new practical attacks (called PII-based attacks), building upon the existing practical attacks in the traditional single leakage case where only the vault’s storage file is compromised. Our experimental results demonstrate that certain PII-based attacks achieve a 63–70% accuracy in distinguishing the real vault from decoys in the best-performing honey vault scheme (Cheng et al. in Incrementally updateable honey password vaults, pp 857–874, 2021). Our scheme reduces these metrics to 41–50%, closely approaching the ideal value of 50%.

Abstract SM9 was established in 2016 as a Chinese official identity-based cryptographic (IBC) standard, and became an ISO standard in 2021. It is well-known that IBC is suitable for Internet of Things (IoT) applications, since a centralized processing of client data (e.g. IoT cloud) is often done by gateways. However, due to limited computation resources inside IoT devices, the performance of SM9 becomes a bottleneck in practical usage. The existing SM9 implementations are often CPU-based, with relatively low latency and low throughput. Consequently, a pivotal challenge for SM9 in large-scale applications is how to reduce the latency while maximizing throughput for numerous concurrent inputs. After a systematic analysis of the SM9 algorithms, we apply optimization techniques including precomputation, resource caching and parallelization to reduce the overhead of SM9. In this work, we introduce the first practical implementation of SM9 and its underlying SM9_P256 curve on GPU. Our GPU implementation combines multiple algorithms and low-level optimizations tailored for GPU’s single instruction, multiple threads architecture in order to achieve high throughput for SM9. Based on these, we propose GAPS, a high-performance Cryptography as a Service (CaaS) for SM9. GAPS adopts a heterogeneous computing architecture that flexibly schedules the inputs across two implementation platforms: a CPU for the low-latency processing of sporadic inputs, and a GPU for the high-throughput processing of batch inputs. According to our benchmark, GAPS only takes a few milliseconds to process a single SM9 request in idle mode. Moreover, when operating in its batch processing mode, GAPS can generate 2,038,071 private keys, 248,239 signatures or 238,001 ciphertexts per second. The results show that GAPS scales seamlessly across inputs of different sizes, preliminarily demonstrating the efficacy of our solution.

Abstract This paper adopts the “baseline scenario method” to construct a comprehensive model for calculating and reducing carbon emissions generated by employee travel, including the accounting of carbon emissions from commuting and business travel, as well as the assessment of green travel for carbon reduction. The study employs methods such as questionnaires and on-site interviews to collect travel data from employees of a research institute in Beijing as a case study. The results show that employees’ commuting methods are diverse, with the subway being the primary mode of travel; however, business travel generates higher carbon emissions, particularly among employees with higher education levels. The research concludes that the model proposed in this paper provides a framework for preliminary carbon emission estimation, but to improve the accuracy of the estimates, more variables and factors need to be considered, and the limitations of the model are pointed out. The research findings have significant implications for policy and institutional practices, suggesting the adoption of more targeted measures to reduce the use of high-carbon-emission travel methods and to encourage the use of green travel options. With the continuous advancement of data collection technologies in the future, it will be possible to further establish a more refined carbon emission accounting model and obtain more accurate and comprehensive travel data, thereby providing solid data support for the development of more effective carbon reduction strategies and policies.

Leaves are the main organ for photosynthesis and organic synthesis in cotton. Leaf shape has important effects on photosynthetic efficiency and canopy formation, thereby affecting cotton yield. Previous studies have shown that LMI1 (LATE MERISTEM IDENTITY1) is the main gene regulating leaf shape. In this study, the LMI1 gene was inserted into the 35S promoter expression vector, and cotton plants overexpressing LMI1 (OE) were obtained through genetic transformation. Statistical analysis of the biological traits of the T1 and T2 populations showed that compared to the wild type (WT), OE plants had significantly larger leaves, thicker stems and significantly greater dry weight. Furthermore, plant sections of the main vein and petiole showed that the numbers of cells in those tissues of OE plants were significantly greater. In addition, RNA-seq analysis revealed the differential expression of genes related to gibberellin synthesis and NAC gene family (genes containing the NAC domain) between the OE and WT plants, suggesting that LMI1 is involved in secondary wall formation and cell proliferation, which promotes stem thickening. Moreover, Gene Ontology (GO) analysis revealed enrichment in the terms of calcium ion binding, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment in the terms of fatty acid degradation, phosphatidylinositol signal transduction system, and cAMP (cyclic adenosine monophosphate) signal pathway. These results suggested that LMI1 OE plants are responsive to gibberellin hormone signals, and have altered messenger signals (cAMP, Ca2+) which amplify this function, to promote stronger aboveground vegetative growth. This study found the LMI1 greatly increased the vegetative growth in cotton, which is the basic requirement for higher yield.

The pipe curtain structure method (PSM) is a novel construction method to control ground deformation strictly. Compared with the traditional pipe-roofing and pipe jacking method, the connection between pipes in large spacings using PSM is widely acknowledged as a unique construction procedure. Further study on this connection procedure is needed to resolve similar cases in that the pipes are inevitably constructed on both sides of existing piles. Cutting the steel plate during the connection procedure is the first step, which is crucial to control the safety and stability of the surrounding environment and existing structures. The deformation mechanism and limit support pressure of the cutting steel plate during the connection between pipes in large spacings are studied in this paper, relying on the undercrossing Yifeng gate tower project of Jianning West Road River Crossing Channel in Nanjing, China. A modified 3D wedge-prism failure model is proposed using the 3D discrete element method. Combined with Terzaghi loose earth pressure theory and the limit equilibrium theory, the analytical solutions for the limit support pressure of the excavation face of the cutting steel plate are derived. The modified 3D wedge-prism failure model and corresponding analytical solutions are categorised into two cases: (a) unilateral cutting scheme, and (b) bilateral cutting scheme. The analytical solutions for the two cases are verified from the numerical simulation and in-situ data and compared with the previous solutions. The comparative analysis between the unilateral and bilateral cutting schemes indicates that the bilateral cutting scheme can be adopted as a priority. The bilateral cutting scheme saves more time and induces less ground deformation than the unilateral one due to the resistance generated from the superimposed wedge. In addition, the parametric sensitivity analysis is carried out using an orthogonal experimental design. The main influencing factors arranged from high to low are the pipe spacing, the cutting size, and the pipe burial depth. The ground deformation increases with the increased cutting size and pipe spacing. The pipe burial depth slightly affects the ground deformation if the other two factors are minor. Cutting steel plates in small sizes, excavating soil under low disturbance, and supporting pipes for high frequency can effectively reduce the ground surface subsidence.

Abstract Apoptosis is a genetically programmed form of cell death that is substantially conserved across the evolutionary tree. Apoptotic cell elimination includes recognition, phagocytosis, and degradation. Failure to clear apoptotic cells can ultimately cause a series of human diseases, such as systemic lupus erythematosus, Alzheimer's disease, atherosclerosis, and cancer. Consequently, the timely and effective removal of apoptotic cells is crucial to maintaining the body's homeostasis. GPCRs belong to the largest membrane receptor family. Its intracellular domain exerts an effect on the trimer G protein. By combining with a variety of ligands, the extracellular domain of G protein initiates the dissociation of G protein trimers and progressively transmits signals downstream. Presently, numerous G protein‐coupled receptors (GPCRs) have been identified as participants in the apoptosis signal transduction pathway and the apoptotic cell clearance pathway. Therefore, studies on the mechanism of GPCRs in the clearance of apoptotic cells is important for the development of GPCRs therapeutics.

Abstract Background This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease. Methods Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed. Results A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107–16.356) tended to experience disease recurrence (p = 0.01). Conclusions Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence. Trial registration This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Asphalt pavement repair areas affect pavement performance and service levels. It is necessary to distinguish the repair areas from normal sections. Based on vehicle vibration signals, this study identified ten pavement repair areas and divided them into four cases by factors including length and form in conjunction with the driving approach. Additionally, time domain analysis, frequency analysis, and probability distribution analysis were used to form the characteristics of the repair cases as well as the normal sections. It was found that the maximum value, extreme deviation, standard deviation in the time domain, maximum amplitude in the frequency domain, and peak of the probability density curve would serve as judgment indexes. A framework for identifying the repair areas was also established based on the five indexes. By validation, the overall accuracy can reach 95.0%, demonstrating a strong generalization capability.

Abstract Background Occupational Bloodborne Exposures (OBEs) are incidents where healthcare workers come into contact with blood or other potentially infectious materials, leading to risks of transmitting bloodborne pathogens. Nursing students, often in direct contact with patients, face heightened risks due to their duties. Methods First, we conducted a cross-sectional survey using a OBEs questionnaire to explore the knowledge, attitudes, practices, and needs regarding OBEs among nursing students. Subsequently, we used a randomized controlled trial (RCT) to compare the impact of the Presentation-Assimilation-Discussion (PAD) method with the traditional lecture-based learning (LBL) method on OBEs education for nursing students. Pre-test, post-test, and retention test were used to observe the teaching effectiveness, and the students’ feedback on the teaching method was also observed. Results In the cross-sectional survey, we found that nursing students lacked sufficient knowledge and management skills regarding OBEs but recognized the importance of standard precautions and expressed a desire for systematic OBEs training during their education and internships. In the RCT, the total, theoretical, and practical scores of the PAD and LBL groups were comparable in the pre-test (56.70 ± 3.47 vs. 56.40 ± 3.95, 33.09 ± 3.39 vs. 33.33 ± 2.44, 23.61 ± 4.66 vs. 23.07 ± 4.84, p > 0.05). After training, the PAD model demonstrated an advantage over the LBL model in immediate total (84.25 ± 4.06 vs. 78.95 ± 4.23, p 0.05). The PAD group benefited more across various learning dimensions but reported a higher study load. Conclusions Our study reveals that the PAD model could be a valuable approach for teaching OBEs to nursing students.

Abstract Background Agricultural irrigation is an important practice to safeguard crops against drought and enhance grain yield in arid regions. The Hexi Corridor, known as a classic arid region, faces significant pressure on agricultural production and food security due to the scarcity of water resources. There is an urgent need to investigate agricultural water use of the irrigated regions. Water use efficiency (WUE), defined as the ratio of gross primary productivity (GPP) to actual evapotranspiration (ET), serves as a valuable indicator linking carbon assimilation and water loss. It enables the quantification of areas where water can be utilized more effectively. However, the long-term spatiotemporal dynamics of WUE and driving mechanism in the irrigated areas of the Hexi Corridor remain unclear. Results This study used GPP calculated by a light use efficiency model (EF-LUE), ET estimated by an ETMonitor model and irrigated cropland maps across China (IrriMap_CN) to examine the spatiotemporal dynamics of irrigated cropland WUE and its controlling factors in the Hexi Corridor from 2001 to 2018. The results are as following: (1) The average annual WUE was approximately 1.34 ± 0.38 g C kg−1 H2O yr−1, with an increasing trend of 0.012 g C kg−1 H2O yr−1, and faster growth observed during 2011–2018 compared to 2001–2010. (2) The contribution of GPP to WUE trends and WUE interannual variability (IAV) was greater than that of ET. (3) The dominant climatic factors of WUE IAV in the Hexi Corridor were SPEI, precipitation, and soil moisture. (4) The standardized Structural Equation Model (SEM), incorporating the relationship between WUE and factors such as water, energy, NDVI, and water-saving irrigation, explained 81% of the variation in irrigated cropland WUE. Here, biological factors (GPP and NDVI) were the primary factors influencing WUE variability, and water-saving irrigation had a stronger indirect effect than climate factors (water and energy) on variation in WUE. Conclusions Our findings offer valuable theoretical insights into the mechanisms governing the interaction between the carbon and water of irrigated cropland, guiding the management of water resources and land in agricultural practices within the Hexi Corridor.

Abstract Chronic lymphocytic leukemia (CLL) presents with heterogeneous clinical outcomes, suggesting varied underlying pathogenic mechanisms. This study aims to elucidate the impact of T follicular helper (Tfh) cells on CLL progression and prognosis. Gene expression profile data for CLL were collected from GSE22762 and GSE39671 datasets. Patients were divided into high and low groups using Tfh levels using the optimal cutoff value based on overall survival (OS) and time-to-first treatment (TTFT). Differential expression analysis was performed between these groups, followed by co-expression network analysis and single-sample Gene Set Enrichment Analysis (ssGSEA). Marker genes of Tfh cells were used to construct prognostic models. Additionally, 40 CLL patients were recruited and categorized based on median Tfh levels. Marker gene expression was assessed using RT-qPCR and Western Blot, and immune cell levels were determined through flow cytometry. The high group showed better prognosis compared to the low group. Among the 1121 differentially expressed genes identified, five co-expression networks were constructed, with the turquoise module showing the highest correlation with Tfh cells. Genes within this module significantly participate in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and natural killer cell mediated cytotoxicity. Tfh cells were significantly negatively correlated with activated B cells and positively correlated with Tregs. The Random Survival Forest (RSF) model identified 10 marker genes, and further analysis using Lasso regression and nomogram selected CLEC4A, RAE1, CD84, and PRDX1 as prognostic markers. In the high group, levels of CLEC4A and RAE1 were higher than in the low group, whereas CD84 and PRDX1 were lower. Flow cytometry revealed that the level of activated B cells in the high Tfh group was significantly lower than in the low Tfh group, while the level of Tregs is significantly higher in the high Tfh group. This study seeks to contribute to a more detailed understanding of the pathogenesis of CLL, delving into the prognostic significance of Tfh.

Abstract Understanding the spatiotemporal characteristics and comprehensive service capabilities of various ecosystem services is crucial for maintaining regional ecosystem security, and clarifying the driving mechanisms of ecosystem services plays a guarantee for achieving regional sustainable development. Based on the ecological issues of Shanxi Province (SXP) in China, an assessment system covering eight targeted ecosystem services were constructed to quantitatively analyze the spatio-temporal patterns and contribution rates of driving factors. The water conservation, sand fixation, environment purification and habitat quality in the Loess Hills of western SXP have improved, with significant increase in hotspots. The comprehensive service capacity of ecosystem services in the Fenwei Basin (central SXP) has deteriorated, and the coldspots have expanded. The water conservation, carbon storage, habitat quality and recreation culture in the Yanshan-Taihang Mountains (eastern SXP) were enhanced, while product supply, carbon storage and environment purification were deteriorated. Land use is the dominant influencing factor on product supply. Water and soil conservation, sand fixation, and environment purification are dominated by climate factors. Carbon storage, habitat quality and recreation culture are influenced by underlying surface conditions. The current study provided a research paradigm, which will help the government with appropriate management policies to ensure the effectiveness of ecological protection and restoration, and offers insights for facilitating ecological sustainability and economic transformation in resource-based regions worldwide.

Abstract Background Gastrointestinal mesenchymal stromal tumors (GISTs) are a group of intramural tumors that exhibit a wide range of morphologies. Dysfunction or loss of interstitial cells of Cajal (ICCs) is correlated with the disorders of gastrointestinal motility. At present, the characterization and molecular mechanisms underlying the role of ICCs in GIST are still not clear. Methods The GSE162115 dataset from Gene Expression Omnibus database was processed using Seurat package for quality control, data normalization, and cell clustering. Differential expression and functional enrichment analyses were performed using the FindAllMarkers function and clusterProfiler package. Cellular heterogeneity was assessed by CytoTRACE and potential regulatory mechanisms of ICCs in GISTs were investigated using SCENIC. Cellular communication was inferred and analyzed applying the CellChat package. Results Eight clusters were identified based on 34,861 cells. Intra-tumor samples had a higher proportion of ICCs than peri-tumor. ICCs were related to cell cycle and glycolytic activity in intra-tumor samples, while those in peri-tumor samples were involved in immune response. Further analysis identified four ICC subgroups (subcluster 1–4), of which subcluster 3 showed the most typical stem cell properties and interacted with the rest of the cells through the MIF-CD74 (CD44) protein. Conclusion This study analyzed the heterogeneity and stem cell properties of ICCs in GISTs, revealing the molecular mechanisms and potential therapeutic targets for GISTs.

Abstract Organic semiconductors (OSCs) are featured by weak spin-orbit coupling due to their light chemical element composition, which enables them to maintain spin orientation for a long spin lifetime and show significant potential in room-temperature spin transport. Carrier mobility and spin lifetime are the two main factors of the spin transport performance of OSCs, however, their ambiguous mechanisms with molecular structure make the development of spintronic materials really stagnant. Herein, the effects of halogen substitution in bay-annulated indigo-based polymers on carrier mobility and spin relaxation have been systematically investigated. The enhanced carrier mobility with an undiminished spin lifetime contributes to a 3.7-fold increase in spin diffusion length and a record-high magnetoresistance of 8.7% at room temperature. By analyzing the spin-orbit coupling and hyperfine interaction, it was found that the distance of the substitution site from the conjugated center and the nitrogen atoms in the molecules play crucial roles in spin relaxation. Based on the above results, we proposed a molecular design strategy of halogen substitution far from conjugate center to enhance spin transport efficiency, presenting a promising avenue for advancing the field of organic spintronics.

Abstract Metal micro/nanoparticle ink-based printed circuits have shown promise for promoting the scalable application of flexible electronics due to enabling superhigh metallic conductivity with cost-effective mass production. However, it is challenging to activate printed metal-particle patterns to approach the intrinsic conductivity without damaging the flexible substrate, especially for high melting-point metals. Here, we report a pressure-constrained sonication activation (PCSA) method of the printed flexible circuits for more than dozens of metal (covering melting points from room temperature to 3422 °C) and even nonmetallic inks, which is integrated with the large-scale roll-to-roll process. The PCSA-induced synergistic heat-softening and vibration-bonding effect of particles can enable multilayer circuit interconnection and join electronic components onto printed circuits without solder within 1 s at room temperature. We demonstrate PCSA-based applications of 3D flexible origami electronics, erasable and foldable double-sided electroluminescent displays, and custom-designed and large-area electronic textiles, thus indicating its potential for universality in flexible electronics.

Abstract Carbon peaking and achieving carbon neutrality have emerged as pivotal strategic imperatives in China. These objectives not only drive a shift in production, lifestyle, and consumption patterns but also illuminate a path towards a comprehensive green metamorphosis in China’s economic and social development landscape. The distinctive nature of museums as quintessential public edifices, requiring sustained regulation of temperature and humidity alongside attracting substantial foot traffic, positions them as crucial pioneers in the pursuit of carbon peaking and neutrality. It is essential for museums to leverage their leadership and advocacy roles to catalyze low-carbon construction practices across society. This study delves into the energy dynamics specific to the museum sector, delving into the recycling of exhibition materials, methodologies for carbon footprint assessments of visitors and museum staff, and the establishment of a standardized carbon emission accounting framework tailored to the museum industry. Through meticulous examination of representative cases and subsequent analysis, this research delineates decarbonization strategies, offering indispensable technical scaffolding for carbon assessment and emission reduction efforts within the museum realm.

Abstract Background Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. Results In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. Conclusions This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Abstract Background This study investigated the clinical value of breast magnetic resonance imaging (MRI) radiomics for predicting axillary lymph node metastasis (ALNM) and to compare the discriminative abilities of different combinations of MRI sequences. Methods This study included 141 patients diagnosed with invasive breast cancer from two centers (center 1: n = 101, center 2: n = 40). Patients from center 1 were randomly divided into training set and test set 1. Patients from center 2 were assigned to the test set 2. All participants underwent preoperative MRI, and four distinct MRI sequences were obtained. The volume of interest (VOI) of the breast tumor was delineated on the dynamic contrast-enhanced (DCE) postcontrast phase 2 sequence, and the VOIs of other sequences were adjusted when required. Subsequently, radiomics features were extracted from the VOIs using an open-source package. Both single- and multisequence radiomics models were constructed using the logistic regression method in the training set. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision of the radiomics model for the test set 1 and test set 2 were calculated. Finally, the diagnostic performance of each model was compared with the diagnostic level of junior and senior radiologists. Results The single-sequence ALNM classifier derived from DCE postcontrast phase 1 had the best performance for both test set 1 (AUC = 0.891) and test set 2 (AUC = 0.619). The best-performing multisequence ALNM classifiers for both test set 1 (AUC = 0.910) and test set 2 (AUC = 0.717) were generated from DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging single-sequence ALNM classifiers. Both had a higher diagnostic level than the junior and senior radiologists. Conclusions The combination of DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging radiomics features had the best performance in predicting ALNM from breast cancer. Our study presents a well-performing and noninvasive tool for ALNM prediction in patients with breast cancer.

Abstract The transcription factor WRKYs play pivotal roles in the adapting to adverse environments in plants. Prior research has demonstrated the involvement of OsWRKY70 in resistance against herbivores and its response to abiotic stress. Here, we reported the functional analysis of OsWRKY70 in immunity against fungal diseases and cold tolerance. The results revealed that OsWRKY70 was induced by various Magnaporthe oryzae strains. Knock out mutants of OsWRKY70, which were generated by the CRISPR/Cas9 system, exhibited enhanced resistance to M. oryzae. This was consistent with fortifying the reactive oxygen species (ROS) burst after inoculation in the mutants, elevated transcript levels of defense-responsive genes (OsPR1b, OsPBZ1, OsPOX8.1 and OsPOX22.3) and the observation of the sluggish growth of invasive hyphae under fluorescence microscope. RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) validations demonstrated that differentially expressed genes were related to plant-pathogen interactions, hormone transduction and MAPK cascades. Notably, OsbHLH6, a key component of the JA signaling pathway, was down-regulated in the mutants compared to wild type plants. Further investigation confirmed that OsWRKY70 bound to the promoter of OsbHLH6 by semi-in vivo chromatin immunoprecipitation (ChIP). Additionally, the loss-function of OsWRKY70 impaired cold tolerance in rice. The enhanced susceptibility in the mutants characterized by excessive ROS production, elevated ion leakage rate and increased malondialdehyde content, as well as decreased activity of catalase (CAT) and peroxidase (POD) under low temperature stress was, which might be attributed to down-regulation of cold-responsive genes (OsLti6b and OsICE1). In conclusion, our findings indicate that OsWRKY70 negatively contributes to blast resistance but positively regulates cold tolerance in rice, providing a strategy for crop breeding with tolerance to stress.

Objective To identify the characteristics of nutritional problems in patients with Parkinsonism who participated in multi-disciplinary team (MDT) and to investigate the correlation between nutritional status and dysphagia in these patients. The predictive value of video fluoroscopic swallowing study (VFSS) and EAT-10 scale for malnutrition was compared. Methods Subjects were patients with Parkinsonism participated in joint MDT consultation project in Peking Union Medical College Hospital from November 2020 to January 2023. Subjective and objective dysphagia were evaluated by EAT-10 scale score and VFSS dysphagia score. Nutritional status of the patients was evaluated by geriatric nutrition risk index (GNRI), albumin, prealbumin, serum folic acid, vitamin B12 and temporal muscle thickness. Results A total of 30 participants met the criteria and were included in the study. The age was 45-82 (66.1±9.0) years old. Six (20%) were at risk of malnutrition shown b a comprehensive nutritional status assessment using GNRI. The areas under receiver operating characteristic(ROC) curves(AUC) of VFSS dysphagia score and EAT-10 score to predict malnutrition were 0.781 (0.568-0.995) and 0.927 (0.827-1.000), respectively. EAT-10 score was correlated with GNRI(r=-0.524, P＜0.01), BMI(r=-0.618, P＜0.001), prealbumin (r=-0.616, P＜0.001). The VFSS dysphagia score was only correlated with BMI (r=-0.446, P＜0.05) and prealbumin(r=-0.387, P＜0.05). Conclusions Patients with Parkinsonism requiring MDT often have multiple micronutrient imbalance. Patients′ subjective perception of dysphagia has a greater impact on their nutritional status than objective assessment of dysphagia.

Abstract Extrusion-based three-dimensional (3D) printing of gelatin (Gel) is crucial for fabricating bone tissue engineering scaffolds via additive manufacturing. However, the thermal instability of Gel remains a persistent challenge, as it tends to collapse at mild temperatures. Current approaches often involve simply mixing Gel particles with various materials, resulting in biomaterial inks that lack uniformity and have inconsistent degradation characteristics. In this study, acetic acid was used to dissolve Gel and polycaprolactone (PCL) separately, producing homogeneous Gel/PCL dispersions with optimal pre-treatment performance. These dispersions were then combined and hybridized with nano-hydroxyapatite (n-HA) to create a composite printing ink. By evaluating the printability of the ink, the optimal conditions were identified: a n-HA concentration of 50% (w/w), a printing temperature of 10–15 ℃, a printing pressure of 2.5 bar, and a printing speed of 7 mm/s. The resulting biomaterial inks, with a composition of 25% Gel, 25% PCL, and 50% n-HA, demonstrated excellent printability and stability, along with significantly enhanced mechanical properties. As a result, 3D scaffolds with high printability and shape fidelity can be printed at room temperature, followed by deep freezing at -80 ℃ and cross-linking with vanillin. The Gel-based composite scaffolds demonstrated excellent biocompatibility, cell adhesion, cell viability and nano-hydroxyapatite absorption in vitro. Additionally, in vivo experiments revealed that the bioactive scaffold biodegraded during implantation and significantly promoted bone regeneration at the defect site. This provides a promising strategy for treating bone defects in clinical setting. In conclusion, the Gel/PCL/n-HA biomaterial inks presented here offer an innovative solution for extrusion bioprinting in the field of bone tissue engineering. Graphical Abstract

Aluminum alloy materials are the primary choice for lightweight components. High-velocity compaction (HVC) enhances the density of diverse materials. This study utilizes HVC to enhance the density of aluminum alloy. This work examined the influence of compaction velocity, response time (Γ), compaction times, and height-diameter ratio on the impact force of HVC. The maximum force increased linearly with higher compaction velocity, reaching up to 700 kN when the compaction velocity was 9.4 m/s, alongside achieving a peak relative density of 95%. Investigation into the influence of compaction times on the impact force of HVC revealed that the state of powders were critical factors affecting the magnitude of impact force. When the total compaction energy was consistent, the maximum force from double strokes was observed to be lower compared to single stroke. Furthermore, in double strokes with the same second stroke of 55 mm, it was noted that the maximum force increased with higher velocity during the initial compaction. Additionally, both the maximum force and green density decreased as the height-diameter ratio increased. When the height-diameter was 0.4, the maximum force and green density were higher 251 kN, 0.22 g/cm3 than that of 1.2.

Evidence regarding the association between cancer and heart failure (HF) is scarce. This study is to investigate the association between HF and cancer and explore the prognostic value of NT-proBNP in cancer patients. This cohort study used National Health and Nutrition Examination Survey data from 1999 to 2018 and linked mortality information until 2019. We included all participants with valid answer to questions regarding self-reported cancer and HF. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Our study included data from 54,847 adult participants. During a median (IQR) follow-up of 9.6 (4.0–15.1) years, 7674 deaths were recorded. HF was associated with an increased occurrence of cancer after propensity score matching (OR = 1.46, 95% CI: 1.17–1.82, p < 0.001). Cancer was associated with a higher occurrence of HF (OR = 1.33, 95% CI: 1.11–1.59, p = 0.002). Kaplan–Meier survival analysis over 10 years revealed the shortest survival in patients with both HF and cancer (log-rank p < 0.0001). Importantly, NT-proBNP was significantly higher in cancer patients, no matter whether with known HF (p < 0.01). In cancer patients without HF, NT-proBNP higher than 51.51 pg/mL was associated with shorter survival (log-rank p < 0.0001). Findings from this cohort study suggest that HF is significantly associated with cancer. NT-proBNP was higher in cancer patients, with significant prognostic value in cancer patients.

Abstract The human insulin gene modified with a C-peptide was synthesized according to the plant-preferred codon, and a fusion gene expression vector of insulin combined with green fluorescent protein (GFP) was constructed. The optimization of the flax callus culturing was undertaken, and a more efficient Agrobacterium-mediated genetic transformation of the flax hypocotyls was achieved. The critical concentration values of hygromycin on the flax hypocotyl development, as well as on its differentiated callus, were explored by the method of antibiotic gradient addition, and the application of antibiotic screening for the verification of positive calluses was assessed. The fusion gene of insulin and GFP was successfully inserted into the flax genome and expressed, as confirmed through polymerase chain reaction and Western blotting. In conclusion, we have established a flax callus culture system suitable for insulin expression. By optimizing the conditions of the flax callus induction, transformation, screening, and verification of a transgenic callus, we have provided an effective way to obtain insulin. Moreover, the herein-employed flax callus culture system could provide a feasible, cheap, and environmentally friendly platform for producing bioactive proteins. Graphical Abstract

Abstract Background Oxidative stress (OS) is one of the major causes of ovarian aging and dysfunction. Indole-3-propionic acid (IPA) is an indole compound derived from tryptophan with free radical scavenging and antioxidant properties, and thus may have potential applications in protecting ovarian function, although the exact mechanisms are unknown. This study aims to preliminarily elucidate the potential mechanisms of IPA that benefit ovarian reserve function through network pharmacology, molecular docking, and experimental verification. Methods The related protein targets of IPA were searched on SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. The potential targets of diminished ovarian reserve (DOR) were identified from OMIM, GeneCards, DrugBank, and DisGeNET databases. The common targets were uploaded directly to the STRING database to construct PPI networks. We then performed GO and KEGG enrichment analysis on the targets. Subsequently, molecular docking and molecular dynamics simulation were used to validate the binding conformation of IPA to candidate targets. Furthermore, we carried out in vitro experiments to validate the prediction results of network pharmacology. Results We identified a total of 61 potential targets for the interaction of IPA with DOR. The PPI network topological parameter analysis yielded 13 hub genes for DOR treatment. The GO biological process enrichment analysis identified 293 entries, mainly enriched in aging, signal transduction, response to hypoxia, negative regulation of apoptotic process, and positive regulation of cell proliferation. The KEGG enrichment analysis mainly included lipid and atherosclerosis, progesterone-mediated oocyte maturation, AGE-RAGE, relaxin, estrogen, and other signaling pathways. The molecular docking further revealed the direct binding of IPA with six hub proteins including NOS3, AKT1, EGFR, PPARA, SRC, and TNF. In vitro experiments showed that IPA pretreatment attenuated H2O2-induced cellular oxidative stress damage, while IPA exerted cytoprotective and antioxidant damage effects by regulating the six hub genes and antioxidant proteins. Conclusion We systematically illustrated the potential protective effects of IPA against DOR through multiple targets and pathways using network pharmacology, and further verified the cytoprotective effect and antioxidant properties of IPA through in vitro experiments. These findings provide new insights into the targets and molecular mechanisms whereby IPA improves DOR.

Abstract Background & aims Perilipin 1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved. Methods Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC progression based on HCC differentially expressed genes and PLIN1 co-expressed genes. Results PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signalling pathways were the three most enriched molecular mechanisms. Conclusion The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.

Abstract Background Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. Methods We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (

Abstract Long non-coding RNAs (lncRNAs) play an important role in breast cancer progression, but the function of lncRNAs in regulating tumor-associated macrophages (TAMs) remains unclear. As carriers of lncRNAs, exosomes play an important role as mediators in the communication between cancer cells and the tumor microenvironment. In this study, we found that lncRNA HAGLROS was highly expressed in breast cancer tissues and plasma exosomes, and its high expression was related to the poor prognosis of breast cancer patients. Functionally, breast cancer cell-derived exosomal lncRNA HAGLROS promotes breast cancer cell proliferation, migration, epithelial-mesenchymal transition (EMT) process and angiogenesis by inducing TAM/M2 polarization. Mechanistically, lncRNA HAGLROS competitively binds to miR-135-3p to prevent the degradation of its target gene COL10A1. Collectively, these results indicated that the lncRNA HAGLROS/miR-135b-3p/COL10A1 axis promoted breast cancer progression, and revealed the interactive communication mechanism between breast cancer cells and TAMs, suggesting that lncRNA HAGLROS may be a potential biomarker and therapeutic target for breast cancer.

Abstract Objective Our aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship. Methods 684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis. Results In the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95% confidence interval [CI]: 1.475–2.625; P

Abstract The insulation performance of oil paper insulation is significantly affected by moisture such that monitoring moisture content is important. However, it is difficult to obtain the moisture content accurately due to its dynamic change under multi physical fields. Studying the moisture transportation in oil paper insulation under multi physical fields becomes a vital method in solving the problem. A multi physical model describing moisture migration was proposed, which considered the effects of temperature on moisture in different existing states in oil‐immersed paper (OIP). The temperature distribution formed a vapour pressure gradient to drive moisture migration and affected migration speed. Then, experiments and simulations of moisture migration were performed, which showed that the experiments were in good agreement with simulation. The results revealed that the temperature gradient caused uneven moisture distribution and the increased temperature reduced OIP moisture content. The established model could fully characterise moisture migration under temperature gradient, which provided a theoretical reference for predicting the risk of partial dampness and evaluating insulation performance.

Abstract Background The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES. Methods In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 μg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile. Results In total, 2 of the 30 (6.7%, 95% CI: 0.82–22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28–45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0–5 years and the 13–18 years groups, and 2 patients experienced FN in the 6–12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0–5 years, 6–12 years, and 13–18 years groups, respectively. Conclusion Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted. Trial registration This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.

Abstract Passivation materials play a crucial role in a wide range of high-efficiency, high-stability photovoltaic applications based on crystalline silicon and state-of-the-art perovskite materials. Currently, for perovskite photovoltaic, the mainstream passivation strategies routinely rely on crystalline materials. Herein, we have invented a new amorphous (lysine)2PbI2 layer-enhanced halide perovskite. By utilizing a solid phase reaction between PbI2 and lysine molecule, an amorphous (lysine)2PbI2 layer is formed at surface/grain boundaries in the perovskite films. The amorphous (lysine)2PbI2 with fewer dangling bonds can effectively neutralize surface/interface defects, achieving an impressive efficiency of 26.27% (certified 25.94%). Moreover, this amorphous layer not only reduces crystal lattice stress but also functions as a barrier against the decomposition of organic components, leading to suppressed de-structuring of perovskite and highly stable perovskite solar cells.

Abstract The ongoing efforts to optimize rechargeable Li-ion batteries led to the interest in intercalation of nanoscale layered compounds, including bilayer graphene. Its lithium intercalation has been demonstrated recently but the mechanisms underpinning the storage capacity remain poorly understood. Here, using magnetotransport measurements, we report in-operando intercalation dynamics of bilayer graphene. Unexpectedly, we find four distinct intercalation stages that correspond to well-defined Li-ion densities. Transitions between the stages occur rapidly (within 1 sec) over the entire device area. We refer to these stages as ‘in-plane’, with no in-plane analogues in bulk graphite. The fully intercalated bilayers represent a stoichiometric compound C14LiC14 with a Li density of ∼2.7·1014 cm−2, notably lower than fully intercalated graphite. Combining the experimental findings and DFT calculations, we show that the critical step in bilayer intercalation is a transition from AB to AA stacking which occurs at a density of ∼0.9·1014 cm−2. Our findings reveal the mechanism and limits for electrochemical intercalation of bilayer graphene and suggest possible avenues for increasing the Li storage capacity.

Abstract In the increasingly intricate electromagnetic environment, the radar receiver may simultaneously encounter multiple intentional or unintentional jamming signals, which results in temporal and spectral overlap of received signals and forms a composite jamming signal. The nature and extent of interference contained in the received signal are often unknown, while they significantly affect the accuracy of radar detection. AnOpen‐Set Compound Jamming Signal Recognition Framework based on Multi‐Task Multi‐Label (MTML‐OCJR) is proposed. Based on the time–frequency characteristic of compound jamming signals, the proposed framework employs multi‐label classification to identify components of compound jamming signals while incorporating an unknown signal detection task into the classification process. Time–frequency image reconstruction combined with extreme value model estimation is used to detect unknown types of jamming signals, enabling simultaneous signal recognition and anomaly detection. The obtained results show that the proposed approach has superior recognition performance for composite jamming signals in closed‐set environments and high anomaly detection ability for unknown signals in open‐set environments. This method has the potential to significantly enhance the effectiveness and reliability of jamming systems in battlefield scenarios.

Abstract Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values

Abstract Background Base editing is a powerful tool for artificial evolution to create allelic diversity and improve agronomic traits. However, the great evolutionary potential for every sgRNA target has been overlooked. And there is currently no high-throughput method for generating and characterizing as many changes in a single target as possible based on large mutant pools to permit rapid gene directed evolution in plants. Results In this study, we establish an efficient germline-specific evolution system to screen beneficial alleles in Arabidopsis which could be applied for crop improvement. This system is based on a strong egg cell-specific cytosine base editor and the large seed production of Arabidopsis, which enables each T1 plant with unedited wild type alleles to produce thousands of independent T2 mutant lines. It has the ability of creating a wide range of mutant lines, including those containing atypical base substitutions, and as well providing a space- and labor-saving way to store and screen the resulting mutant libraries. Using this system, we efficiently generate herbicide-resistant EPSPS, ALS, and HPPD variants that could be used in crop breeding. Conclusions Here, we demonstrate the significant potential of base editing-mediated artificial evolution for each sgRNA target and devised an efficient system for conducting deep evolution to harness this potential.

Abstract The wave equation revealing the wave propagation in chiral phononic crystals, established through force equilibrium law, conceals the underlying physical information, such as the essence of the motion coupling and the inertial amplification effect. This has led to a controversy over the bandgap mechanism. In this article, we theoretically unveil the reason for this controversy, and put forward an alternative approach from wave behavior to formulate the wave equation, offering an alternative pathway to articulate the bandgap physics directly. Based on the physics revealed by our theory method, we identify the obstacles in coupled acoustic and optic branches to widen and lower the bandgap. Then we introduce an approach based on spherical hinges to decrease the barriers, for customizing the bandgap frequency and width. Finally, we validate our proposal through numerical simulation and experimental demonstration.

Abstract Background Owing to the lack of evidence-based medical studies with large sample sizes, the surgical approach for the radical resection of rectal neuroendocrine tumors remains controversial. Methods We retrospectively collected the medical records of patients with rectal neuroendocrine tumors who underwent radical resection at 17 large tertiary care hospitals in China between January 1, 2010, and April 30, 2022. All patients were divided into laparoscopic and open surgery groups. After propensity score matching to reduce confounders, the postoperative and oncologic outcomes were compared between the groups. Results We enrolled 174 patients with rectal neuroendocrine tumors who underwent radical surgery. After random matching, 124 patients were included in the comparison (62, laparoscopic surgery group; 62, open surgery group). The laparoscopic surgery group had fewer complications (14.5% vs. 35.5%, P = 0.007) and superior relapse-free survival (P = 0.048). Subgroup analysis revealed that the laparoscopic surgery group had fewer complications (10.9% vs. 34.7%, P = 0.004), shorter postoperative hospital stays (9.56 ± 5.21 days vs. 12.31 ± 8.61 days, P = 0.049) and superior relapse-free survival (P = 0.025) in the rectal neuroendocrine tumors ≤ 4 cm subgroup. Conclusions Laparoscopic surgery was associated with improved postoperative outcomes and oncologic prognosis for patients with rectal neuroendocrine tumors ≤ 4 cm; it can serve as a safe and feasible option for radical surgery of rectal neuroendocrine tumors.

Abstract Background Calcification is common in advanced atheromatous plaque, but its clinical significance remains unclear. This study aimed to assess the prevalence of plaque calcification in the moderate-to-severe internal carotid artery stenosis and investigate its relationship with ipsilateral ischemia. Methods The retrospective study included 178 patients detected with proximal internal carotid artery (pICA) stenosis of ≥ 50% on multidetector computed tomography at Zhejiang Hospital from January 2019 to March 2023. Association between plaque calcification characteristics (calcification thickness, position, type, circumferential extent, calcium volume and calcium score) and ipsilateral cerebrovascular events was analyzed. Results The 178 patients (mean age 71.24 ± 10.02 years, 79.78% males) had 224 stenosed pICAs overall. Plaque calcification was noted in 200/224 (89.29%) arteries. Calcification rates were higher in older age-groups. Calcification volume (r = 0.219, p