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[Objective] In recent years, climate warming and other factors have led to a rise in extreme weather events globally. Simultaneously, under the "carbon peak - carbon neutral" goal, the integration of fluctuating renewable energy including wind and solar energy, extensive use of power electronics and long-distance ultra-high-voltage transmission have reshaped traditional power grids. These changes have increased the exposure of primary equipment to harsh environments, intensifying the vulnerability of power systems to extreme weather impacts. [Method] This paper reviewed the impact of recent extreme weather events, such as typhoons, heavy rainfall and ice storms, on power system equipment and operations. It explored systemic risk performance in depth in new power systems through case studies and proposed strategies for refined modeling, systemic risk assessment and cross-disciplinary collaboration across disaster scenarios. [Result] The research shows that extreme weather significantly increases the risks of equipment failures and system instability, with high renewable energy penetration amplifying the impact of failure propagation. [Conclusion] The safe operation of power systems under the dual pressure of in-depth construction of new power systems and intensified impact of extreme weather relies on improvement of equipment risk modeling, systemic risk control and cross- disciplinary collaboration mechanisms. Therefore, future research should focus on building multi-dimensional joint risk assessment of power systems. In addition, the paper points out the significance of strengthening in-depth integration of power systems and meteorological systems for enhancing risk prediction and dynamic response capabilities of the system, thus providing scientific basis and technical support for improving the system resilience.

Abstract Predicting protein-ligand binding affinity is essential for understanding protein-ligand interactions and advancing drug discovery. Recent research has demonstrated the advantages of sequence-based models and graph-based models. In this study, we present a novel hybrid multimodal approach, DeepTGIN, which integrates transformers and graph isomorphism networks to predict protein-ligand binding affinity. DeepTGIN is designed to learn sequence and graph features efficiently. The DeepTGIN model comprises three modules: the data representation module, the encoder module, and the prediction module. The transformer encoder learns sequential features from proteins and protein pockets separately, while the graph isomorphism network extracts graph features from the ligands. To evaluate the performance of DeepTGIN, we compared it with state-of-the-art models using the PDBbind 2016 core set and PDBbind 2013 core set. DeepTGIN outperforms these models in terms of R, RMSE, MAE, SD, and CI metrics. Ablation studies further demonstrate the effectiveness of the ligand features and the encoder module. The code is available at: https://github.com/zhc-moushang/DeepTGIN . Scientific contribution DeepTGIN is a novel hybrid multimodal deep learning model for predict protein-ligand binding affinity. The model combines the Transformer encoder to extract sequence features from protein and protein pocket, while integrating graph isomorphism networks to capture features from the ligand. This model addresses the limitations of existing methods in exploring protein pocket and ligand features.

Objective: We investigated the relation between man papillomavirus (HPV) integration status and the immediate risk of cervical intraepithelial neoplasia (CIN), as well as the triage strategy based on HPV integration test. Methods: 4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective, population-based, clinical observational study to evaluate the triage performance of HPV integration. Cervical exfoliated cells were collected for HPV testing and cytologic test. If high-risk HPV was positive, HPV integration test was performed at baseline, 2-year and 5-year follow-up. Results: At baseline, HPV integration was positively correlated with the severity of cervical pathology, ranging from 5.0% (15/301) in normal diagnosis, 6.9% (4/58) in CIN1, 31.0% (9/29) in CIN2, 70% (14/20) in CIN3, and 100% (2/2) in cervical cancer (P < 0.001). Compared with cytology, HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+, higher specificity (92.8% [90.2%–95.4%] vs. 75.5% [71.2%–79.8%], P < 0.001) and higher positive predictive value (36.4% [22.1%–50.6%] vs. 15.2% [8.5%–21.8%], P < 0.001). HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy (10.7% [44/410] vs. 27.3% [112/410], P < 0.001). The HPV integration-negative group exhibited the lowest immediate risk for CIN3+ (1.6%) and accounted for the largest proportion of the total population (89.3%), when compared with the normal cytology group (risk, 1.7%; proportion, 72.7%). Conclusion: As a key molecular basis for the development of cervical cancer, HPV integration might be a promising triage strategy for HPV-positive patients.

In order to study the effects of lychee wood chips with different toasting degrees used in the aging process on the flavor of lychee brandy, the quality and volatile flavor components of lychee brandy aged with lightly toasted (LT), moderately toasted (MT) or heavily toasted (HT) lychee wood chips were evaluated and analyzed using sensory evaluation, electronic nose and gas chromatography-mass spectrometry. Raw and aged lychee brandy with heavily toasted oak chips were used as controls. The results of electronic nose analysis were in good agreement with those of sensory evaluation, and the brandy aged with heavily roasted lychee wood chip wood had the highest overall sensory score. A total of 44 volatile aroma compounds were identified in the five brandy samples, and the types and contents of volatile components varied greatly among these samples, each with their unique olefinic flavor substances. The major volatile components of aged lychee brandy were alcohols, esters, olefins, along with lesser amounts of aldehydes and ketones, alkanes, and aromatic hydrocarbons. Ethyl decanoate, ethyl acetate, ethyl caprylate, 2-methylbutanol, isoamyl alcohol, isobutanol, alpha stigmasterol and beta stigmasterol together constituted the major flavor profile of the aged lychee brandy. Therefore, aging with a moderate amount of heavily roasted lychee wood chips resulted in better improvement in the quality of lychee brandy compared to heavily toasted oak chips.

The laser direct energy deposition (L-DED) is well-suited for metal manufacturing, offering advantages of excellent performance, high precision, intricate structures and material flexibility, etc. In this study, the microstructure and mechanical property of Ti–6Al–4V alloy were investigated using L-DED under various printing parameters. A large-area, high-resolution Electron Backscatter Diffraction (EBSD) mapping technique, enabling to characterize the coarse columnar β-grains with individual crystals up to a centimeter along the building direction, and the sub-grain acicular α′ phase down to 50 nm in the same image, was utilized to analyze the crystalline phases and their lattice orientations in additively manufactured Ti–6Al–4V parts. The microstructure evolution, involving the high temperature β grain structures, β+α phase transformation, as well as acicular α′ martensitic phases, were studied during the periodically attenuated thermal cycles of L-DED. The formation of the “fish-scale” morphology results primarily from the radically different α phase in size between the interior and edges of the “fish-scale” morphology. Additionally, the effect of processing parameters, i.e., scanning speed and laser power, on microstructures and mechanical properties is discussed in detail.

Abstract With the increase in mining depth and intensity, dynamic disasters such as rockburst in mines are becoming more severe. Deep resource extraction is characterized by a high in-situ stress geological environment, closely associated with geological dynamic disasters. However, there is currently no quantitative analysis method for the correlation between the two. In this study, an elastic energy density calculation method is employed, considering the dissipative effect of the self-weight stress field on the tectonic stress field. The remaining energy, referred to as impact energy, is used to classify the risk of coal seam impact, providing a computational method for rapid assessment of impact risk before mining production. The proposed calculation method is compared with 22 mine impact engineering practices in the literature, showing accurate predictions for 21 mines. Since measuring in-situ stress and coal seam physical and mechanical properties is a preliminary work in coal seam extraction, the comprehensive analysis of these data holds significant research and practical value.

Rock shed is an effective protection measure against rockfall. To investigate the influences of falling rock’s shape and impact angle on the impact effect of the cushioned rock shed, a modeling approach for a rock shed with a cushion layer using PFC-FLAC. The granular cushion is modeled as an aggregate of discrete non-cohesion particles, while the concrete plate and the beam are modeled as zones. The falling rock with different sphericities and impact angles is modeled as a rigid assembly. The numerical model is validated by comparing the simulation results with experimental and numerical results from previous literature. This model is applied to analyze the effects of rock shape and impact angle on the dynamic interaction effects between falling rock and cushioned rock shed, including the impact force, transmitted bottom force, penetration depth, and plate deflection. The numerical results show that the variation in the falling rock’s shape has different effects on the falling rock with different impact angles. These findings could support rock shed design by revealing the limitations of the assumptions in the past research, which may result in unsafe rock sheds for some rockfall cases.

Abstract With the shift of coal seam mining to the deep, the in-situ stress of coal and rock mass increases gradually. High ground stress can limit the generation of rock cracks caused by blasting, and blasting usually shows different crushing states than low stress conditions. In order to study the blasting expansion rule of rock mass with cavity under high ground stress and the rock mass fracture state under different side stress coefficients. In this paper, the effective range of blasting and the stress distribution under blasting load are analyzed theoretically. The RHT (Riedel-Hiermaier-Thoma) model is used to numerically simulate the blasting process of rock mass with cavity under different ground stress, and the influence of ground stress and lateral pressure coefficient on the crack growth of rock mass is studied. The results show that when there is no ground stress, the damage cracks in rock mass are more concentrated in the horizontal direction and the fracture development tends to the direction where the holes are located, which confirms the guiding effect and stress concentration effect of the holes in rock mass, which helps to promote the crack penetration between the hole and the hole. The length difference of horizontal and vertical damage cracks in rock mass increases with the increase of horizontal and vertical stress difference. Under the same lateral stress coefficient, the larger the horizontal and vertical stress difference is, the stronger the inhibition effect on crack formation is. For blasting of rock mass with high ground stress, the crack formation length between gun holes decreases with the increase of stress level, and the crack extends preferentially in the direction of higher stress. Therefore, the placement of gun holes along the direction of greater stress and the shortening of hole spacing are conducive to the penetration of cracks between gun holes and empty holes. The research can provide reference for rock breaking behavior of deep rock mass blasting.

Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls. This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope, and the qualitative and quantitative study of the complex phenomena impact on three-dimensional (3D) discrete fracture network (DFN) modeling. As the studies of the outcrop fracture pattern have been so far focused on local variations, thus, we put forward a statistical analysis of global variations. The entire outcrop is partitioned into several subzones, and the subzone-scale variability of fracture geometric properties is analyzed (including the orientation, the density, and the trace length). The results reveal significant variations in fracture characteristics (such as the concentrative degree, the average orientation, the density, and the trace length) among different subzones. Moreover, the density of fracture sets, which is approximately parallel to the slope surface, exhibits a notably higher value compared to other fracture sets across all subzones. To improve the accuracy of the DFN modeling, the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed. Subsequently, the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions. The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3–4 times. The study results present precise geological structural information, improve modeling accuracy, and provide practical solutions for addressing complex outcrop issues.

BackgroundThrough its extensive connection with the cortex, the thalamus constitutes the hub of cortico-subcortical circuits and participants in multi-dimensional functions. However, the differential involvements of thalamic functional connectivity in chronic capsular and pontine stroke are still unknown.MethodsThe research recruited 66 left-lesion chronic stroke patients, including 46 capsular strokes (CS) and 20 pontine stroke (PS) patients, and 67 normal controls (NC). The thalamic subfields functional connectivities were compared between groups using a two-way repeated analysis of variance (ANOVA), corrected for confounders including age, gender, education and scanners. Spearman partial correlation was used to explore the potential association between altered thalamic FC and clinical variables.ResultsThe ipsilesional thalamus of CS patients had abnormally decreased FC with widespread cognitive-related areas while increased FC with visual- and somatic-motor areas. In contrast, the ipsilesional thalamus of PS patients mainly demonstrated increased FC in these sensorimotor areas. Even in the contralesional thalamus, we observed similar (with the ipsilesional) but less extensive functional dysconnectivity patterns in both the CS and PS patients (P < 0.05, corrected using family-wise error [FWE] at the voxel level). Finally, we found significant group x subfields interactions on thalamic functional connectivity, where capsular vs. pontine stroke demonstrate varied functional dysconnectivity with specific thalamic subfields. Finally, a weak correlation was found between FC of both ipsilesional/contralesional thalamic subfields and motor, working and verbal memory.ConclusionsThe thalamic functional dysconnectivity after chronic stroke are lesion-location and subfields dependent. Moreover, functional dysconnectivity were shown in both the ipsilesional and contralesional thalamus with similar patterns.

IntroductionA rapid, accurate, and specific ultrafiltration with ultra-performance liquid chromatographic-tandem mass spectrometry method was validated for the simultaneous determination of the protein binding rate of atorvastatin in uremic patients. Methods: The plasma samples were centrifuged at 6,000 r/min for 15 min at 37°C and the ultrafiltrate was collected. An ACQUITY UPLC® BEH C18 Column with gradient elution of water (0.1% formic acid) and acetonitrile was used for separation at a flow rate of 0.4 ml/min.ResultsThe calibration curves of two analytes in the serum showed excellent linearity over the concentration ranges of 0.05-20.00 ng/ml for atorvastatin, and 0.05-20.00 ng/ml for orthohydroxy atorvastatin, respectively. This method was validated according to standard US food and drug administration and European medicines agency guidelines in terms of selectivity, linearity, detection limits, matrix effects, accuracy, precision, recovery, and stability. This assay can be easily implemented in clinical practice to determine the free and combined concentrations of atorvastatin in the plasma of uremic patients. The final result showed that the average plasma protein binding rate in uremic patients was 86.58 ± 2.04%, relative standard deviation (RSD) (%) = 1.98, while the plasma protein binding rate in patients with normal renal function was 97.62 ± 1.96%, RSD (%) = 2.04. There was a significant difference in the protein binding rate in different types of plasma (P < 0.05), and the protein binding rate decreased with increasing creatinine until it stabilized at nearly 80%. The mean metabolite/prototype ratio of atorvastatin in patients with normal renal function and in patients with uremia was 1.085 and 0.974, respectively.DiscussionThe metabolic process of atorvastatin may be inhibited in uremic hemodialysis patients, but the total concentration of atorvastatin did not change significantly; due to the decrease of protein binding rate increase the drug distribution of atorvastatin in the liver or muscle tissue, which may increase the risk of certain adverse reactions. We recommend that clinicians use free drug concentration monitoring to adjust the dose of atorvastatin to ensure patient safety for uremic hemodialysis patients.

Abstract Cistrome‐wide association studies (CWAS) are pivotal for identifying genetic determinants of diseases by correlating genetically regulated cistrome states with phenotypes. Traditional CWAS typically develops a model based on cistrome and genotype data to associate predicted cistrome states with phenotypes. The random effect cistrome‐wide association study (RECWAS), reevaluates the necessity of cistrome state prediction in CWAS. RECWAS utilizes either a linear model or marginal effect for initial feature selection, followed by kernel‐based feature aggregation for association testing is introduced. Through simulations and analysis of prostate cancer data, a thorough evaluation of CWAS and RECWAS is conducted. The results suggest that RECWAS offers improved power compared to traditional CWAS, identifying additional genomic regions associated with prostate cancer. CWAS identified 102 significant regions, while RECWAS found 50 additional significant regions compared to CWAS, many of which are validated. Validation encompassed a range of biological evidence, including risk signals from the GWAS catalog, susceptibility genes from the DisGeNET database, and enhancer‐domain scores. RECWAS consistently demonstrated improved performance over traditional CWAS in identifying genomic regions associated with prostate cancer. These findings demonstrate the benefits of incorporating kernel methods into CWAS and provide new insights for genetic discovery in complex diseases.

BackgroundAcute ischemic stroke (AIS) is an acute brain injury caused by sudden occlusion of a blood vessel. Endovascular therapy is the most effective way to restore blood flow. However, despite the restoration of blood flow in some patients, their clinical prognosis often remains unsatisfactory. Albumin has shown neuroprotective effects in animal models of AIS. Therefore, this study aims to evaluate the safety, feasibility, and efficacy of local arterial infusions of 20% human serum albumin solution as an adjuvant therapy after endovascular therapy in patients with AIS.MethodsThis study is a prospective, therapeutic exploratory, non-randomized, open-label, phase 1 clinical trial testing the use of 20% human serum albumin solution injected via the artery immediately after successful reperfusion in patients with AIS. The study is divided into two stages. In the first stage, a single-dose-finding will explore the maximum safe dose according to the 3 + 3 dose escalation principle;, with the maximum dose being 0.60 g/kg. After recanalizing the occluded blood vessel, human serum albumin solution will be injected into the internal carotid artery region through a guiding catheter for 30 min. The second stage involves an albumin adjuvant therapy cohort (AT) and an endovascular treatment lonely cohort (ET). The AT cohort will encompass at least 15 additional participants to complete safety trials at the maximum safe dose determined in the first stage. The ET cohort will include well-matched patients receiving endovascular therapy alone, derived from a contemporaneous prospective registry, who will be excluded from having cardiopulmonary disorders and from receiving any neuroprotective therapy. The primary outcome of this study will be symptomatic intracranial hemorrhage. Efficacy outcomes will include the proportion of patients with the progression of cerebral infarction volume, a modified Rankin Scale of 0–2 on day 90 after randomization. An exploratory secondary outcome will be the analysis of thromboinflammatory and neuroprotective molecule profiles.ConclusionThis pilot trial aims to explore the safety and efficacy of arterial infusion of an albumin solution after occlusive vessel opening in AIS. The results will provide data parameters for subsequent tests on the arterial infusion of albumin solutions.Clinical trial registrationClinicalTrials.gov, NCT05953623.

Abstract Background The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC. Methods We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies. Results A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61–0.85; P

Abstract The theory and technology of rock bolting are fundamental research topics for strata control in civil and mining engineering. Rebar bolts are commonly used for roadway primary support in underground coal mine. To adapt to deep resource mining, a new left threaded rebar bolt has been developed. Compared to conventional rebar bolts, the result of installation test showed that the new bolt reduced of 41.5% and 57.9% in stirring resistance force and torque, respectively. In laboratory pullout tests, PVC and aluminum sleeves were used to simulate weak and medium strength surrounding rocks. The average peak pullout force, displacement at the peak load and energy absorption increased by 27%, 107% and 108%, respectively, using PVC sleeve; and increased by 113%, 109% and 212%, respectively, using aluminum sleeve. Field tests were conducted under soft coal, hard coal and medium strength rock geo-conditions. Different borehole depths were selected to precisely calculate the average anchorage performance of the new bolt. Results showed that the average peak pullout force of the new bolt increased by 37%, 38% and 28%, respectively, under different surrounding rock conditions. Moreover, based on on-site test results, the pullout curves in field-testing were summarised and classified into 6 different patterns, which were discussed from a viewpoint of causality mechanism. The research findings validate that the newly developed bolt has better anchorage performance compared to conventional rebar bolts, making it a new anchorage material for deep resource mining.

Landslides and ground subsidence pose significant threats to the successful construction and operation of transmission line projects in the Loess Plateau region. This study aims to explore an accurate early identification method for geological hazards, providing support for the construction and smooth operation of the transmission project along the route from Baishui County, Weinan City, Shaanxi Province to Lantian County, Xi’an City, Shaanxi Province. Small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technology was used to acquire the surface deformation data of the study area from 4 February 2018 to 21 May 2023. The deformation data were spatially analyzed through kernel density analysis, which quickly and intuitively identified 52 potential geological hazard points in the region, including eight landslides and 44 ground subsidence. Detailed field investigations of the hazards confirmed the accuracy of the identification results. A thorough analysis of typical hazards, such as landslide No. 9 and ground subsidence No. 29, revealed severe deformation, posing a threat to the proposed transmission project. This study indicates that combining InSAR, kernel density analysis, and field investigations can accurately and quickly identify geological hazards around transmission lines, providing support for the site selection and implementation of transmission projects.

BackgroundThe combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is currently the standard first-line treatment for patients with metastatic hormone receptor positive (HR+), and HER2-negative (HER2-) breast cancer. However, the impact of HER2 status on the prognosis of patients receiving CDK4/6i and ET remains unclear. The meta-analysis was conducted to evaluate different outcomes between HER2-low and HER2-zero patients in advanced HR+ breast cancer receiving CDK4/6i and ET.MethodsA systematic search was performed in PubMed and EMBASE databases for relevant published literature. Objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) were pooled by fixed or random effects models.ResultsOverall, 12 studies with 3567 patients were eligible for analysis. The pooled analysis suggested that no significant differences were observed in terms of ORR and OS between HER2-low and HER2-zero patients who underwent CDK4/6i and ET. Similarly, no significant difference in PFS was found between HER2-low and HER2-zero patients who underwent post-line CDK4/6i and ET or first-line Palbociclib and ET. However, in patients who received mixed-line (not a single treatment line) or first-line CDK4/6i and ET, the PFS was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup (mixed-line: HR = 1.36; 95% CI = 1.11–1.65; P = 0.002; first-line: HR = 1.14; 95% CI = 1.01–1.28; P = 0.04). A similar phenomenon was observed in patients who received mixed-line or post-line Palbociclib and ET (mixed-line: HR = 1.60; 95% CI = 1.09–2.34; P = 0.02; post-line: HR = 1.43; 95% CI = 1.03–2.00; P = 0.03).ConclusionThese results indicated that HER2-low status did not have a significant association with ORR and OS, but it may have a worse impact on PFS in patients who received mixed-line or first-line CDK4/6i and ET, as well as mixed-line or post-line palbociclib plus ET.

Age-related cataract (ARC) is the predominant cause of global blindness, linked to the progressive aging of the lens, oxidative stress, perturbed calcium homeostasis, hydration irregularities, and modifications in crystallin proteins. Currently, surgical intervention remains the sole efficacious remedy, albeit carrying inherent risks of complications that may culminate in irreversible blindness. It is urgent to explore alternative, cost-effective, and uncomplicated treatment modalities for cataracts. Lanosterol has been widely reported to reverse cataracts, but the mechanism of action is not yet clear. In this study, we elucidated the mechanism through which lanosterol operates in the context of cataract reversal. Through the targeted suppression of sterol regulatory element-binding protein 2 (SREBP2) followed by lanosterol treatment, we observed the restoration of lipid metabolism disorders induced by SREBP2 knockdown in lens epithelial cells (LECs). Notably, lanosterol exhibited the ability to effectively counteract amyloid accumulation and cellular apoptosis triggered by lipid metabolism disorders. In summary, our findings suggest that lanosterol, a pivotal intermediate in lipid metabolism, may exert its therapeutic effects on cataracts by influencing lipid metabolism. This study shed light on the treatment and pharmaceutical development targeting Age-related Cataracts (ARC).

Abstract Background Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy. Methods This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR. Results The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68–0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index

Rock burst is one of the disasters that seriously affect the safe and effective mining of coal in mine mining. It is of great significance and value to study the principle and technology of bolt anti-impact support to prevent and control the rock burst disaster in roadway. Through the summary and analysis of the geological conditions and failure characteristics of the rock burst of the whole coal body in the roadway, it is considered that the hard roof and hard coal seam are the important geological characteristics of this type of rock burst, and the overall slippage of the coal body in the roadway is the main impact failure characteristics. On this basis, taking the sliding coal body of roadway side as the research object, the mechanical model of roof-roadway-floor composite structure is established, and the limit equilibrium equation of horizontal sliding of roadway side coal body is established, and each parameter is analyzed. The results show that due to the rebound of the roof, the vertical pressure of the roadway side coal body is reduced, and the roadway side coal body is pushed into the roadway by the tectonic stress to cause rock burst. Based on the occurrence mechanism model, it is considered that the current bolt support design system has some shortcomings in preventing and controlling the rock burst of the coal body in the roadway. Based on its occurrence and failure characteristics, the design principle of bolt anti-impact support for the overall slippage type rock burst of the coal body in the roadway is established, that is, the anchoring ends of the roof and bottom bolts are respectively penetrated into the stable roof and floor, and the long anchor cable is used to replace the middle side bolt to provide the anti-impact effect of bolt support. Based on the newly established design method of bolt anti-scour support, taking the anti-scour support of 7305 working face of Kongzhuang Coal Mine in Datun Mining Area as the engineering background, the anti-scour design is adopted in the bolt support of roadway side in the wide coal pillar section. The roof and bottom bolts and reinforcing anchor cables are anchored inside the roof and floor, which can effectively absorb the sliding kinetic energy of the coal body and improve the safety.

Abstract Based on the disaster characteristics and the geo-conditions at the scene, in this study, the occurrence mechanism of a serious rock burst accident that occurred in the Tangshan Coal Mine, China, was analysed. Ground stress measurements showed that the mine is in a high ground stress area dominated by horizontal tectonic stress around 33 MPa. Laboratory testing revealed that the coal was a hard seam of 8.3 MPa over bedded by a thick and hard roof stratum with uniaxial compressive strength of 66 MPa. The calculation results indicated that the accident occurred in the roof rebounding area. It is proposed that the hard roof and the hard coal seam formed a seesaw structure around the working face. The vertical pressure relief caused the rib coal mass to lose its clamping forces from the roof and floor and rush into the roadway, resulting in a rock burst accident. Based on the causality mechanism of the rock burst disaster developed in this study, pertinent coal bump prevention measures have been undertaken in practice. Large-diameter boreholes were drilled to eliminate the pivot effect of the seam. Roof blasting was undertaken to prevent the roof from forming a seesaw plank. To summarize, a new causality mechanism for rock burst in coal mines under hard roof and hard seam geo-conditions was developed.

Land subsidence caused by human engineering activities is a serious problem worldwide. We selected Qian’an County as the study area to explore the evolution of land subsidence and predict its deformation trend. This study utilized synthetic aperture radar interferometry (InSAR) technology to process 64 Sentinel-1 data covering the area, and high-precision and high-resolution surface deformation data from January 2017 to December 2021 were obtained to analyze the deformation characteristics and evolution of land subsidence. Then, land subsidence was predicted using the intelligence neural network theory, machine learning methods, time-series prediction models, dynamic data processing techniques, and engineering geology of ground subsidence. This study developed three time-series prediction models: a support vector regression (SVR), a Holt Exponential Smoothing (Holt) model, and multi-layer perceptron (MLP) models. A time-series prediction analysis was conducted using the surface deformation data of the subsidence funnel area of Zhouzi Village, Qian’an County. In addition, the advantages and disadvantages of the three models were compared and analyzed. The results show that the three developed time-series data prediction models can effectively capture the time-series-related characteristics of surface deformation in the study area. The SVR and Holt models are suitable for analyzing fewer external interference factors and shorter periods, while the MLP model has high accuracy and universality, making it suitable for predicting both short-term and long-term surface deformation. Ultimately, our results are valuable for further research on land subsidence prediction.

To accurately estimate the 6D pose of objects, most methods employ a two-stage algorithm. While such two-stage algorithms achieve high accuracy, they are often slow. Additionally, many approaches utilize encoding–decoding to obtain the 6D pose, with many employing bilinear sampling for decoding. However, bilinear sampling tends to sacrifice the accuracy of precise features. In our research, we propose a novel solution that utilizes implicit representation as a bridge between discrete feature maps and continuous feature maps. We represent the feature map as a coordinate field, where each coordinate pair corresponds to a feature value. These feature values are then used to estimate feature maps of arbitrary scales, replacing upsampling for decoding. We apply the proposed implicit module to a bidirectional fusion feature pyramid network. Based on this implicit module, we propose three network branches: a class estimation branch, a bounding box estimation branch, and the final pose estimation branch. For this pose estimation branch, we propose a miniature dual-stream network, which estimates object surface features and complements the relationship between 2D and 3D. We represent the rotation component using the SVD (Singular Value Decomposition) representation method, resulting in a more accurate object pose. We achieved satisfactory experimental results on the widely used 6D pose estimation benchmark dataset Linemod. This innovative approach provides a more convenient solution for 6D object pose estimation.

Abstract Breast cancer is the most prevalent cancer globally, endangering women’s physical and mental health. Phospholipase D3 (PLD3) belongs to the phosphodiesterase family (PLD). PLD3 is related to insulin-mediated phosphorylation of the AKT pathway, suggesting that it may play a role in the occurrence and development of malignant tumors. This study may further explore the molecular mechanism of PLD3 inhibiting breast cancer cell proliferation. In this study, we demonstrated that PLD3 and miR-6796 are co-expressed in breast cancer. PLD3 can bind with CDK1 and inhibit its expression, leading to mitotic arrest and inhibiting breast cancer proliferation. Wild-type p53 regulates PLD3 and miR-6796 expression by competitively binding to the PLD3 promoter with ZEB1. DNMT3B, as the target gene of miR-6796, is recruited into the PLD3 promoter by combining with ZEB1 to regulate the DNA methylation of the PLD3 promoter and ultimately affect PLD3 and miR-6796 expression. In conclusion, we revealed the role and molecular mechanism of PLD3 and its embedded miR-6796 in breast cancer proliferation, providing clues and a theoretical foundation for future research and development of therapeutic targets and prognostic markers for breast cancer.

Corneal neovascularization (CoNV)is a major cause of blindness in many ocular diseases. Substantial evidence indicates that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of corneal neovascularization. Previous evidence showed that artemisinin may inhibit angiogenesis through down regulation of the VEGF receptors. We designed and synthesized artemisinin derivatives, and validated their inhibitory effect on neovascularization in cell and animal models, and explored the mechanisms by which they exert an inhibitory effect on CoNV. Among these derivatives, P31 demonstrated significant anti-angiogenic effects in vivo and in vitro. Besides, P31 inhibited VEGF-induced HUVECs angiogenesis and neovascularization in rabbit model via AKT and ERK pathways. Moreover, P31 alleviated angiogenic and inflammatory responses in suture rabbit cornea. In conclusion, as a novel artemisinin derivative, P31 attenuates corneal neovascularization and has a promising application in ocular diseases.

IntroductionFood quality is closely related to food safety. Improving food quality, especially staple foods quality, is crucial to ensuring sustainable food safety. China's government is making efforts to improve the quality of staple foods and has improved quality standards of purchase policy for staple food. However, the actual effects of the new quality standards of purchase policy in implementation have not been verified.MethodsBased on this background, applying difference-in-differences models, this paper examines whether the new quality standards of purchase policy can improve the quality of staple food supply based on the wheat market transaction data.Results and discussionThe results show that the new quality standard of purchase policy has a significant positive impact on the quality of staple food supply. The conclusion remains robust through several alternative tests. Further research shows that the new quality standards of purchase policy significantly expand the degree of quality premiums in the market, thereby improving the staple food supply quality. Our research provides an insight for policy or standard makers to change relevant purchase quality limits following consumer demand to ensure sustainable food security.