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Abstract This study investigates the deformation and damage characteristics of the surrounding rock along the top return mining roadway of an isolated island working face at different stages and reveals its damage mechanism and evolution law. Utilizing a mine in Yangquan City, Shanxi Province, China, as the engineering background, this research employs FLAC 3D numerical simulation and on-site measurements. The findings suggest that the evolution of the plastic zone along the top roadway of the 15,106 island face is largely similar during both the excavation and mining periods. The plastic zones on either side of the roadway are expanding asymmetrically and gradually merging into the plastic zone of the coal pillar. In the destructive stage, the sub-gangs of the roadway are penetrated, indicating the progression into the plastic zone. The investigation points to extensive damage on the larger side of the roadway, the development of fissures, and the significant depth of damage as primary causes of roadway deformation. Moreover, the extent of the plastic zones on both sides of the roadway correlates positively with their relative distance. Continuous monitoring reveals an ongoing increase in roadway displacement, consistent with general observations in coal mining. The results provide valuable insights for optimizing support structures in similar mining environments.

Abstract Backgrounds Long nonconding RNAs (lncRNAs) have been found to be a vital regulatory factor in the development process of human cancer, and could regarded as diagnostic or prognostic biomarkers for human cancers. Here, we aim to confirm the expression and molecular mechanism of RP11-171K16.5 (lnc171) in hepatocellular carcinoma (HCC). Methods Screening of differentially expressed lncRNAs by RNA sequencing. Expression level of gene was studied by quantitative real-time PCR (qRT-PCR). The effects of lnc171, mir-873-5p, and ethanol on migration and invasion activity of cells were studied used transwell assay, and luciferase reporter assay was used to confirm the binding site. Results RNA sequencing showed that lnc171 was markedly up-regulated in HCC. siRNA-mediated knockdown of lnc171 repressed the migration and invasion ability of HCC cells. Bioinformatic analysis, dual luciferase reporter assay, and qRT-PCR indicated that lnc171 interacted with mir-873-5p in HCC cells, and Zin-finger E-box binding homeobox (ZEB1) was a downstream target gene of mir-873-5p. In addition, lnc171 could enhance migration and invasion ability of HCC cells by up-regulating ZEB1 via sponging mir-873-5p. More interestingly, ethanol stimulation could up-regulate the increase of lnc171, thereby regulating the expression of competing endogenous RNA (ceRNA) network factors which lnc171 participated in HCC cells. Conclusions Our date demonstrates that lnc171 was a responsive factor of ethanol, and plays a vital role in development of HCC via binding of mir-873-5p.

Abstract The asymmetric calibration method is a very interesting technology for differential output probes. It has been proven that the asymmetric calibration method (ACM) can broaden the application scenarios of the electromagnetic field dual probe. However, ACM is not verified on a back‐to‐back double‐loop differential magnetic field probing system. This paper calibrates a back‐to‐back double‐loop differential magnetic field probing system by inserting a connector for creating an asymmetry using ACM. The calibration results show that ACM can be used to calibrate an asymmetric back‐to‐back double‐loop differential magnetic field probing system. The calibration results are further verified by measuring the standing wave magnetic field, and the verification results show that the asymmetric calibration method is effective in eliminating the asymmetry of the back‐to‐back double‐loop differential magnetic field probing system and the work frequency band reaches up to 12 GHz.

Background: Idiosyncratic drug-induced liver injury (IDILI) is a serious side effect of drugs, Epimedii Folium (EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Fructus Ligustri Lucidi (FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

Abstract Background The laparoscopically harvested omental flap (LHOF) has been used in partial or total breast reconstruction, but most studies on LHOF were case reports or small case series. However, the clinical feasibility and oncological safety of LHOF in oncoplastic breast surgery remains controversial. This study reported our experience applying LHOF for immediate breast reconstruction. Methods Between June 2018 and March 2022, 300 patients underwent oncoplastic breast surgery using LHOF at our institution. Their clinicopathological data, complications, cosmetic outcomes, and oncologic outcomes were evaluated. Results All patients underwent total breast reconstruction using LHOF after nipple-sparing mastectomy. The median operation time was 230 min (ranging from 155 to 375 min). The median operation time for harvesting the omental flap was 55 min (ranging from 40 to 105 min). The success rate of the laparoscopically harvested pedicled omental flap was over 99.0%. Median blood loss was 70 ml, ranging from 40 to 150 ml. The volume of the flap was insufficient in 102 patients (34.0%). The overall complication rate was 12.3%. Subcutaneous fluid in the breast area (7%) was the most common reconstruction-associated complication, but most cases were relieved spontaneously. The incidence rate of omental flap necrosis was 3.3%. LHOF-associated complications occurred in two cases, including one case of incisional hernia and one case of vascular injury. Cosmetic outcomes were satisfactory in 95.1% of patients on a four-point scale by three-panel assessment and 97.2% using the BCCT.core software. Two local and one systemic recurrence were observed during a median follow-up period of 32 months. Conclusions The LHOF for immediate breast reconstruction is a safe and feasible method that involves minimal donor-site morbidity, satisfactory cosmetic outcomes, and promising oncologic safety.

Abstract Background Facial fractures are common injuries causing cosmetic, functional, and psychological damage. The purpose of this study was to assess the incidence, prevalence, and years lived with disability (YLDs) of facial fractures from 1990 to 2019 using the Global Burden of Disease (GBD). Methods Detailed data for the disease burden of facial fractures were obtained from online available public data (Global Health Data Exchange) derived from the GBD study. The incidence, prevalence, and YLDs of facial fractures from 1990 to 2019 were analyzed by country, region, age, gender, sociodemographic index (SDI), and cause. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized YLDs rate (ASYR), and estimated annual percentage change (EAPC) were calculated to evaluate the disease burden and quantify the trends over time. The main causes of facial fractures in different years and ages were assessed. Results Globally, there were 8.9 million incident cases, 1.5 million cases prevalent cases, and 98.1 thousand years YLDs in 2019. Compared with 1990, the number of incident cases, prevalent cases, and YLDs increased, while ASIR (EAPC, − 0.47; 95% uncertainty interval [UI], − 0.57 to − 0.37), ASPR (EAPC, − 0.39; 95% UI, − 0.46 to − 0.31), ASYR (EAPC, − 0.39; 95% UI, − 0.47 to − 0.32) showed a downward trend. The high SDI region held the highest ASIR, ASPR, and ASYR both in 1990 and 2019, such as New Zealand, Slovenia, and Australia. The burden was higher in men than in women from 1990 to 2019, while the ASRs in women exceeded that of men in the elderly. The ASIR peaked in the young adult group, however, the ASPR and ASYR increased with age. Falls and road injuries were the leading causes of facial fractures. Conclusions Facial fractures continue to cause a heavy burden on public health worldwide. More targeted strategies need to be established to control the burden of facial fractures.

Abstract Michaelis constant (KM) is one of essential parameters for enzymes kinetics in the fields of protein engineering, enzyme engineering, and synthetic biology. As overwhelming experimental measurements of KM are difficult and time-consuming, prediction of the KM values from machine and deep learning models would increase the pace of the enzymes kinetics studies. Existing machine and deep learning models are limited to the specific enzymes, i.e., a minority of enzymes or wildtype enzymes. Here, we used a deep learning framework PaddlePaddle to implement a machine and deep learning approach (GraphKM) for KM prediction of wildtype and mutant enzymes. GraphKM is composed by graph neural networks (GNN), fully connected layers and gradient boosting framework. We represented the substrates through molecular graph and the enzymes through a pretrained transformer-based language model to construct the model inputs. We compared the difference of the model results made by the different GNN (GIN, GAT, GCN, and GAT-GCN). The GAT-GCN-based model generally outperformed. To evaluate the prediction performance of the GraphKM and other reported KM prediction models, we collected an independent KM dataset (HXKm) from literatures.

With the gradual advancement of the Healthy China strategy, the comprehensive healthcare industry represented by “homology of medicine and food” has gradually become a hot topic. As one of the most consumed condiments in China, chili can be used for medicinal and culinary purposes. Capsaicin (CAP), a major bioactive substance in chili, possesses biological effects such as analgesic, antioxidant, anti-inflammatory, anti-cancer, anti-obesity and cardioprotective and has been extensively studied for its pharmacological functions and potential action mechanisms. Considering that the application of CAP has some problems including high irritation, poor water solubility and low bioavailability, this paper reviews the evaluation of novel delivery systems for improving the oral bioavailability of capsaicin, including liposomes, micelles, micro/nanoemulsions, Pickering emulsions and nanoparticles based on stability, encapsulation rate and biological properties. This review aims to provide a theoretical basis for the development of capsaicin into functional nutraceuticals.

Abstract A large number of burnt rocks in some open-pit mines in Xinjiang, Inner Mongolia and Ningxia have a great influence on the blasting effect. For this kind of rock, through the analysis of physical and chemical changes, combined with ANSYS/LS-DYNA and PFC 2D numerical simulation software, a burnt rock model with multiple joint cracks and irregular distribution is constructed to simulate the blasting process of burnt rock under the combined action of stress wave and detonation gas. The results show that the fracture of rock mass affects the propagation of blasting cracks in the fracture area, resulting in stress concentration and stress hindrance. The action time of stress wave is reduced, and the energy of blasting gas is partially absorbed by the fracture, resulting in uneven stress on the burnt rock bench and seriously affecting the bench blasting effect.

Abstract Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction.

Abstract Study objective This meta-analysis aimed to assess whether continuous intravenous administration of DEX during surgery can be part of the measures to prevent the onset of postoperative delirium and postoperative cognitive dysfunction in elderly individuals following regional anesthesia. Methods We searched the databases of PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (by June 1, 2023) for all available randomized controlled trials assessing whether intravenous application of dexmedetomidine can help with postoperative delirium and postoperative cognitive dysfunction in the elderly with regional anesthesia. Subsequently, we carried out statistical analysis and graphing using Review Manager software (RevMan version 5.4.1) and STATA software (Version 12.0). Main results Within the scope of this meta-analysis, a total of 18 randomized controlled trials were included. Among them, 10 trials aimed to assess the incidence of postoperative delirium as the primary outcome, while the primary focus of the other 8 trials was on the incidence of postoperative cognitive dysfunction. The collective evidence from these 10 studies consistently supports a positive relationship between the intravenous administration of dexmedetomidine and a decreased risk of postoperative delirium (RR: 0.48; 95%CI: 0.37 to 0.63, p

Abstract Background Abnormal dynamics of the Golgi apparatus reshape the tumor microenvironment and immune landscape, playing a crucial role in the prognosis and treatment response of cancer. This study aims to investigate the potential role of Golgi apparatus-related genes (GARGs) in the heterogeneity and prognosis of head and neck squamous cell carcinoma (HNSCC). Methods Transcriptional data and corresponding clinical information of HNSCC were obtained from public databases for differential expression analysis, consensus clustering, survival analysis, immune infiltration analysis, immune therapy response assessment, gene set enrichment analysis, and drug sensitivity analysis. Multiple machine learning algorithms were employed to construct a prognostic model based on GARGs. A nomogram was used to integrate and visualize the multi-gene model with clinical pathological features. Results A total of 321 GARGs that were differentially expressed were identified, out of which 69 were associated with the prognosis of HNSCC. Based on these prognostic genes, two molecular subtypes of HNSCC were identified, which showed significant differences in prognosis. Additionally, a risk signature consisting of 28 GARGs was constructed and demonstrated good performance for assessing the prognosis of HNSCC. This signature divided HNSCC into the high-risk and low-risk groups with significant differences in multiple clinicopathological characteristics, including survival outcome, grade, T stage, chemotherapy. Immune response-related pathways were significantly activated in the high-risk group with better prognosis. There were significant differences in chemotherapy drug sensitivity and immune therapy response between the high-risk and low-risk groups, with the low-risk group being more suitable for receiving immunotherapy. Riskscore, age, grade, and radiotherapy were independent prognostic factors for HNSCC and were used to construct a nomogram, which had good clinical applicability. Conclusions We successfully identified molecular subtypes and prognostic signature of HNSCC that are derived from GARGs, which can be used for the assessment of HNSCC prognosis and treatment responses.

AIM: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. RESULTS: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. CONCLUSION: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

IntroductionScreening for effective antiviral compounds from traditional Mongolian medicine not only aids in the research of antiviral mechanisms of traditional medicines, but is also of significant importance for the development of new antiviral drugs targeting influenza A virus. Our study aimed to establish high-throughput, rapid screening methods for antiviral compounds against influenza A virus from abundant resources of Mongolian medicine.MethodsThe use of GFP-based reporter viruses plays a pivotal role in antiviral drugs screening by enabling rapid and precise identification of compounds that inhibit viral replication. Herein, a GFP-based reporter influenza A virus was used to identify potent anti-influenza compounds within traditional Mongolian medicine.ResultsOur study led to the discovery of three active compounds: Cardamonin, Curcumin, and Kaempferide, all of which exhibited significant antiviral properties in vitro. Subsequent analysis confirmed that their effectiveness was largely due to the stimulation of the antiviral signaling pathways of host cells, rather than direct interference with the viral components, such as the viral polymerase.DiscussionThis study showcased the use of GFP-based reporter viruses in high-throughput screening to unearth antiviral agents from traditional Mongolian medicine, which contains rich antiviral compounds and deserves further exploration. Despite certain limitations, fluorescent reporter viruses present substantial potential for antiviral drug screening research due to their high throughput and efficiency.

Abstract Objective Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation. The aim of this study was to determine the incidence of mobilization failure and characterize the risk factors associated with poor mobilization (PM) of MM patients in novel therapies era. Methods We conducted a retrospective study of 211 MM patients who received their first peripheral blood stem cells (PBSC) mobilization at our single center. The following data were collected: age, gender, clinical stage, disease status, complete blood cell count, induction regimen, CD34+ cell count in peripheral blood (PB), and PBSC collections. Results In addition to conventional drugs, 22 (10.4%) patients received daratumumab containing induction, and 33 (15.6%) patients used plerixafor for poor mobilization (pre‐apheresis PB CD34+ cells 41 g/L before mobilization, and steady‐state mobilization were risk factors for PM in subgroups of patients treated with lenalidomide for

The gearbox is a critical component of electromechanical systems. The occurrence of multiple faults can significantly impact system accuracy and service life. The vibration signal of the gearbox is an effective indicator of its operational status and fault information. However, gearboxes in real industrial settings often operate under variable working conditions, such as varying speeds and loads. It is a significant and challenging research area to complete the gearbox fault diagnosis procedure under varying operating conditions using vibration signals. This data article presents vibration datasets collected from a gearbox exhibiting various fault degrees of severity and fault types, operating under diverse speed and load conditions. These faults are manually implanted into the gears or bearings through precise machining processes, which include health, missing teeth, wear, pitting, root cracks, and broken teeth. Several kinds of actual compound faults are also encompassed. The development of these datasets facilitates testing the effectiveness and reliability of newly developed fault diagnosis methods.

In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

Multifunctional materials are highly desired for the design of compact engineering structures, such as aircraft where weight reduction, sound absorption, load carrying, and energy harvesting are key considerations. However, design challenge remains in the balance of multiple functionalities. Here, we combine the sandwich structure with the neck-embedded cavities to design a cellular metamaterial having sound-absorption, compression/impact resistance and energy harvesting functionalities. For sound absorption, an autoencoder-like neural network is constructed to generate an instant design, after which a probabilistic module is inserted to optimize it by searching solutions in a slightly expanded design space. This inverse design has been experimentally validated, showing broadband sound absorption from 400 to 650 Hz merely with nine ultra-thin resonators. Beyond serving as absorber, the resonant cavities, once installed with well-tuned piezoelectric membranes, can gather broadband acoustic energy at low frequencies. Additionally, the cellular metamaterial inherits the excellent mechanical properties of honeycomb cores, having a low density of 0.64 g/cm3 yet displaying a high yield strength (21.2 MPa) in out-of-plane compression test and a superior energy absorption capability (8.6 J/cm3) in low-velocity impact tests. This work presents an effective approach to design lightweight metamaterials of superior mechanical and acoustic functionalities highly sought-after in practical engineering.